bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of AI-driven prediction models to realize real-time tumor tracking during radiotherapy
Authors: Zhou Dejun , Nakamura Mitsuhiro , Mukumoto Nobutaka , Tanabe Hiroaki , Iizuka Yusuke , Yoshimura Michio , Kokubo Masaki , Matsuo Yukinori , Mizowaki Takashi 
Published: February 2022

Abstract
Background
In infrared reflective (IR) marker-based hybrid real-time tumor tracking (RTTT), the internal target position is predicted with the positions of IR markers attached on the patient’s body surface using a prediction model. In this work, we developed two artificial intelligence (AI)-driven prediction models to improve RTTT radiotherapy, namely, a convolutional neural network (CNN) and an adaptive neuro-fuzzy inference system (ANFIS) model. The models aim to improve the accuracy in predicting three-dimensional tumor motion.

Methods
From patients whose respiration-induced motion of the tumor, indicated by the fiducial markers, exceeded 8 mm, 1079 logfiles of IR marker-based hybrid RTTT (IR Tracking) with the gimbal-head radiotherapy system were acquired and randomly divided into two datasets. All the included patients were breathing freely with more than four external IR markers. The historical dataset for the CNN model contained 1003 logfiles, while the remaining 76 logfiles complemented the evaluation dataset. The logfiles recorded the external IR marker positions at a frequency of 60 Hz and fiducial markers as surrogates for the detected target positions every 80–640 ms for 20–40 s. For each logfile in the evaluation dataset, the prediction models were trained based on the data in the first three quarters of the recording period. In the last quarter, the performance of the patient-specific prediction models was tested and evaluated. The overall performance of the AI-driven prediction models was ranked by the percentage of predicted target position within 2 mm of the detected target position. Moreover, the performance of the AI-driven models was compared to a regression prediction model currently implemented in gimbal-head radiotherapy systems.

Results
The percentage of the predicted target position within 2 mm of the detected target position was 95.1%, 92.6% and 85.6% for the CNN, ANFIS, and regression model, respectively. In the evaluation dataset, the CNN, ANFIS, and regression model performed best in 43, 28 and 5 logfiles, respectively.

Conclusions
The proposed AI-driven prediction models outperformed the regression prediction model, and the overall performance of the CNN model was slightly better than that of the ANFIS model on the evaluation dataset.
Shone’s complex and aortic dissection: case report and review of a rare, underdiagnosed congenital heart disease
Authors: Sinfield Steven , Ranasinghe Sachini , Wang Stephani , Mendoza Fernando , Khoynezhad Ali 
Published: February 2022

AbstractBackgroundShone’s complex is a rare congenital heart disease consisting of a variety of left ventricular inflow and outflow tract lesions. Patients typically present in childhood requiring early surgical intervention; however, with improved surgical techniques, these patients are surviving later into adulthood. This increased survival comes with a new set of medical complications that providers need to be aware of.Case presentationA 27 year old man with a complex cardiac history including an incomplete Shone’s complex and persistent symptomatic atrial flutter presented with sharp chest pain radiating to his back. He was found to have type A aortic dissection on imaging in the setting of severe patient-prosthesis mismatch. He had multiple valvular surgeries in childhood. The patient was being followed-up as an outpatient for an enlarging chronic aortic aneurysm and was non-compliant with his medications. He was taken emergently to the operating room for a skirted Bentall procedure, aortic valve replacement, and right sided MAZE.ConclusionsShone’s complex is a rare congenital heart disease associated with significant morbidities including atrial flutter, patient-prosthesis mismatch, and aortic dissection. As patients continue to live longer into adulthood with this disease, it is important to raise awareness of this rare syndrome for providers and highlight its potential complications. Further research is needed to determine appropriate guidelines for when to intervene on aortopathy-associated CHD.
Development and validation of a risk prediction model for postoperative pneumonia in adult patients undergoing Stanford type A acute aortic dissection surgery: a case control study
Authors: Wang Dashuai , Abuduaini Xiaerzhati , Huang Xiaofan , Wang Hongfei , Chen Xing , Le Sheng , Chen Manhua , Du Xinling 
Published: February 2022

Abstract
Background
Pneumonia is a common complication after Stanford type A acute aortic dissection surgery (AADS) and contributes significantly to morbidity, mortality, and length of stay. The purpose of this study was to identify independent risk factors associated with pneumonia after AADS and to develop and validate a risk prediction model.

Methods
Adults undergoing AADS between 2016 and 2019 were identified in a single-institution database. Patients were randomly divided into training and validation sets at a ratio of 2:1. Preoperative and intraoperative variables were included for analysis. A multivariate logistic regression model was constructed using significant variables from univariate analysis in the training set. A nomogram was constructed for clinical utility and the model was validated in an independent dataset.

Results
Postoperative pneumonia developed in 170 of 492 patients (34.6%). In the training set, multivariate analysis identified seven independent predictors for pneumonia after AADS including age, smoking history, chronic obstructive pulmonary disease, renal insufficiency, leucocytosis, low platelet count, and intraoperative transfusion of red blood cells. The model demonstrated good calibration (Hosmer–Lemeshow χ2 = 3.31, P = 0.91) and discrimination (C-index = 0.77) in the training set. The model was also well calibrated (Hosmer–Lemeshow χ2 = 5.73, P = 0.68) and showed reliable discriminatory ability (C-index = 0.78) in the validation set. By visual inspection, the calibrations were good in both the training and validation sets.

Conclusion
We developed and validated a risk prediction model for pneumonia after AADS. The model may have clinical utility in individualized risk evaluation and perioperative management.
Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson’s disease
Authors: Cai Waijiao , Srivastava Pranay , Feng Danielle , Lin Yue , Vanderburg Charles R. , Xu Yuehang , Mclean Pamela , Frosch Matthew P. , Fisher David E. , Schwarzschild Michael A. , Chen Xiqun 
Published: February 2022

Abstract
Background
Epidemiological studies suggest a link between the melanoma-related pigmentation gene melanocortin 1 receptor (MC1R) and risk of Parkinson’s disease (PD). We previously showed that MC1R signaling can facilitate nigrostriatal dopaminergic neuron survival. The present study investigates the neuroprotective potential of MC1R against neurotoxicity induced by alpha-synuclein (αSyn), a key player in PD genetics and pathogenesis.

Methods
Nigral dopaminergic neuron toxicity induced by local overexpression of aSyn was assessed in mice that have an inactivating mutation of MC1R, overexpress its wild-type transgene, or were treated with MC1R agonists. The role of nuclear factor erythroid 2-related factor 2 (Nrf2) in MC1R-mediated protection against αSyn was characterized in vitro. Furthermore, MC1R expression was determined in human postmortem midbrain from patients with PD and unaffected subjects.

Results
Targeted expression of αSyn in the nigrostriatal pathway induced exacerbated synuclein pathologies in MC1R mutant mice, which were accompanied by neuroinflammation and altered Nrf2 responses, and reversed by the human MC1R transgene. Two MC1R agonists were neuroprotective against αSyn-induced dopaminergic neurotoxicity. In vitro experiments showed that Nrf2 was a necessary mediator of MC1R effects. Lastly, MC1R was present in dopaminergic neurons in the human substantia nigra and appeared to be reduced at the tissue level in PD patients.

Conclusion
Our study supports an interaction between MC1R and αSyn that can be mediated by neuronal MC1R possibly through Nrf2. It provides evidence for MC1R as a therapeutic target and a rationale for development of MC1R-activating strategies for PD.
Dendritic cell-based vaccine prolongs survival and time to next therapy independently of the vaccine cell number
Authors: Hawlina Simon , Chowdhury Helena H. , Smrkolj Tomaž , Zorec Robert 
Published: February 2022

AbstractIn 2009, new EU legislation regulating advanced therapy medicinal products (ATMPs), consisting of gene therapy, tissue engineering and cell-based medicines, was introduced. Although less than 20 ATMPs were authorized since that time, the awarding of the Nobel Prize for Physiology or Medicine in 2018 revived interest in developing new cancer immunotherapies involving significant manipulation of the patient's own immune cells, including lymphocytes and dendritic cells. The lymphocytes are mainly thought to directly affect tumour cells, dendritic cells are involved in indirect mechanisms by antigen presentation to other leukocytes orchestrating the immune response. It is the latter cells that are the focus of this brief review. Based on the recent results of our study treating patients with castration-resistant prostate cancer (CRPC) with an immunohybridoma cell construct (termed aHyC), produced by electrofusion of autologous tumour and dendritic cells, we compare their effectiveness with a matched documented control group of patients. The results revealed that cancer-specific survival and the time to next in-line therapy (TTNT) were both significantly prolonged versus controls. When patients were observed for longer periods since the time of diagnosis of CRPC, 20% of patients had not yet progressed to the next in-line therapy even though the time under observation was ~ 80 months. Interestingly, analysis of survival of patients revealed that the effectiveness of treatment was independent of the number of cells in the vaccine used for treatment. It is concluded that autologous dendritic cell-based immunotherapy is a new possibility to treat not only CRPC but also other solid tumours.
Eco-evolutionary significance of domesticated retroelements in microbial genomes
Authors: Paul Blair G. , Eren A. Murat 
Published: February 2022

AbstractSince the first discovery of reverse transcriptase in bacteria, and later in archaea, bacterial and archaeal retroelements have been defined by their common enzyme that coordinates diverse functions. Yet, evolutionary refinement has produced distinct retroelements across the tree of microbial life that are perhaps best described in terms of their programmed RNA—a compact sequence that preserves core information for a sophisticated mechanism. From this perspective, reverse transcriptase has been selected as the modular tool for carrying out nature’s instructions in various RNA templates. Beneficial retroelements—those that can provide a fitness advantage to their host—evolved to their extant forms in a wide array of microorganisms and their viruses, spanning nearly all habitats. Within each specialized retroelement class, several universal features seem to be shared across diverse taxa, while specific functional and mechanistic insights are based on only a few model retroelement systems from clinical isolates. Currently, little is known about the diversity of cellular functions and ecological significance of retroelements across different biomes. With increasing availability of isolate, metagenome-assembled, and single-amplified genomes, the taxonomic and functional breadth of prokaryotic retroelements is coming into clearer view. This review explores the recently characterized classes of beneficial, yet accessory retroelements of bacteria and archaea. We describe how these specialized mechanisms exploit a form of fixed mobility, whereby the retroelements do not appear to proliferate selfishly throughout the genome. Moreover, we discuss computational approaches for systematic identification of retroelements from vast sequence repositories and highlight recent discoveries in terms of their apparent distribution and ecological significance in nature. Lastly, we present a new perspective on the eco-evolutionary significance of these genetic elements in marine bacteria and demonstrate approaches that enable the characterization of their environmental diversity through metagenomics.
5-Methylcytosine profiles in mouse transcriptomes suggest the randomness of m5C formation catalyzed by RNA methyltransferase
Authors: Liu Junfeng 
Published: February 2022

Abstract
Objective
5-Methylcytosine (m5C) is a type of chemical modification on the nucleotides and is widespread in both DNA and RNA. Although the DNA m5C has been extensively studied over the past years, the distribution and biological function of RNA m5C still remain to be elucidated. Here, I explored the profiles of RNA m5C in four mouse tissues by applying a RNA cytosine methylation data analysis tool to public mouse RNA m5C data.

Results
I found that the methylation rates of cytosine were the same with the averages of methylation level at single-nucleotide level. Furthermore, I gave a mathematical formula to describe the observed relationship and analyzed it deeply. The sufficient necessary condition for the given formula suggests that the methylation levels at most m5C sites are the same in four mouse tissues. Therefore, I proposed a hypothesis that the m5C formation catalyzed by RNA methyltransferase is random and with the same probability at most m5C sites, which is the methylation rate of cytosine. My hypothesis can be used to explain the observed profiles of RNA m5C in four mouse tissues and will be benefit to future studies of the distribution and biological function of RNA m5C in mammals.
Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins
Authors: Alrumayyan Nora , Slauenwhite Drew , McAlpine Sarah M. , Roberts Sarah , Issekutz Thomas B. , Huber Adam M. , Liu Zaiping , Derfalvi Beata 
Published: February 2022

AbstractBackgroundProlidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in thePEPDgene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used.Case presentationPatient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in thePEPDgene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Tregcells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+TEMcells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+CD8+TEMcells in both patients and overexpression of the activation marker HLA-DR on CD4+TEMcells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+Tfhcells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high.ConclusionsImmunologic abnormalities including skewed frequencies of activated inflammatory CD4+and CD8+TEMcells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.
Exosomes from tendon derived stem cells promote tendon repair through miR-144-3p-regulated tenocyte proliferation and migration
Authors: Song Kai , Jiang Tao , Pan Pin , Yao Yao , Jiang Qing 
Published: February 2022

Abstract
Background
Tendon derived stem cells (TDSCs) have proven to be effective in tendon repair by secreting paracrine factors, which modulate the function of resident cells and inflammatory process. Exosomes, which are secreted from cells to mediate intercellular communication, may be used to treat tendon injuries. Here, we aimed to determine the effects of exosomes from TDSCs (TDSC-Exos) on tendon repair and to explore the underlying mechanism by investigating the role of microRNAs (miRNAs).

Methods
TDSC-Exos were isolated from TDSC conditioned medium. In vitro studies were performed to investigate the effects of TDSC-Exos on the proliferation, migration, cytoprotection, collagen production and tendon-specific markers expression in tenocytes. In order to determine the therapeutic effects of TDSC-Exos in vivo, we used a scaffold of photopolymerizable hyaluronic acid (p-HA) loaded with TDSC-Exos (pHA-TDSC-Exos) to treat tendon defects in the rat model. Subsequently, RNA sequencing and bioinformatic analyses were used to screen for enriched miRNAs in TDSC-Exos and predict target genes. The miRNA-target transcript interaction was confirmed by a dual-luciferase reporter assay system. In order to determine the role of candidate miRNA and its target gene in TDSC-Exos-regulated tendon repair, miRNA mimic and inhibitor were transfected into tenocytes to evaluate cell proliferation and migration.

Results
Treatment with TDSC-Exos promoted proliferation, migration, type I collagen production and tendon-specific markers expression in tenocytes, and also protected tenocytes from oxidative stress and serum deprivation. The scaffold of pHA-TDSC-Exos could sever as a sustained release system to treat the rat model of tendon defects. In vivo study showed that TDSC-Exos promoted early healing of injured tendons. Rats treated with TDSC-Exos had better fiber arrangement and histological scores at the injury site. Besides, the injured tendons treated with TDSC-Exos had better performance in the biomechanical testing. Therefore, the pHA-TDSC-Exos scaffold proved to facilitate tendon repair in the rat model. miR-144-3p was enriched in TDSC-Exos and promoted tenocyte proliferation and migration via targeting AT-rich interactive domain 1A (ARID1A).

Conclusions
TDSC-Exos enhanced tenon repair through miR-144-3p-regulated tenocyte proliferation and migration. These results suggest that TDSC-Exos can serve as a promising strategy to treat tendon injuries.
A large osteoderm-bearing rib from the Upper Triassic Kössen Formation (Norian/Rhaetian) of eastern Switzerland
Authors: Scheyer Torsten M. , Oberli Urs , Klein Nicole , Furrer Heinz 
Published: February 2022

AbstractAn important component of the Alpine vertebrate record of Late Triassic age derives from the Kössen Formation, which crops out extensively in the eastern Alps. Here, we present an isolated and only partially preserved large rib, which carries an osteoderm on a low uncinate process. Osteological comparison indicates that the specimen likely belongs to a small clade of marine reptiles, Saurosphargidae. Members of the clade are restricted to the western (today Europe) and eastern margins of the Tethys (today China) and were so far known only from the Anisian stage of the Middle Triassic. The assignment of the new find to cf. Saurosphargidae, with potential affinities to the genus Largocephalosaurus from the Guanling Formation of Yunnan and Guizhou Provinces, China, would extend the occurrence of the clade about 35 million years into the Late Triassic.
Electric circuit element boundary conditions in the finite element method for full-wave passive electromagnetic devices
Authors: Ciuprina Gabriela , Ioan Daniel , Sabariego Ruth V. 
Published: February 2022

AbstractA natural coupling of a circuit with an electromagnetic device is possible if special boundary conditions, called Electric Circuit Element (ECE), are used for the electromagnetic field formulation. This contribution shows how these ECE boundary conditions can be implemented into the 3D-finite element method for solving coupled full-wave electromagnetic (EM) field-circuit problems in the frequency domain. The frequency response allows the extraction of a reduced order model of the analyzed device, accounting for all the EM field effects. The implementation is based on a weak formulation that uses the electric field strength E strictly inside the domain and a scalar potential V defined solely at the boundary. Edge elements for E are used inside the three-dimensional domain and nodal elements for V are used on its two-dimensional boundary. The weak formulation is described and implemented in the free environment Open Numerical Engineering LABoratory (onelab). The validation is carried out on 3D examples.
Dissipation patterns of acrinathrin and metaflumizone in Aster scaber
Authors: Lee Somin , Ko Rakdo , Lee Kwanghun , Kim Jinchan , Kang Seokhyeon , Lee Jiho 
Published: February 2022

AbstractThe establishment of preharvest residue limits (PHRLs) is important to minimize damage to producer and consumers caused by agricultural products which pesticide residue exceeds maximum residue limits (MRLs). Dissipation patterns of acrinathrin and metaflumizone in Aster scaber in greenhouse were studied during 10 days in order to determine a pre-harvest interval after application. Acrinathrin and metaflumizone were applied in two different greenhouse, located in Taean-gun (field 1) and Gwangyang-si (field 2). Samples were collected at 0, 1, 2, 3, 5, 7, and 10 days after insecticides application. The recoveries of two insecticides analyzed by LC–MS/MS and HPLC–DAD were ranged from 77.1 to 111.3%. The half-lives of acrinathrin and metaflumizone residues respectively were 3.8 and 5.9 days in field 1 and 9.2 and 4.5 days in field 2. The PHRLs 10 days before harvesting A. scaber were 0.610 mg/kg (field 1), 0.946 mg/kg (field 2) for acrinathrin, and 5.930 mg/kg (field 1), 5.147 mg/kg (field 2) for metaflumizone. This results can be used as basic data for the establishment of PHRL in A. scaber.