bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers of mitochondrial dysfunction in acute respiratory distress syndrome: A systematic review and meta-analysis
Authors: McClintock Catherine R. , Mulholland Niamh , Krasnodembskaya Anna D. 
Published: December 2022

IntroductionAcute respiratory distress syndrome (ARDS) is one of the main causes of Intensive Care Unit morbidity and mortality. Metabolic biomarkers of mitochondrial dysfunction are correlated with disease development and high mortality in many respiratory conditions, however it is not known if they can be used to assess risk of mortality in patients with ARDS.ObjectivesThe aim of this systematic review was to examine the link between recorded biomarkers of mitochondrial dysfunction in ARDS and mortality.MethodsA systematic review of CINAHL, EMBASE, MEDLINE, and Cochrane databases was performed. Studies had to include critically ill ARDS patients with reported biomarkers of mitochondrial dysfunction and mortality. Information on the levels of biomarkers reflective of energy metabolism and mitochondrial respiratory function, mitochondrial metabolites, coenzymes, and mitochondrial deoxyribonucleic acid (mtDNA) copy number was recorded. RevMan5.4 was used for meta-analysis. Biomarkers measured in the samples representative of systemic circulation were analyzed separately from the biomarkers measured in the samples representative of lung compartment. Cochrane risk of bias tool and Newcastle-Ottawa scale were used to evaluate publication bias (Prospero protocol: CRD42022288262).ResultsTwenty-five studies were included in the systematic review and nine had raw data available for follow up meta-analysis. Biomarkers of mitochondrial dysfunction included mtDNA, glutathione coupled mediators, lactate, malondialdehyde, mitochondrial genetic defects, oxidative stress associated markers. Biomarkers that were eligible for meta-analysis inclusion were: xanthine, hypoxanthine, acetone, N-pentane, isoprene and mtDNA. Levels of mitochondrial biomarkers were significantly higher in ARDS than in non-ARDS controls (P = 0.0008) in the blood-based samples, whereas in the BAL the difference did not reach statistical significance (P = 0.14). mtDNA was the most frequently measured biomarker, its levels in the blood-based samples were significantly higher in ARDS compared to non-ARDS controls (P = 0.04). Difference between mtDNA levels in ARDS non-survivors compared to ARDS survivors did not reach statistical significance (P = 0.05).ConclusionIncreased levels of biomarkers of mitochondrial dysfunction in the blood-based samples are positively associated with ARDS. Circulating mtDNA is the most frequently measured biomarker of mitochondrial dysfunction, with significantly elevated levels in ARDS patients compared to non-ARDS controls. Its potential to predict risk of ARDS mortality requires further investigation.Systematic review registration[https://www.crd.york.ac.uk/prospero], identifier [CRD42022288262].
Use of complementary and alternative medicine by patients with hypermobile Ehlers–Danlos Syndrome: A qualitative study
Authors: Doyle Tom A. , Halverson Colin M. E. 
Published: December 2022

BackgroundPatients with hypermobile Ehlers–Danlos Syndrome (hEDS) often make use of complementary and alternative medical (CAM) techniques to manage their chronic pain and other symptoms. Nevertheless, how they use CAM, which techniques they favor, and how CAM use affects their allopathic care remain unclear. The purpose of this qualitative study was to understand patients’ personal experiences with CAM and its role in their symptom management.Materials and methodsThirty individuals living with hEDS completed a brief online survey related to their CAM use. Thereafter, in-depth interviews were conducted with 24 of the survey respondents, qualitatively investigating their experiences with CAM. Data were analyzed using thematic analysis.ResultsParticipants described massage therapy (N = 21), medical cannabis (N = 12), and mindfulness (N = 13) as some of the most useful CAM modalities for managing symptoms related to hEDS, but they expressed a general interest in pursuing any treatment that could potentially reduce their chronic pain. They suggested an overall trust in CAM modalities and practitioners and ascribed greater empathy to CAM practitioners than to conventional medical providers. However, they also described a critical skepticism of CAM (and conventional) therapies and recounted instances of injury from such treatments.ConclusionParticipants made extensive use of CAM therapies. They described both critical benefits as well as harms from the use of these non-conventional modalities. These results underscore the importance of clinicians maintaining communicative and compassionate relationships with their patients, and of an openness to the discussion and use of CAM treatments.
Blind detection of circular image rotation angle based on ensemble transfer regression and fused HOG
Authors: Dong Wenxin , Zhang Jianxun , Zhou Yuechuan , Gao Linfeng , Zhang Xinyue 
Published: December 2022

IntroductionAiming at the problems of low accuracy in estimating the rotation angle after the rotation of circular image data within a wide range (0°–360°) and difficulty in blind detection without a reference image, a method based on ensemble transfer regression network, fused HOG, and Rotate Loss is adopted to solve such problems.MethodsThe proposed Rotate Loss was combined to solve the angle prediction error, especially the huge error when near 0°. Fused HOG was mainly used to extract directional features. Then, the feature learning was conducted by the ensemble transfer regression model combined with the feature extractor and the ensemble regressors to estimate an exact rotation angle. Based on miniImageNet and Minist, we made the circular random rotation dataset Circular-ImageNet and random rotation dataset Rot-Minist, respectively.ResultsExperiments showed that for the proposed evaluation index MSE_Rotate, the best single regressor could be as low as 28.79 on the training set of Circular-ImageNet and 2686.09 on the validation set. For MSE_Rotate, MSE, MAE, and RMSE on the test set were 1,702.4325, 0.0263, 0.0881, and 0.1621, respectively. And under the ensemble transfer regression network, it could continue to decrease by 15%. The mean error rate on Rot-Minist could be just 0.59%, significantly working easier in a wide range than other networks in recent years. Based on the ensemble transfer regression model, we also completed the application of image righting blindly.
Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients
Authors: Al Jurdi Ayman , Liu Esther C. , Salinas Thalia , Aull Meredith J. , Lubetzky Michelle , Drelick Alexander L. , Small Catherine B. , Kapur Sandip , Hartono Choli , Muthukumar Thangamani 
Published: December 2022

BackgroundKidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of de novo malignancy and BK viremia in these patients is lacking.MethodsWe performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of de novo malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival.ResultsTwenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively.ConclusionrATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of de novo malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.
Progressive multifocal leukoencephalopathy genetic risk variants for pharmacovigilance of immunosuppressant therapies
Authors: Hatchwell Eli , Smith Edward B. , Jalilzadeh Shapour , Bruno Christopher D. , Taoufik Yassine , Hendel-Chavez Houria , Liblau Roland , Brassat David , Martin-Blondel Guillaume , Wiendl Heinz , Schwab Nicholas , Cortese Irene , Monaco Maria Chiara , Imberti Luisa , Capra Ruggero , Oksenberg Jorge R. , Gasnault Jacques , Stankoff Bruno , Richmond Todd A. , Rancour David M. , Koralnik Igor J. , Hanson Barbara A. , Major Eugene O. , Chow Christina R. , Eis Peggy S. 
Published: December 2022

BackgroundProgressive multifocal leukoencephalopathy (PML) is a rare and often lethal brain disorder caused by the common, typically benign polyomavirus 2, also known as JC virus (JCV). In a small percentage of immunosuppressed individuals, JCV is reactivated and infects the brain, causing devastating neurological defects. A wide range of immunosuppressed groups can develop PML, such as patients with: HIV/AIDS, hematological malignancies (e.g., leukemias, lymphomas, and multiple myeloma), autoimmune disorders (e.g., psoriasis, rheumatoid arthritis, and systemic lupus erythematosus), and organ transplants. In some patients, iatrogenic (i.e., drug-induced) PML occurs as a serious adverse event from exposure to immunosuppressant therapies used to treat their disease (e.g., hematological malignancies and multiple sclerosis). While JCV infection and immunosuppression are necessary, they are not sufficient to cause PML.MethodsWe hypothesized that patients may also have a genetic susceptibility from the presence of rare deleterious genetic variants in immune-relevant genes (e.g., those that cause inborn errors of immunity). In our prior genetic study of 184 PML cases, we discovered 19 candidate PML risk variants. In the current study of another 152 cases, we validated 4 of 19 variants in both population controls (gnomAD 3.1) and matched controls (JCV+ multiple sclerosis patients on a PML-linked drug ≥ 2 years).ResultsThe four variants, found in immune system genes with strong biological links, are: C8B, 1-57409459-C-A, rs139498867; LY9 (alias SLAMF3), 1-160769595-AG-A, rs763811636; FCN2, 9-137779251-G-A, rs76267164; STXBP2, 19-7712287-G-C, rs35490401. Carriers of any one of these variants are shown to be at high risk of PML when drug-exposed PML cases are compared to drug-exposed matched controls: P value = 3.50E-06, OR = 8.7 [3.7–20.6]. Measures of clinical validity and utility compare favorably to other genetic risk tests, such as BRCA1 and BRCA2 screening for breast cancer risk and HLA-B*15:02 pharmacogenetic screening for pharmacovigilance of carbamazepine to prevent Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.ConclusionFor the first time, a PML genetic risk test can be implemented for screening patients taking or considering treatment with a PML-linked drug in order to decrease the incidence of PML and enable safer use of highly effective therapies used to treat their underlying disease.
Multimodal brain age prediction fusing morphometric and imaging data and association with cardiovascular risk factors
Authors: Mouches Pauline , Wilms Matthias , Aulakh Agampreet , Langner Sönke , Forkert Nils D. 
Published: December 2022

IntroductionThe difference between the chronological and biological brain age, called the brain age gap (BAG), has been identified as a promising biomarker to detect deviation from normal brain aging and to indicate the presence of neurodegenerative diseases. Moreover, the BAG has been shown to encode biological information about general health, which can be measured through cardiovascular risk factors. Current approaches for biological brain age estimation, and therefore BAG estimation, either depend on hand-crafted, morphological measurements extracted from brain magnetic resonance imaging (MRI) or on direct analysis of brain MRI images. The former can be processed with traditional machine learning models while the latter is commonly processed with convolutional neural networks (CNNs). Using a multimodal setting, this study aims to compare both approaches in terms of biological brain age prediction accuracy and biological information captured in the BAG.MethodsT1-weighted MRI, containing brain tissue information, and magnetic resonance angiography (MRA), providing information about brain arteries, from 1,658 predominantly healthy adults were used. The volumes, surface areas, and cortical thickness of brain structures were extracted from the T1-weighted MRI data, while artery density and thickness within the major blood flow territories and thickness of the major arteries were extracted from MRA data. Independent multilayer perceptron and CNN models were trained to estimate the brain age from the hand-crafted features and image data, respectively. Next, both approaches were fused to assess the benefits of combining image data and hand-crafted features for brain age prediction.ResultsThe combined model achieved a mean absolute error of 4 years between the chronological and predicted biological brain age. Among the independent models, the lowest mean absolute error was observed for the CNN using T1-weighted MRI data (4.2 years). When evaluating the BAGs obtained using the different approaches and imaging modalities, diverging associations between cardiovascular risk factors were found. For example, BAGs obtained from the CNN models showed an association with systolic blood pressure, while BAGs obtained from hand-crafted measurements showed greater associations with obesity markers.DiscussionIn conclusion, the use of more diverse sources of data can improve brain age estimation modeling and capture more diverse biological deviations from normal aging.
Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA
Authors: Wang Yingwei , Wang Qixin , Chen Zan , Yang Jian , Liu Hanxiang , Peng Dengsai , Lei Lei , Liu Lin , Wang Li , Xing Naiguo , Qiu Lin , Feng Yue , Chen Yue 
Published: December 2022

PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-DOTA-IBA had a radiochemical purity of &gt;97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease.
Knowledge mapping of alternative splicing of cancer from 2012 to 2021: A bibliometric analysis
Authors: Tian Bo , Bian Yan , Bian De-Jian , Gao Ye , Zhang Xun , Zhou Si-Wei , Zhang Yan-Hui , Pang Ya-Nan , Li Zhao-Shen , Wang Luo-Wei 
Published: December 2022

BackgroundAs a processing method of RNA precursors, alternative splicing (AS) is critical to normal cellular activities. Aberrant AS events are associated with cancer development and can be promising targets to treat cancer. However, no detailed and unbiased study describes the current state of AS of cancer research. We aim to measure and recognize the current state and trends of AS cancer research in this study.MethodsThe Web of Science Core Collection was used to acquire the articles. Utilizing three bibliometric tools (CiteSpace, VOSviewer, R-bibliometrix), we were able to measure and recognize the influence and collaboration data of individual articles, journals, and co-citations. Analysis of co-occurrence and burst information helped us identify the trending research areas related to AS of cancer.ResultsFrom 2012 to 2021, the total number of papers on AS of cancer published in 766 academic journals was 3,507, authored by 20,406 researchers in 405 institutions from 80 countries/regions. Research involving AS of cancer genes was primarily conducted in the United States and China; simultaneously, the Chinese Academy of Sciences, Fudan University, and National Cancer Institute were the institutions with strong research capabilities. Scorilas Andreas is the scholar with the most publications, while the most co-citations were generated by Wang, Eric T. Plos One published the most papers on AS of cancer, while J Biol Chem was the most co-cited academic journal in this field. The results of keyword co-occurrence analysis can be divided into three types: molecular (P53, CD44, androgen receptor, srsf3, esrp1), pathological process (apoptosis, EMT, metastasis, angiogenesis, proliferation), and disease (breast cancer, colorectal cancer, prostate cancer, hepatocellular carcinoma, gastric cancer).ConclusionResearch on AS of cancer has been increasing in intensity over the past decade. Current AS of cancer studies focused on the hallmarks of AS in cancer and AS signatures including diagnostic and therapeutic targets. Among them, the current trends are splicing factors regulating epithelial–mesenchymal transition and other hallmarks, aberrant splicing events in tumors, and further mechanisms. These might give researchers interested in this field a forward-looking perspective and inform further research.
Nanopore sequencing of clonal IGH rearrangements in cell-free DNA as a biomarker for acute lymphoblastic leukemia
Authors: Sampathi Shilpa , Chernyavskaya Yelena , Haney Meghan G. , Moore L. Henry , Snyder Isabel A. , Cox Anna H. , Fuller Brittany L. , Taylor Tamara J. , Yan Donglin , Badgett Tom C. , Blackburn Jessica S. 
Published: December 2022

BackgroundAcute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, and patients with relapsed ALL have a poor prognosis. Detection of ALL blasts remaining at the end of treatment, or minimal residual disease (MRD), and spread of ALL into the central nervous system (CNS) have prognostic importance in ALL. Current methods to detect MRD and CNS disease in ALL rely on the presence of ALL blasts in patient samples. Cell-free DNA, or small fragments of DNA released by cancer cells into patient biofluids, has emerged as a robust and sensitive biomarker to assess cancer burden, although cfDNA analysis has not previously been applied to ALL.MethodsWe present a simple and rapid workflow based on NanoporeMinION sequencing of PCR amplified B cell-specific rearrangement of the (IGH) locus in cfDNA from B-ALL patient samples. A cohort of 5 pediatric B-ALL patient samples was chosen for the study based on the MRD and CNS disease status.ResultsQuantitation of IGH-variable sequences in cfDNA allowed us to detect clonal heterogeneity and track the response of individual B-ALL clones throughout treatment. cfDNA was detected in patient biofluids with clinical diagnoses of MRD and CNS disease, and leukemic clones could be detected even when diagnostic cell-count thresholds for MRD were not met. These data suggest that cfDNA assays may be useful in detecting the presence of ALL in the patient, even when blasts are not physically present in the biofluid sample.ConclusionsThe Nanopore IGH detection workflow to monitor cell-free DNA is a simple, rapid, and inexpensive assay that may ultimately serve as a valuable complement to traditional clinical diagnostic approaches for ALL.
Construction of an immune-related ceRNA network in cervical cancer based on HPV E6 splicing
Authors: Jiang Senwei , Zhou Yun , Ye Minjuan , Li Xiaomao , Zhang Lan , Yang Yuebo 
Published: December 2022

BackgroundCervical cancer is one of the leading causes of cancer-related deaths worldwide. The unspliced human papillomavirus (HPV) E6 plays an important role in tumor progression and immune regulation. Improved immunotherapy implementation might benefit from a better knowledge of HPV E6 splicing-related immune gene expressions and immunocyte infiltration in cervical cancer. This study aimed to identify the potential therapeutic and prognostic roles of unspliced/spliced E6 ratio (E6 ratio) in cervical cancer.MethodsData from the TCGA were used to analyze the E6 condition and clinical information. Nomogram and K-M analysis were used to analyze assess the prognostic significance, IOBR was used to investigate immunological infiltrates. Functions and pathway enrichment analysis of DEGs were investigated through GO analysis and KEGG pathway analysis, respectively. A core module was taken from the competitive endogenous RNA (ceRNA) network and used to build a lncRNA-miRNA-mRNA network. QT-qPCR was used to detect the expression of genes. CCK-8, colony formation, wound healing and migration assays were used to detect cell functions.ResultsOur study found that HPV E6 ratio had significantly correlation with overall survival. In cervical cancer, a high E6 ratio was adversely linked with infiltrating levels of aDC, M1 macrophages, monocytes, NKT, and Tgd. High E6 ratio phenotypes were shown to be implicated in immune response regulation, cell adhesion, and Wnt signaling pathways, according to functional enrichment analysis. Subsequently, we constructed an immune-related ceRNA network based on E6 splicing in cervical cancer, including three lncRNA (LINC00943, LIFR-AS1, DANT2, and RASSF8-AS1), four miRNA (miR-205-5p, miR-181d-5p, miR-222-3p, and miR-221-3p), and seven mRNA (FGFR1, PRLR, CXCL2, ISG20, ISG15, SDC1, and NR2F2). Among them, CXCL2, SDC1, and miR-221-3p were associated with survival and immune cell infiltration.ConclusionsThese data imply that a high E6 ratio in cervical cancer contributes to the immune-related ceRNA network, resulting in a low amount of infiltrating effector immune cells and tumor growth. As a result, the E6 ratio might be employed as a biomarker in cervical cancer to determine prognosis and treatment success.