bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavior Problems Following Childhood TBI: The Role of Sex, Age, and Time Since Injury
Authors: Wade Shari L. , Kaizar Eloise E. , Narad Megan E. , Zang Huaiyu , Kurowski Brad G. , Miley Aimee E. , Moscato Emily L. , Aguilar Jessica M. , Yeates Keith Owen , Taylor H. Gerry , Zhang Nanhua 
Published: February 2020

Objective:
To examine the frequency of behavioral problems after childhood traumatic brain injury (TBI) and their associations with injury severity, sex, and social environmental factors.

Setting:
Children's hospitals in the Midwestern/Western United States.

Participants:
381 boys and 210 girls with moderate (n = 359) and severe (n = 227) TBI, with an average age at injury of 11.7 years (range 0.3-18) who were injured ≤3 years ago.

Design:
Secondary data analysis of a multistudy cohort.

Main Measures:
Child Behavior Checklist (CBCL) administered pretreatment.

Results:
Thirty-seven percent had borderline/clinical elevations on the CBCL Total Problem Scale, with comparable rates of Internalizing and Externalizing problems (33% and 31%, respectively). Less parental education was associated with higher rates of internalizing, externalizing, and total problems. Time since injury had a linear association with internalizing symptoms, with greater symptoms at longer postinjury intervals. Younger boys had significantly higher levels of oppositional defiant symptoms than girls, whereas older girls had significantly greater attention-deficit hyperactivity disorder symptoms than boys.

Conclusions:
Pediatric TBI is associated with high rates of behavior problems, with lower socioeconomic status predicting substantially elevated risk. Associations of higher levels of internalizing symptoms with greater time since injury highlight the importance of tracking children over time.
Insulin-like growth factor 2 binding protein 3 expression on endoscopic ultrasound guided fine needle aspiration specimens in pancreatic ductal adenocarcinoma
Authors: Tadic Mario , Stoos-Veic Tajana , Kujundzic Milan , Turcic Petra , Aralica Gorana , Boskoski Ivo 
Published: February 2020

Background:
Despite numerous investigations, we still do not have a specific marker for pancreatic ductal adenocarcinoma. Only guideline-recommended biomarker for pancreatic ductal adenocarcinoma is the CA19-9, but it is also present in other gastrointestinal diseases. IMP3 is a new potential biomarker that is over-expressed in some cancers. The aims of our study were (1) to assess IMP3 in benign pancreatic lesions and pancreatic cancer, and (2) to estimate its concentrations in localized and advanced pancreatic cancer.

Patients and methods:
Seventy-five patients with solid pancreatic lesions who underwent EUS-FNA were included. Patients were divided into three groups: benign lesions, cancer localized only on the pancreas, and patients with advanced pancreatic cancer (locally advanced or with distal metastases). Immunoreactivity of IMP3 was assessed on cytological smears sampled by endoscopic ultrasound.

Results:
IMP3 was expressed in 89% of the patients with pancreatic cancer and not in benign lesions. Stronger expression of IMP3 protein and stage of the pancreatic cancer was statistically significant. IMP3 was expressed in all localized cancers and in 85% of patients with advanced pancreatic cancer. In the subgroup with locally advanced cancer, IMP3 was expressed in 88%, and in 83% of patients in the subgroup with distal metastasis (P = 0.007). In the present study, sensitivity was 89%, specificity 100%, with positive predictive value of 100% and negative predictive value of 63%.

Conclusion:
There is a positive correlation between IMP3 expression and TNM stages of the pancreatic cancer. Higher expression of IMP3 on EUS-FNA specimens can suggest poorer prognosis.
Assessment of Lesion Detectability in Dynamic Whole-Body PET Imaging Using Compartmental and Patlak Parametric Mapping
Authors: Zaker Neda , Kotasidis Fotis , Garibotto Valentina , Zaidi Habib 
Published: February 2020

Purpose
Hybrid dynamic imaging allows not only the estimation of whole-body (WB) macroparametric maps but also the estimation of microparameters in the initial bed position targeting the blood pool region containing the pathology owing to the limited axial field of view of PET scanners. In this work, we assessed the capability of multipass WB 18F-FDG PET parametric imaging in terms of lesion detectability through qualitative and quantitative evaluation of simulation and clinical studies.

Methods
Simulation studies were conducted by generating data incorporating 3 liver and 3 lung lesions produced by 3 noise levels and 20 noise realizations for each noise level to estimate bias and lesion detection features. The total scan time for the clinical studies of 8 patients addressed for lung and liver lesions staging, including dynamic and static WB imaging, lasted 80 minutes. An in-house–developed MATLAB code was utilized to derive the microparametric and macroparametric maps. We compared lesion detectability and different image-derived PET metrics including the SUVs, Patlak-derived influx rate constant (K
i) and distribution volume (V) and K1, k2, k3, blood volume (bv) microparameters, and K
i estimated using the generalized linear least square approach.

Results
In total, 104 lesions were detected, among which 47 were located in the targeted blood pool bed position where all quantitative parameters were calculated, thus enabling comparative analysis across all parameters. The evaluation encompassed visual interpretation performed by an expert nuclear medicine specialist and quantitative analysis. High correlation coefficients were observed between SUVmax and K
imax derived from the generalized linear least square approach, as well as K
i generated by Patlak graphical analysis. Moreover, 3 contrast-enhanced CT-proven malignant lesions located in the liver and a biopsy-proven malignant liver lesion not visible on static SUV images and Patlak maps were clearly pinpointed on K1 and k2 maps.

Conclusions
Our results demonstrate that full compartmental modeling for the region containing the pathology has the potential of providing complementary information and, in some cases, more accurate diagnosis than conventional static SUV imaging, favorably comparing to Patlak graphical analysis.
18F-FDG PET/CT in Tuberculosis
Authors: Sood Apurva , Mittal Bhagwant Rai , Modi Manish , Chhabra Rajesh , Verma Roshan , Rana Nivedita , Parihar Ashwin Singh , Satapathy Swayamjeet , Kumar Rajender 
Published: February 2020

Purpose of the Report
Tuberculosis (TB) is a major health problem. Activated macrophages in TB lesions show high metabolic activity and can be assessed using 18F-FDG PET/CT. This retroprospective study was done to evaluate the utility of 18F-FDG PET/CT in initial assessment and therapeutic response in patients with TB.

Materials and Methods
Eighty-seven patients (male-to-female ratio, 46:41) diagnosed with pulmonary TB and extrapulmonary TB underwent whole-body 18F-FDG PET/CT for initial assessment and a follow-up scan 3 to 4 months after initiation of antitubercular therapy (ATT). Visual and semiquantitative (SUVmax) analyses were used for scan assessment. Treatment responses on interim scans were categorized as complete metabolic response (CMR), favorable response to therapy (FRT), stable disease (SD), and disease progression (DP). CMR, FRT, and SD cases were considered as responders and DP cases as nonresponders. Treatment response was correlated with clinical outcome (mortality) and ATT duration.

Results
Baseline 18F-FDG PET/CT scans were positive in all the patients and detected additional disease sites than suspected clinically in 72% patients. On interim PET/CT, 13 patients showed CMR, 43 showed FRT, 8 showed SD, and 23 showed DP. A longer duration of ATT was seen in nonresponders (P ≤ 0.001) than responders. During follow-up, 9/87 patients died, out of which 8 patients were of DP group and 1 patient belonged to SD. Nonresponders showed 35% mortality compared with 1.6% in the responder group (P ≤ 0.001).

Conclusions

18F-FDG PET/CT is a valuable imaging modality for disease mapping and assessing therapeutic response. Treatment response in the interim PET/CT done at 3 to 4 months predicted the duration of ATT and clinical outcome of the patients.
Nlrp3 Inflammasome Inhibitor MCC950 Ameliorates Obliterative Bronchiolitis by Inhibiting Th1/Th17 Response and Promoting Treg Response After Orthotopic Tracheal Transplantation in Mice
Authors: Xu Kai-Ying , Tong Song , Wu Chuang-Yan , Ding Xiang-Chao , Chen Jiu-Ling , Ming Yu , Wang Si-Hua 
Published: February 2020

Background.
Obliterative bronchiolitis (OB) remains the major complication limiting long-term survival of patients after lung transplantation. We aimed to explore the effects of the selective NACHT, LRR, and PYD domains-containing protein 3 (Nlrp3) inflammasome inhibitor MCC950 on the pathogenesis of OB.

Methods.
Mouse orthotopic tracheal transplants were performed to mimic OB. MCC950 (50 mg/kg) or saline was intraperitoneally injected daily. The luminal occlusion rate and collagen deposition were evaluated by hematoxylin and eosin and Masson’s trichrome staining, respectively. Infiltration of CD4+, CD8+ T cells, and neutrophils was detected with immunohistochemical staining. The frequencies of T helper 1 cell (Th1), T helper 17 cell (Th17), and regulatory T cells (Treg) were measured by flow cytometry. Cytokine levels were measured by ELISA kits.

Results.
MCC950 treatment significantly inhibited Nlrp3 inflammasome activation after allogeneic tracheal transplant and markedly decreased the luminal occlusion rate and collagen deposition in the allograft. The numbers of infiltrating CD4+, CD8+ T cells, and neutrophils in the allograft were also significantly reduced by MCC950 treatment. MCC950 dramatically decreased the frequencies of Th1/Th17 cells and the levels of interferon gamma/interleukin (IL)-17A and increased the Treg cell frequencies and IL-10 level; however, these effects were abolished by the addition of IL-1β and IL-18 both in vitro and in vivo. OB was also rescued by the addition of IL-1β and/or IL-18.

Conclusions.
Blocking Nlrp3 inflammasome activation with MCC950 ameliorates OB lesions. The mechanistic analysis showed that MCC950 regulated the balance of Th1/Th17 and Treg cells and that this process is partially mediated by inhibition of IL-1β and IL-18. Therefore, targeting the Nlrp3 inflammasome is a promising strategy for controlling OB after lung transplantation.
External Validation of the DynPG for Kidney Transplant Recipients
Authors: Lenain Rémi , Dantan Etienne , Giral Magali , Foucher Yohann , Asar Özgür , Naesens Maarten , Hazzan Marc , Fournier Marie-Cécile 
Published: February 2020

Background.
In kidney transplantation, dynamic prediction of patient and kidney graft survival (DynPG) may help to promote therapeutic alliance by delivering personalized evidence-based information about long-term graft survival for kidney transplant recipients. The objective of the current study is to externally validate the DynPG.

Methods.
Based on 6 baseline variables, the DynPG can be updated with any new serum creatinine measure available during the follow-up. From an external validation sample of 1637 kidney recipients with a functioning graft at 1-year posttransplantation from 2 European transplantation centers, we assessed the prognostic performance of the DynPG.

Results.
As one can expect from an external validation sample, differences in several recipient, donor, and transplantation characteristics compared with the learning sample were observed. Patients were mainly transplanted from deceased donors (91.6% versus 84.8%; P < 0.01), were less immunized against HLA class I (18.4% versus 32.7%; P < 0.01) and presented less comorbidities (62.2% for hypertension versus 82.7%, P < 0.01; 25.1% for cardiovascular disease versus 33.9%, P < 0.01). Despite these noteworthy differences, the area under the ROC curve varied from 0.70 (95% confidence interval [CI], 0.64-0.76) to 0.76 (95% CI, 0.64-0.88) for prediction times at 1 and 6 years posttransplantation respectively, and calibration plots revealed reasonably accurate predictions.

Conclusions.
We validated the prognostic capacities of the DynPG in terms of both discrimination and calibration. Our study showed the robustness of the DynPG for informing both the patient and the physician, and its transportability for a cohort presenting different features than the one used for the DynPG development.
Whole-body integration of gene expression and single-cell morphology
Authors: Vergara Hernando M. , Pape Constantin , Meechan Kimberly I. , Zinchenko Valentyna , Genoud Christel , Wanner Adrian A. , Titze Benjamin , Templin Rachel M. , Bertucci Paola Y. , Simakov Oleg , Machado Pedro , Savage Emily L. , Schwab Yannick , Friedrich Rainer W. , Kreshuk Anna , Tischer Christian , Arendt Detlev 
Published: February 2020

SummaryAnimal bodies are composed of hundreds of cell types that differ in location, morphology, cytoarchitecture, and physiology. This is reflected by cell type-specific transcription factors and downstream effector genes implementing functional specialisation. Here, we establish and explore the link between cell type-specific gene expression and subcellular morphology for the entire body of the marine annelidPlatynereis dumerilii. For this, we registered a whole-body cellular expression atlas to a high-resolution electron microscopy dataset, automatically segmented all cell somata and nuclei, and clustered the cells according to gene expression or morphological parameters. We show that collective gene expression most efficiently identifies spatially coherent groups of cells that match anatomical boundaries, which indicates that combinations of regionally expressed transcription factors specify tissue identity. We provide an integrated browser as a Fiji plugin to readily explore, analyse and visualise multimodal datasets with remote on-demand access to all available datasets.
KDM3A regulates alternative splicing of cell-cycle genes following DNA damage
Authors: Baker Mai , Petasny Mayra , Bentata Mercedes , Kay Gillian , Engal Eden , Nevo Yuval , Siam Ahmad , Dahan Sara , Salton Maayan 
Published: February 2020

ABSTRACTChanges in the cellular environment result in chromatin structure alteration, which in turn regulates gene expression. To learn about the effect of the cellular environment on the transcriptome, we studied the H3K9 de-methylase KDM3A. Using RNA-seq, we found that KDM3A regulates the transcription and alternative splicing of genes associated with cell cycle and DNA damage. We showed that KDM3A undergoes phosphorylation by PKA at serine 265 following DNA damage, and that the phosphorylation is important for a proper cell cycle regulation. We demonstrated that SAT1 alternative splicing, regulated by KDM3A, plays a role in cell cycle regulation. Furthermore we found that KDM3A’s demethylase activity is not needed for SAT1 alternative splicing regulation. In addition, we identified KDM3A’s protein partner ARID1A, the SWI/SNF subunit, and SRSF3 as regulators of SAT1 alternative splicing and showed that KDM3A is essential for SRSF3 binding to SAT1 pre-mRNA. These results suggest that KDM3A serves as a sensor of the environment and an adaptor for splicing factor binding. Our work reveals chromatin sensing of the environment in the regulation of alternative splicing.
Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue
Authors: Aquilano Katia , Sciarretta Francesca , Turchi Riccardo , Li Bo-Han , Rosina Marco , Ceci Veronica , Guidobaldi Giulio , Arena Simona , D’Ambrosio Chiara , Audano Matteo , Salvatori Illari , Colella Barbara , Faraonio Raffaella , Panebianco Concita , Pazienza Valerio , Caruso Donatella , Mitro Nico , Bartolomeo Sabrina Di , Scaloni Andrea , Li Jing-Ya , Lettieri-Barbato Daniele 
Published: February 2020

ABSTRACTLow-protein/high-carbohydrate (LPHC) diet promotes metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1- and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.
TIRAP drives myelosuppression through an Ifnγ-Hmgb1 axis that disrupts the marrow microenvironment
Authors: Ibrahim Rawa , Gopal Aparna , Fuller Megan , Umlandt Patricia , Chang Linda , Wegrzyn-Woltosz Joanna , Lam Jeffrey , Li Jenny , Lu Melody , Parker Jeremy , Karsan Aly 
Published: February 2020

AbstractActivation of inflammatory pathways is associated with bone marrow failure syndromes, but how specific molecules impact on the marrow microenvironment is not well elucidated. We report a novel role for the miR-145 target, Toll/Interleukin-1 receptor domain containing adaptor protein (TIRAP), in driving bone marrow failure. We show that TIRAP is overexpressed in various types of myelodysplastic syndromes (MDS), and suppresses all three major hematopoietic lineages.. Constitutive expression of TIRAP in hematopoietic stem/progenitor cells (HSPC) promotes upregulation ofIfnγ, leading to bone marrow failure. Myelopoiesis is suppressed through Ifnγ-Ifnγr-mediated release of the alarmin, Hmgb1, which disrupts the marrow endothelial niche. Deletion ofIfnγor Ifnγr blocks Hmgb1 release and is sufficient to reverse the endothelial defect and prevent myelosuppression. In contrast, megakaryocyte and erythroid production is repressed independently of the Ifnγ receptor. Contrary to current dogma, TIRAP-activated Ifnγ-driven marrow suppression is independent of T cell function or pyroptosis. In the absence of Ifnγ, TIRAP drives myeloproliferation, implicating Ifnγ in suppressing the transformation of bone marrow failure syndromes to myeloid malignancy. These findings reveal novel, non-canonical roles of TIRAP, Hmgb1 and Ifnγ function in the marrow microenvironment,and provide insight into the pathophysiology of preleukemic syndromes.Graphical Abstract: Model of proposed mechanism of TIRAP-induced BMFConstitutive TIRAP expression in marrow cells releases Ifnγ, which directly impacts on megakaryocyte and erythroid production, but indirectly suppresses myelopoiesis through the release of the alarmin, Hmgb1, which disrupts the marrow endothelial compartment.
Automated detection of glaucoma with interpretable machine learning using clinical data and multi-modal retinal images
Authors: Mehta Parmita , Petersen Christine , Wen Joanne C. , Banitt Michael R. , Chen Philip P. , Bojikian Karine D. , Egan Catherine , Lee Su-In , Balazinska Magdalena , Lee Aaron Y. , Rokem Ariel ,   The UK Biobank Eye and Vision Consortium
Published: February 2020

AbstractGlaucoma, the leading cause of irreversible blindness worldwide, is a disease that damages the optic nerve. Current machine learning (ML) approaches for glaucoma detection rely on features such as retinal thickness maps; however, the high rate of segmentation errors when creating these maps increase the likelihood of faulty diagnoses. This paper proposes a new, comprehensive, and more accurate ML-based approach for population-level glaucoma screening. Our contributions include: (1) a multi-modal model built upon a large data set that includes demographic, systemic and ocular data as well as raw image data taken from color fundus photos (CFPs) and macular Optical Coherence Tomography (OCT) scans, (2) model interpretation to identify and explain data features that lead to accurate model performance, and (3) model validation via comparison of model output with clinician interpretation of CFPs. We also validated the model on a cohort that was not diagnosed with glaucoma at the time of imaging but eventually received a glaucoma diagnosis. Results show that our model is highly accurate (AUC 0.97) and interpretable. It validated biological features known to be related to the disease, such as age, intraocular pressure and optic disc morphology. Our model also points to previously unknown or disputed features, such as pulmonary capacity and retinal outer layers.