bluuebunny/crossref_metadata_2025_split huggingface dataset:
68Ga-DOTATATE PET/CT Imaging of Refractory Pituitary Macroadenoma Invading the Orbit
Authors: Lybik Noah , Wale Daniel J. , Wong Ka Kit , Liao Eric , Viglianti Benjamin L. 
Published: March 2021

Abstract
In addition to gastroenteropancreatic neuroendocrine neoplasms, a wide variety of tumors express somatostatin receptors. Somatostatin receptor imaging, heavily utilized in neuroendocrine oncology, may also have utility in the diagnosis of other neoplasms and raises the possibility of potential therapeutic options. We describe the case of a 60-year-old man who underwent 68Ga-DOTATATE PET/CT, demonstrating an avid invasive pituitary macroadenoma. This mass was persistent and refractory despite traditional treatment options. Because of the avidity, 177Lu-DOTATATE therapy was offered, although not ultimately performed, demonstrating a potential treatment for challenging cases utilizing the principles of theranostics.
Complementary Role of 68Ga–Prostate-Specific Membrane Antigen and 18F-FDG PET/CT for Evaluation of Metastases and Treatment Response in Renal Cell Carcinoma
Authors: Has Simsek Duygu , Civan Caner , Erdem Selcuk , Sanli Yasemin 
Published: March 2021

Abstract
We present a case of clear cell renal cell carcinoma, which demonstrates complementary FDG and prostate-specific membrane antigen (PSMA) uptake on metastases in PET/CT, as an example of tumor heterogeneity. The patient had non–FDG-avid lung and bone metastases with PSMA uptake, whereas metastatic cervical and axillary lymph nodes showed vice versa, and skeletal muscle metastasis to vastus lateralis, which is an unusual region for metastasis, showed both PSMA and FDG positivity. In response assessment, mix response was detected. It seems that 68Ga-PSMA and 18F-FDG may have a complementary role in demonstration of metastasis accurately and assessment of treatment response in clear cell renal cell carcinoma.
68Ga-DOTATOC PET/CT and MR in the Evaluation of Meningeal Metastasis From Esthesioneuroblastoma
Authors: Dondi Francesco , Albano Domenico , Bertoli Mattia , Bertagna Francesco , Giubbini Raffaele 
Published: March 2021

Abstract
Esthesioneuroblastoma is a rare malignant tumor arising from olfactory neuroepithelium. PET/CT with different tracers such as 18F-FDG and 68Ga-somatostatin-receptor tracers has demonstrated its utility for the evaluation of disease. We present the case of a woman previously treated for esthesioneuroblastoma performing MR and 18Ga-DOTATOC PET/CT demonstrating dural metastasis of disease with a strong correspondence between conventional and functional imaging.
Diffuse 18F-FDG PET/CT Uptake of the Bilateral Atrial Walls in Atrioventricular Nodal Re-entrant Tachycardia
Authors: El Yaagoubi Yacine , Prunier-Aesch Caroline , Chetanneau Alain , Delannoy Eric , Antoine Clémence 
Published: March 2021

Abstract
An 84-year-old man was referred for the evaluation of a suspected gastrointestinal neoplasia. 18F-FDG PET/CT scan was performed showing, in addition to the physiological myocardial FDG uptake in the left ventricular wall, an unusual diffuse FDG uptake of the bilateral atrial walls. During his visit to the nuclear medicine unit, the patient became unwell, and an ECG was performed, suggestive of an atrioventricular nodal re-entrant tachycardia. Our case highlights the importance of including supraventricular arrhythmia such as atrioventricular nodal re-entrant tachycardia in the differential diagnosis of atrial FDG uptake.
Delayed PET/CT of Pericardial Synovial Sarcoma
Authors: Stefanelli Antonella , Savelli Giordano , Bonacina Mattia , Zaniboni Alberto 
Published: March 2021

Abstract
Pericardial synovial sarcoma is a rare malignancy. We report the case of a patient who was referred to our institution for a large pericardial effusion requiring pericardiocentesis. CT imaging revealed an inhomogeneous pericardial mass beside the right atrium, and then a PET/CT scan was performed. Standard images were inconclusive whether delayed images showed an FDG-avid pericardial lesion that was surgically removed with histological diagnosis of a poorly differentiated biphasic synovial sarcoma. When considering mediastinal or pericardial mass, a delayed PET/CT may improve lesion-to-background contrast by reducing blood pool activity.
18F-FDG PET/CT in Uterine Follicular Dendritic Cell Sarcoma
Authors: Yang Yuhua , Liu Lisha , Lin Juyi , Huang Shengcai 
Published: March 2021

Abstract
A 46-year-old woman presented with menorrhagia, abdominal distension, and neck mass for 3 months. Ultrasonography detected a large intra-abdominal mass and enlarged neck lymph nodes. Further 18F-FDG PET/CT scan revealed lesions with intense 18F-FDG avidity in abdominal cavity and neck. The patient underwent a biopsy of the uterine, and the diagnosis of uterine follicular dendritic cell sarcoma was finally achieved. After 6 cycles of CHOP-like chemotherapy, 18F-FDG PET/CT showed complete metabolic and morphologic resolution for follicular dendritic cell sarcoma.
PET Imaging of Meningioma Using the Novel SSTR-Targeting Peptide 18F-SiTATE
Authors: Unterrainer Marcus , Lindner Simon , Beyer Leonie , Gildehaus Franz J. , Todica Andrei , Mittlmeier Lena M. , Jurkschat Klaus , Wängler Carmen , Wängler Bjoern , Schirrmacher Ralf , Tonn Jörg C. , Albert Nathalie L. , Bartenstein Peter , Ilhan Harun 
Published: March 2021

Abstract
PET using 68Ga-labeled somatostatin receptor (SSTR) ligands adds significant information in meningioma patients. 18F-SiTATE is a novel, 18F-labeled SSTR-targeting peptide with remarkable imaging properties. Here, we present a 72-year-old woman with falx meningioma and transosseous extension. 18F-SiTATE PET/CT was performed 12 months after the previous 68Ga-DOTATOC PET/CT with comparable quantitative uptake and very good spatial resolution. So far, the widespread use of SSTR ligands for NET and meningioma imaging is hampered by cost-intensive 68Ge/68Ga generators, low activity amounts, lower spatial resolution, and short half-life. 18F-SiTATE might foster widespread use of SSTR ligands, overcoming the shortcomings of 68Ga-labeled ligands.
Levodopa-Induced Dyskinesia in Parkinson Disease Specifically Associates With Dopaminergic Depletion in Sensorimotor-Related Functional Subregions of the Striatum
Authors: Labrador-Espinosa Miguel A. , Grothe Michel J. , Macías-García Daniel , Jesús Silvia , Adarmes-Gómez Astrid , Muñoz-Delgado Laura , Fernández-Rodríguez Paula , Martín-Rodríguez Juan Francisco , Huertas Ismael , García-Solís David , Mir Pablo 
Published: March 2021

Purpose
To determine whether the development of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) specifically relates to dopaminergic depletion in sensorimotor-related subregions of the striatum.

Methods
Our primary study sample consisted of 185 locally recruited PD patients, of which 73 (40%) developed LID. Retrospective 123I-FP-CIT SPECT data were used to quantify the specific dopamine transporter (DAT) binding ratio within distinct functionally defined striatal subregions related to limbic, executive, and sensorimotor systems. Regional DAT levels were contrasted between patients who developed LID (PD + LID) and those who did not (PD-LID) using analysis of covariance models controlled for demographic and clinical features. For validation of the findings and assessment of the evolution of LID-associated DAT changes from an early disease stage, we also studied serial 123I-FP-CIT SPECT data from 343 de novo PD patients enrolled in the Parkinson Progression Marker’s Initiative using mixed linear model analysis.

Results
Compared with PD-LID, DAT level reductions in PD + LID patients were most pronounced in the sensorimotor striatal subregion (F = 5.99, P = 0.016) and also significant in the executive-related subregion (F = 5.30, P = 0.023). In the Parkinson Progression Marker’s Initiative cohort, DAT levels in PD + LID (n = 161, 47%) were only significantly reduced compared with PD-LID in the sensorimotor striatal subregion (t = −2.05, P = 0.041), and this difference was already present at baseline and remained largely constant over time.

Conclusion
Measuring DAT depletion in functionally defined sensorimotor-related striatal regions of interest may provide a more sensitive tool to detect LID-associated dopaminergic changes at an early disease stage and could improve individual prognosis of this common clinical complication in PD.
Meeting the New Joint Commission's Maternal Safety Requirements
Authors: Hayes Cindy L. , Piehl Anne Marie , Rooney Deborah M. 
Published: March 2021

Introduction
Recently, the American College of Obstetricians and Gynecologists Committee on Obstetric Practice encouraged the use of quantitative and cumulative assessment of maternal blood loss (QBL) as part of safety bundles for prevention of postpartum hemorrhage. The aim of this study was to determine whether our train-the-trainer QBL program improved process and patient outcomes.

Methods
In this pre-post interventional study, 26 “champions” participated in the QBL train-the-trainer program in preparation for patient safety bundle rollout. The multipart program included at least 3 simulated C-section hemorrhage scenarios and rapid-cycle debriefing. Champions used the curriculum for broad staff training for 2 months before safety bundle implementation.
Six months each of preintervention and postintervention data were collected from medical records of all qualified cases (N = 4413). Process outcomes were evaluated by comparing number of women who received QBL. Patient outcomes were evaluated by comparing blood transfusion rates and number of morbid cases (≥4 packed red blood cell units). χ2 test was used for analyses.

Results
Review of medical records indicated that 99.8% of 2218 women received QBL posttraining compared with 16.6% of 2195 women receiving QBL before training (P = 0.0001.) Transfusion rates increased from 54.47 to 69.25 units/1000 mothers. The rate of morbid cases (≥4 red blood cell units) dropped from 2.13 to 0.48 cases/1000 mothers.

Conclusions
Our findings suggest the train-the-trainer QBL program was associated with improved process and decreased morbidity when implemented with a hemorrhage safety bundle. Further research is required to examine components of simulation-based QBL training methods and implementation to evaluate their impact on clinical outcomes.
Targeting B cells in multiple sclerosis
Authors: Sellebjerg Finn , Weber Martin S. 
Published: March 2021

Purpose of review
Treatments targeting B cells are increasingly used for patients with multiple sclerosis (MS). We review the mechanisms of action, clinical effectiveness and safety of treatment, with emphasis on recently published studies.

Recent findings
Several monoclonal antibodies targeting the surface molecule CD20 on B cells are approved or being developed for treatment of MS. Overall, they seem comparable in terms of strongly suppressing radiological disease activity and relapse biology. Novel approaches include anti-CD19 antibody therapy and treatment with oral drugs targeting Bruton's tyrosine kinase (BTK). The main safety issue with persistent B cell depletion is an increased risk of infections – possibly including an increased risk of severe COVID-19. Vaccine responses are also blunted in patients treated with anti-CD20 antibodies. Lower doses or longer infusion intervals may be sufficient for control of disease activity. Whether this might also improve the safety of treatment and increase vaccination responses remains to be determined.

Summary
Available data support the widespread use of therapies targeting B cells in MS. Whether novel approaches targeting CD19 or BTK will have advantages compared to anti-CD20 antibody therapy remains to be established. Furthermore, trials investigating alternative dosing regimens for anti-CD20 antibody treatment are warranted.
Proteomic identification of the UDP-GlcNAc : PI α1-6 GlcNAc-transferase subunits of the glycosylphosphatidylinositol biosynthetic pathway ofTrypanosoma brucei
Authors: Ji Zhe , Tinti Michele , Ferguson Michael A.J. 
Published: March 2021

AbstractThe first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis in all eukaryotes is the addition of N-acetylglucosamine (GlcNAc) to phosphatidylinositol (PI) which is catalysed by a UDP-GlcNAc : PI α1-6 GlcNAc-transferase. This enzyme has been shown to be a complex of at least seven subunits in mammalian cells and a similar complex of homologous subunits has been postulated in yeast. Homologs of most of these mammalian and yeast subunits were identified in theTrypanosoma bruceipredicted protein database. The putative catalytic subunit of theT. bruceicomplex, TbGPI3, was epitope tagged with three consecutive c-Myc sequences at its C-terminus. Immunoprecipitation of TbGPI3-3Myc followed by native polyacrylamide gel electrophoresis and anti-Myc Western blot showed that it is present in a ~240 kDa complex. Label-free quantitative proteomics were performed to compare anti-Myc pull-downs from lysates of TbGPI-3Myc expressing and wild type cell lines. TbGPI3-3Myc was the most highly enriched protein in the TbGPI3-3Myc lysate pull-down and partner proteins TbGPI15, TbGPI9, TbGPI2, TbGPI1 and TbERI1 were also identified with significant enrichment. Our proteomics data also suggest that an Arv1-like protein (TbArv1) is a subunit of theT. bruceicomplex. Yeast and mammalian Arv1 have been previously implicated in GPI biosynthesis, but here we present the first experimental evidence for physical association of Arv1 with GPI biosynthetic machinery. A putative E2-ligase has also been tentatively identified as part of theT. bruceiUDP-GlcNAc : PI α1-6 GlcNAc-transferase complex.Graphical abstractFirst step of GPI anchor biosynthesis pathway inT.bruceiBSF is catalysed by TbGPI3 complex.
Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection
Authors: Bariola J. Ryan , McCreary Erin K. , Wadas Richard J. , Kip Kevin E. , Marroquin Oscar C. , Minnier Tami , Koscumb Stephen , Collins Kevin , Schmidhofer Mark , Shovel Judith A. , Wisniewski Mary Kay , Sullivan Colleen , Yealy Donald M. , Nace David A , Huang David T. , Haidar Ghady , Khadem Tina , Linstrum Kelsey , Seymour Christopher W. , Montgomery Stephanie K. , Angus Derek C. , Snyder Graham M. 
Published: March 2021

ABSTRACTBackgroundMonoclonal antibody (mAb) treatment may prevent complications of COVID-19. We sought to quantify the impact of bamlanivimab monotherapy on hospitalizations and mortality, as well as Emergency Department (ED) visits without hospitalization, among outpatients at high risk of COVID-19 complications.MethodsWe compared patients receiving mAb to patients who met criteria but did not receive mAb from December 2020 through March 2021. The study population selection used propensity scores to match 1:1 by likelihood to receive mAb. The primary outcome was hospitalization or all-cause mortality within 28 days; the secondary outcome was hospitalization or ED visit without hospitalization within 28 days. Odds ratios (OR) calculation used logistic regression modeling including propensity score and mAb receipt predictors.ResultsThe study population included 234 patients receiving mAb and 234 matched comparator patients not receiving mAb. Patients receiving mAb were less likely to experience hospitalization or mortality (OR 0.31, 95% confidence interval [95%CI] 0.17-0.56, p=0.00001) and hospitalization or ED visit without hospitalization (OR 0.50, 95%CI 0.43-0.83, p=0.007). The impact of mAb was more pronounced in prevention of hospitalization (among all age groups, OR 0.35, 95%CI 0.19-0.66, p=0.001) than mortality or ED visit without hospitalization, and most strongly associated with patients age 65 years and older (primary outcome OR 0.28, 95%CI 0.14-0.56, p=0.0003).ConclusionsBamlanivimab monotherapy was associated with reduction in the composite outcome of hospitalizations and mortality in patients with mild-moderate COVID-19. The benefit may be strongest in preventing hospitalization in patients ages 65 years or older.
Increased transmissibility of the B.1.1.7 SARS-CoV-2 variant: Evidence from contact tracing data in Oslo, January to February 2021
Authors: Lindstrøm Jonas Christoffer , Engebretsen Solveig , Bråthen Kristoffersen Anja , Øyvind Isaksson Rø Gunnar , Palomares Alfonso Diz-Lois , Engø-Monsen Kenth , Madslien Elisabeth Henie , Forland Frode , Nygård Karin Maria , Hagen Frode , Gantzel Gunnar , Wiklund Ottar , Frigessi Arnoldo , de Blasio Birgitte Freiesleben 
Published: March 2021

AbstractWe use data from contact tracing in Oslo, Norway, to estimate the new SARS-CoV-2 B.1.1.7 lineage’s relative transmissibility. Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants.
Context-dependent transcriptional regulation of microglial proliferation
Authors: Belhocine Sarah , Xavier Andre Machado , Distéfano-Gagné Félix , Fiola Stéphanie , Rivest Serge , Gosselin David 
Published: March 2021

SummaryMicroglia proliferation occurs during brain development and brain lesions, but how this is coordinated at the transcriptional level is not well understood. Here, we investigated transcriptional mechanisms underlying proliferation of mouse microglia during postnatal development and in adults in models of induced microglial depletion-repopulation and brain demyelination. While each proliferative subset displayed globally a distinct signature of gene expression, they also co-expressed a subgroup of 1,370 genes at higher levels than quiescent microglia. Furthermore, expression of these may be coordinated by one of two modes of regulation. A first mode augments expression of genes already expressed in quiescent microglia and is subject to regulation by Klf/Sp, Nfy, and Ets transcription factors. Alternatively, a second mode enables de novo transcription of cell cycle genes and requires additional regulatory input from Lin54 and E2f factors. Overall, proliferating microglia integrate regulation of cell cycle gene expression with their broader, context-dependent, transcriptional landscape.
ID-Seg: An Accurate and Reliable Infant Deep learning Segmentation Framework for Limbic Structures
Authors: Wang Yun , Haghpanah Fateme Sadat , Zhang Xuzhe , Santamaria Katie , da Costa Aguiar Alves Gabriela Koch , Bruno Elizabeth , Aw Natalie , Maddocks Alexis , Duarte Cristiane S , Monk Catherine , Laine Andrew , Posner Jonathan 
Published: March 2021

AbstractEarly postnatal period brain magnetic resonance imaging (MRI) is becoming an important approach to measure the impact of prenatal exposures on neurodevelopment and to investigate early biomarkers for risk. Among brain structures, Limbic structures are particular of interest in psychiatric disorder-related research. However, despite the promise of infant neuroimaging and the success of initial infant MRI studies, assessing limbic regions’ structure and function remains a significant challenge due to low inter-regional intensity contrast and high curvature (e.g., hippocampus). In addition, the agreement between existing automatic techniques and manual segmentation remains either untested or insufficient, particularly for the amygdala and hippocampus. In this work, we developed an accurate (based on three segmentation evaluation metrics), reliable and efficient infant deep learning segmentation framework (ID-Seg) to address the aforementioned challenges. Specifically, we leveraged a large dataset of 473 infant MRI scans to train ID-Seg and rigorously evaluated ID-Seg’s performance on internal and external datasets with manual segmentations. Compared with a state-of-the-art segmentation pipeline, we demonstrated that ID-Seg significantly improved the segmentation accuracy of limbic structures (hippocampus and amygdala) in newborn infants. Moreover, in a medium-size dataset, we found that ID-Seg-derived morphometric measures yield strong brain-behavior associations. As such, our ID-Seg may improve our capacity and efficiency to measure MRI-based brain features relevant to neuropsychological development and ultimately advance the success of quantitative analyses on large-scale datasets.
Systematic analysis of CD39, CD103, CD137 and PD-1 as biomarkers for naturally occurring tumor antigen-specific TILs
Authors: Eiva Monika A. , Omran Dalia K. , Chacon Jessica , Powell Daniel J. 
Published: March 2021

AbstractThe detection of tumor-specific T cells in solid tumors is integral to the interrogation of endogenous antitumor responses and to the advancement of downstream therapeutic applications, such as checkpoint immunotherapy and adoptive cell transfer. A number of biomarkers are reported to identify endogenous tumor-specific tumor infiltrating lymphocytes (TILs), namely CD137, PD-1, CD103, and CD39, however a direct comparison of these molecules has yet to be performed. Here, we evaluate these biomarkers in primary human high-grade serous ovarian tumor samples using single-cell mass cytometry to characterize and compare their relative phenotypic profiles, as well as their response to autologous tumor cellsex vivo. CD137+, PD-1+, CD103+, and CD39+ TILs are all detectable in tumor samples with CD137+ TILs being the least abundant. PD-1+, CD103+, and CD39+ TILs all express a subset of CD137+ cells, while CD137+ TILs highly co-express the aforementioned markers. CD137+ TILs exhibit the highest expression of cytotoxic effector molecules, such as IFNγ and Granzyme B, compared to PD-1+, CD103+ or CD39+ TILs. Removal of CD137+ TILs from PD-1+, CD103+, or CD39+ TILs results in lower secretion of IFNγ in response to autologous tumor stimulation, while CD137+ TILs highly secrete IFNγ in an HLA-dependent manner. CD137+ TILs exhibited an exhausted phenotype with CD28 co-expression, suggestive of antigen recognition and receptiveness to reinvigoration via immune checkpoint blockade. Together, our findings demonstrate that the antitumor abilities of PD-1+, CD103+, and CD39+ TILs are mainly derived from a subset of TILs expressing CD137, implicating CD137 is a more selective biomarker for naturally occurring tumor-specific TILs.
Inhibition of PLK1-dependent EBNA2 phosphorylation promotes lymphomagenesis in EBV-infected mice
Authors: Zhang Xiang , Schuhmachers Patrick , Mourão André , Giansanti Piero , Murer Anita , Thumann Sybille , Kuklik-Roos Cornelia , Beer Sophie , Hauck Stefanie M. , Hammerschmidt Wolfgang , Küppers Ralf , Kuster Bernhard , Raab Monika , Strebhardt Klaus , Sattler Michael , Münz Christian , Kempkes Bettina 
Published: March 2021

ABSTRACTWhile Epstein-Barr virus (EBV) establishes a life-long latent infection in apparently healthy human immunocompetent hosts, immunodeficient individuals are at particular risk to develop lymphoproliferative B cell malignancies caused by EBV. A key EBV protein is the transcription factor EBV nuclear antigen 2 (EBNA2), which initiates B cell proliferation. Here, we combine biochemical, cellular and in vivo experiments demonstrating that the mitotic polo-like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain and thereby inhibits its biological activity. EBNA2 mutants that impair PLK1 binding or prevent EBNA2 phosphorylation are gain-of-function mutants. They have enhanced transactivation capacities, accelerate the proliferation of infected B cells and promote the development of monoclonal B cell lymphomas in infected mice. Thus, PLK1 coordinates the activity of EBNA2 to attenuate the risk of tumor incidences in favor of the establishment of latency in the infected but healthy host.