bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local and Topical Anesthetics for Pediatric Patients in the Emergency Department
Authors: Mace Sharon E. , Whiteman Paula , Avarello Jahn T. , Ojo Aderonke , Rose Emily , Valente Jonathan , Joseph Madeline 
Published: November 2020

AbstractPainful diagnostic and therapeutic procedures are common in the emergency department. Adequately treating pain, including the pain of procedures is an essential component of the practice of emergency medicine. Pain management is also part of the core competency for emergency medicine residencies and pediatric emergency medicine fellowships. There are many benefits to providing local and/or topical anesthesia before performing a medical procedure, including better patient and family satisfaction and increased procedural success rates. Local and topical anesthetics when used appropriately, generally, have few, if any, systemic side effects, such as hypotension or respiratory depression, which is an advantage over procedural sedation. Use of local and topical anesthetics can do much toward alleviating the pain and anxiety of pediatric patients undergoing procedures in the emergency department.
Statin exposure and risk of cancer in people with and without HIV infection
Authors: Bedimo Roger J. , Park Lesley S. , Shebl Fatima M. , Sigel Keith , Rentsch Christopher T. , Crothers Kristina , Rodriguez-Barradas Maria C. , Goetz Matthew Bidwell , Butt Adeel A. , Brown Sheldon T. , Gibert Cynthia , Justice Amy C. , Tate Janet P. 
Published: November 2020

Objective:
To determine whether statin exposure is associated with decreased cancer and mortality risk among persons with HIV (PWH) and uninfected persons. Statins appear to have immunomodulatory and anti-inflammatory effects and may reduce cancer risk, particularly among PWH as they experience chronic inflammation and immune activation.

Design:
Propensity score-matched cohort of statin-exposed and unexposed patients from 2002 to 2017 in the Veterans Aging Cohort Study (VACS), a large cohort with cancer registry linkage and detailed pharmacy data.

Methods:
We calculated Cox regression hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, microbial cancers (associated with bacterial or oncovirus coinfection), nonmicrobial cancers, and mortality.

Results:
:The propensity score-matched sample (N = 47 940) included 23 970 statin initiators (31% PWH). Incident cancers were diagnosed in 1160 PWH and 2116 uninfected patients. Death was reported in 1667 (7.0%) statin-exposed, and 2215 (9.2%) unexposed patients. Statin use was associated with 24% decreased risk of microbial-associated cancers (hazard ratio 0.76; 95% CI 0.69–0.85), but was not associated with nonmicrobial cancer risk (hazard ratio 1.00; 95% CI 0.92–1.09). Statin use was associated with 33% lower risk of death overall (hazard ratio 0.67; 95% CI 0.63–0.72). Results were similar in analyses stratified by HIV status, except for non-Hodgkin lymphoma where statin use was associated with reduced risk (hazard ratio 0.56; 95% CI 0.38–0.83) for PWH, but not for uninfected (P interaction = 0.012).

Conclusion:
In both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not nonmicrobial cancer incidence, and with decreased mortality.
Ultrasound Contrast
Authors: Klibanov Alexander L. 
Published: November 2020

Abstract
Gas-filled microbubbles are currently in clinical use as blood pool contrast agents for ultrasound imaging. The goal of this review is to discuss the trends and issues related to these relatively unusual intravascular materials, which are not small molecules per se, not polymers, not even nanoparticles, but larger micrometer size structures, compressible, flexible, elastic, and deformable. The intent is to connect current research and initial studies from 2 to 3 decades ago, tied to gas exchange between the bubbles and surrounding biological medium, in the following areas of focus: (1) parameters of microbubble movement in relation to vasculature specifics; (2) gas uptake and loss from the bubbles in the vasculature; (3) adhesion of microbubbles to target receptors in the vasculature; and (4) microbubble interaction with the surrounding vessels and tissues during insonation.
Microbubbles are generally safe and require orders of magnitude lower material doses than x-ray and magnetic resonance imaging contrast agents. Application of microbubbles will soon extend beyond blood pool contrast and tissue perfusion imaging. Microbubbles can probe molecular and cellular biomarkers of disease by targeted contrast ultrasound imaging. This approach is now in clinical trials, for example, with the aim to detect and delineate tumor nodes in prostate, breast, and ovarian cancer. Imaging of inflammation, ischemia-reperfusion injury, and ischemic memory is also feasible. More importantly, intravascular microbubbles can be used for local deposition of focused ultrasound energy to enhance drug and gene delivery to cells and tissues, across endothelial barrier, especially blood-brain barrier.
Overall, microbubble behavior, stability and in vivo lifetime, bioeffects upon the action of ultrasound and resulting enhancement of drug and gene delivery, as well as targeted imaging are critically dependent on the events of gas exchange between the bubbles and surrounding media, as outlined in this review.
Liver Abscess With High 18F-FDG Uptake and No 18F-Fluorothymidine Uptake
Authors: Fujimoto Kengo , Norikane Takashi , Mitamura Katsuya , Yamamoto Yuka , Okano Keiichi , Suzuki Yasuyuki , Nishiyama Yoshihiro 
Published: November 2020

Abstract

18F-FDG accumulates not only in malignant lesions but also in infectious and inflammatory ones. 3′-deoxy-3′-18F-fluorothymidine (FLT) has been investigated as a promising PET tracer for evaluating tumor proliferating activity. We report a case of liver abscess during therapy of pancreatic cancer that underwent FDG PET/CT and FLT PET/CT studies. Although FDG PET/CT demonstrated several regions of increased uptake in the liver, FLT PET/CT showed no increased uptake in the liver.
Increased Uptake of 68Ga-Pentixafor in Thymic Rebound After Chemotherapy in a Patient With Multiple Myeloma
Authors: Pan Qingqing , Luo Yaping , Cao Xinxin , Li Jian 
Published: November 2020

Abstract
A 38-year-old man with newly diagnosed multiple myeloma underwent 68Ga-pentixafor PET/CT for baseline assessment. 68Ga-pentixafor PET/CT demonstrated multiple focal bone and bone marrow lesions with intense radioactivity. After 9 cycles of chemotherapy against multiple myeloma, the patient experienced serologically complete remission of myeloma. Consistently, the follow-up 68Ga-pentixafor PET/CT for PET response showed significantly reduced uptake in the previously chemokine receptor 4–positive bone lesions. However, intense and homogeneous uptake of 68Ga-pentixafor was noted in the thymus with a smooth contour and slightly increased density, which is possibly caused by thymic hyperplasia after chemotherapy.
Focal Liver 18F-FDG Uptake in a Patient Who Underwent Thrombolysis for Brachiocephalic and Subclavian Thrombosis
Authors: Huot Daneault Alexis , Le Blanc Richard , Voyer Nathalie , Turcotte Éric , Rousseau Etienne 
Published: November 2020

Abstract
A 19-year-old woman presented with a primary mediastinal B-cell lymphoma invading the superior vena cava with associated thrombosis of the left brachiocephalic and subclavian vein. She underwent thrombolysis followed by chemotherapy. The midtreatment 18F-FDG PET/CT demonstrated important regression of the primary mediastinal B-cell lymphoma, but showed intense focal hepatic uptake in segment IV, without a corresponding lesion on ultrasonography, non–contrast-enhanced low-dose CT, and MRI. This focal uptake disappeared on a subsequent 18F-FDG PET/CT study when the radiotracer was injected in the foot, suggesting an anomalous venous return pathway that persisted despite thrombolysis.
Malakoplakia Presenting as a Mass in the Transplanted Kidney
Authors: Kalimuthu Lokeshwaran Madurai , Ora Manish , Nazar Aftab Hasan , Gambhir Sanjay 
Published: November 2020

Abstract
Malakoplakia is a rare inflammatory condition that can affect many organ systems, including the genitourinary tract. It is associated with impaired immune function. Isolated renal parenchymal involvement has been reported in very few cases. Urinary tract and digestive malakoplakia have been reported in transplant recipients, but the involvement of transplant itself is rare. Variable clinical manifestations and nonspecific radiological appearance make the diagnosis difficult. The differential diagnosis includes infective etiologies and malignancy. We report a case of renal allograft malakoplakia, mimicking as a malignancy on 18F-FDG PET/CT.
Orthognathic Surgery in Cleidocranial Dysplasia
Authors: Pourtaheri Navid , Allam Omar , Chandler Ludmila , Steinbacher Derek M. 
Published: November 2020

Abstract
Optimal surgical correction of the craniofacial manifestations of cleidocranial dysplasia (CCD) has not been established due to the rarity of the condition. A 27-year-old female with CCD is presented. She underwent virtual surgical planning (VSP) followed by LeFort-I disimpaction, bone grafting, bilateral sagittal-split osteotomy, genioplasty, submental lipectomy, and targeted facial fat grafting. The patient necessitated 15-mm of vertical maxillary disimpaction centrally, stabilized with wide maxillary plates and interpositional allogenic fibula grafts. Six-month postoperative examination demonstrated improved appearance and functional symptoms. Skeletal relationships were normalized on computed tomography (CT) and there was minimal change between immediate and 6-month postoperative CT measurements, demonstrating a stable result. Orthognathic surgery used to establish dentofacial harmony in patients with CCD can test the extremes of single-stage facial skeletal expansion. Use of VSP, wide maxillary plates, and interpositional bone grafts can help optimize maxillary expansion and stability, while concurrent fat redistribution optimizes facial aesthetics.
Anatomical and Volumetric Analysis of the Sphenoid Sinus by Semiautomatic Segmentation of Cone Beam Computed Tomography
Authors: Lentzen Max-Philipp , Zirk Matthias , Riekert Maximilian , Buller Johannes , Kreppel Matthias 
Published: November 2020

AbstractThis investigation was performed to analyze and evaluate anatomical and volumetric data of the sphenoid sinus by semiautomatic segmentation of cone beam computed tomography (CBCT) datasets.This analysis was carried out on cone beam computed tomography images of 100 patients. By using the discretionary software “ITK-Snap”, the volumetric investigation of 197 sphenoid sinuses was conducted. The statistical analyses were carried out by using the paired and independent Studentt-test. In addition, thePearsonschi-square test was performed.PvaluesP < 0.05 were considered significant.The volumetric mean was 4.438 ± 2.434 cm3for the right and 4.809 ± 3.000 for the left side. Results did not indicate statistically significant differences according to the side, irrespective of gender (P > 0.05). The further investigation of differences between male and female patients did assess significant results (P < 0.05), males (10.477 ± 3.851 cm3) present a larger total sinus volume than females (8.219 ± 3.574 cm3). In accordance to patients‘ age (median 54 years), smaller volumes were related to younger patients and larger volumes to older ones. But, no statistically significant results in accordance to age could be detected (χ2 = 1.258;P > 0.05).Endoscopic sinus surgery of the vulnerable and intricate anatomy of the sphenoid sinus requires an explicit knowledge and orientation about the anatomical variations such as septums and volumetric capacity. Concerning this matter, semiautomatic segmentation of CBCT images can aid the surgeon in preoperative planning. Our investigation shows that a small sinus volume, that is, affecting female patients and a complex sinus anatomy by the occurrence of a septum, especially located close to neurovascular structures could essentially aggravate endoscopic sphenoid sinus surgery. In this regard, volumetric analysis of the sphenoid sinus by CBCT images can provide presurgical information and facilitates an individualized treatment.
Unification of the M/ORF3-related proteins points to a diversified role for ion conductance in pathogenesis of coronaviruses and other nidoviruses
Authors: Tan Yongjun , Schneider Theresa , Shukla Prakash K. , Chandrasekharan Mahesh B. , Aravind L , Zhang Dapeng 
Published: November 2020

ABSTRACTThe new coronavirus, SARS-CoV-2, responsible for the COVID-19 pandemic has emphasized the need for a better understanding of the evolution of virus-host conflicts. ORF3a in both SARS-CoV-1 and SARS-CoV-2 are ion channels (viroporins) and involved in virion assembly and membrane budding. Using sensitive profile-based homology detection methods, we unify the SARS-CoV ORF3a family with several families of viral proteins, including ORF5 from MERS-CoVs, proteins from beta-CoVs (ORF3c), alpha-CoVs (ORF3b), most importantly, the Matrix (M) proteins from CoVs, and more distant homologs from other nidoviruses. By sequence analysis and structural modeling, we show that these viral families utilize specific conserved polar residues to constitute an ion-conducting pore in the membrane. We reconstruct the evolutionary history of these families, objectively establish the common origin of the M proteins of CoVs and Toroviruses. We show that the divergent ORF3a/ORF3b/ORF5 families represent a duplication stemming from the M protein in alpha- and beta-CoVs. By phyletic profiling of major structural components of primary nidoviruses, we present a model for their role in virion assembly of CoVs, ToroVs and Arteriviruses. The unification of diverse M/ORF3 ion channel families in a wide range of nidoviruses, especially the typical M protein in CoVs, reveal a conserved, previously under-appreciated role of ion channels in virion assembly, membrane fusion and budding. We show that the M and ORF3 are under differential evolutionary pressures; in contrast to the slow evolution of M as core structural component, the CoV-ORF3 clade is under selection for diversification, which indicates it is likely at the interface with host molecules and/or immune attack.IMPORTANCECoronaviruses (CoVs) have become a major threat to human welfare as the causative agents of several severe infectious diseases, namely Severe Acute Respiratory Syndrome (SARS), Middle Eastern Respiratory Syndrome (MERS), and the recently emerging human coronavirus disease 2019 (COVID-19). The rapid spread, severity of these diseases, as well as the potential re-emergence of other CoV-associated diseases have imposed a strong need for a thorough understanding of function and evolution of these CoVs. By utilizing robust domain-centric computational strategies, we have established homologous relationships between many divergent families of CoV proteins, including SARS-CoV/SARS-CoV-2 ORF3a, MERS-CoV ORF5, proteins from both beta-CoVs (ORF3c) and alpha-CoVs (ORF3b), the typical CoV Matrix proteins, and many distant homologs from other nidoviruses. We present evidence that they are active ion channel proteins, and the Cov-specific ORF3 clade proteins are under selection for rapid diversification, suggesting they might have been involved in interfering host molecules and/or immune attack.
The Treatment of Clear Cell Ovarian Cancer with the Poly(ADP- Ribose) Polymerase (PARP1) Inhibitors (AG14361,Veliparib,Olaparib) as Chemosensitizers
Authors: de Soto Joseph Angel 
Published: November 2020

AbstractIntroductionMost of those who get ovarian cancer will die from this cancer. Of the major types of ovarian cancer clear cell carcinoma is the most aggressive and chemoresistant type of epithelial ovarian cancer. Here the sensitivity of clear cell ovarian carcinoma to poly adenosine diphosphate [ADP-ribose] polymerase (PARP) inhibitors is tested.MethodologyOvarian cancer cell lines were treated with the PARP inhibitors AG14361, Veliparib, or Olaparib alone or in combination with cisplatin, carboplatinum, doxorubicin, 5-fluorouracil (5-FU), gemcitabine and paclitaxel for 72 hours. The IC50 concentrations were calculated. Each experiment was replicated 10 times.ResultsAs single agents the PARP inhibition of ovarian cancer among serous, endometroid and clear cell ovarian cancer cell lines was similar. Clear cell ovarian cancer seemed particularly susceptible to chemo-sensitization by PARP inhibitors with paclitaxel, 5-FU, carboplatin, doxorubicin and/or cisplatin. Antagonism was seen with gemcitabine.ConclusionPARP inhibitors are exceptional chemosensitizers of clear cell ovarian cancer to treatment with most standard chemotherapy agents.
Enzyme catalysis prior to aromatic residues: reverse engineering of a dephosphoCoA kinase
Authors: Makarov Mikhail , Meng Jingwei , Tretyachenko Vyacheslav , Srb Pavel , Březinová Anna , Giacobelli Valerio Guido , Bednárová Lucie , Vondrášek Jiří , Dunker A. Keith , Hlouchová Klára 
Published: November 2020

AbstractIt is well-known that the large diversity of protein functions and structures is derived from the broad spectrum of physicochemical properties of the 20 canonical amino acids. According to the generally accepted hypothesis, protein evolution was continuously associated with enrichment of this alphabet, increasing stability, specificity and spectrum of catalytic functions. Aromatic amino acids are considered the latest addition to genetic code.The main objective of this study was to test whether enzymatic catalysis can spare the aromatic amino acids (aromatics) by determining the effect of amino acid alphabet reduction on structure and function of dephospho-CoA kinase (DPCK). We designed two mutant variants of a putative DPCK fromAquifex aeolicusby substituting (i) Tyr, Phe and Trp or (ii) all aromatics (including His), i.e. ∼10% of the total sequence. Their structural characterization indicates that removal of aromatic amino acids may support rich secondary structure content although inevitably impairs a firm globular arrangement. Both variants still possess ATPase activity, although with 150-300 times lower efficiency in comparison with the wild-type phosphotransferase activity. The transfer of the phosphate group to the dephospho-CoA substrate is however heavily uncoupled and only one of the variants is still able to perform the reaction.Here we provide support to the hypothesis that proteins in the early stages of life could support at least some enzymatic activities, despite lower efficiencies resulting from the lack of a firm hydrophobic core. Based on the presented data we hypothesize that further protein scaffolding role may be provided by ligands upon binding.SignificanceAll extant proteins rely on the standard coded amino acid alphabet. However, early proteins lacked some of these amino acids that were incorporated into the genetic code only after the evolution of their respective metabolic pathways, aromatic amino acids being among the last additions. This is intriguing because of their crucial role in hydrophobic core packing, indispensable for enzyme catalysis.We designed two aromatics-less variants of a highly conserved enzyme from the CoA synthesis pathway, capable of enzyme catalysis and showing significant ordering upon substrate binding. To our knowledge, this is the first example of enzyme catalysis in complete absence of aromatic amino acids and presents a possible mechanism of how aromatics-less enzymes could potentially support an early biosphere.
Long read metagenomics, the next step?
Authors: Haro-Moreno Jose M. , López-Pérez Mario , Rodríguez-Valera Francisco 
Published: November 2020

ABSTRACTBackgroundThird-generation sequencing has penetrated little in metagenomics due to the high error rate and dependence for assembly on short-read designed bioinformatics. However, 2nd generation sequencing metagenomics (mostly Illumina) suffers from limitations, particularly in allowing assembly of microbes with high microdiversity or retrieving the flexible (adaptive) compartment of prokaryotic genomes.ResultsHere we have used different 3rd generation techniques to study the metagenome of a well-known marine sample from the mixed epipelagic water column of the winter Mediterranean. We have compared Oxford Nanopore and PacBio last generation technologies with the classical approach using Illumina short reads followed by assembly. PacBio Sequel II CCS appears particularly suitable for cellular metagenomics due to its low error rate. Long reads allow efficient direct retrieval of complete genes (473M/Tb) and operons before assembly, facilitating annotation and compensates the limitations of short reads or short-read assemblies. MetaSPAdes was the most appropriate assembly program when used in combination with short reads. The assemblies of the long reads allow also the reconstruction of much more complete metagenome-assembled genomes, even from microbes with high microdiversity. The flexible genome of reconstructed MAGs is much more complete and allows rescuing more adaptive genes.ConclusionsFor most applications of metagenomics, from community structure analysis to ecosystem functioning, long-reads should be applied whenever possible. Particularly for in-silico screening of biotechnologically useful genes, or population genomics, long-read metagenomics appears presently as a very fruitful approach and can be used from raw reads, before a computing-demanding (and potentially artefactual) assembly step.
Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV
Authors: Giron Leila B. , Palmer Clovis S. , Liu Qin , Yin Xiangfan , Papasavvas Emmanouil , Damra Mohammad , Goldman Aaron R. , Tang Hsin-Yao , Johnston Rowena , Mounzer Karam , Kostman Jay R. , Tebas Pablo , Landay Alan , Montaner Luis J. , Jacobson Jeffrey M. , Li Jonathan Z. , Abdel-Mohsen Mohamed 
Published: November 2020

ABSTRACTNon-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammationin vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74-76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.