bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of [11C]-PBR28 Binding Between Persons Living With HIV and HIV-Uninfected Individuals
Authors: Boerwinkle Anna H. , Strain Jeremy F. , Burdo Tricia , Doyle John , Christensen Jon , Su Yi , Wisch Julie K. , Cooley Sarah A. , Vaida Florin , Smith Mandy D. , Jafri Hussain , Paul Robert H. , Benzinger Tammie L.S. , Ances Beau M. 
Published: July 2020

Objective:
Despite combined antiretroviral therapy, neuroinflammation may persist in persons living with HIV (PLWH) and contribute to cognitive impairment in this population. Positron emission tomography (PET) imaging targeting 18 kDa translocator protein (TSPO) has been used to localize neuroinflammation. We aimed to use TSPO-PET imaging to evaluate neuroinflammation in PLWH.

Design:
Twenty-four virologically suppressed PLWH on combined antiretroviral therapy and 13 HIV-negative (HIV−) controls completed TSPO-PET imaging using the radiotracer [11C]PBR28. Because of tracer complexity and differing procedures used in previous studies, we employed an expansive methodological approach, using binding potential (BP) and standard uptake value ratio and multiple different reference regions to estimate [11C]PBR28 binding.

Methods:
[11C]PBR28 binding was measured in 30 cortical and subcortical regions and compared between PLWH and HIV− controls. Pearson correlation evaluated the association between [11C]PBR28 binding and cognition and clinical measures of HIV.

Results:
Analyses conducted using multiple reference regions and measures of tracer uptake revealed no significant differences between [11C]PBR28 binding in PLWH compared with HIV− controls. In addition, [11C]PBR28 binding in PLWH was not significantly associated with clinical measures of HIV or plasma biomarkers of inflammation. [11C]PBR28 binding was not significantly elevated in cognitively impaired PLWH compared with unimpaired PLWH, but there were inverse relationships between cognitive performance (executive and global function) and [11C]PBR28 binding in PLWH.

Conclusions:
Our results suggest that neuroinflammation may play a role in cognitive deficits, but overall neuroinflammatory levels as measured by TSPO-PET imaging in PLWH are not significantly different from those seen in HIV− controls.
Derivation and Validation of an HIV Risk Prediction Score Among Gay, Bisexual, and Other Men Who Have Sex With Men to Inform PrEP Initiation in an STD Clinic Setting
Authors: Tordoff Diana M. , Barbee Lindley A. , Khosropour Christine M. , Hughes James P. , Golden Matthew R. 
Published: July 2020

Background:
Clinicians and health departments would ideally undertake targeted efforts to promote HIV pre-exposure prophylaxis (PrEP) and frequent HIV testing using data-based criteria to identify populations at elevated risk for HIV. We developed an HIV risk prediction score for men who have sex with men (MSM) to identify individuals at substantial risk for HIV acquisition.

Methods:
We created a retrospective cohort of MSM who tested HIV-negative at the sexually transmitted disease clinic in Seattle, WA, from 2001 to 2015, and identified seroconversions using HIV surveillance data. We split the cohort randomly 2:1 into derivation and validation data sets, and used Cox proportional hazards to estimate the hazard of acquiring HIV associated with behavioral and clinical predictors, and the Akaike information criterion to determine which variables to retain in our model.

Results:
Among 16,448 MSM, 640 seroconverted over a 14.3-year follow-up period. The best prediction model included 13 variables and had an area under the receiver operating characteristic curve of 0.73 (95% confidence interval: 0.71 to 0.76), 76% sensitivity, and 63% specificity at a score cutoff ≥11. A simplified model restricted to 2011–2015 included 4 predictors [methamphetamine use, condomless receptive anal intercourse (CRAI), ≥10 partners, and current diagnosis or self-reported gonorrhea/syphilis in the past year]. This model, the Seattle PrEP Score, had an area under the receiver operating characteristic curve of 0.69 (95% confidence interval: 0.64 to 0.73), 62% sensitivity, and 70% specificity. One-year incidence was 0.5% for a score of 0, 0.7% for a score of 1, and 2.1% for scores ≥2.

Conclusions:
The Seattle PrEP Score was predictive of HIV acquisition and could help clinicians and public health agencies identify MSM who could benefit from PrEP and frequent HIV testing.
Hyaluronic Acid Injections to Correct Lips Deformity Following Surgical Removal of Permanent Implant
Authors: Rauso Raffaele , Federico Francesco , Zerbinati Nicola , De Cicco Davide , Nicoletti Giovanni Francesco , Tartaro Gianpaolo 
Published: July 2020

Abstract
One of the most attractive areas of the face are the lips, they are crucial for emotion and communication, both during animation and at rest. Throughout the years, several techniques to obtain permanent lip enhancement have been introduced, such as the use of nonresorbable fillers. The main problem related to permanent fillers is that undesirable results could not always be repaired; although lip sequelae can be addressed surgically, some surgeons will not perform this type of procedure due to its complexity and the lack of guidelines.
In this paper, the authors present a case of a labial incompetence developed after lips implant removal performed elsewhere; after clinical examination the patient was planned for surgery, although during preoperative instrumental examination (chest X-ray) a solitary pulmonary nodule was noted; further investigation performed with needle biopsy revealed a lung cancer. For this reason, the surgical procedure planned for lip restoration was not performed; however, the patient asked for a minimally invasive procedure, thus to improve, although temporarily, her lips appearance.
For the aforementioned reasons, the patient was treated just with hyaluronic acid injections achieving a pleasant result, solving also the labial incompetence at rest.
To the best of the author's knowledge, this paper represents the first one describing the use of hyaluronic acid injections to restore lip competence following surgical removal of permanent implant.
Co-Culture of Adipose-Derived Stem Cells and Chondrocytes With Transforming Growth Factor-Beta 3 Promotes Chondrogenic Differentiation
Authors: Ma Xiao-Fei , Ma Xiao-Bing , Qian Wen-Jiang , Zhao Hong-Yi , Ding Jin-Ping , Zhao Tian-Lan 
Published: July 2020

Abstract
Tissue engineering cartilage is a promising strategy to reconstruct the craniofacial cartilaginous defects. It demands plenty of chondrocytes to generate human-sized craniofacial frameworks. Partly replacement of chondrocytes by adipose-derived stem cells (ADSCs) can be an alternative strategy.
The study aimed at evaluating the chondrogenic outcome of ADSCs and chondrocytes in direct co-culture with transforming growth factor-beta (TGF-β3). Porcine ADSCs and chondrocytes were obtained from abdominal wall and external ears. Four groups: ADSCs or chondrocytes monocultured in medium added with TGF-β3; ADSCs and ACs co-cultured with or without TGF-β3. Cell growth rate was performed to evaluate the cell proliferation. Morphological, histologic and real-time polymerase chain reaction analysis were performed to characterize the chondrogenic outcome of pellets. ADSCs had favorable multi-lineage differentiation potential. Further, when ADSCs were co-cultured with chondrocytes in medium added with TGF-β3, the cell proliferation was promoted and the chondrogenic differentiation of ADSCs was enhanced. We demonstrate that pellet co-culture of ADSCs and chondrocyte with TGF-β3 could construct high quantity cartilages. It suggests that this strategy might be useful in future cartilage repair.
Prevalence of Frontal Sinus Aplasia in Jordanian Individuals
Authors: Al-Balas Hasan Ibrahim , Nuseir Amjad , Alzoubi Firas , Alomari Ahmad , Bani-Ata Majid , Almehzaa Sumaya , Aleshawi Abdelwahab 
Published: July 2020

Abstract
Our paper aims to investigate the prevalence of frontal sinus aplasia among Jordanian individuals and compare it with values from different populations. Retrospectively, the study was done for 167 of the paranasal sinuses coronal tomography (CT) for patients who attended the clinic from January 2019 to August 2019 in King Abdullah University Hospital Irbid, Jordan. The authors analyzed the multiplanar CT scans to perform our work. The authors excluded the following images from our study: patients younger than 18 years old, patients with history of skull base trauma that impaired visualization of the frontal sinus, and images with fibro-osseous lesions that impaired the visualization of the frontal sinus. The prevalence of bilateral frontal sinus aplasia is 4.2% among Jordanian individuals and 6.6% is the prevalence of unilateral frontal sinus aplasia. Both values are consistent with average values among different populations. Moreover, we noticed the higher prevalence in both the bilateral and unilateral frontal sinus aplasia in males compared to females. The prevalence of frontal sinus aplasia among Jordanian individuals is almost within the same values among different populations. These numbers regarding the bilateral and unilateral frontal sinus aplasia is crucial to push the surgeon to evaluate CT of the paranasal sinuses preoperatively and focus on the presence of frontal sinuses on CT images to prevent unwanted complications during sinus surgeries.
Effects of plant community history, soil legacy and plant diversity on soil microbial communities
Authors: Schmid Marc W. , van Moorsel Sofia J. , Hahl Terhi , De Luca Enrica , Deyn Gerlinde B. , Wagg Cameron , Niklaus Pascal A. , Schmid Bernhard 
Published: July 2020

AbstractPlant and soil microbial diversity are linked through a range of interactions, including the exchange of carbon and nutrients but also herbivory and pathogenic effects. Over time, associations between plant communities and their soil microbiota may strengthen and become more specific, resulting in stronger associations between plant and soil microbial diversity. We tested this hypothesis in a 4-year long field experiment in which we factorially combined plant community history and soil legacy with plant diversity (1, 2, 4, 8, 60 species). Plant community history and soil legacy refer to the presence (“old”) or absence (“new”) of a common history of plants and soils in 52 different plant species compositions during 8 years in a long-term biodiversity experiment in Jena, Germany. After 4 years of growth, we took soil samples in the new field experiment and determined soil bacterial and fungal composition in terms of operational taxonomic units (OTUs) using 16S rRNA gene and ITS DNA sequencing. Plant community history did not affect overall soil community composition but differentially affected bacterial richness and abundances of specific bacteria taxa in association with particular plant species compositions. Soil legacy markedly increased soil bacterial richness and evenness and decreased fungal evenness. Soil fungal richness increased with plant species richness, regardless of plant community history or soil legacy, with the strongest difference between plant monocultures and mixtures. Particular plant species compositions and functional groups were associated with particular bacterial and fungal community compositions. Grasses increased and legumes decreased fungal richness and evenness. Our findings indicate that as experimental ecosystems varying in plant diversity develop over 8 years, plant species associate with specific soil microbial taxa. This can have long-lasting effects on belowground community composition in re-assembled plant communities, as reflected in strong soil legacy signals still visible after 4 years of growing new plant communities. Effects of plant community history on soil communities are subtle and may take longer to fully develop.
Which animals are at risk? Predicting species susceptibility to Covid-19
Authors: Alexander MR , Schoeder CT , Brown JA , Smart CD , Moth C , Wikswo JP , Capra JA , Meiler J , Chen W , Madhur MS 
Published: July 2020

AbstractIn only a few months, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, leaving physicians, scientists, and public health officials racing to understand, treat, and contain this zoonotic disease. SARS-CoV-2 has made the leap from animals to humans, but little is known about variations in species susceptibility that could identify potential reservoir species, animal models, and the risk to pets, wildlife, and livestock. While there is evidence that certain species, such as cats, are susceptible, the vast majority of animal species, including those in close contact with humans, have unknown susceptibility. Hence, methods to predict their infection risk are urgently needed. SARS-CoV-2 spike protein binding to angiotensin converting enzyme 2 (ACE2) is critical for viral cell entry and infection. Here we identified key ACE2 residues that distinguish susceptible from resistant species using in-depth sequence and structural analyses of ACE2 and its binding to SARS-CoV-2. Our findings have important implications for identification of ACE2 and SARS-CoV-2 residues for therapeutic targeting and identification of animal species with increased susceptibility for infection on which to focus research and protection measures for environmental and public health.
A novel computational method to design BH3-mimetic peptide inhibitors that can bind specifically to Mcl-1 or Bcl-XL
Authors: Reddy C. Narendra , Manzar Nishat , Ateeq Bushra , Sankararamakrishnan Ramasubbu 
Published: July 2020

AbstractInteractions between pro- and anti-apoptotic B cell lymphoma 2 (Bcl-2) proteins decide the fate of the cell. BH3 (Bcl-2 homology 3) domain of pro-apoptotic Bcl-2 proteins interacts with the exposed hydrophobic groove of anti-apoptotic counterparts. Design and development of BH3 mimetics that target the hydrophobic groove of specific anti-apoptotic Bcl-2 proteins have the potential to become anti-cancer drugs. We have developed a novel computational method to design sequences with BH3 domain features that can bind specifically to anti-apoptotic Mcl-1 or Bcl-XL. In this method, we retained the four highly conserved hydrophobic and aspartic residues of wild-type BH3 sequences and randomly substituted all other positions to generate a large number of BH3-like sequences. We modeled 20000 complex structures with Mcl-1 or Bcl-XLusing the BH3-like sequences derived from five wild-type pro-apoptotic BH3 peptides. Peptide-protein interaction energies calculated from these models for each set of BH3-like sequences resulted in negatively-skewed extreme value distributions. The selected BH3-like sequences from the extreme negative tail regions have distinctly different distribution of charged residues for Mcl-1 and Bcl-XL. BH3-like sequences with highly favorable interaction energies prefer to have acidic residues for Mcl-1 and are enriched with basic residues when they bind to Bcl-XL. With the charged residues often away from the binding interface, the overall electric field generated by the charged residues result in highly favorable long-range electrostatic interaction energies between the peptide and the protein giving rise to high specificity. Cell viability studies of representative BH3-like peptides further validated the predicted specificity.
Reduced biomechanical models for precision-cut lung-slice stretching experiments
Authors: Pybus Hannah J. , Edgar Lowell T. , O’Dea Reuben D. , Brook Bindi S. 
Published: July 2020

AbstractPrecision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely usedex vivoassay to investigate bronchoconstriction and, more recently, mechanical activation of pro-remodelling cytokines in asthmatic airways. We develop a nonlinear fibre-reinforced biomechanical model accounting for smooth muscle contraction and extracellular matrix strain-stiffening. Through numerical simulation, we describe the stresses and contractile responses of an airway within a PCLS of finite thickness, exposing the importance of smooth muscle contraction on the local stress state within the airway. We then consider two simplifying limits of the model (a membrane representation and an asymptotic reduction in the thin-PCLS-limit), that permit analytical progress. Comparison against numerical solution of the full problem shows that the asymptotic reduction successfully captures the key elements of the full model behaviour. The more tractable reduced model that we develop is suitable to be employed in investigations to elucidate the time-dependent feedback mechanisms linking airway mechanics and cytokine activation in asthma.
AMPA receptor anchoring at CA1 synapses is determined by an interplay of N-terminal domain and TARP γ8 interactions
Authors: Watson Jake F. , Pinggera Alexandra , Ho Hinze , Greger Ingo H. 
Published: July 2020

AbstractAMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings and super-resolution imaging, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity.
Activity Mapping the Acyl Carrier Protein - Elongating Ketosynthase Interaction in Fatty Acid Biosynthesis
Authors: Mindrebo Jeffrey T. , Misson Laetitia E. , Johnson Caitlin , Noel Joseph P. , Burkart Michael D. 
Published: July 2020

ABSTRACTElongating ketosynthases (KSs) catalyze carbon-carbon bond forming reactions during the committed step for each round of chain extension in both fatty acid synthases (FASs) and polyketide synthases (PKSs). A small α-helical acyl carrier protein (ACP) shuttles fatty acyl intermediates between enzyme active sites. To accomplish this task, ACP relies on a series of dynamic interactions with multiple partner enzymes of FAS and associated FAS-dependent pathways. Recent structures of theEscherichia coliFAS ACP, AcpP, in covalent complexes with its two cognate elongating KSs, FabF and FabB, provide high-resolution detail of these interfaces, but a systematic analysis of specific interfacial interactions responsible for stabilizing these complexes has not yet been undertaken. Here, we use site-directed mutagenesis with bothin vitroandin vivoactivity analyses to quantitatively evaluate these contacting surfaces between AcpP and FabF. We delineate the FabF interface into three interacting regions and demonstrate the effects of point mutants, double mutants, and region delete variants. Results from these analyses reveal a robust and modular FabF interface capable of tolerating seemingly critical interface mutations with only the deletion of entire regions significantly compromising activity. Structure and sequence analysis of FabF orthologs from related type II FAS pathways indicate significant conservation of type II FAS KS interface residues and, overall, support its delineation into interaction regions. These findings strengthen our mechanistic understanding of molecular recognition events between ACPs and FAS enzymes and provide a blueprint for engineering ACP-dependent biosynthetic pathways.
Prognostic Value of Long Noncoding RNA NORAD in Various cancers: a meta-analysis
Authors: Yang Qin , Zhang Zheng , Gong Yuan-Yuan , Li Zhi-Ran , Zhang Hua-Zhu , He Gong-Hao 
Published: July 2020

AbstractObjectiveAccumulating studies reported that noncoding RNA activated by DNA damage (NORAD) was correlated with poor survival outcomes for patients in different cancers. However, the effects of NORAD on cancer prognosis were controversial. Therefore, a meta-analysis was carried out to elucidate this issue.MethodsLiterature search was performed to collect eligible relevant publications until June 2020. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of NORAD with prognosis and clinical features in diverse cancers. In addition, bioinformatics analysis was also utilized to validate the results of the meta-analysis.ResultsFourteen relevant articles involving 867 patients were enrolled in the present study. The pooled results showed that elevated expression of NORAD was a risk factor for overall survival (HR = 1.46, 95% CI: 1.06-2.01, P = 0.020), disease-free survival (HR = 1.74, 95% CI: 1.18-2.57, P = 0.005) and recurrence-free survival. Besides, overexpression of NORAD significantly correlated with lymph node metastasis and T stage. Additionally, bioinformatics analysis further strengthened and complemented the results of the present study.ConclusionOur results showed that NORAD was a risk factor for survival outcomes and clinicopathological parameters in cancer patients. These findings indicated that NORAD may be a promising candidate for prognosis prediction and potential therapeutic target in diverse cancers.
Somatic transposition in theDrosophilaintestine occurs in active chromatin and is associated with tumor suppressor gene inactivation
Authors: Siudeja Katarzyna , van den Beek Marius , Riddiford Nick , Boumard Benjamin , Wurmser Annabelle , Stefanutti Marine , Lameiras Sonia , Bardin Allison J. 
Published: July 2020

AbstractTransposable elements (TEs) play a significant role in evolution by contributing to genetic variation through germline insertional activity. However, how TEs act in somatic cells and tissues is not well understood. Here, we address the prevalence of transposition in a somatic tissue, exploiting theDrosophilamidgut as a model system. Using whole-genome sequencing ofin vivoclonally expanded gut tissue, we map hundreds of high-confidence somatic TE integration sites genome-wide. We show that somatic retrotransposon insertions are associated with inactivation of the tumor suppressorNotch, likely contributing to neoplasia formation. Moreover, by applying Oxford Nanopore long-read sequencing technology, as well as by mapping germline TE activity, we provide evidence suggesting tissue-specific differences in retrotransposition. By comparing somatic TE insertional activity with transcriptomic and small RNA sequencing data, we demonstrate that transposon mobility cannot be simply predicted by whole tissue TE expression levels or by small RNA pathway activity. Finally, we reveal that somatic TE insertions in the adult fly intestine are found preferentially in genic regions and open, transcriptionally active chromatin. Together, our findings provide clear evidence of ongoing somatic transposition inDrosophilaand delineate previously unknown underlying features of somatic TE mobilityin vivo.