bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Intravenous Aminocaproid Acid on Blood Loss and Transfusion Requirements After Bilateral Varus Rotational Osteotomy: A Double-blind, Placebo-controlled Randomized Trial
Authors: Swarup Ishaan , Nguyen Joseph , Edmonds Chris , Dodwell Emily , Scher David 
Published: December 2019

Background:
ε-Aminocaproic acid (EACA) is an antifibrinolytic agent that has been shown to decrease blood loss and transfusion requirements in several populations undergoing various surgical procedures. However, the efficacy of EACA has not been assessed in pediatric patients with cerebral palsy undergoing bilateral varus rotational femoral osteotomies. The purpose of this study was to assess the efficacy of intravenous EACA in reducing calculated intraoperative blood loss and transfusions in this population.

Methods:
Patients aged 18 years or younger were eligible. Patients were randomized to receive EACA or placebo (saline), and randomization was stratified based on sex and whether or not additional soft tissue or osseous procedures were performed. On the basis of retrospective data, the calculated sample size was 12 patients per arm to detect a difference of 250-mL blood loss. The primary outcome was calculated intraoperative blood loss. Secondary outcomes included transfusion requirements, 24-hour drain output, length of stay, and incidence of complications.

Results:
The mean age of patients in this study was 8 years (SD: 2.4 y). There were no differences in age, sex, height, weight, type of anesthesia, operative time, and associated procedures between the EACA and placebo groups (P>0.05). Preoperative hematocrit was lower in the EACA group (37.1 vs. 40.0, P=0.04). Calculated intraoperative blood loss was 536 mL in the EACA group and 628 mL in the placebo group (P=0.45). Transfusions were required in 62% of patients in the EACA group and 67% of patients in the placebo group (P=0.68). Total 24-hour drain output was 72.5 mL in the EACA group and 103.3 mL in the placebo group (P=0.37). Length of stay was similar between both groups, and there were no drug or placebo-related complications in either group.

Conclusions:
There was no difference in blood loss or transfusion requirements associated with EACA compared with placebo; however, this study is underpowered to detect smaller differences in blood loss. Additional studies with larger sample sizes are needed to confirm these findings and further elucidate the indications for antifibrinolytic agents in pediatric patients.

Level of Evidence
Level I.
Polypharmacy in HIV: recent insights and future directions
Authors: Edelman E. Jennifer , Rentsch Christopher T. , Justice Amy C. 
Published: December 2019

Purpose of review
Update findings regarding polypharmacy among people with HIV (PWH) and consider what research is most needed.

Recent findings
Among PWH, polypharmacy is common, occurs in middle age, and is predominantly driven by nonantiretroviral (ARV) medications. Many studies have demonstrated strong associations between polypharmacy and receipt of potentially inappropriate medications (PIMS), but few have considered actual adverse events. Falls, delirium, pneumonia, hospitalization, and mortality are associated with polypharmacy among PWH and risks remain after adjustment for severity of illness.

Summary
Polypharmacy is a growing problem and mechanisms of injury likely include potentially inappropriate medications, total drug burden, known pairwise drug interactions, higher level drug interactions, drug--gene interactions, and drug--substance use interactions (alcohol, extra-medical prescription medication, and drug use). Before we can effectively design interventions, we need to use observational data to gain a better understanding of the modifiable mechanisms of injury. As sicker individuals take more medications, analyses must account for severity of illness. As self-report of substance use may be inaccurate, direct biomarkers, such as phosphatidylethanol (PEth) for alcohol are needed. Large samples including electronic health records, genetics, accurate measures of substance use, and state of the art statistical and artificial intelligence techniques are needed to advance our understanding and inform clinical management of polypharmacy in PWH.
Pseudocarcinomatous Hyperplasia, Squamous Cell Carcinoma, and Keratoacanthoma Associated to Lymphomas of the Skin and External Mucous Membranes: A Case Report and Literature Review
Authors: Jeunon Thiago , Assoni Ariane , Verdolin Annelise 
Published: December 2019

Abstract:
Pseudocarcinomatous hyperplasia (PCH) is a benign reactive epithelial proliferation that may be associated to lymphomas of the skin or external mucous membranes. We present a case of single lesion mycosis fungoides (Woringer-Kollop's reticulosis pagetoid) associated with PCH that was initially misdiagnosed as squamous cell carcinoma (SCC) and review all PubMed-indexed previously reported cases on lymphomas of the skin or external mucous membranes associated to PCH, SCC, and keratoacanthomas. Including our own case, we collected data of 114 cases of cutaneous or mucosal lymphoproliferative disorders associated to PCH, 3 cases associated to SCC, and other 3 cases associated to keratoacanthomas. All cases were tabulated to the following parameters whenever data was available: sex, age, previous medical conditions, number of lesions (single × multiple), site of involvement (mucosa, skin or both), clinical impression, initial equivocal histopathologic diagnosis, final diagnosis, keratinocytic atypia (presence × absence), lymphocytic atypia (presence × absence), CD30-status, and treatment.
Rapid BRAF Mutation Testing in Pigmented Melanomas
Authors: Petty Danielle R. , Hassan Omer A. , Barker Callie S. , O'Neill Stacey S. 
Published: December 2019

Abstract:

BRAF mutations are present in ∼40%–60% of melanomas, and targeted therapy in advanced-stage melanoma is associated with improvement in overall and progression-free survival. Accordingly, BRAF mutation determination is standard-of-care in metastatic melanoma, and a rapid, accurate assay is desirable. Melanin can present unique challenges due to inhibition of the polymerase chain reaction. The novel cartridge-based Idylla platform offers rapid molecular oncology testing; however, a formal evaluation of the impact of melanin on testing heretofore has not been explored. In this study, we evaluated the performance of Idylla BRAF mutation detection in 23 melanomas including resections, small biopsies, and cytology cell blocks. Pathologists assigned each case a pigment score from 0 to 2 based on extent of melanin content. Samples with a pigment score of 2 were successfully resulted, thus demonstrating that high melanin content did not inhibit the assay. Sensitivity and specificity of BRAF mutation detection were 100% compared with reference laboratory testing. Tissue input requirements were low, with the Idylla successfully detecting a BRAF mutation in cell block material containing only ∼400 tumor cells. The assay was simple and quick to perform, with total hands-on time of 5–10 minutes and instrument time ∼90 minutes. In summary, the Idylla BRAF mutation assay provides rapid, robust testing for melanomas with high melanin content, including samples with limited material. The assay requires minimal technical expertise, making mutation status determination accessible in a range of clinical laboratory settings. The total assay time of <2 hours facilitates prompt results to guide patient care decisions.
Diagnosis and management of low-flow, low-gradient aortic stenosis
Authors: Salemi Arash , Hameed Irbaz , Khan Faiza M. , Gaudino Mario 
Published: December 2019

Purpose of review
The severity of low-flow, low-gradient aortic stenosis cases continue to be misunderstood because of challenging diagnosis, and treatment remains complex. We discuss current diagnostic and treatment modalities for low-flow, low-gradient aortic stenosis.

Recent findings
This article summarizes current guidelines and best practices for the management of low-flow, low-gradient aortic stenosis.

Summary
Low-flow, low-gradient aortic stenosis is a difficult entity to diagnose and treat. Various diagnostic modalities are needed to accurately determine the severity of aortic stenosis and potential treatment benefit. True-severe classical and paradoxical low-flow, low-gradient aortic stenosis can be distinguished from pseudo-severe aortic stenosis by dobutamine stress echocardiography and/or multidetector computed tomography. Once the distinction is made, aortic valve replacement results in better outcomes compared with conservative management. Although both surgical and transcatheter aortic valve replacement result in adequate outcomes, the decision between the two treatment strategies is based on patient characteristics, valve morphology, and other risk factors.
THICKNESSES OF SCLERA AND LAMINA CRIBROSA IN PATIENTS WITH CENTRAL RETINAL VEIN OCCLUSION
Authors: Adiyeke Seda Karaca , Kutlu Neslisah , Aytogan Hasan , Aras Buket , Yoyler Gokhan , Ture Gamze , Talay Ekrem , Talay Dayangac Gulsah 
Published: December 2019

Purpose:
To evaluate thicknesses of sclera and lamina cribrosa (LC) in central retinal vein occlusion (CRVO).

Method:
Thirty-two patients with CRVO (mean age 62.2 ± 11.6 years, women/men 18/14) and 35 age- and sex-matched healthy volunteers were included into the study. Scleral thickness was measured at scleral spur and at 1 to 3 mm from scleral spur in four quadrants (temporal, nasal, super, and inferior) using anterior segment optical coherence tomography. Lamina cribrosa was measured using optic disk enhanced depth imaging optical coherence tomography.

Results:
The sclera was thicker in affected eyes of the CRVO group than healthy subjects at scleral spur in four quadrants (738.7 ± 30.9 µm vs. 702 ± 30.8 µm in temporal, 700.4 ± 19.7 µm vs. 673 ± 13.7 µm in superior, 693 ± 19.3 µm vs. 665.3 ± 24.2 µm in nasal, 810.7 ± 28.9 µm vs. 784.5 ± 23.7 µm in inferior quadrants, respectively; P ˂ 0.05 for all). Lamina cribrosa thickness in affected eyes of the CRVO group was significantly higher than that of healthy subjects (285.2 ± 12.7 µm vs. 266.4 ± 10.7 µm, respectively; P ˂ 0.01). The correlation between scleral thickness and LC thickness was moderate at scleral spur of temporal and superior quadrants of affected eyes (r = 0.510 and r = 0.420, respectively).

Conclusion:
Thicknesses of sclera and LC are increased in the CRVO, which may play a role in the pathogenesis of the disease.
CLINICAL OUTCOME OF POLYPOIDAL CHOROIDAL VASCULOPATHY/ANEURYSMAL TYPE 1 NEOVASCULARIZATION ACCORDING TO CHOROIDAL VASCULAR MORPHOLOGY
Authors: Baek Jiwon , Lee Jae Hyung , Lee Kook , Chung Byung Joo , Lee Won Ki 
Published: December 2019

Purpose:
To determine the impact of choroidal vascular morphology on clinical outcomes in patients with polypoidal choroidal vasculopathy/aneurysmal Type 1 neovascularization.

Methods:
Sixty-six eyes with polypoidal choroidal vasculopathy/aneurysmal Type 1 were included. Eyes were subdivided according to the choroidal vascular morphology of the large vessel layer on optical coherence tomography en face images: focal (n = 39) versus diffuse (n = 27) pachyvessels. All patients were treated with intravitreal ranibizumab pro re nata with or without rescue photodynamic therapy.

Results:
Best-corrected visual acuity at baseline, 6, and 12 months did not differ between groups (P = 0.394, 0.142, and 0.292). At Month 3, best-corrected visual acuity was worse, and the proportion of eyes with fluid was higher in the focal group (P = 0.016 and 0.024). Among responders, the number of injections during 12-month follow-up was higher in the focal group (P = 0.033). During the total follow-up period, photodynamic therapy was required in 15 eyes (10 focal and 5 diffuse group, P = 0.497). The injection-free period after the photodynamic therapy was shorter in the focal group (P = 0.018).

Conclusion:
The polypoidal choroidal vasculopathy/aneurysmal Type 1 eyes with a diffuse pattern of pachyvessels required fewer injections during 12-month follow-up and showed a longer injection-free period after rescue photodynamic therapy.
Spatial Hearing as a Function of Presentation Level in Moderate-to-Severe Unilateral Conductive Hearing Loss
Authors: Thompson Nicholas J. , Kane Stacey L. G. , Corbin Nicole E. , Canfarotta Michael W. , Buss Emily 
Published: December 2019

Hypothesis:
Patients with moderate-to-severe unilateral conductive hearing loss (UCHL) can make use of binaural difference cues when stimuli are presented at a high enough intensity to provide audibility in the affected ear.

Background:
Spatial hearing is essential for listening in complex environments and sound source localization. Patients with UCHL have decreased access to binaural difference cues, resulting in poorer spatial hearing abilities compared with listeners with normal hearing.

Methods:
Twelve patients with moderate-to-severe UCHL, most due to atresia (83.3%), and 12 age-matched controls with normal hearing bilaterally participated in this study. Outcome measures included: 1) spatial release from masking, and 2) sound source localization. Speech reception thresholds were measured with target speech (Pediatric AzBio sentences) presented at 0 degree and a two-talker masker that was either colocated with the target (0 degree) or spatially separated from the target (symmetrical, ±90 degrees). Spatial release from masking was quantified as the difference between speech reception thresholds in these two conditions. Localization ability in the horizontal plane was assessed in a 180 degree arc of 11 evenly-spaced loudspeakers. These two tasks were completed at 50 and 75 dB SPL.

Results:
Both children and adults with UCHL performed more poorly than controls when recognizing speech in a spatially separated masker or localizing sound; however, this group difference was larger at 50 than 75 dB SPL.

Conclusion:
Patients with UCHL experience improved spatial hearing with the higher presentation level, suggesting that the auditory deprivation associated with a moderate-to-severe UCHL does not preclude exposure to—or use of—binaural difference cues.
Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment–Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials
Authors: Cahn Pedro , Madero Juan Sierra , Arribas José R. , Antinori Andrea , Ortiz Roberto , Clarke Amanda E. , Hung Chien-Ching , Rockstroh Jürgen K. , Girard Pierre-Marie , Sievers Jörg , Man Choy Y. , Urbaityte Rimgaile , Brandon Daisy J. , Underwood Mark , Tenorio Allan R. , Pappa Keith A. , Wynne Brian , Gartland Martin , Aboud Michael , van Wyk Jean , Smith Kimberly Y. 
Published: December 2019

Background:
The 2-drug regimen dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL in treatment-naive adults in the 48-week primary analysis of the GEMINI trials. We present results from the prespecified 96-week secondary analyses.

Setting:
One hundred eighty-seven centers in 21 countries.

Methods:
GEMINI-1 and GEMINI-2 are identical, double-blind phase III studies. Participants with screening HIV-1 RNA ≤500,000 copies/mL were randomized 1:1 to once-daily dolutegravir + lamivudine or dolutegravir + tenofovir disoproxil fumarate/emtricitabine.

Results:
At week 96, dolutegravir + lamivudine (N = 716) was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (N = 717) in achieving HIV-1 RNA <50 copies/mL (Snapshot algorithm; −10% noninferiority margin) in the pooled analysis (proportion of responders, 86.0% vs 89.5%, respectively; adjusted treatment difference [95% CI], −3.4% [−6.7 to 0.0007]), GEMINI-1 (−4.9% [−9.8 to 0.03]), and GEMINI-2 (−1.8% [−6.4 to 2.7]). Proportions of participants in the HIV-1 RNA ≥50 copies/mL Snapshot category were largely unchanged from week 48 to 96. Eleven participants taking dolutegravir + lamivudine and 7 taking dolutegravir + tenofovir disoproxil fumarate/emtricitabine met confirmed virologic withdrawal criteria through week 96; none had treatment-emergent resistance mutations. Dolutegravir + lamivudine had a lower rate of drug-related adverse events than dolutegravir + tenofovir disoproxil fumarate/emtricitabine (19.6% vs 25.0%; relative risk ratio, 0.78; 95% CI: 0.64 to 0.95). Renal and bone biomarker changes favored dolutegravir + lamivudine.

Conclusions:
Consistent with 48-week data, dolutegravir + lamivudine demonstrated long-term, noninferior efficacy vs dolutegravir + tenofovir disoproxil fumarate/emtricitabine without increased risk of treatment-emergent resistance, supporting its use in treatment-naive HIV-1–infected individuals.
Examining the relationships between phenotypic plasticity and local environments with genomic structural equation models
Authors: Campbell Malachy T. , Yu Haipeng , Momen Mehdi , Morota Gota 
Published: December 2019

AbstractEnvironmental association analyses (EAA) seek to identify genetic variants associated with local adaptation by regressing local environmental conditions at collection sites on genome-wide polymorphisms. The rationale is that environmental conditions impose selective pressure on trait(s), and these traits are regulated in part by variation at a genomic level. Here, we present an alternative multivariate genomic approach that can be utilized when both phenotypic and environmental data are available for the population. This framework utilizes Bayesian networks (BN) to elucidate interdependancies between local environmental conditions and empirical phenotypes, and jointly estimates the direct and indirect genetic covariances between empirical phenotypes and environmental conditions using a mixed-effects structural equation model (SEM). Direct genomic covariance between empirical phenotypes and environmental conditions may provide insight into whether QTL that affect adaptation to an environmental gradient also affects the observed phenotype. To demonstrate the utility of this approach, we leveraged two existing datasets consisting of 55 climate variables for 1,130Arabidopsisaccessions and empirical phenotypes for fitness and phenology collected on 515 accessions in two common garden locations in Europe. BN showed that plasticity for fitness and phenology was highly dependant on local environmental conditions. Moreover, genomic SEM revealed relatively high positive genomic correlation between plasticity in fitness and environmental variables that describe the favorability of the local environment for plant growth, indicating the presence of common QTL or independent QTL that are tightly linked. We believe the frameworks presented in this manuscript can provide new insights into the genetic basis of local adaptation.
Track-Control, an automatic video-based real-time closed-loop behavioral control toolbox
Authors: Zhang Guang-Wei , Shen Li , Li Zhong , Tao Huizhong W. , Zhang Li I. 
Published: December 2019

AbstractApproaches of optogenetic manipulation of neuronal activity have boosted our understanding of the functional architecture of brain circuits underlying various behaviors. In the meantime, rapid development in computer vision greatly accelerates the automation of behavioral analysis. Real-time and event-triggered interference is often necessary for establishing a tight correlation between neuronal activity and behavioral outcome. However, it is time consuming and easily causes variations when performed manually by experimenters. Here, we describe our Track-Control toolbox, a fully automated system with real-time object detection and low latency closed-loop hardware feedback. We demonstrate that the toolbox can be applied in a broad spectrum of behavioral assays commonly used in the neuroscience field, including open field, plus maze, Morris water maze, real-time place preference, social interaction, and sensory-induced defensive behavior tests. The Track-Control toolbox has proved an efficient and easy-to-use method with excellent flexibility for functional extension. Moreover, the toolbox is free, open source, graphic processing unit (GPU)-independent, and compatible across operating system (OS) platforms. Each lab can easily integrate Track-Control into their existing systems to achieve automation.
The DNA end-binding protein Ku associates with human telomeres primarily via protein-protein interactions
Authors: Sukumar Ann T. , Williams Christopher L. , Jones Celina Y. , Asik Elif , Morris Danna K. , Baldan Alessandro , Indiviglio Sandra M. , Chiodi Ilaria , Mondello Chiara , Bertuch Alison A. 
Published: December 2019

ABSTRACTThe Ku heterodimer (Ku70/Ku80) binds DNA ends with high affinity but without sequence specificity and, upon binding ends created by double-stranded breaks (DSBs), initiates canonical nonhomologous end-joining (c-NHEJ). Ku also localizes to functional telomeres where its c-NHEJ activity is inhibited. Interestingly, Ku has been co-opted at telomeres across species, where it performs varied telomeric functions. In humans, Ku is essential for its role in telomere maintenance, but how it associates with human telomeres is not known. Analysis of Ku’s telomere association in different populations of cen3tel cells, which had a wide range of average telomere lengths, supported Ku’s localization at human telomeres primarily via protein-protein interaction. We also found that the Ku70 and Ku80 α5 helices, which are on opposing sides of the heterodimer and were previously implicated inSaccharomyces cerevisiaeKu’s NHEJ and telomeric functions, respectively, participated in Ku’s telomere association in human cells. While the Ku70 α5 mutant showed increased interaction with TRF2, the Ku80 α5 mutant was not impacted for TRF2 association. Interestingly, residues altered to impair Ku’s DNA end-binding function were also involved in TRF2 interaction and telomere association. Overall, our results suggest protein-protein interactions as the primary mode by which Ku associates with human telomeres.
Sustained virome diversity in Antarctic penguins and their ticks: geographical connectedness and no evidence for low pathogen pressure
Authors: Wille Michelle , Harvey Erin , Shi Mang , Gonzalez-Acuña Daniel , Holmes Edward C. , Hurt Aeron C. 
Published: December 2019

AbstractDespite its isolation and extreme climate, Antarctica is home to diverse fauna and associated microorganisms. It has been proposed that the most iconic Antarctic animal, the penguin, experiences low pathogen pressure, accounting for their disease susceptibility in foreign environments. However, there is a limited understanding of virome diversity in Antarctic species, the extent of in situ virus evolution, or how it relates to that in other geographic regions. To test the idea that penguins have limited microbial diversity we determined the viromes of three species of penguins and their ticks sampled on the Antarctic peninsula. Using total RNA-Sequencing we identified 107 viral species, comprising likely penguin associated viruses (n = 13), penguin diet and microbiome associated viruses (n = 82) and tick viruses (n = 8), two of which may have the potential to infect penguins. Notably, the level of virome diversity revealed in penguins is comparable to that seen in Australian waterbirds, including many of the same viral families. These data therefore reject the theory that penguins are subject to lower pathogen pressure. The repeated detection of specific viruses in Antarctic penguins also suggests that rather than being simply spill-over hosts, these animals may act as key virus reservoirs.