bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a Treatment for Gulf War Illness: A Consensus Docking Approach
Authors: Jaundoo Rajeev , Bohmann Jonathan , Gutierrez Gloria E , Klimas Nancy , Broderick Gordon , Craddock Travis J A 
Published: February 2020

AbstractIntroductionGulf War Illness (GWI) currently has no known cure and affects soldiers deployed during the Persian Gulf War. It is thought to originate from exposure to neurotoxicants combined with battlefield stress, and previous research indicates that treatment first involves inhibition of interleukin-2 and tumor necrosis factor alpha, followed by the glucocorticoid receptor. However, the off-target effects of pharmaceuticals hinder development of a drug treatment therapy.Materials and MethodsAutoDock 4.2, AutoDock Vina, and Schrodinger’s Glide were used to perform consensus docking, a computational technique where pharmaceuticals are screened against targets using multiple scoring algorithms to obtain consistent binding affinities. FDA approved pharmaceuticals were docked against the above-mentioned immune and stress targets to determine a drug therapy for GWI. Additionally, the androgen and estrogen targets were screened to avoid pharmaceuticals with off-target interactions.ResultsWhile suramin bound to both immune targets with high affinity, top binders of the hormonal and glucocorticoid targets were non-specific towards their respective proteins, possibly due to high structure similarity between these proteins.ConclusionsDevelopment of a drug treatment therapy for GWI is threatened by the tight interplay between the immune and hormonal systems, often leading to drug interactions. Increasing knowledge of these interactions can lead to break-through therapies.
Army Antimalarial Drug Development: An Advanced Development Case Study for Tafenoquine
Authors: Zottig Victor E , Carr Katherine A , Clarke John G , Shmuklarsky Moshe J , Kreishman-Deitrick Mara 
Published: February 2020

Abstract
Malaria is classified as a top-tier infectious disease threat associated with a high risk for mortality among U.S. service members deployed overseas. As malarial drug resistance degrades the efficacy of current gold standard drugs for malarial prophylaxis and treatment, it is vitally important to maintain a robust drug pipeline to discover and develop improved, next-generation antimalarial prevention and treatment tools. The U.S. Army Medical Materiel Development Activity (USAMMDA) manages the medical product development of the malarial drug tafenoquine for malarial prophylaxis to address the threat to U.S. service members. Tafenoquine is an effective prophylactic drug against all parasite life cycle stages and all malaria species that infect humans. Thus, it provides broad capabilities in a single drug for malarial prophylaxis and treatment. Partnerships with industry are a crucial part of USAMMDA’s medical product development strategy, by leveraging their drug development experience and manufacturing capabilities to achieve licensure and commercial availability. Additionally, these partnerships capitalize on expertise in the commercial market and help ensure that USAMMDA successfully translates a Department of Defense capability gap into a commercially available product. This article will highlight the strategies used to move this critical antimalarial drug through the development pipeline.
The X-ray and radio activity of typical and luminous Ly α emitters from z ∼ 2 to z ∼ 6: evidence for a diverse, evolving population
Authors: Calhau João , Sobral David , Santos Sérgio , Matthee Jorryt , Paulino-Afonso Ana , Stroe Andra , Simmons Brooke , Barlow-Hall Cassandra , Adams Benjamin 
Published: February 2020

ABSTRACT
Despite recent progress in understanding Ly α emitters (LAEs), relatively little is known regarding their typical black hole activity across cosmic time. Here, we study the X-ray and radio properties of ∼4000 LAEs at 2.2 &lt; $z$ &lt; 6 from the SC4K survey in the COSMOS field. We detect 254 ($6.8{\rm{ per\ cent}} \pm 0.4{\rm{ per\ cent}}$) LAEs individually in the X-rays (S/N &gt; 3) with an average luminosity of $\rm 10^{44.31\pm 0.01}\, erg\, s^{-1}$ and average black hole accretion rate (BHAR) of $\rm 0.72 \pm 0.01$ M⊙ yr−1, consistent with moderate to high accreting active galactic neuclei (AGNs). We detect 120 sources in deep radio data (radio AGN fraction of $3.2{\rm{ per\ cent}} \pm 0.3{\rm{ per\ cent}}$). The global AGN fraction ($\rm 8.6{\rm{ per\ cent}} \pm 0.4{\rm{ per\ cent}}$) rises with Ly α luminosity and declines with increasing redshift. For X-ray-detected LAEs, Ly α luminosities correlate with the BHARs, suggesting that Ly α luminosity becomes a BHAR indicator. Most LAEs ($93.1{\rm{ per\ cent}} \pm 0.6{\rm{ per\ cent}}$) at 2 &lt; $z$ &lt; 6 have no detectable X-ray emission (BHARs &lt; 0.017 M⊙ yr−1). The median star formation rate (SFR) of star-forming LAEs from Ly α and radio luminosities is $7.6^{+6.6}_{-2.8}$ M⊙ yr−1. The black hole to galaxy growth ratio (BHAR/SFR) for LAEs is &lt;0.0022, consistent with typical star-forming galaxies and the local BHAR/SFR relation. We conclude that LAEs at 2 &lt; $z$ &lt; 6 include two different populations: an AGN population, where Ly α luminosity traces BHAR, and another with low SFRs which remain undetected in even the deepest X-ray stacks but is detected in the radio stacks.
The chemical compositions of accreted and in situ galactic globular clusters according to SDSS/APOGEE
Authors: Horta Danny , Schiavon Ricardo P , Mackereth J Ted , Beers Timothy C , Fernández-Trincado José G , Frinchaboy Peter M , García-Hernández D A , Geisler Doug , Hasselquist Sten , Jönsson Henrik , Lane Richard R , Majewski Steven R , Mészáros Szabolcs , Bidin Christian Moni , Nataf David M , Roman-Lopes Alexandre , Nitschelm Christian , Vargas-González J , Zasowski Gail 
Published: February 2020

ABSTRACT
Studies of the kinematics and chemical compositions of Galactic globular clusters (GCs) enable the reconstruction of the history of star formation, chemical evolution, and mass assembly of the Galaxy. Using the latest data release (DR16) of the SDSS/APOGEE survey, we identify 3090 stars associated with 46 GCs. Using a previously defined kinematic association, we break the sample down into eight separate groups and examine how the kinematics-based classification maps into chemical composition space, considering only α (mostly Si and Mg) elements and Fe. Our results show that (i) the loci of both in situ and accreted subgroups in chemical space match those of their field counterparts; (ii) GCs from different individual accreted subgroups occupy the same locus in chemical space. This could either mean that they share a similar origin or that they are associated with distinct satellites which underwent similar chemical enrichment histories; (iii) the chemical compositions of the GCs associated with the low orbital energy subgroup defined by Massari and collaborators is broadly consistent with an in situ origin. However, at the low-metallicity end, the distinction between accreted and in situ populations is blurred; (iv) regarding the status of GCs whose origin is ambiguous, we conclude the following: the position in Si–Fe plane suggests an in situ origin for Liller 1 and a likely accreted origin for NGC 5904 and NGC 6388. The case of NGC 288 is unclear, as its orbital properties suggest an accretion origin, its chemical composition suggests it may have formed in situ.
DNA nanotechnology assisted nanopore-based analysis
Authors: Ding Taoli , Yang Jing , Pan Victor , Zhao Nan , Lu Zuhong , Ke Yonggang , Zhang Cheng 
Published: February 2020

AbstractNanopore technology is a promising label-free detection method. However, challenges exist for its further application in sequencing, clinical diagnostics and ultra-sensitive single molecule detection. The development of DNA nanotechnology nonetheless provides possible solutions to current obstacles hindering nanopore sensing technologies. In this review, we summarize recent relevant research contributing to efforts for developing nanopore methods associated with DNA nanotechnology. For example, DNA carriers can capture specific targets at pre-designed sites and escort them from nanopores at suitable speeds, thereby greatly enhancing capability and resolution for the detection of specific target molecules. In addition, DNA origami structures can be constructed to fulfill various design specifications and one-pot assembly reactions, thus serving as functional nanopores. Moreover, based on DNA strand displacement, nanopores can also be utilized to characterize the outputs of DNA computing and to develop programmable smart diagnostic nanodevices. In summary, DNA assembly-based nanopore research can pave the way for the realization of impactful biological detection and diagnostic platforms via single-biomolecule analysis.
Convergent adaptation of the genomes of woody plants at the land–sea interface
Authors: He Ziwen , Xu Shaohua , Zhang Zhang , Guo Wuxia , Lyu Haomin , Zhong Cairong , Boufford David E , Duke Norman C ,   The International Mangrove Consortium, Shi Suhua 
Published: February 2020

Abstract
Sequencing multiple species that share the same ecological niche may be a new frontier for genomic studies. While such studies should shed light on molecular convergence, genomic-level analyses have been unsuccessful, due mainly to the absence of empirical controls. Woody plant species that colonized the global tropical coasts, collectively referred to as mangroves, are ideal for convergence studies. Here, we sequenced the genomes/transcriptomes of 16 species belonging in three major mangrove clades. To detect convergence in a large phylogeny, a CCS+ model is implemented, extending the more limited CCS method (convergence at conservative sites). Using the empirical control for reference, the CCS+ model reduces the noises drastically, thus permitting the identification of 73 convergent genes with Ptrue (probability of true convergence) &gt; 0.9. Products of the convergent genes tend to be on the plasma membrane associated with salinity tolerance. Importantly, convergence is more often manifested at a higher level than at amino-acid (AA) sites. Relative to &gt;50 plant species, mangroves strongly prefer 4 AAs and avoid 5 others across the genome. AA substitutions between mangrove species strongly reflect these tendencies. In conclusion, the selection of taxa, the number of species and, in particular, the empirical control are all crucial for detecting genome-wide convergence. We believe this large study of mangroves is the first successful attempt at detecting genome-wide site convergence.
Processing of Laser-Evoked Potentials in Patients with Chronic Whiplash-Associated Disorders, Chronic Fatigue Syndrome, and Healthy Controls: A Case–Control Study
Authors: Goudman Lisa , Daenen Liesbeth , Mouraux Andre , Nijs Jo , Cras Patrick , Roussel Nathalie , Moens Maarten , Coppieters Iris , Huysmans Eva , De Kooning Margot 
Published: February 2020

Abstract

Objective
Laser-evoked potentials (LEPs) are among the reliable neurophysiological tools to investigate patients with neuropathic pain, as they can provide an objective account of the functional status of thermo-nociceptive pathways. The goal of this study was to explore the functioning of the nociceptive afferent pathways by examining LEPs in patients with chronic whiplash-associated disorders (cWAD), patients with chronic fatigue syndrome (CFS), and healthy controls (HCs).

Design
Case–control study.

Setting
A single medical center in Belgium.

Subjects
The LEPs of 21 patients with cWAD, 19 patients with CFS, and 18 HCs were analyzed in this study.

Methods
All participants received brief nociceptive CO2 laser stimuli applied to the dorsum of the left hand and left foot while brain activity was recorded with a 32-channel electroencephalogram (EEG). LEP signals and transient power modulations were compared between patient groups and HCs.

Results
No between-group differences were found for stimulus intensity, which was supraliminal for Aδ fibers. The amplitudes and latencies of LEP wave components N1, N2, and P2 in patients with cWAD and CFS were statistically similar to those of HCs. There were no significant differences between the time–frequency maps of EEG oscillation amplitude between HCs and both patient populations.

Conclusions
EEG responses of heat-sensitive Aδ fibers in patients with cWAD and CFS revealed no significant differences from the responses of HCs. These findings thus do not support a state of generalized central nervous system hyperexcitability in those patients.
The Impact of Music on Nociceptive Processing
Authors: Chai Peter R , Gale Jasmine Y , Patton Megan E , Schwartz Emily , Jambaulikar Guruprasad D , Wade Taylor S , Edwards Robert R , Boyer Edward W , Schreiber Kristin L 
Published: February 2020

Abstract
Objective. Music has been shown to modulate pain, although the impact of music on specific aspects of nociceptive processing is less well understood. Using quantitative sensory testing (QST), we assessed the impact of a novel music app on specific aspects of nociceptive processing. Design. Within-subjects paired comparison of pain processing in control vs music condition. Setting. Human psychophysical laboratory. Subjects. Sixty healthy adult volunteers. Methods. Subjects were assessed for baseline anxiety, depression, and catastrophizing using validated questionnaires. QSTs measured included 1) pain threshold and tolerance to deep muscle pressure, 2) pain with mechanical pinprick, 3) temporal summation of pain (TSP) with a repeated pain stimulus, and 4) conditioned pain modulation (CPM) with a second painful stimulus. QSTs were performed in the absence and presence of music delivered through a music app. Results. We found an increase in pressure pain thresholds in both the forearm (P = 0.007) and trapezius (P = 0.002) with music, as well as a decrease in the amount of pinprick pain (P &lt; 0.001) and TSP (P = 0.01) with music. Interestingly, CPM was also significantly diminished (P &lt; 0.001) in the music condition. No significant difference in cold pain, anxiety, or situational catastrophizing was observed with music. Higher baseline pain catastrophizing scores were associated with less music-induced pressure pain reduction. Conclusions. Several measures of mechanical pain sensitivity were reduced with music. TSP, a measure of central sensitization, also decreased with music, but CPM, a measure of descending modulation of pain, was not further augmented by music.
A disconnect between classroom and professional writing: we are not teaching public health students to write effective titles
Authors: Anderson Olivia , August Ella 
Published: February 2020

ABSTRACTTitles are considered a crucial element of grant applications, journal articles, reports and other public health documents, but they are often overlooked in student writing assignments. In this article, we argue that public health instructors should teach students how to write compelling document titles. Our argument about titles is part of a broader assertion that public health students should be asked to write in professional formats such as grant applications, reports and journal articles. Requiring students to engage with important writing conventions like titles that are used in the professional workplace helps them make connections between the content they are writing about and the activities, roles, values and context of public health practice. We recommend that instructors explicitly incorporate titles into their assigned writing in three ways: first, instructors should require titles; second, instructors should provide criteria for a good title that are appropriate to the document type and finally, instructors should award points for a good title.
Vaping-Associated Respiratory Distress Syndrome: Case Classification and Clinical Guidance
Authors: Lilly Craig M. , Khan Shahzad , Waksmundzki-Silva Kathryn , Irwin Richard S. 
Published: February 2020

Objectives:
Exposure to vaping is associated with a growing list of respiratory syndromes including an acute progressive form with life-threatening hypoxemic respiratory failure and pathologic changes of lung injury termed vaping-associated respiratory distress syndrome.

Data Sources:
Center from Disease Control, Departments of Public Health, MEDLINE (via PubMed), and the Cochrane Library.

Study Selection, Data Extraction and Data Synthesis:
Cases, series, and public health reports of cases that met the Centers for Disease Control and Prevention case definition of vaping-associated respiratory disease were extracted by an author with perfect verification by a second. Cases were classified on the basis of toxin exposure, symptoms, oxygen saturation, progression to respiratory failure, and pathologic features, and a clinically actionable system of classification was based on expert opinion.

Conclusions:
The reported spectrum of vaping-associated respiratory diseases allows clinical classification of cases into groups with distinct evaluation, management, and recommendations for prevention and follow-up. Clinical stratification also identifies a small proportion of vaping-exposed patients who are at risk for progression to hypoxemic respiratory failure and an acute respiratory distress syndrome–like illness.
Implementation of a Multidisciplinary Care Pathway via an Emergency Department-ICU to Improve Care of Emergency Department Patients Presenting With Leukostasis
Authors: Haas Nathan L. , Nafday Abhinav , Cranford James A. , Yentz Sarah E. , Bixby Dale L. , Bassin Benjamin S. 
Published: February 2020

Objectives:
Leukostasis is a life-threatening complication of acute hyperleukocytic leukemia, and is associated with substantial mortality. Management of leukostasis requires time-sensitive diagnostics and therapeutics, and leukapheresis remains a mainstay of treatment in select patients. Leukapheresis requires coordination of multi-disciplinary resources, which can prove challenging in the emergency department setting, and delays in treatment due to the complexity and coordination required are common. The objective of this study was to assess the effect of utilization of an emergency department-ICU and a multidisciplinary care pathway on outcomes of critically ill leukostasis patients presenting to the emergency department.

Design:
Retrospective cohort study.

Setting:
Single large academic medical center in the United States.

Patients:
Adult emergency department patients with signs and symptoms of leukostasis requiring emergent leukapheresis from 2012-2019.

Interventions:
Implementation of a hybrid emergency department-ICU setting (emergency critical care center) and a multidisciplinary care pathway with members from Emergency Medicine, Hematology, Blood Bank, and Clinical Pathology.

Measurements and Main Results:
A total of 70 patients were identified and included for analysis: 14 preemergency critical care center; 32 postemergency critical care center, premultidisciplinary care pathway; and 24 postemergency critical care center, postmultidisciplinary care pathway. A statistically significant reduction in the time from emergency department presentation to initiation of leukapheresis was observed from preemergency critical care center to postemergency critical care center, premultidisciplinary care pathway and postemergency critical care center, postmultidisciplinary care pathway (11.5 vs 7.9 vs 7.7 hr; p = 0.004). Statistically significant reductions in in-hospital mortality were observed from preemergency critical care center to postemergency critical care center, premultidisciplinary care pathway and postemergency critical care center, postmultidisciplinary care pathway (64.3% vs 21.9% vs 25.0%; p = 0.01). A trend toward decreased inpatient ICU utilization was observed, although was not statistically significant (35.7% vs 12.5% vs 25.0%; p = 0.14.)

Conclusions and Relevance:
Implementation of a multidisciplinary care pathway via use of an emergency department-ICU for critically ill patients with leukostasis was associated with statistically significant reductions in time to leukapheresis and in-hospital mortality. These findings suggest an emergency department-ICU model may allow for maximal resource and care coordination at the point of contact with critically ill patients and improved clinical outcomes.
New approaches to congenital diaphragmatic hernia
Authors: Blumenfeld Yair J. , Belfort Michael A. 
Published: February 2020

Purpose of reviewCongenital diaphragmatic hernia (CDH) is a structural birth defect that results in significant neonatal morbidity and mortality. CDH occurs in 2–4 per 10 000 pregnancies, and despite meaningful advances in neonatal intensive care, the mortality rate in infants with isolated CDH is still 25–30%. In this review, we will present data on the molecular underpinnings of pathological lung development in CDH, prenatal diagnosis, and prognostication in CDH cases, existing fetal therapy modalities, and future directions.Recent findingsDevelopments in the prenatal assessment and in-utero therapy of pregnancies complicated by congenital diaphragmatic hernia are rapidly evolving. Although ultrasound has been the mainstay of prenatal diagnosis, fetal MRI appears to be an increasingly important modality for severity classification. While fetal endoscopic tracheal occlusion (FETO) may have a role in the prenatal management of severe CDH cases, it is possible that future therapeutic paradigms will incorporate adjunct medical interventions with either stem cells or sildenafil in order to address the vascular effects of CDH on the developing lung.SummaryBoth animal and human data have shown that the pathophysiological underpinnings of CDH are multifactorial, and it appears that future prenatal assessments and therapies will likely be as well.
IDIOPATHIC FOVEAL HYPOPLASIA
Authors: Le Hoang Mai , Souied Eric H. , Pedinielli Alexandre , Zambrowski Olivia , Miere Alexandra 
Published: February 2020

Purpose:To evaluate vascular density (VD), fractal dimension, and skeletal density on optical coherence tomography angiography in eyes with idiopathic foveal hypoplasia (IFH).Methods:Patients presenting with IFH to Creteil University Eye Clinic between January 2015 and October 2018 and age-matched healthy controls were retrospectively evaluated. Vascular density, skeletal density, and fractal dimension analyses were computed on optical coherence tomography angiography superficial capillary plexa (SCP) and deep capillary plexa (DCP) images on the whole image using a custom algorithm. Vascular density on the central 1 mm2and the peripheral 8 mm2for the two groups was performed.Results:Thirty-six eyes of 21 patients (18 eyes with IFH and 18 control eyes) were included. A decrease of VD at the level of the SCP and DCP was found in eyes with IFH compared with healthy control eyes (P= 0.005 for VD at the level of the SCP andP= 0.003 for VD at the level of the DCP, respectively). On the central 1 mm2, VD was decreased in healthy eyes (32.3% ± 4.8) at the level of the SCP compared to IFH eyes (55.6% ± 46.3) (P< 0.001). Skeletal density was decreased in IFH eyes in both SCP and DCP (P=< 0.001). Fractal dimension was lower in IFH eyes in both SCP and DCP (P< 0.001).Conclusion:Vascular density, skeletal density, and fractal dimension are reduced at the level of SCP and DCP in patients with IFH compared with controls, reflecting a particular anatomical and vascular organization. Quantitative analysis using optical coherence tomography angiography could help to evaluate the severity of IFH.