bluuebunny/crossref_metadata_2025_split huggingface dataset:
Submillimetre flux as a probe of molecular ISM mass in high-z galaxies
Authors: Liang Lichen , Feldmann Robert , Faucher-Giguère Claude-André , Kereš Dušan , Hopkins Philip F , Hayward Christopher C , Quataert Eliot , Scoville Nick Z 
Published: April 2018

Abstract
Recent long-wavelength observations on the thermal dust continuum suggest that the Rayleigh–Jeans tail can be used as a time-efficient quantitative probe of the dust and interstellar medium (ISM) mass in high-z galaxies. We use high-resolution cosmological simulations from the Feedback in Realistic Environment (FIRE) project to analyse the dust emission of M* ≳ 1010 M⊙ galaxies at z= 2–4. Our simulations (MassiveFIRE) explicitly include various forms of stellar feedback, and they produce the stellar masses and star formation rates of high-z galaxies in agreement with observations. Using radiative transfer modelling, we show that sub-millimetre (sub-mm) luminosity and molecular ISM mass are tightly correlated and that the overall normalization is in quantitative agreement with observations. Notably, sub-mm luminosity traces molecular ISM mass even during starburst episodes as dust mass and mass-weighted temperature evolve only moderately between z = 4 and z = 2, including during starbursts. Our finding supports the empirical approach of using broadband sub-mm flux as a proxy for molecular gas content in high-z galaxies. We thus expect single-band sub-mm observations with ALMA to dramatically increase the sample size of high-z galaxies with reliable ISM masses in the near future.
The Puzzle of HIV Neutral and Selective Evolution
Authors: Leitner Thomas 
Published: April 2018

AbstractHIV is one of the fastest evolving organisms known. It evolves about 1 million times faster than its host, humans. Because HIV establishes chronic infections, with continuous evolution, its divergence within a single infected human surpasses the divergence of the entire humanoid history. Yet, it is still the same virus, infecting the same cell types and using the same replication machinery year after year. Hence, one would think that most mutations that HIV accumulates are neutral. But the picture is more complicated than that. HIV evolution is also a clear example of strong positive selection, that is, mutants have a survival advantage. How do these facts come together?
Comparative Analysis Between Lateral Orbital Rim Preservation and Osteotomy for Transorbital Endoscopic Approaches to the Cavernous Sinus: An Anatomic Study
Authors: Noiphithak Raywat , Yanez-Siller Juan C , Revuelta Barbero Juan Manuel , Otto Bradley A , Carrau Ricardo L , Prevedello Daniel M 
Published: April 2018

Abstract

BACKGROUND
Transorbital endoscopic approach (TOEA) to the cavernous sinus (CS) is a novel surgical technique. However, the necessity of lateral orbital rim (LOR) osteotomy is questionable.

OBJECTIVE
To illustrate the surgical dissection of TOEAs to CS and to investigate the additional benefit of LOR osteotomy.

METHODS
Anatomic dissections were carried out in 7 cadaveric heads (14 sides). The TOEAs were performed before and after LOR osteotomy; herein referred as the lateral transorbital approach (LTOA) and the lateral orbital wall approach (LOWA), respectively. The stereotactic measurements of the area of exposure, surgical freedom, and angles of attack around CS were quantified.

RESULTS
LOWA increased larger area of exposure than LTOA at entry site (5.3 ± 0.6 cm2 and 2.6 ± 0.6 cm2, respectively; P < .001) but both of these techniques provided similar area of exposure at the surgical target site. With regard to the surgical freedoms, those afforded by LOWA were all significantly superior at all of the surgical targets with the difference ranged from 106.6% to 172.5%. No significant differences were found between the vertical angles produced by either approach. On the other hand, the horizontal angles achieved by LOWA were significantly more favorable.

CONCLUSION
The TOEAs, either with or without LOR osteotomy are feasible for CS exposure. Although the incremental effect of maneuverability is attained following the LOR osteotomy, it should be performed selectively. Additional research is needed to further validate the safety and efficacy, as well as for precisely defining the clinical application of these techniques.
The Interface of Pancreatic Cancer With Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities
Authors: Abbruzzese James L. , Andersen Dana K. , Borrebaeck Carl A.K. , Chari Suresh T. , Costello Eithne , Cruz-Monserrate Zobeida , Eibl Guido , Engleman Edgar G. , Fisher William E. , Habtezion Aida , Kim Seung K. , Korc Murray , Logsdon Craig , Lyssiotis Costas A. , Pandol Stephen J. , Rustgi Anil , Wolfe Bruce M. , Zheng Lei , Powers Alvin C. 
Published: April 2018

Abstract
A workshop on “The Interface of Pancreatic Cancer with Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities” was held by the National Institute of Diabetes and Digestive and Kidney Diseases on October 12, 2017. The purpose of the workshop was to explore the relationship and possible mechanisms of the increased risk of pancreatic ductal adenocarcinoma (PDAC) related to diabetes, the role of altered intracellular energy metabolism in PDAC, the mechanisms and biomarkers of diabetes caused by PDAC, the mechanisms of the increased risk of PDAC associated with obesity, and the role of inflammatory events and mediators as contributing causes of the development of PDAC. Workshop faculty reviewed the state of the current knowledge in these areas and made recommendations for future research efforts. Further knowledge is needed to elucidate the basic mechanisms contributing to the role of hyperinsulinemia, hyperglycemia, adipokines, and acute and chronic inflammatory events on the development of PDAC.
Postpartum Depression Screening for New Mothers at Well Child Visits
Authors: Emerson Margaret R. , Mathews Therese L. , Struwe Leeza 
Published: April 2018

Abstract

Background:
Postpartum depression (PPD) is a debilitating emotional experience that can affect mothers and their infants. Screening for PPD is encouraged during pediatric well-child visits (WCVs); however, the frequency, referral process, and documentation relative to screening in clinical practice require further study.

Objectives:
There were three purposes to this study: 1) determine prevalence of mothers who scored in the at-risk range using the Edinburgh Postnatal Depression Scale (EPDS) at each of the 2-, 4-, and 6-month WCVs in a pediatric outpatient practice; 2) examine feasibility factors relative to extending the current standard of care for PPD screening; and 3) examine visit documentation for at-risk mothers.

Design:
A prospective cohort study design was used to screen mothers during their infants' 6-month WCV for PPD using the EPDS. Feasibility in adding the 6-month time frame was assessed using an investigator-designed clinical team survey. Visit documentation content was obtained through medical record review.

Results:
Forty-three postpartum women were included in the study. Prevalence rates among participants were 10%, 12.5%, and 14% for 2-month, 4-month, and 6-month WCVs, respectively. The clinical team found the additional screening at the 6-month visit to be feasible. Documentation for mothers identified to be at-risk varied greatly.Conclusions: Prevalence of PPD among participants is consistent with previously reported rates. Areas identified for improved clinical practice include the content of the visit that is documented in the medical record and reviewed with mothers identified to be at-risk, time allotted for the clinical team to screen new mothers, and appropriate referral to outside sources.
Use of Tranexamic Acid to Reduce Blood Loss in Liposuction
Authors: Cansancao Alvaro Luiz , Condé-Green Alexandra , David Joshua A. , Cansancao Bethania , Vidigal Rafael A. 
Published: April 2018

Background:
The use of tranexamic acid for blood loss prevention has gained popularity in many specialties, including plastic surgery. However, its use in liposuction has not been studied. The authors present a prospective, double-blind, nonrandomized study evaluating the efficacy of tranexamic acid in reducing perioperative blood loss during liposuction.

Methods:
Twenty women undergoing liposuction were divided into two cohorts. Group 1 (n = 10) received a standard dose of 10 mg/kg of tranexamic acid intravenously in the preoperative and postoperative periods, whereas group 2 (n = 10) received a placebo. Patient hematocrit levels were evaluated preoperatively and postoperatively. Blood volume in the infranatant of the lipoaspirate was also measured; t tests were used for statistical analysis.

Results:
Age, body mass index, and volume of lipoaspirate were comparable between the two cohorts. The volume of blood loss for every liter of lipoaspirate was 56.2 percent less in the tranexamic group compared with the control group (p < 0.001). Hematocrit levels at day 7 postoperatively were 48 percent less in group 1 compared with group 2 (p = 0.001). Furthermore, a 1 percent drop in the hematocrit level was found after liposuction of 812 ± 432 ml in group 1 and 379 ± 204 ml in group 2. Thus, the use of tranexamic acid could allow for aspiration of 114 percent more fat, with comparable variation in hematocrit levels.

Conclusions:
Tranexamic acid has been shown to be effective for minimizing perioperative blood loss in liposuction. Further large randomized controlled studies are required to corroborate this effect.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Addressing the Opioid Epidemic: A Review of the Role of Plastic Surgery
Authors: Wang Annie M. Q. , Retrouvey Helene , Wanzel Kyle R. 
Published: April 2018

Summary:
The opioid epidemic has been a growing public health threat in the United States and Canada for the past 30 years, with alarming and steadily increasing opioid-related mortality rates. Originating with well-intentioned efforts by physicians to relieve pain and suffering in their patients, the source of the opioid epidemic and much of its ammunition continues to be the sales of legally produced pharmaceutical opioids. Although surgeons are increasingly recognizing the important role they can play in mitigating this crisis, the recognition and evaluation of the opioid epidemic in plastic surgery has been lacking. The authors identified several aspects of plastic surgery that make judicious prescription of opioids in this field uniquely complex, including high variability of cases managed, large volume of ambulatory procedures, and frequent involvement in collaborative care with other surgical specialties. Additional research in plastic surgery is needed to both increase current knowledge of opioid prescribing practices and provide evidence for recommendations that can successfully combat the opioid epidemic.
Predictive Value of Soluble Programmed Death-1 for Severe Sepsis and Septic Shock During the First Week in an Intensive Care Unit
Authors: Zhao Yongzhen , Jia Yumei , Li Chunsheng , Shao Rui , Fang Yingying 
Published: April 2018

ABSTRACT

Objective:
Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) exists in both membrane-bound and soluble forms. In this study, we evaluated the predictive value of soluble PD-1 (sPD-1) for severity and 28-day mortality in patients with severe sepsis and septic shock during the first week in an intensive care unit (ICU).

Methods:
In this prospective cohort study, patients were classified into the severe sepsis group or the septic shock group according to the severity of their condition on ICU admission. All patients were also separated into the survivor or nonsurvivor groups according to their 28-day outcomes. Peripheral blood sPD-1 and soluble PD-L1 (sPD-L1) levels, PD-1 expression on CD4+ and CD8+ T cells, and PD-L1 expression on monocytes were measured and compared between the groups on days 1 and 7 after ICU admission.

Results:
In all, 45 healthy volunteers and 112 patients were recruited. Serum sPD-1 levels were positively correlated with the severity of sepsis, sPD-L1 levels, PD-1 expression on CD4+ or CD8+ T cells, and PD-L1 expression on monocytes. The sPD-1 was an independent predictive factor for 28-day mortality both on day 1 and day 7. The area under the curve (AUC) of the sPD-1 on day 7 (0.871) was higher than that on day 1 (0.785) (P < 0.05), and better than the AUC of the percentages of PD-L1 on monocytes (0.770) on day 7 (P < 0.05).

Conclusion:
Serum sPD-1 shows valuable predictive ability for the severity and 28-day mortality of severe sepsis and septic shock during the first week of ICU treatment.
Single Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression
Authors: Bernard Vincent , Semaan Alexander , Huang Jonathan , Lucas F. Anthony San , Mulu Feven C , Stephens Bret M , Guerrero Paola A. , Huang Yanqing , Zhao Jun , Kamyabi Nabiollah , Sen Subrata , Scheet Paul A , Taniguchi Cullen M , Kim Michael P , Tzeng Ching-Wei , Katz Matthew H , Singhi Aatur D , Maitra Anirban , Alvarez Hector A 
Published: April 2018

AbstractBackgroundEarly detection of pancreatic ductal adenocarcinoma (PDAC) remains elusive. Precursor lesions of PDAC, specifically, intraductal papillary mucinous neoplasms (IPMNs) represent abona fidepathway to invasive neoplasia, although the molecular correlates of progression remain to be fully elucidated. Single cell transcriptomics provides a unique avenue for dissecting both the epithelial and microenvironmental heterogeneity that accompany multistep progression from non-invasive IPMNs to PDAC.MethodsSingle cell RNA-sequencing was performed through droplet-based sequencing on 5,403 cells from two low-grade IPMNs (LGD-IPMN), two high-grade IPMNs (HGD-IPMN), and two PDACs (all surgically resected).ResultsAnalysis of single cell transcriptomes revealed heterogeneous alterations within the epithelium and the tumor microenvironment during the progression of non-invasive dysplasia to invasive cancer. While HGD-IPMNs expressed many core-signaling pathways described in PDAC, LGD-IPMNs harbored subsets of single cells with a transcriptomic profile that overlapped with invasive cancer. Notably, a pro-inflammatory immune component was readily seen in low-grade IPMNs, comprised of cytotoxic T-cells, activated T-helper cells, and dendritic cells, which was progressively depleted during neoplastic progression, accompanied by infiltration of myeloid-derived suppressor cells. Finally, stromal myofibroblast populations were heterogeneous, and acquired a previously described tumor-promoting and immune-evading phenotype during invasive carcinogenesis.ConclusionsThis study demonstrates the ability to perform high resolution profiling of the transcriptomic changes that occur during multistep progression of cystic PDAC precursors to cancer. Notably, single cell analysis provides an unparalleled insight into both the epithelial and microenvironmental heterogeneity that accompany early cancer pathogenesis, and might be a useful substrate to identify targets for cancer interception.
Frequency shifts and depth dependence of premotor beta band activity during perceptual decision-making
Authors: Chandrasekaran Chandramouli , Bray Iliana E. , Shenoy Krishna V. 
Published: April 2018

ABSTRACTNeural activity in the premotor and motor cortex shows prominent structure in the beta frequency range (13-30 Hz). Currently, the behavioral relevance of beta band activity (BBA) in premotor and motor regions is not well understood. The underlying source of motor BBA and how it changes as a function of cortical depth is also unknown. Here, we addressed these unresolved questions by investigating BBA recorded using laminar electrodes in the dorsal premotor cortex (PMd) of two male rhesus macaques performing a visual reaction time (RT) reach discrimination task. We observed robust BBA before and after the onset of the visual stimulus but not during the arm movement. While post-stimulus BBA was positively correlated with RT throughout the beta frequency range, pre-stimulus correlation varied by frequency. Low beta frequencies (~15 to 20 Hz) were positively correlated with RT and high beta frequencies (~25 to 30 Hz) were negatively correlated with RT. Simulations suggested that these frequency-dependent correlations could be due to a shift in the component frequencies of the pre-stimulus BBA as a function of RT, such that faster RTs are accompanied by greater power in high beta frequencies. We also observed a laminar dependence of BBA, with deeper electrodes demonstrating stronger power in low beta frequencies both pre- and post-stimulus. The heterogeneous nature of BBA and the changing relationship between BBA and RT in different task epochs may be a sign of the differential network dynamics involved in expectation, decision-making, and motor preparation.
Characterization of the apicomplexan amino acid transporter (ApiAT) family inToxoplasma gondii
Authors: Parker Kathryn E. R. , Fairweather Stephen J. , Rajendran Esther , Blume Martin , McConville Malcolm J. , Bröer Stefan , Kirk Kiaran , van Dooren Giel G. 
Published: April 2018

AbstractApicomplexan parasites are auxotrophic for a range of amino acids which must be salvaged from their host cells, either through direct uptake or degradation of host proteins. Here, we describe a family of plasma membrane-localized amino acid transporters, termed the Apicomplexan Amino acid Transporters (ApiATs), that are ubiquitous in apicomplexan parasites. Functional characterization of the ApiATs ofToxoplasma gondiiindicate that several of these transporters are important for intracellular growth of the tachyzoite stage of the parasite, which is responsible for acute infections. We demonstrate that the ApiAT proteinTgApiAT5-3 is an exchanger for aromatic and large neutral amino acids, with particular importance for L-tyrosine scavenging and amino acid homeostasis, and thatTgApiAT5-3 is critical for parasite virulence. Our data indicate thatT. gondiiexpresses additional proteins involved in the uptake of aromatic amino acids, and we present a model for the uptake and homeostasis of these amino acids. Our findings identify a family of amino acid transporters in apicomplexans, and highlight the importance of amino acid scavenging for the biology of this important phylum of intracellular parasites.Author SummaryThe Apicomplexa comprise a large number of parasitic protozoa that have obligate intracellular lifestyles and cause significant human and animal diseases, including malaria, cryptosporidiosis, toxoplasmosis, coccidiosis in poultry, and various cattle fevers. Apicomplexans must scavenge essential nutrients from their hosts in order to proliferate and cause disease, including a range of amino acids. The direct uptake of these nutrients is presumed to be mediated by transporter proteins located in the plasma membrane of intracellular stages, although the identities of these proteins are poorly defined. Using a combination of bioinformatic, genetic, cell biological, and physiological approaches, we have characterized a family of plasma membrane-localized transporter proteins that we have called the Apicomplexan Amino acid Transporters (ApiATs). The family is found in apicomplexans and their closest free-living relatives. We show thatTgApiAT5-3, a member of the family in the apicomplexanToxoplasma gondii, is an exchanger for aromatic and large neutral amino acids. In particular, it is critical for uptake of tyrosine, and for parasite virulence in a mouse infection model. We conclude that ApiATs are a family of plasma membrane transporters that play crucial roles in amino acid scavenging by apicomplexan parasites.
Defining of MAbs-neutralizing sites on the surface glycoproteins Gn and Gc of a hantavirus using vesicular stomatitis virus pseudotypes and site-directed mutagenesis
Authors: Levanov Lev , Iheozor-Ejiofor Rommel Paneth , Lundkvist Åke , Vapalahti Olli , Plyusnin Alexander 
Published: April 2018

ABSTRACTEarlier four Monoclonal antibodies (MAbs) against surface glycoproteins Gn and Gc of Puumala virus (PUUV, genus Orthohantavirus, family Hantaviridae, order Bunyavirales) were generated and for three MAbs with neutralizing capacity the localization of binding epitopes was predicted using pepscan and phage-display techniques. In this work, we produced vesicular stomatitis virus (VSV) particles pseudotyped with the Gn and Gc glycoproteins of PUUV and applied site-directed mutagenesis to dissect the structure of neutralizing epitopes. Replacement of cysteine amino acid (aa) residues with alanines resulted in pseudotype particles with diminished (16 to 18%) neut-titers; double Cys→Ala mutants, as well as mutants with bulky aromatic and charged residues replaced with alanines, have shown even stronger reduction in neut-titers (from 25% to the escape phenotype). In silico modelling of the neut-epitopes supported the hypothesis that these critical residues are located on the surface of viral glycoprotein molecules and thus can be recognized by the antibodies indeed. Similar pattern was observed in experiments with mutant pseudotypes and sera collected from patients suggesting that these neut-epitopes are utilized in a course of human PUUV infection.IMPORTANCENeutralization of viruses by antibodies is one of the key events in infection. We identified a set of mutations in the surface proteins of PUUV that reduced the virus-neutralizing activity of MAbs. Moreover, we found three mutants with escaped phenotype. These data will help understanding the mechanisms of hantavirus neutralization and assist construction of vaccine candidates.
Transcranial photoacoustic imaging of NMDA-evoked focal circuit dynamics in rat hippocampus
Authors: Kang Jeeun , Kadam Shilpa D. , Elmore Joshua S. , Sullivan Brennan J. , Valentine Heather , Malla Adarsha P. , Harraz Maged M. , Rahmim Arman , Kang Jin U. , Loew Leslie M. , Baumann Michael , Grace Anthony A. , Gjedde Albert , Boctor Emad M. , Wong Dean F. 
Published: April 2018

AbstractTranscranial functional photoacoustic (fPA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of current neuroimaging modalities. The technique previously distinguished global seizure activity from control neural activity in groups of rats. To validate the focal specificity of transcranial fPA neuroimaging in vivo, we now present proofs-of-concept that the results differentiate between low- and high-dose N-methyl-D-aspartate (NMDA) evoked neural activity in rat hippocampus. Concurrent quantitative EEG (qEEG) and microdialysis recorded real-time circuit dynamics and glutamate concentration change, respectively. We hypothesized that location-specific fPA VSD contrast would identify the neural dynamics in hippocampus with the correlation to NMDA evoked focal glutamate release and time-specific EEG signals. To test the hypothesis, we infused 0.3 to 3.0 mM NMDA at 2 μl/min over 60 min via an implanted microdialysis probe. The dialysate samples collected every 20 min during the infusion were analyzed for focal changes in extracellular glutamate release. Transcranial fPA VSD imaging provided NMDA-evoked VSD responses with positive correlation to extracellular glutamate concentration change at the contralateral side of the microdialysis probe. The graded response represents the all-or-none gating system of the dentate gyrus (DG) in hippocampus. Quantitative EEG (qEEG) successfully confirmed induction of focal seizure activity during NMDA infusion. We conclude that transcranial fPA VSD imaging distinguished graded DG gatekeeping functions, based on the VSD redistribution mechanism sensitive to electrophysiologic membrane potential. The results suggest the potential future use of this emerging technology in clinics and science as an innovative and significant functional neuroimaging modality.