bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating the immune microenvironment of prostate cancer induced bone disease
Authors: Ihle Claire L. , Owens Philip 
Published: March 2020

AbstractProstate cancer (PCa) is the most frequently diagnosed cancer for men in the U.S. but does not impede patient survival until the disease is metastatic. Metastatic lesions most frequently occur in the bone, which exhibits a distinct microenvironment of immune and bone cell populations. Advances in the diagnosis and treatment of primary PCa allow for the use of tailored therapeutic approaches based on biomarkers, protein expression, and histopathology. Understanding the molecular and cellular characteristics of primary tumors has advanced therapeutic development and survival for patients with PCa. Personalized medicine has only recently emerged for the treatment of metastatic bone lesions. Tumor induced bone disease (TIBD) in patients with PCa can be classified into lytic, blastic, or mixed pathologies, with most patients exhibiting the blastic phenotype. Progress has been made in treating TIBD, but metastatic PCa has yet to be cured. Immune checkpoint inhibitors have exhibited limited responses in immunosuppressive PCa tumors, but have yet to be assessed in metastatic sites which may be susceptible to an increased inflammatory response. Recent discoveries have uncovered distinct tumor microenvironments (TMEs) of blastic and lytic bone metastases from patients with PCa, identifying actionable targets for therapeutic applications, including immune checkpoint inhibitors and targeted therapeutics. Enrichment for macrophages and T cells in patient samples suggests metastatic sites may be reappraised as immunologically targetable, despite their immunologically “cold” primary tumors. The practice of performing bone biopsies will help identify unique cellular and protein targets in the bone TME that can guide therapy decisions.
Clinical, molecular and cytopathological characterization of a Newcastle disease virus from an outbreak in Baghdad, Iraq
Authors: Al‐Shammari Ahmed M. , Hamad Mohammed A. , AL‐Mudhafar Murtadha A. , Raad Khansaa , Ahmed Aeser 
Published: March 2020

AbstractBackgroundThe frequent outbreaks of Newcastle disease virus (NDV) in Iraq pose a constant threat to commercial poultry, despite the introduction of routine vaccination programmes. Several factors, particularly stress factors and coinfections, might play a role in increasing NDV outbreaks in poultry species.ObjectivesThe current study was aimed to characterize an NDV isolate from an outbreak in North Baghdad, Iraq.MethodsClinical pathogenicity of the isolate was determined experimentally in chickens. In vitro studies included cytopathological examination, as well as molecular and phylogenetic analyses.ResultsBased on the clinical studies and pathogenicity indices (mean death time and intracerebral and intravenous pathogenicity indices), the isolate was characterized as velogenic (highly virulent). Reverse transcriptase polymerase chain reaction targeting the partial fusion protein gene of the NDV genome confirmed the detection. Partial sequencing of the hypervariable region of the fusion gene identified the presence of an avirulent (lentogenic) fusion protein motif (GRQGRL). Phylogenetic analysis of the new isolate along with previously known regional isolates revealed that the new isolate was related to genotype II strains. Additionally, sequence analysis indicated a distinct genetic lineage of the new isolate, which was related to some of the lineages identified in previous outbreaks in the Middle East.ConclusionThe current study offers essential information on the epidemiology, characteristics and diagnosis of NDV for disease control in Iraq. The isolate was found to belong to genotype II and possess an avirulent fusion protein motif.
Measuring the top energy asymmetry at the LHC: QCD and SMEFT interpretations
Authors: Basan Alexander , Berta Peter , Masetti Lucia , Vryonidou Eleni , Westhoff Susanne 
Published: March 2020

Abstract
The energy asymmetry in top-antitop-jet production is an observable of the top charge asymmetry designed for the LHC. We perform a realistic analysis in the boosted kinematic regime, including effects of the parton shower, hadronization and expected experimental uncertainties. Our predictions at particle level show that the energy asymmetry in the Standard Model can be measured with a significance of 3σ during Run 3, and with more than 5σ significance at the HL-LHC. Beyond the Standard Model the energy asymmetry is a sensitive probe of new physics with couplings to top quarks. In the framework of the Standard Model Effective Field Theory, we show that the sensitivity of the energy asymmetry to effective four-quark interactions is higher or comparable to other top observables and resolves blind directions in current LHC fits. We suggest to include the energy asymmetry as an important observable in global searches for new physics in the top sector.
Cognitive swarming in complex environments with attractor dynamics and oscillatory computing
Authors: Monaco Joseph D. , Hwang Grace M. , Schultz Kevin M. , Zhang Kechen 
Published: March 2020

AbstractNeurobiological theories of spatial cognition developed with respect to recording data from relatively small and/or simplistic environments compared to animals’ natural habitats. It has been unclear how to extend theoretical models to large or complex spaces. Complementarily, in autonomous systems technology, applications have been growing for distributed control methods that scale to large numbers of low-footprint mobile platforms. Animals and many-robot groups must solve common problems of navigating complex and uncertain environments. Here, we introduce the NeuroSwarms control framework to investigate whether adaptive, autonomous swarm control of minimal artificial agents can be achieved by direct analogy to neural circuits of rodent spatial cognition. NeuroSwarms analogizes agents to neurons and swarming groups to recurrent networks. We implemented neuron-like agent interactions in which mutually visible agents operate as if they were reciprocally connected place cells in an attractor network. We attributed a phase state to agents to enable patterns of oscillatory synchronization similar to hippocampal models of theta-rhythmic (5–12 Hz) sequence generation. We demonstrate that multi-agent swarming and reward-approach dynamics can be expressed as a mobile form of Hebbian learning and that NeuroSwarms supports a single-entity paradigm that directly informs theoretical models of animal cognition. We present emergent behaviors including phase-organized rings and trajectory sequences that interact with environmental cues and geometry in large, fragmented mazes. Thus, NeuroSwarms is a model artificial spatial system that integrates autonomous control and theoretical neuroscience to potentially uncover common principles to advance both domains.
Speech Acoustic Features: A Comparison of Gay Men, Heterosexual Men, and Heterosexual Women
Authors: Suire Alexandre , Tognetti Arnaud , Durand Valérie , Raymond Michel , Barkat-Defradas Melissa 
Published: March 2020

AbstractPotential differences between homosexual and heterosexual men have been studied on a diverse set of social and biological traits. Regarding acoustic features of speech, researchers have hypothesized a feminization of such characteristics in homosexual men, but previous investigations have so far produced mixed results. Moreover, most studies have been conducted with English-speaking populations, which calls for further cross-linguistic examinations. Lastly, no studies investigated so far the potential role of testosterone in the association between sexual orientation and speech acoustic features. To fill these gaps, we explored potential differences in acoustic features of speech between homosexual and heterosexual native French men and investigated whether the former showed a trend toward feminization by comparing theirs to that of heterosexual native French women. Lastly, we examined whether testosterone levels mediated the association between speech acoustic features and sexual orientation. We studied four sexually dimorphic acoustic features relevant for the qualification of feminine versus masculine voices: the fundamental frequency, its modulation, and two understudied acoustic features of speech, the harmonics-to-noise ratio (a proxy of vocal breathiness) and the jitter (a proxy of vocal roughness). Results showed that homosexual men displayed significantly higher pitch modulation patterns and less breathy voices compared to heterosexual men, with values shifted toward those of heterosexual women. Lastly, testosterone levels did not influence any of the investigated acoustic features. Combined with the literature conducted in other languages, our findings bring new support for the feminization hypothesis and suggest that the feminization of some acoustic features could be shared across languages.
High consistency mechano-enzymatic pretreatment for kraft fibres: effect of treatment consistency on fibre properties
Authors: Rahikainen Jenni , Mattila Outi , Maloney Thaddeus , Lovikka Ville , Kruus Kristiina , Suurnäkki Anna , Grönqvist Stina 
Published: March 2020

AbstractFibre reactivity is essential for cellulose dissolution and derivatisation and a porous fibre structure is one key determinant for a highly reactive pulp. Mechanical and enzymatic treatments are known to improve fibre reactivity and more recently, the combination of mechano-enzymatic treatment has been shown to synergistically enhance the beneficial effect. The aim of this work was to do a systematic study on the effect of dry matter content during enzymatic modification of fibres and define the conditions that optimally improve fibre porosity. The combined mechano-enzymatic treatments at 15–25 w% consistency had the most pronounced effect on fibre porosity and morphology analysed by solute exclusion technique, nitrogen sorption and scanning electron microscopy. Light microscopy imaging confirmed that the combined mechano-enzymatic treatment at high consistency (> 10 w%) resulted in extensive fibrillation of the treated fibres which was not observed after sole mechanical or enzymatic treatments.
Governing the Global Antimicrobial Commons: Introduction to Special Issue
Authors: Hoffman Steven J. , Savulescu Julian , Giubilini Alberto , Kirchhelle Claas , Rogers Van Katwyk Susan , Weldon Isaac , Campus Brooke , Harrison Mark , Maslen Hannah , McLean Angela 
Published: March 2020

AbstractAntimicrobial resistance is one of the greatest public health crises of our time. The natural biological process that causes microbes to become resistant to antimicrobial drugs presents a complex social challenge requiring more effective and sustainable management of the global antimicrobial commons—the common pool of effective antimicrobials. This special issue of Health Care Analysis explores the potential of two legal approaches—one long-term and one short-term—for managing the antimicrobial commons. The first article explores the lessons for antimicrobial resistance that can be learned from recent climate change agreements, and the second article explores how existing international laws can be adapted to better support global action in the short-term.
Social Discounting and the Cost of Public Funds: A Practitioner’s Perspective
Authors: Spackman Michael 
Published: March 2020

AbstractSocial discounting conventions vary widely. Some differences reflect institutional constraints, but many reflect differing assumptions about how a social discount rate should be derived and applied. The divide between advocates of social opportunity cost and social time preference (STP) frameworks seems unbridgeable. There is no consensus among STP advocates on whether the social cost of funding $1 of public spending is barely more than $1 of consumption or perhaps more than $2; or on whether the covariance of public service benefits with income merits a discount rate premium that is trivial or a few percentage points. The practicalities of government fund raising are sometimes overlooked. The issues are here reviewed in the light of the literature and of experience with developing and applying social discounting regimes and extended debates within government.
Ardmosteges Orchamus New Genus, New Species, in the Early Pennsylvanian of Oklahoma–Possible Ancestor to the Permian Richthofenoid Brachiopods
Authors: Sutherland Patrick K. 
Published: March 2020

Ardmosteges orchamus, new genus, new species, from the Early Pennsylvanian Morrowan sequence in southern Oklahoma, is characterized by a well-developed early aulostegid stage, followed by a fully developed richthofenoid stage. It differs markedly from any previously described genus. The nature of the early development, with a rounded aulostegid shell and a prominent interarea in the ventral valve, suggests that it evolved from the Aulostegidae. The most unique feature of Ardmosteges is that it shows for the first time, a documented mechanism for the addition of new shell material above the hinge area in the ventral valve in shells that proceeded to develop a richthofenoid cone. Shell layers were extended posteriorly from the margins of the ventral valve onto the interarea of that valve indicating that the mantle grew onto the hinge area from each side. This irregular and asymmetrical process gradually filled the space above the hinge and was followed by the upward growth of a typical richthofenoid cone. In the proposed development of the Permian richthofenoids from Ardmosteges it is postulated that the characteristic interarea of Ardmosteges was suppressed during extreme development of a distinctly cylindrical cone.Ardmosteges provides the missing link between the Aulostegidae and the Richthofenoidea. Its characters are primitive compared to those of the Permian richthofenoids but it is similar in having a deeply recessed opercular dorsal valve, protective spines in the vestibule above the dorsal valve, and in being attached by rhizoid spines.
Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response
Authors: Kim Min Hwan , Kim Jae-Hwan , Lee Ji Min , Choi Jae Woo , Jung Dongmin , Cho Hojin , Kang Hyundeok , Hong Min Hee , Heo Su Jin , Kim Se Heon , Choi Eun Chang , Kim Da Hee , Park Young Min , Kim Sangwoo , Yoon Sun Och , Koh Yoon Woo , Cho Byoung Chul , Kim Hye Ryun 
Published: March 2020

Abstract
Background
Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown.

Methods
We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data.

Results
All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-β signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients).

Conclusion
Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.
Pädiatrische ausgedehnte zerebrale Sinusvenenthrombose mit benignem Verlauf
Authors: Alsayed Ahmad Hussam 
Published: March 2020

ZusammenfassungWir berichten über ein 14-jähriges Mädchen mit einem akuten Kopfschmerzsyndrom unter Einnahme von einem Kontrazeptivum, das ausgedehnte zerebrale Sinusvenenthrombose hat. Laborchemisch zeigte sich ein Nachweis einer homozygoten Faktor-V-Leiden-Mutation. Die initiale Behandlung erfolgte mit Heparin mit anschließender Umstellung auf Coumadin. Der Verlauf blieb komplikationslos. Interessant war in diesem Fall erstens, dass die initialen Kopfschmerzen gut auf Sumatriptan angesprochen haben, was sich die Diagnose verspätet feststellen ließ, mit der Annahme einer möglichen Erstmanifestation einer Migräne, zweitens, dass trotz dem stark ausgedehnten bildmorphologischen Befund die Patientin ohne fokale neurologische Defizite blieb.
Management of Recurrent or Progressing Skull Base Chondrosarcomas: Predictors of Long-Term Outcomes
Authors: Breshears Jonathan D. , DeMonte Franco , Habib Ahmed , Gidley Paul W. , Raza Shaan M. 
Published: March 2020

Abstract
Background Skull base chondrosarcomas (CSA) are difficult tumors to cure and there is little data regarding salvage therapy.
Objective This study aims to identify presentation and treatment-related factors which impact the progression free survival (PFS) and disease specific survival (DSS) for recurrent CSA, and to identify salvage treatment factors associated with successful restoration to the natural history following primary treatment.
Methods This single-institution retrospective review included patients with recurrent/progressive CSA over a 25-year period. Survival analysis for factors impacting PFS and DSS was performed. Salvage treatment factors associated with achieving PFS ≥newly diagnosed median PFS were identified using univariate statistics. Analysis was performed on first recurrences and all recurrences combined.
Results A total of 47 recurrence/progression events were analyzed from 17 patients (median two events/patient, range = 1–8). The overall PFS and DSS for the initial recurrence was 32 (range = 3–267) and 79 (range = 3–285) months, respectively. Conventional grade III or mesenchymal histology significantly predicted shorter PFS and DSS (p < 0.0001). After stratification by histology, previous radiation predicted shorter PFS for low-grade tumors (p = 0.009). Gross total resection (GTR) after a first time recurrence was significantly associated with successful salvage treatment (p < 0.05); however, this was rare.
Conclusion In this series, high grade histology and prior radiation treatment negatively impacted salvage treatment outcomes, while GTR was associated with restoration to natural history following primary treatment. Careful consideration of histology, systemic disease status, previous treatments, and the anatomic extent of the skull base disease can optimize the outcomes of salvage intervention.
A Comparison of Respiratory Syncytial Viral Prophylaxis in Multiple Births versus Singletons in the Canadian Registry of Palivizumab
Authors: Paes Bosco , Li Abby , Kim Doyoung , Lanctot Krista L. , Mitchell Ian ,   CARESS Investigators
Published: March 2020

Abstract
Objective The aim of this study is to compare respiratory illness-related hospitalization (RIH) and respiratory syncytial virus (RSV)-related hospitalization (RSVH) in multiple births versus singletons, who received palivizumab during the RSV season and participated in the Canadian registry of palivizumab (CARESS).
Study Design Prospective, observational study of infants aged <2 years recruited across 32 centers over 12 RSV seasons from 2005 to 2017. Demographic data were collected at enrolment and RIH events were recorded monthly.
Results A total of 25,003 infants were enrolled of whom 6,949 (27.8%) were of multiple birth, and 18,054 (72.2%) were singletons. A significantly larger proportion of the multiple births were premature (80.2%) compared with the singleton group (56.8%). Multiples had a lower gestational age (mean ± standard deviation): 31.2 ± 3.2 versus 33.2 ± 5.5 weeks and birth weight (mean: 1,590 ± 606.8 vs. 2,069.4 ± 1068.5 g; both p < 0.0005). They were younger at enrolment (4.5 ± 5.0 vs. 6.1 ± 6.8 months), and fewer attended daycare (1.9 vs. 4.6%), and experienced exposure to smoking (24.5 vs. 29.9%), but more lived in a crowded household (36.7 vs. 19.4%); all p < 0.0005. Multiples had a longer length of neonatal stay (51.1 ± 65.9 vs. 47.9 ± 67.8 days), and more required respiratory support (65.7 vs. 57.7%), but for shorter duration (22.6 ± 32.9 vs. 24.7 ± 40.6 days); all p < 0.001. RIH and RSVH rates (%) in multiples versus singletons were 4.7; 7.7 and 1.4; and 1.6, respectively. Cox regression showed that multiples had a lower risk of RIH compared with singletons (hazard ratio [HR] = 0.616, 95% confidence interval [CI]: 0.543–0.698, p < 0.0005), but not RSVH (HR: 0.77, 95% CI: 0.57–1.02, p = 0.071).
Conclusion Multiple birth infants, who are known to be at greater risk for severe RSVH compared with singletons, are well protected by palivizumab, provided adherence to the monthly injection scheme is guaranteed.
Maternal Metabolic Biomarkers are Associated with Obesity and Excess Gestational Weight Gain
Authors: Antony Kathleen M. , Romezi Mona , Lindgren Kourtnee , Mitchell Kristen B. , Venable Susan F. , Racusin Diana A. , Suter Melissa A. , Aagaard Kjersti M. 
Published: March 2020

Abstract
Objective The purpose of this study was to evaluate the independent contribution of maternal obesity and gestational weight gain (GWG) in excess of the Institute of Medicine's guidelines on levels of maternal serum inflammatory and metabolic measures.
Study Design Banked maternal serum samples from 120 subjects with documented prepregnancy or first trimester body mass index (BMI) were utilized for analyte analyses. Validated, BMI-specific formulas were utilized to categorize GWG as either insufficient, at goal or excess based on the Institute of Medicine guidelines with gestational age adjustments. Serum was analyzed for known inflammatory or metabolic pathway intermediates using the Luminex xMap system with the MILLIPLEX Human Metabolic Hormone Magnetic Bead Panel. Measured analytes included interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α and metabolic markers amylin, c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, pancreatic polypeptide, and peptide YY. Kruskal–Wallis ANOVA and Pearson's correlation coefficients were calculated for each marker.
Results C-peptide, insulin, and leptin all varied significantly with both obesity and GWG while glucagon-like peptide-1 varied by BMI but not GWG. These analytes covaried with other metabolic analytes, but not with inflammatory analytes.
Conclusion Maternal metabolic biomarkers at delivery vary significantly with both obesity and GWG. Taken together, these findings suggest that GWG (with and without comorbid obesity) is an important mediator of measurable metabolites in pregnancy but is not necessarily accompanied by inflammatory measures in serum. These findings are consistent with GWG being an independent risk factor for metabolic disturbances during pregnancy.