bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic characteristics of HER2-positive metaplastic squamous cell carcinoma of the breast
Authors: Lei Ting , Pu Tianjie , Wei Bing , Fan Yingying , Yang Libo , Shen Mengjia , Chen Min , Yang Jieliang , Zhang Yu , Zhang Zhang , Bu Hong 
Published: November 2020

AimsThe aim of this study was to analyse the clinicopathological features and prognosis of human epidermal growth factor receptor-2 (HER2)-positive metaplastic squamous cell carcinoma (MSCC).MethodsFifty-eight patients with MSCC of the breast who were classified into 45 triple-negative and 13 HER2-positive subgroups diagnosed at the West China Hospital, Sichuan University, from 2004 to 2018, were enrolled. Clinicopathological features were collected and compared between HER2-positive MSCC, triple-negative MSCC, HER2-positive invasive breast carcinoma of no special type (NST) and triple-negative NST groups. In the prognostic survival analysis, HER2-positive MSCCs was compared with triple-negative MSCCs, HER2-positive NSTs and triple-negative NSTs.ResultsCompared with triple-negative MSCCs, more patients with Ki-67 low expression were in HER2-positive MSCCs (p<0.05). More patients with HER2-positive MSCC than patients with HER2-positive NST were postmenopausal (p<0.05). Compared among HER2-positive MSCCs, triple-negative MSCCs and triple-negative NSTs, patients of HER2-positive MSCCs with high Ki-67 expression were the least, and HER2-positive MSCCs had more strongly associated with postmenopausal disease status (p<0.05). In survival analyses, HER2-positive MSCCs had a high risk of recurrence and poor prognosis (p<0.05). Lymph node status was significantly associated with the disease-free survival of patients with HER2-positive MSCC.ConclusionIn conclusion, our study indicates that HER2-positive MSCC is an aggressive disease with unique clinicopathological characteristics. Both HER2-positive status and an SCC component are critical factors for poor prognosis. HER2-positive MSCC and triple-negative MSCC are distinct subgroups. Corresponding targeted therapy recommendations should be made for this HER2-positive MSCC group.
Early changes in immune cell subsets with corticosteroids in patients with solid tumors: implications for COVID-19 management
Authors: Marté Jennifer L , Toney Nicole J , Cordes Lisa , Schlom Jeffrey , Donahue Renee N , Gulley James L 
Published: November 2020

BackgroundThe risk–benefit calculation for corticosteroid administration in the management of COVID-19 is complex and urgently requires data to inform the decision. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation associated with poor prognosis in both COVID-19 and cancer. Investigating NLR as an inflammatory marker and lymphocyte levels as a critical component of antiviral immunity may inform the dilemma of reducing toxic hyperinflammation while still maintaining effective antiviral responses.MethodsWe performed a retrospective analysis of NLR, absolute neutrophil counts (ANCs) and absolute lymphocyte counts (ALCs) in patients with cancer enrolled in immunotherapy trials who received moderate-dose to high-dose corticosteroids. We compared paired presteroid and available poststeroid initiation values daily during week 1 and again on day 14 using the Wilcoxon signed-rank test. Associated immune subsets by flow cytometry were included where available.ResultsPatients (n=48) with a variety of solid tumors received prednisone, methylprednisolone, or dexamethasone alone or in combination in doses ranging from 20 to 190 mg/24 hours (prednisone equivalent). The median NLR prior to steroid administration was elevated at 5.0 (range: 0.9–61.2). The corresponding median ANC was 5.1 K/µL (range: 2.03–22.31 K/µL) and ALC was 1.03 K/µL (0.15–2.57 K/µL). One day after steroid administration, there was a significant transient drop in median ALC to 0.54 K/µL (p=0.0243), driving an increase in NLR (median 10.8, p=0.0306). Relative lymphopenia persisted through day 14 but was no longer statistically significant. ANC increased steadily over time, becoming significant at day 4 (median: 7.31 K/µL, p=0.0171) and remaining significantly elevated through day 14. NLR was consistently elevated after steroid initiation, significantly at days 1, 7 (median: 8.2, p=0.0272), and 14 (median: 15.0, p=0.0018). Flow cytometry data from 11 patients showed significant decreases in activated CD4 cells and effector memory CD8 cells.ConclusionsThe early drop in ALC with persistent lymphopenia as well as the prolonged ANC elevation seen in response to corticosteroid administration are similar to trends associated with increased mortality in several coronavirus studies to include the current SARS-CoV-2 pandemic. The affected subsets are essential for effective antiviral immunity. This may have implications for glucocorticoid therapy for COVID-19.
Transcriptome analysis of IPF fibroblastic foci identifies key pathways involved in fibrogenesis
Authors: Guillotin Delphine , Taylor Adam R , Platé Manuela , Mercer Paul F , Edwards Lindsay M , Haggart Ross , Miele Gino , McAnulty Robin J , Maher Toby M , Hynds Robert E , Jamal-Hanjani Mariam , Marshall Richard P , Fisher Andrew J , Blanchard Andy D , Chambers Rachel C 
Published: November 2020

IntroductionFibroblastic foci represent the cardinal pathogenic lesion in idiopathic pulmonary fibrosis (IPF) and comprise activated fibroblasts and myofibroblasts, the key effector cells responsible for dysregulated extracellular matrix deposition in multiple fibrotic conditions. The aim of this study was to define the major transcriptional programmes involved in fibrogenesis in IPF by profiling unmanipulated myofibroblasts within fibrotic foci in situ by laser capture microdissection.MethodsThe challenges associated with deriving gene calls from low amounts of RNA and the absence of a meaningful comparator cell type were overcome by adopting novel data mining strategies and by using weighted gene co-expression network analysis (WGCNA), as well as aneigengene-based approach to identify transcriptional signatures, which correlate with fibrillar collagen gene expression.ResultsWGCNA identified prominent clusters of genes associated with cell cycle, inflammation/differentiation, translation and cytoskeleton/cell adhesion. Collagen eigengene analysis revealed that transforming growth factor β1 (TGF-β1), RhoA kinase and the TSC2/RHEB axis formed major signalling clusters associated with collagen gene expression. Functional studies using CRISPR-Cas9 gene-edited cells demonstrated a key role for the TSC2/RHEB axis in regulating TGF-β1-induced mechanistic target of rapamycin complex 1 activation and collagen I deposition in mesenchymal cells reflecting IPF and other disease settings, including cancer-associated fibroblasts.ConclusionThese data provide strong support for the human tissue-based and bioinformatics approaches adopted to identify critical transcriptional nodes associated with the key pathogenic cell responsible for fibrogenesis in situ and further identify the TSC2/RHEB axis as a potential novel target for interfering with excessive matrix deposition in IPF and other fibrotic conditions.
Exploring new boundary conditions for $$\mathcal {N}=(1,1)$$ extended higher-spin $$AdS_3$$ supergravity
Authors: Özer H. T. , Filiz Aytül 
Published: November 2020

AbstractIn this paper, we present a candidate for $$\mathcal {N}=(1,1)$$

N
=
(
1
,
1
)

extended higher-spin $$AdS_3$$

A
d

S
3

supergravity with the most general boundary conditions discussed by Grumiller and Riegler recently. We show that the asymptotic symmetry algebra consists of two copies of the $$\mathfrak {osp}(3|2)_k$$

osp

(
3
|
2
)

k

affine algebra in the presence of the most general boundary conditions. Furthermore, we impose some certain restrictions on gauge fields on the most general boundary conditions and that leads us to the supersymmetric extension of the Brown–Henneaux boundary conditions. We eventually see that the asymptotic symmetry algebra reduces to two copies of the $$\mathcal {SW}(\frac{3}{2},2)$$

SW
(

3
2

,
2
)

algebra for $$\mathcal {N}=(1,1)$$

N
=
(
1
,
1
)

extended higher-spin supergravity.
Global monopole as a generator of a bulk-brane structure in Brans–Dicke bulk gravity
Authors: Caramês Thiago R. P. , da Silva J. M. Hoff 
Published: November 2020

AbstractWe investigate a braneworld model generated by a global monopole in the context of Brans–Dicke gravity. After solving the dynamical equations we found a model capable to alleviate the so-called hierarchy problem. The obtained framework is described by a hybrid compactification scheme endowed with a seven-dimensional spacetime, in which the brane has four non-compact dimensions and two curled extra dimensions. The relevant aspects of the resulting model are studied and the requirements to avoid the well known seesaw-like behavior are discussed. We show that under certain conditions it is possible to circumvent such a pathological behavior that characterizes most of the models that exhibit hybrid compactification. Lastly, we deepen our analysis by considering possible extensions of this model to a setup with multiple branes and orbifold-like extra dimension. For this, we compute the consistency conditions to be obeyed by this more general configuration as predicted by the braneworld sum rules formalism. This study indicates the possibility of exclusively positive brane tensions in the model.
Spectrum of scalar and pseudoscalar glueballs from functional methods
Authors: Huber Markus Q. , Fischer Christian S. , Sanchis-Alepuz Hèlios 
Published: November 2020

AbstractWe provide results for the spectrum of scalar and pseudoscalar glueballs in pure Yang–Mills theory using a parameter-free fully self-contained truncation of Dyson–Schwinger and Bethe–Salpeter equations. The only input, the scale, is fixed by comparison with lattice calculations. We obtain ground state masses of $$1.9\,\text {GeV}$$

1.9

GeV

and $$2.6\,\text {GeV}$$

2.6

GeV

for the scalar and pseudoscalar glueballs, respectively, and $$2.6\,\text {GeV}$$

2.6

GeV

and $$3.9\,\text {GeV}$$

3.9

GeV

for the corresponding first excited states. This is in very good quantitative agreement with available lattice results. Furthermore, we predict masses for the second excited states at $$3.7\,\text {GeV}$$

3.7

GeV

and $$4.3\,\text {GeV}$$

4.3

GeV

. The quality of the results hinges crucially on the self-consistency of the employed input. The masses are independent of a specific choice for the infrared behavior of the ghost propagator providing further evidence that this only reflects a nonperturbative gauge completion.
Optimized lepton universality tests in $$B\rightarrow V \ell {\bar{\nu }}$$ decays
Authors: Isidori Gino , Sumensari Olcyr 
Published: November 2020

AbstractWe propose improved lepton flavor universality (LFU) ratios in semileptonic $$P\rightarrow V \ell {\bar{\nu }}$$

P
→
V
ℓ

ν

¯

decays, when comparing $$\mu $$
μ
and $$\tau $$
τ
modes, that minimize the theoretical form-factor uncertainties. These optimized ratios are obtained with simple cuts or reweighting of the dilepton mass distributions, which imply a minimum loss of signal on the rare tauonic modes while maximizing the cancellation of theoretical uncertainties among the two modes. We illustrate the usefulness of these observables in $$B_c\rightarrow J/\psi $$

B
c

→
J
/
ψ

, $$B_c\rightarrow \psi (2S)$$

B
c

→
ψ

(
2
S
)

, $$B\rightarrow D^*$$

B
→

D
∗

and $$B_s\rightarrow D_s^*$$

B
s

→

D
s
∗

transitions, showing that in all cases we can reach $${\mathcal {O}}(1\%)$$

O
(
1
%
)

uncertainties on the SM predictions of the improved LFU ratios employing conservative form-factor uncertainties.
Generalized Lomb–Scargle analysis of $${^{123}\mathrm{I}}$$ and $${^{99\mathrm{m}}\mathrm{Tc}}$$ decay rate measurements
Authors: Gururajan Gautham , Desai Shantanu 
Published: November 2020

AbstractWe apply the generalized Lomb–Scargle periodogram to the $${^{123}\text {I}}$$

123

I

and $${^{99\mathrm{m}}\text {Tc}}$$

99
m

Tc

decay rate measurements based on data taken at the Bronson Methodist Hospital. The aim of this exercise was to carry out an independent search for sinusoidal modulation for these radionuclei (to complement the analysis in Borrello et al.) at frequencies for which other radionuclei have shown periodicities. We do not find such a modulation at any frequencies, including annual modulation or at frequencies associated with solar rotation. Our analysis codes and datasets have been made publicly available.
The Array of Long Baseline Antennas for Taking Radio Observations from the Sub-Antarctic
Authors: Chiang H. C. , Dyson T. , Egan E. , Eyono S. , Ghazi N. , Hickish J. , Jáuregui-Garcia J. M. , Manukha V. , Ménard T. , Moso T. , Peterson J. , Philip L. , Sievers J. L. , Tartakovsky S. 
Published: November 2020

Measurements of redshifted 21[Formula: see text]cm emission of neutral hydrogen at [Formula: see text][Formula: see text]MHz have the potential to probe the cosmic “dark ages,” a period of the universe’s history that remains unobserved to date. Observations at these frequencies are exceptionally challenging because of bright Galactic foregrounds, ionospheric contamination, and terrestrial radio-frequency interference. Very few sky maps exist at [Formula: see text][Formula: see text]MHz, and most have modest resolution. We introduce the Array of Long Baseline Antennas for Taking Radio Observations from the Sub-Antarctic (ALBATROS), a new experiment that aims to image low-frequency Galactic emission with an order-of-magnitude improvement in resolution over existing data. The ALBATROS array will consist of antenna stations that operate autonomously, each recording baseband data that will be interferometrically combined offline. The array will be installed on Marion Island and will ultimately comprise 10 stations, with an operating frequency range of 1.2–125[Formula: see text]MHz and maximum baseline lengths of [Formula: see text][Formula: see text]km. We present the ALBATROS instrument design and discuss pathfinder observations that were taken from Marion Island during 2018–2019.
Seismic modelling of outcrop carbonate systems: an application to the Cretaceous platform-to-basin system of the Maiella Mountain (central Apennines, Italy)
Authors: Mascolo Valentina , Lecomte Isabelle 
Published: November 2020

Abstract
Forward seismic models of outcrop analogues are used in hydrocarbon exploration to generate more coherent geological–geophysical models that provide an important scale link between outcrops and seismic survey data. Exploration within slope carbonate plays can be problematic with uncertainties about the reservoir geometries, distribution and volumes owing to complex seismic imaging and lack of closely spaced wells. This seismic modelling study provides a synthetic seismic characterization of the carbonate platform-to-slope-to-basin transition exposed across the Maiella Mountain, central Italy. This outcrop represents an analogue for exploration in carbonate slope strata in the Adriatic offshore area. Integration of original and previously published data allows 2D and 3D geological modelling, providing a better characterization of relationships between the palaeoescarpment and resedimented deposits. The seismic response of the various geological features of this transitional carbonate system is simulated via synthetic seismic modelling using innovative, modern techniques. The seismic simulation was performed in both post-stack-time- and pre-stack-depth-migrated domains. These synthetic seismic models help in understanding and predicting the seismic architecture and character of the palaeoescarpment and resedimented slope deposits.
Assessing controls on isolated carbonate platform development in Central Luconia, NW Borneo, from a regional 3D seismic facies and geomorphology investigation
Authors: Ting King King , Tan Yan Eng , Chiew Edwin , Lee Ee Lin , Azudin Ahmad Nazmi , Ishak Noor Alyani 
Published: November 2020

Abstract
The Central Luconia province in the South China Sea, offshore Sarawak, features extensive development of Middle to Late Miocene isolated carbonate platforms. This study presents a regional seismic architecture – seismic facies review of platform flank geometries and off-platform depositional styles, with the goals of understanding their patterns and exploring the controlling processes. The information on flank steepness and predominant shedding direction is contextualized with respect to extrinsic and intrinsic factors of carbonate platform growth, including tectonics, eustatic sea-level fluctuations, hydrodynamics and regional palaeogeography. Results reveal that flank geometries are consistent throughout the Middle to Late Miocene. In the north of the province eastern flanks are dominantly aggradational, steep and sediment-starved escarpments, whereas western flanks show more progradation and are accretionary in nature. Discrepancies from this pattern are observed among closely spaced platforms. The eastern-aggrading flanks are interpreted to have been highly influenced by monsoonal wind-driven currents. Further south in the province tidal currents, antecedent topography and syn-depositional tectonics were more important controls on platform architectural development. This study of regional processes and geomorphic products provides a basis for enhanced conceptual facies models and reservoir quality predictions.
High-dose per Fraction Radiotherapy Induces Both Antitumor Immunity and Immunosuppressive Responses in Prostate Tumors
Authors: Lin Lin , Kane Nathanael , Kobayashi Naoko , Kono Evelyn A. , Yamashiro Joyce M. , Nickols Nicholas G. , Reiter Robert E. 
Published: November 2020

Abstract

Purpose:
The use of high-dose per fraction radiotherapy delivered as stereotactic body radiotherapy is a standard of care for prostate cancer. It is hypothesized that high-dose radiotherapy may enhance or suppress tumor-reactive immunity. The objective of this study was to assess both antitumor and immunosuppressive effects induced by high-dose radiotherapy in prostate cancer coclinical models, and ultimately, to test whether a combination of radiotherapy with targeted immunotherapy can enhance antitumor immunity.

Experimental Design:
We studied the effects of high-dose per fraction radiotherapy with and without anti-Gr-1 using syngeneic murine allograft prostate cancer models. The dynamic change of immune populations, including tumor-infiltrating lymphocytes (TIL), T regulatory cells (Treg), and myeloid-derived suppressive cells (MDSC), was evaluated using flow cytometry and IHC.

Results:
Coclinical prostate cancer models demonstrated that high-dose per fraction radiotherapy induced a rapid increase of tumor-infiltrating MDSCs and a subsequent rise of CD8 TILs and circulating CD8 T effector memory cells. These radiation-induced CD8 TILs were more functionally potent than those from nonirradiated controls. While systemic depletion of MDSCs by anti-Gr-1 effectively prevented MDSC tumor infiltration, it did not enhance radiotherapy-induced antitumor immunity due to a compensatory expansion of Treg-mediated immune suppression.

Conclusions:
In allograft prostate cancer models, high-dose radiotherapy induced an early rise of MDSCs, followed by a transient increase of functionally active CD8 TILs. However, systemic depletion of MDSC did not augment the antitumor efficacy of high-dose radiotherapy due to a compensatory Treg response, indicating blocking both MDSCs and Tregs might be necessary to enhance radiotherapy-induced antitumor immunity.
Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib
Authors: Silverman Ian M. , Hollebecque Antoine , Friboulet Luc , Owens Sherry , Newton Robert C. , Zhen Huiling , Féliz Luis , Zecchetto Camilla , Melisi Davide , Burn Timothy C. 
Published: November 2020

Abstract

Pemigatinib, a selective FGFR1–3 inhibitor, has demonstrated antitumor activity in FIGHT-202, a phase II study in patients with cholangiocarcinoma harboring FGFR2 fusions/rearrangements, and has gained regulatory approval in the United States. Eligibility for FIGHT-202 was assessed using genomic profiling; here, these data were utilized to characterize the genomic landscape of cholangiocarcinoma and to uncover unique molecular features of patients harboring FGFR2 rearrangements. The results highlight the high percentage of patients with cholangiocarcinoma harboring potentially actionable genomic alterations and the diversity in gene partners that rearrange with FGFR2. Clinicogenomic analysis of pemigatinib-treated patients identified mechanisms of primary and acquired resistance. Genomic subsets of patients with other potentially actionable FGF/FGFR alterations were also identified. Our study provides a framework for molecularly guided clinical trials and underscores the importance of genomic profiling to enable a deeper understanding of the molecular basis for response and nonresponse to targeted therapy.

Significance:
We utilized genomic profiling data from FIGHT-202 to gain insights into the genomic landscape of cholangiocarcinoma, to understand the molecular diversity of patients with FGFR2 fusions or rearrangements, and to interrogate the clinicogenomics of patients treated with pemigatinib. Our study highlights the utility of genomic profiling in clinical trials.
This article is highlighted in the In This Issue feature, p. 211
Short‐Term Variability of the QT Interval Can be Used for the Prediction of Imminent Ventricular Arrhythmias in Patients With Primary Prophylactic Implantable Cardioverter Defibrillators
Authors: Smoczyńska Agnieszka , Loen Vera , Sprenkeler David J. , Tuinenburg Anton E. , Ritsema van Eck Henk J. , Malik Marek , Schmidt Georg , Meine Mathias , Vos Marc A. 
Published: November 2020

Background

Short‐term variability of the QT interval (STV
QT
) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STV
QT
can predict imminent ventricular arrhythmias in patients.

Methods and Results

In 2331 patients with primary prophylactic implantable cardioverter defibrillators, 24‐hour ECG Holter recordings were obtained as part of the EU‐CERT‐ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators) study. ECG Holter recordings showing ventricular arrhythmias of >4 consecutive complexes were selected for the arrhythmic groups (n=170), whereas a control group was randomly selected from the remaining Holter recordings (n=37). STV
QT
was determined from 31 beats with fiducial segment averaging and calculated as

, where

D
n

represents the QT interval. STV
QT
was determined before the ventricular arrhythmia or 8:00
am
in the control group and between 1:30 and 4:30
am
as baseline. STV
QT
at baseline was 0.84±0.47 ms and increased to 1.18±0.74 ms (
P
<0.05) before the ventricular arrhythmia, whereas the STV
QT
in the control group remained unchanged. The arrhythmic patients were divided into three groups based on the severity of the arrhythmia: (1) nonsustained ventricular arrhythmia (n=32), (2) nonsustained ventricular tachycardia (n=134), (3) sustained ventricular tachycardia (n=4). STV
QT
increased before nonsustained ventricular arrhythmia, nonsustained ventricular tachycardia, and sustained ventricular tachycardia from 0.80±0.43 ms to 1.18±0.78 ms (
P
<0.05), from 0.90±0.49 ms to 1.14±0.70 ms (
P
<0.05), and from 1.05±0.22 ms to 2.33±1.25 ms (
P
<0.05). This rise in STV
QT
was significantly higher in sustained ventricular tachycardia compared with nonsustained ventricular arrhythmia (+1.28±1.05 ms versus +0.24±0.57 ms [
P
<0.05]) and compared with nonsustained ventricular arrhythmia (+0.34±0.87 ms [
P
<0.05]).

Conclusions

STV
QT
increases before imminent ventricular arrhythmias in patients, and the extent of the increase is associated with the severity of the ventricular arrhythmia.