bluuebunny/crossref_metadata_2025_split huggingface dataset:
Background independent exact renormalisation
Authors: Falls Kevin 
Published: February 2021

AbstractA geometric formulation of Wilson’s exact renormalisation group is presented based on a gauge invariant ultraviolet regularisation scheme without the introduction of a background field. This allows for a manifestly background independent approach to quantum gravity and gauge theories in the continuum. The regularisation is a geometric variant of Slavnov’s scheme consisting of a modified action, which suppresses high momentum modes, supplemented by Pauli–Villars determinants in the path integral measure. An exact renormalisation group flow equation for the Wilsonian effective action is derived by requiring that the path integral is invariant under a change in the cutoff scale while preserving quasi-locality. The renormalisation group flow is defined directly on the space of gauge invariant actions without the need to fix the gauge. We show that the one-loop beta function in Yang–Mills and the one-loop divergencies of General Relativity can be calculated without fixing the gauge. As a first non-perturbative application we find the form of the Yang–Mills beta function within a simple truncation of the Wilsonian effective action.
Low-energy probes of no-scale SU(5) super-GUTs
Authors: Ellis John , Evans Jason L. , Nagata Natsumi , Olive Keith A. , Velasco-Sevilla L. 
Published: February 2021

AbstractWe explore the possible values of the $$\mu \rightarrow e \gamma $$

μ
→
e
γ

branching ratio, $$\text {BR}(\mu \rightarrow e\gamma )$$

BR
(
μ
→
e
γ
)

, and the electron dipole moment (eEDM), $$d_e$$

d
e

, in no-scale SU(5) super-GUT models with the boundary conditions that soft supersymmetry-breaking matter scalar masses vanish at some high input scale, $$M_\mathrm{in}$$

M
in

, above the GUT scale, $$M_{\mathrm{GUT}}$$

M
GUT

. We take into account the constraints from the cosmological cold dark matter density, $$\Omega _{CDM} h^2$$

Ω

CDM

h
2

, the Higgs mass, $$M_h$$

M
h

, and the experimental lower limit on the lifetime for $$p \rightarrow K^+ \bar{\nu }$$

p
→

K
+

ν

¯

, the dominant proton decay mode in these super-GUT models. Reconciling this limit with $$\Omega _{CDM} h^2$$

Ω

CDM

h
2

and $$M_h$$

M
h

requires the Higgs field responsible for the charge-2/3 quark masses to be twisted, and possibly also that responsible for the charge-1/3 and charged-lepton masses, with model-dependent soft supersymmetry-breaking masses. We consider six possible models for the super-GUT initial conditions, and two possible choices for quark flavor mixing, contrasting their predictions for proton decay with versions of the models in which mixing effects are neglected. We find that $$\tau \left( p\rightarrow K^+ \bar{\nu }\right) $$

τ

p
→

K
+

ν

¯

may be accessible to the upcoming Hyper-Kamiokande experiment, whereas all the models predict $$\text {BR}(\mu \rightarrow e\gamma )$$

BR
(
μ
→
e
γ
)

and $$d_e$$

d
e

below the current and prospective future experimental sensitivities or both flavor choices, when the dark matter density, Higgs mass and current proton decay constraints are taken into account. However, there are limited regions with one of the flavor choices in two of the models where $$\mu \rightarrow e$$

μ
→
e

conversion on a heavy nucleus may be observable in the future. Our results indicate that there is no supersymmetric flavor problem in the class of no-scale models we consider.
Regular rotating MOG dark compact object
Authors: Moffat J. W. 
Published: February 2021

AbstractA regular rotating MOG (modified gravity) compact object is derived that reduces to the Kerr black hole when the parameter $$\alpha =0$$

α
=
0

. Physical consequences of the dark compact object, which is regular everywhere in spacetime for $$\alpha > \alpha _\mathrm{crit}=0.674$$

α
>

α
crit

=
0.674

and is a rotating Kerr-MOG black hole for $$\alpha < \alpha _\mathrm{crit}$$

α
<

α
crit

are investigated.
Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial
Authors: Edlund Karolina , Madjar Katrin , Lebrecht Antje , Aktas Bahriye , Pilch Henryk , Hoffmann Gerald , Hofmann Manfred , Kolberg Hans-Christian , Boehm Daniel , Battista Marco , Seehase Martina , Stewen Kathrin , Gebhard Susanne , Cadenas Cristina , Marchan Rosemarie , Brenner Walburgis , Hasenburg Annette , Koelbl Heinz , Solbach Christine , Gehrmann Mathias , Tanner Berno , Weber Karsten E. , Loibl Sibylle , Sachinidis Agapios , Rahnenführer Jörg , Schmidt Marcus , Hengstler Jan G. 
Published: February 2021

Abstract

Purpose:
Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT.

Patients and Methods:
We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619).

Results:
A 20-gene classifier established in the EXPRESSION cohort using a Youden index–based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer.

Conclusions:
The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.
Safety, Antitumor Activity, and T-cell Responses in a Dose-Ranging Phase I Trial of the Oncolytic Peptide LTX-315 in Patients with Solid Tumors
Authors: Spicer James , Marabelle Aurélien , Baurain Jean-Francois , Jebsen Nina Louise , Jøssang Dag Erik , Awada Ahmad , Kristeleit Rebecca , Loirat Delphine , Lazaridis George , Jungels Christiane , Brunsvig Paal , Nicolaisen Berit , Saunders Andrew , Patel Hamina , Galon Jérôme , Hermitte Fabienne , Camilio Ketil André , Mauseth Brynjar , Sundvold Vibeke , Sveinbjørnsson Baldur , Rekdal Øystein 
Published: February 2021

Abstract

Purpose:
LTX-315 is a first-in-class, 9-mer membranolytic peptide that has shown potent immunomodulatory properties in preclinical models. We conducted a phase I dose-escalating study of intratumoral LTX-315 administration in patients with advanced solid tumors.

Patients and Methods:
Thirty-nine patients were enrolled, receiving LTX-315 injections into accessible tumors. The primary objective was to assess the safety and tolerability of this approach, with antitumor and immunomodulatory activity as secondary objectives. Tumor biopsies were collected at baseline and posttreatment for analysis of immunologic parameters.

Results:
The most common treatment-related grade 1–2 adverse events were vascular disorders including transient hypotension (18 patients, 46%), flushing (11 patients, 28%), and injection site reactions in 38% of patients. The most common grade 3 LTX-315–related toxicities were hypersensitivity or anaphylaxis (4 patients, 10%). Analysis of immune endpoints in serial biopsies indicated that LTX-315 induces necrosis and CD8+ T-cell infiltration into the tumor microenvironment. Sequencing of the T-cell receptor repertoire in peripheral blood identified significant expansion of T-cell clones after treatment, of which 49% were present in available tumor biopsies after treatment, suggesting that they were tumor associated. Substantial volume reduction (≥30%) of injected tumors occurred in 29% of the patients, and 86% (12/14 biopsies) had an increase in intralesional CD8+ T cells posttreatment. No partial responses by immune-related response criteria were seen, but evidence of abscopal effect was demonstrated following treatment with LTX-315.

Conclusions:
LTX-315 has an acceptable safety profile, is clinically active, induces changes in the tumor microenvironment and contributes to immune-mediated anticancer activity.
Targeting DNA Damage Repair Functions of Two Histone Deacetylases, HDAC8 and SIRT6, Sensitizes Acute Myeloid Leukemia to NAMPT Inhibition
Authors: Zhang Pu , Brinton Lindsey T. , Williams Katie , Sher Steven , Orwick Shelley , Tzung-Huei Lai , Mims Alice S. , Coss Christopher C. , Kulp Samuel K. , Youssef Youssef , Chan Wing Keung , Mitchell Shaneice , Mustonen Allison , Cannon Matthew , Phillips Hannah , Lehman Amy M. , Kauffman Tierney , Beaver Larry , Canfield Daniel , Grieselhuber Nicole R. , Alinari Lapo , Sampath Deepa , Yan Pearlly , Byrd John C. , Blachly James S. , Lapalombella Rosa 
Published: February 2021

Abstract

Purpose:
Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors (NAMPTi) are currently in development, but may be limited as single-agent therapy due to compound-specific toxicity and cancer metabolic plasticity allowing resistance development. To potentially lower the doses of NAMPTis required for therapeutic benefit against acute myeloid leukemia (AML), we performed a genome-wide CRISPRi screen to identify rational disease-specific partners for a novel NAMPTi, KPT-9274.

Experimental Design:
Cell lines and primary cells were analyzed for cell viability, self-renewal, and responses at RNA and protein levels with loss-of-function approaches and pharmacologic treatments. In vivo efficacy of combination therapy was evaluated with a xenograft model.

Results:
We identified two histone deacetylases (HDAC), HDAC8 and SIRT6, whose knockout conferred synthetic lethality with KPT-9274 in AML. Furthermore, HDAC8-specific inhibitor, PCI-34051, or clinical class I HDAC inhibitor, AR-42, in combination with KPT-9274, synergistically decreased the survival of AML cells in a dose-dependent manner. AR-42/KPT-9274 cotreatment attenuated colony-forming potentials of patient cells while sparing healthy hematopoietic cells. Importantly, combined therapy demonstrated promising in vivo efficacy compared with KPT-9274 or AR-42 monotherapy. Mechanistically, genetic inhibition of SIRT6 potentiated the effect of KPT-9274 on PARP-1 suppression by abolishing mono-ADP ribosylation. AR-42/KPT-9274 cotreatment resulted in synergistic attenuation of homologous recombination and nonhomologous end joining pathways in cell lines and leukemia-initiating cells.

Conclusions:
Our findings provide evidence that HDAC8 inhibition- or shSIRT6-induced DNA repair deficiencies are potently synergistic with NAMPT targeting, with minimal toxicity toward normal cells, providing a rationale for a novel–novel combination-based treatment for AML.
A Novel Mouse Model of Radiation-Induced Cardiac Injury Reveals Biological and Radiological Biomarkers of Cardiac Dysfunction with Potential Clinical Relevance
Authors: Dreyfuss Alexandra D. , Goia Denisa , Shoniyozov Khayrullo , Shewale Swapnil V. , Velalopoulou Anastasia , Mazzoni Susan , Avgousti Harris , Metzler Scott D. , Bravo Paco E. , Feigenberg Steven J. , Ky Bonnie , Verginadis Ioannis I. , Koumenis Constantinos 
Published: February 2021

Abstract

Purpose:
Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury.

Experimental Design:
Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9–11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies.

Results:
Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P &lt; 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed (P &lt; 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P = 0.021) and TNFα (P = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r = 0.89, P = 0.0001) with mean heart dose.

Conclusions:
We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.
How Did We Get a COVID-19 Vaccine in Less Than 1 Year?
Authors: Wherry E. John , Jaffee Elizabeth M. , Warren Nicholas , D'Souza Gypsyamber , Ribas Antoni 
Published: February 2021

Abstract
The successful development of COVID-19 vaccines within an unprecedented short time needs to be followed by rapid vaccine uptake, in particular, in high-risk populations such as patients with cancer. It is important for the scientific research community and cancer physicians to convey the knowledge behind the COVID-19 vaccine development and contribute to build the required trust on their use.
Molecular Targeting of RRM2, NF-κB, and Mutant TP53 for the Treatment of Triple-Negative Breast Cancer
Authors: Wilson Elizabeth A. , Sultana Nahid , Shah Khyati N. , Elford Howard L. , Faridi Jesika S. 
Published: February 2021

Abstract
Doxorubicin and other anthracycline derivatives are frequently used as part of the adjuvant chemotherapy regimen for triple-negative breast cancer (TNBC). Although effective, doxorubicin is known for its off-target and toxic side effect profile, particularly with respect to the myocardium, often resulting in left ventricular (LV) dysfunction and congestive heart failure when used at cumulative doses exceeding 400 mg/m2. Previously, we have observed that the ribonucleotide reductase subunit M2 (RRM2) is significantly overexpressed in estrogen receptor (ER)–negative cells as compared with ER-positive breast cancer cells. Here, we inhibited RRM2 in ER-negative breast cancer cells as a target for therapy in this difficult-to-treat population. We observed that through the use of didox, a ribonucleotide reductase inhibitor, the reduction in RRM2 was accompanied by reduced NF-κB activity in vitro. When didox was used in combination with doxorubicin, we observed significant downregulation of NF-κB proteins accompanied by reduced TNBC cell proliferation. As well, we observed that protein levels of mutant p53 were significantly reduced by didox or combination therapy in vitro. Xenograft studies showed that combination therapy was found to be synergistic in vivo, resulting in a significantly reduced tumor volume as compared with doxorubicin monotherapy. In addition, the use of didox was also found to ameliorate the toxic myocardial effects of doxorubicin in vivo as measured by heart mass, LV diameter, and serum troponin T levels. The data present a novel and promising approach for the treatment of TNBC that merits further clinical evaluation in humans.
A new fossil species of Procellaria (Aves: Procellariiformes) from the Pliocene of New Zealand
Authors: Tennyson Alan James Drummond , Tomotani Barbara Mizumo 
Published: February 2021

We describe a new Procellaria petrel species from the late Pliocene of Taranaki, New Zealand. The new species is most similar morphologically to the White-Chinned Petrel (P. aequinoctialis), Spectacled Petrel (P. conspicillata) and the Westland Petrel (P. westlandica). Compared with those taxa, the new species has a deeper and shorter premaxilla, longer coracoid and shorter wings, while its legs are a similar size. Today, New Zealand is the centre of global diversity of the genus, with four breeding species. This is the first fossil species of Procellaria to be described from New Zealand, attesting to a reasonably long history of this genus in the region.
Filmes e vídeos como formas de conhecimento: desenvolvimentos atuais e possibilidades futuras
Authors: Villela Alice 
Published: February 2021

Resenha de The Routledge International Handbook of Ethnographic Film and Video, Ed. Phillip Vannini. London and New York: Routledge. 2020. 359p. ISBN: 978-0-367-18582-4 (hbk) ISBN: 978-0-429-19699-7 (ebk)
Review of the tiger beetle genus Calomera Motschulsky, 1862 (Coleoptera: Cicindelidae) of the Philippines
Authors: Medina Milton Norman , Anichtchenko Alexander , Wiesner Jürgen 
Published: February 2021

The genus Calomera Motschulsky, 1862 from the Philippines is reviewed. Five species C. angulata Fabricuis, 1798, C. cabigasi Cassola, 2011, C. despectata (Horn, 1892), C. lacrymosa (Dejean, 1825), and C. mindanaoensis (Cassola, 2000) are described with diagnoses, illustrations, notes on their ecology, and distribution remarks. Status of the taxa C. insularis (Blanchard, 1853) is discussed. Images of endophallus structures of C. lacrymosa and C. mindanaoensis are given for the first time. A key to the Philippine Calomera species is provided.
Early Detection of Aortic Degeneration in a Mouse Model of Sporadic Aortic Aneurysm and Dissection Using Nanoparticle Contrast-Enhanced Computed Tomography
Authors: Ghaghada Ketan B. , Ren Pingping , Devkota Laxman , Starosolski Zbigniew , Zhang Chen , Vela Deborah , Stupin Igor V. , Tanifum Eric A. , Annapragada Ananth V. , Shen Ying H. , LeMaire Scott A. 
Published: February 2021

Objective:
Early detection of aortic degeneration is critical for improving outcomes in patients with aortic aneurysm and dissection. We investigated nanoparticle contrast-enhanced computed tomography for the early detection of aortic injury.

Approach and Results:
In a mouse model of sporadic aortic aneurysm and dissection, C57BL/6J mice were challenged with a high-fat diet and Ang II (angiotensin II) infusion (n=20). Unchallenged control mice received a standard laboratory diet and saline infusion (n=19). Computed tomography angiography (CTA) was performed to evaluate aortic enlargement, and delayed nanoparticle contrast-enhanced computed tomography (CTD) imaging was performed to detect wall signal enhancement indicative of aortic wall degeneration. Aortic segments that exhibited CTD findings but appeared normal on CTA were termed preclinical aortic disease. Aortic aneurysm and dissection development was determined upon the gross examination of excised aortas. Aortic degeneration and inflammation were examined by performing histological and immunofluorescence analyses. Leakage of Evans blue dye into the aortic wall was used to validate changes in vascular permeability. In challenged mice, gross findings of aortic disease were found in 41% of aortic segments. CTA findings of mild disease (dilatation) and advanced disease (aortic aneurysm and dissection with the presence of false lumen) were seen in 33% of aortic segments. CTD findings of wall signal enhancement were seen in 63% of aortic segments. Of those, 48% appeared normal on CTA. Aortic segments with CTD findings showed aortic wall degeneration and inflammation on histological and immunofluorescence analyses. Immunofluorescence analysis and Evans blue dye uptake suggested passive leakage of nanoparticle contrast agent due to endothelial injury as a potential mechanism underlying the detection of aortic disease on CTD.

Conclusions:
In mice, CTD imaging exhibits high sensitivity for detecting aortic wall degeneration and inflammation before vessel enlargement becomes evident on CTA.
Serum Metabolomic Signatures Can Predict Subclinical Atherosclerosis in Patients With Systemic Lupus Erythematosus
Authors: Coelewij Leda , Waddington Kirsty E. , Robinson George A. , Chocano Elvira , McDonnell Thomas , Farinha Filipa , Peng Junjie , Dönnes Pierre , Smith Edward , Croca Sara , Bakshi Jyoti , Griffin Maura , Nicolaides Andrew , Rahman Anisur , Jury Elizabeth C. , Pineda-Torra Ines 
Published: February 2021

Objective:
Patients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular disease. Standard serum lipid measurements in clinical practice do not predict cardiovascular disease risk in patients with SLE. More detailed analysis of lipoprotein taxonomy could identify better predictors of cardiovascular disease risk in SLE.

Approach and Results:
Eighty women with SLE and no history of cardiovascular disease underwent carotid and femoral ultrasound scans; 30 had atherosclerosis plaques (patients with SLE with subclinical plaque) and 50 had no plaques (patients with SLE with no subclinical plaque). Serum samples obtained at the time of the scan were analyzed using a lipoprotein-focused metabolomics platform assessing 228 metabolites by nuclear magnetic resonance spectroscopy. Data were analyzed using logistic regression and 5 binary classification models with 10-fold cross validation. Patients with SLE had global changes in complex lipoprotein profiles compared with healthy controls despite having clinical serum lipid levels within normal ranges. In the SLE cohort, univariate logistic regression identified 4 metabolites associated with subclinical plaque; 3 subclasses of VLDL (very low-density lipoprotein; free cholesterol in medium and large VLDL particles and phospholipids in chylomicrons and extremely large VLDL particles) and leucine. Together with age, these metabolites were also within the top features identified by the lasso logistic regression (with and without interactions) and random forest machine learning models. Logistic regression with interactions differentiated between patients with SLE with subclinical plaque and patients with SLE with no subclinical plaque groups with the greatest accuracy (0.800). Notably, free cholesterol in large VLDL particles and age differentiated between patients with SLE with subclinical plaque and patients with SLE with no subclinical plaque in all models.

Conclusions:
Serum metabolites are promising biomarkers to uncover and predict multimetabolic phenotypes of subclinical atherosclerosis in SLE.