bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence prediction for breast phyllodes tumours: validation of the Singapore nomogram in Korean women
Authors: Choi Jung Eun , Kang Su Hwan , Tan Puay Hoon , Bae Young Kyung 
Published: December 2020

AimThe Singapore nomogram was developed to predict recurrence risk of phyllodes tumours (PTs) of the breast based on histological features of stromal atypia, stromal mitoses, stromal overgrowth and surgical margin status. We aimed to validate the utility of the Singapore nomogram in a Korean PT cohort.MethodsOne hundred and twenty-four patients with Korean PT who underwent surgical resection between 1996 and 2015 were included in this study. Pathology reports and slides were reviewed to obtain histopathologic features and acquire Singapore nomogram scores. The probability of concordance between predicted and observed survivals by means of the Singapore nomogram was evaluated using a concordance index (C-index).ResultsOf the 124 cases, 57 (46%) were diagnosed as benign, 50 (40.3%) as borderline and 17 (13.7%) as malignant. Recurrences occurred in 25 (20.2%) patients. Univariate analysis showed PTs with higher stromal mitotic counts, marked stromal cellularity, stromal overgrowth, positive surgical margin, marked stromal atypia or a malignant grade presented higher risks of recurrence. Multivariate analysis showed stromal mitoses and surgical margin status independently predicted recurrence-free survival. Patients with high nomogram scores were at greater risk of recurrence (HR=1.05, 95% CI: 1.02 to 1.07, p<0.001) with a C-index of 0.762.ConclusionThe Singapore nomogram provided a useful means of predicting PT outcomes in a Korean PT cohort.
Neutrino amplitude decomposition: toward observing the atmospheric-solar wave interference
Authors: Minakata Hisakazu 
Published: December 2020

AbstractObservation of the interference between the atmospheric and solar oscillation waves with the correct magnitude would provide another manifestation of the three-generation structure of leptons. As a prerequisite for such analyses we develop a method for decomposing the oscillation S matrix into the atmospheric and solar amplitudes. Though the similar method was recently proposed successfully in vacuum, once an extension into the matter environment is attempted, it poses highly nontrivial problems. Even for an infinitesimal matter potential, inherent mixture of the atmospheric and solar oscillation waves occurs, rendering a simple extension of the vacuum definition untenable. We utilize general kinematic structure as well as analyses of the five perturbative frameworks, in which the nature of matter-dressed atmospheric and solar oscillations are known, to understand the origin of the trouble, how to deal with the difficulty, and to grasp the principle of decomposition. Then, we derive the amplitude decomposition formulas in these frameworks, and discuss properties of the decomposed probabilities. We mostly discuss the $$\nu _{\mu } \rightarrow \nu _{e}$$

ν
μ

→

ν
e

channel, but a comparison with the $$\nu _{\mu } \rightarrow \nu _{\tau }$$

ν
μ

→

ν
τ

channel reveals an interesting difference.
Testing dissipative dark matter in causal thermodynamics
Authors: Cruz Norman , González Esteban , Palma Guillermo 
Published: December 2020

In this paper we study the consistency of a cosmological model representing a universe filled with a one-component dissipative dark matter fluid, in the framework of the causal Israel–Stewart theory, where a general expression arising from perturbation analysis for the relaxation time [Formula: see text] is used. This model is described by an exact analytic solution recently found in [N. Cruz, E. González and G. Palma, Gen. Relat. Gravit. 52, 62 (2020), which depends on several model parameters as well as integration constants, allowing the use of Type Ia Supernovae and Observational Hubble data to perform by an astringent observational tests. The constraint regions found for the parameters of the solution allow the existence of an accelerated expansion of the universe at late times, after the domination era of the viscous pressure, which holds without the need of including a cosmological constant. Nevertheless, the fitted parameter values lead to drawbacks as a very large non-adiabatic contribution to the speed of sound, and some inconsistencies, not totally conclusive, with the description of the dissipative dark matter as a fluid, which is nevertheless a common feature of these kind of models.
ANALYTICAL SOLUTION OF THE FRACTAL CUBIC–QUINTIC DUFFING EQUATION
Authors: ELÍAS-ZÚÑIGA ALEX , PALACIOS-PINEDA LUIS MANUEL , JIMÉNEZ-CEDEÑO ISAAC H. , MARTÍNEZ-ROMERO OSCAR , OLVERA-TREJO DANIEL 
Published: December 2020

In this work, the fractal cubic–quintic Duffing’s equation analytical solution is obtained using the two-scale transform and elliptic functions. Then, the analytical solution is used to study wave propagation in a fractal medium. Since the value of the fractal parameter adjusts the pulse frequency and wavelength propagation velocity, depending upon the fractal medium physical properties, it is found that the information contained in the pulse can be carried out faster over long distances without distortion or loss of intensities. This paper offers a new light on the applicability of the two-scale transform of fractal theory to comprehend natural phenomena.
The Role of Intrinsic Signaling Pathways in Cell Proliferation
Authors: Coleman Holly , Abedin Muhammad Raisul , Powers Kaitlyne , Barua Sutapa 
Published: December 2020

Programmed cell death, or apoptosis, and controlled cell division, or mitosis, are two highly regulated processes in the cell cycle. A balance between apoptosis and mitosis is critical for multiple distinct states including embryonic development, immune cell activation, stem cell differentiation, tissue formation (wound healing), and tumor prevention, among others. A cell undergoing apoptosis shows a series of characteristic morphological changes similar to normal mitosis and an aberrant form of mitosis. During each of these processes, nuclear chromatin condenses, the nuclear lamina and cytoplasmic membranes disintegrate, and cells decrease in volume. The morphological resemblance among cells undergoing these processes suggests that the underlying intracellular signaling pathways influence the mitotic cell fate. In this paper, the relationship of intracellular signaling pathways, cell cycle dynamics, and apoptotic cell signaling pathways is discussed. The mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/Ras/Raf/ERK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Janus kinase/signal transducer and activator of transcription (JAK/STAT), wingless-related integration site (Wnt), and transforming growth factor beta (TGF-[Formula: see text] are major cell signaling pathways that transmit signals from multiple cell surface receptors to transcription factors in the nucleus. The pathways are stimulated by cytokines, growth factors, and external stimuli, i.e., reactive oxygen species which induce signal transduction pathways and regulate complex processes such as cell cycle progression, cell proliferation, cellular growth, differentiation, and apoptosis. Aberrant mutations in particular genes and proteins of these pathways contribute to cancers usually by inhibiting pro-apoptotic proteins (e.g., Bak, Bax, Noxa, Puma, etc.) and stimulating antiapoptotic proteins (e.g., Bcl-2, Bcl-XL, Mcl-1, etc.). The cell cycle is regulated by intracellular signaling pathways such as the MAPK/Ras/Raf/ERK and PI3K pathways to produce the synthesis of cyclin D and other mitosis regulating proteins (Myc and Jun). Cyclin D1 binds to cyclin-dependent kinase (CDK) 4 and CDK 6 (CDK4/6) to form an effective complex, activate several substrates, and initiate the cell cycle. The prominent molecules that regulate signaling pathways in normal and cancer cells are described.
Coincidencia de hallazgos endoscópicos e histológicos en el diagnóstico de esófago de Barrett
Authors: Piamo Morales Alberto José , Arzuaga Anderson Isnerio , Palma Machado Lourdes , Chávez Jiménez Digna , Ferrer Marrero Daisy 
Published: December 2020

Introducción: el esófago de Barrett es una alteración en la cual la mucosa esofágica se transforma desde un epitelio escamoso a un epitelio columnar con metaplasia intestinal. Endoscópicamente esta lesión se corresponde con la presencia de una mucosa columnar de color rojo salmón por encima de la unión gatroesofágica. Para su diagnóstico se requiere de la sospecha endoscópica y la confirmación histológica. Objetivo: determinar los niveles de coincidencia entre los diagnósticos endoscópicos y las características histopatológicas del esófago de Barrett, a partir del análisis de una serie de casos. Métodos: se realizó un estudio retrospectivo, en el Hospital Clínico Quirúrgico “Joaquín Albarrán” de La Habana, Cuba entre enero de 2017 a junio de 2019, obteniéndose los datos de los registros de biopsias e historias clínicas. Se realizaron cálculos de frecuencias absolutas y relativas y, para evaluar la fuerza de coincidencia entre endoscopia e histología, se utilizó el estadístico Chi cuadrado. Resultados: en los 67 casos con diagnóstico endoscópico la coincidencia con histopatológica fue del 44,8%, en el restante 55,2% de los pacientes las lesiones diagnosticadas fue esofagitis crónica (p = 0,005). Conclusiones: el esófago de Barrett es una de las entidades clínicas con una epidemiología de alta variabilidad y su diagnóstico endoscópicos requiere de la confirmación histológica ya que existe una baja coincidencia entre el diagnóstico endoscópico e histopatológico del EB el cual es el estándar de oro para el diagnóstico de EB.
PLK1 Induces Chromosomal Instability and Overrides Cell-Cycle Checkpoints to Drive Tumorigenesis
Authors: Gheghiani Lilia , Wang Lei , Zhang Youwei , Moore Xavier T.R. , Zhang Jinglei , Smith Steven C. , Tian Yijun , Wang Liang , Turner Kristi , Jackson-Cook Colleen K. , Mukhopadhyay Nitai D. , Fu Zheng 
Published: December 2020

Abstract

Polo-like kinase 1 (PLK1) is an essential cell-cycle regulator that is frequently overexpressed in various human cancers. To determine whether Plk1 overexpression drives tumorigenesis, we established transgenic mouse lines that ubiquitously express increased levels of Plk1. High Plk1 levels were a driving force for different types of spontaneous tumors. Increased Plk1 levels resulted in multiple defects in mitosis and cytokinesis, supernumerary centrosomes, and compromised cell-cycle checkpoints, allowing accumulation of chromosomal instability (CIN), which resulted in aneuploidy and tumor formation. Clinically, higher expression of PLK1 positively associated with an increase in genome-wide copy-number alterations in multiple human cancers. This study provides in vivo evidence that aberrant expression of PLK1 triggers CIN and tumorigenesis and highlights potential therapeutic opportunities for CIN-positive cancers.

Significance:
These findings establish roles for PLK1 as a potent proto-oncogene and a CIN gene and provide insights for the development of effective treatment regimens across PLK1-overexpressing and CIN-positive cancers.
IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy
Authors: Teijeira Alvaro , Garasa Saray , Ochoa Maria C. , Villalba Maria , Olivera Irene , Cirella Assunta , Eguren-Santamaria Iñaki , Berraondo Pedro , Schalper Kurt A. , de Andrea Carlos E. , Sanmamed Miguel F. , Melero Ignacio 
Published: December 2020

AbstractOne of the most important mechanisms by which cancer fosters its own development is the generation of an immune microenvironment that inhibits or impairs antitumor immune responses. A cancer permissive immune microenvironment is present in a large proportion of the patients with cancer who do not respond to immunotherapy approaches intended to trigger preexisting antitumor immune responses, for instance, immune checkpoint blockade. High circulating levels of IL8 in patients with cancer quite accurately predict those who will not benefit from checkpoint-based immunotherapy. IL8 has been reported to favor cancer progression and metastases via different mechanisms, including proangiogenesis and the maintenance of cancer stem cells, but its ability to attract and functionally modulate neutrophils and macrophages is arguably one of the most important factors. IL8 does not only recruit neutrophils to tumor lesions, but also triggers the extrusion of neutrophil extracellular traps (NET). The relevance and mechanisms underlying the contribution of both neutrophils and NETs to cancer development and progression are starting to be uncovered and include both direct effects on cancer cells and changes in the tumor microenvironment, such as facilitating metastasis, awakening micrometastases from dormancy, and facilitating escape from cytotoxic immune cells. Blockade of IL8 or its receptors (CXCR1 and CXCR2) is being pursued in drug development, and clinical trials alone or in combination with anti-PD-L1 checkpoint inhibitors are already ongoing.
Phase IB Study of Osimertinib in Combination with Navitoclax in EGFR-mutant NSCLC Following Resistance to Initial EGFR Therapy (ETCTN 9903)
Authors: Bertino Erin M. , Gentzler Ryan D. , Clifford Sarah , Kolesar Jill , Muzikansky Alona , Haura Eric B. , Piotrowska Zofia , Camidge D. Ross , Stinchcombe Thomas E. , Hann Christine , Malhotra Jyoti , Villaruz Liza C. , Paweletz Cloud P. , Lau Christie L. , Sholl Lynette , Takebe Naoko , Moscow Jeffrey A. , Shapiro Geoffrey I. , Jänne Pasi A. , Oxnard Geoffrey R. 
Published: December 2020

Abstract

Purpose:
Osimertinib is an effective therapy in EGFR-mutant non–small cell lung cancer (NSCLC), but resistance invariably develops. Navitoclax is an oral inhibitor of BCL-2/BCL-xL that has exhibited synergy with osimertinib in preclinical models of EGFR-mutant NSCLC. In hematologic malignancies, BCL-2 family inhibitors in combination therapy effectively increase cellular apoptosis and decrease drug resistance.

Patients and Methods:
This single-arm phase Ib study evaluated safety, tolerability, and feasibility of osimertinib and navitoclax, including dose expansion in T790M-positive patients at the recommended phase II dose (RP2D). Eligible patients had advanced EGFR-mutant NSCLC with prior tyrosine kinase inhibitor exposure. Five dose levels were planned with osimertinib from 40 to 80 mg orally daily and navitoclax from 150 to 325 mg orally daily.

Results:
A total of 27 patients were enrolled (18 in the dose-escalation cohort and nine in the dose-expansion cohort): median age 65, 67% female, 48% exon 19 del, and 37% L858R, median one prior line of therapy. The most common adverse events were lymphopenia (37%), fatigue (22%), nausea (22%), and thrombocytopenia (37%). No dose-limiting toxicities were seen in dose-escalation cohort; osimertinib 80 mg, navitoclax 150 mg was chosen as the RP2D. Most patients (78%) received &gt;95% of planned doses through three cycles. In expansion cohort, objective response rate was 100% and median progression-free survival was 16.8 months. A proapoptotic effect from navitoclax was demonstrated by early-onset thrombocytopenia.

Conclusions:
Oral combination therapy with navitoclax and osimertinib was safe and feasible at RP2D with clinical efficacy. Early thrombocytopenia was common, supporting an target engagement by navitoclax. Further study of BCL-2/BCL-xL inhibition to enhance osimertinib activity is warranted.
Association Between Silent Myocardial Infarction and Long‐Term Risk of Sudden Cardiac Death
Authors: Cheng Yun‐Jiu , Jia Yu‐He , Yao Feng‐Juan , Mei Wei‐Yi , Zhai Yuan‐Sheng , Zhang Ming , Wu Su‐Hua 
Published: December 2020

Background
Although silent myocardial infarction (SMI) is prognostically important, the risk of sudden cardiac death (SCD) among patients with incident SMI is not well established.

Methods and Results

We examined 2 community‐based cohorts: the ARIC (Atherosclerosis Risk in Communities) study (n=13 725) and the CHS (Cardiovascular Health Study) (n=5207). Incident SMI was defined as
electrocardiographic
evidence of new myocardial infarction during follow‐up visits that was not present at the baseline. The primary study end point was physician‐adjudicated SCD. In the ARIC study, 513 SMIs, 441 clinically recognized myocardial infarctions (CMIs), and 527 SCD events occurred during a median follow‐up of 25.4 years. The multivariable hazard ratios of SMI and CMI for SCD were 5.20 (95% CI, 3.81–7.10) and 3.80 (95% CI, 2.76–5.23), respectively. In the CHS, 1070 SMIs, 632 CMIs, and 526 SCD events occurred during a median follow‐up of 12.1 years. The multivariable hazard ratios of SMI and CMI for SCD were 1.70 (95% CI, 1.32–2.19) and 4.08 (95% CI, 3.29–5.06), respectively. The pooled hazard ratios of SMI and CMI for SCD were 2.65 (2.18–3.23) and 3.99 (3.34–4.77), respectively. The risk of SCD associated with SMI is stronger with White individuals, men, and younger age. The population‐attributable fraction of SCD was 11.1% for SMI, and SMI was associated with an absolute risk increase of 8.9 SCDs per 1000 person‐years. Addition of SMI significantly improved the predictive power for both SCD and non‐SCD.

Conclusions
Incident SMI is independently associated with an increased risk of SCD in the general population. Additional research should address screening for SMI and the role of standard post–myocardial infarction therapy.
Left Atrial Reservoir Strain by Speckle Tracking Echocardiography: Association With Exercise Capacity in Chronic Kidney Disease
Authors: Gan Gary C.H. , Bhat Aditya , Chen Henry H.L. , Gu Kennith H. , Fernandez Fernando , Kadappu Krishna K. , Byth Karen , Eshoo Suzanne , Thomas Liza 
Published: December 2020

Background
Left atrial (LA) function plays a pivotal role in modulating left ventricular performance. The aim of our study was to evaluate the relationship between resting LA function by strain analysis and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its utility compared with exercise E/e'.

Methods and Results

Consecutive patients with stage 3 and 4 CKD without prior cardiac history were prospectively recruited from outpatient nephrology clinics and underwent clinical evaluation and resting and exercise stress echocardiography. Resting echocardiographic parameters including E/e' and phasic LA strain (LA reservoir [LASr], conduit, and contractile strain) were measured and compared with exercise E/e'. A total of 218 (63.9±11.7 years, 64% men) patients with CKD were recruited. Independent clinical parameters associated with exercise capacity were age, estimated glomerular filtration rate, body mass index, and sex (
P
<0.01 for all), while independent resting echocardiographic parameters included E/e', LASr, and LA contractile strain (
P
<0.01 for all). Among resting echocardiographic parameters, LASr demonstrated the strongest positive correlation to metabolic equivalents achieved (r=0.70;
P
<0.01). Receiver operating characteristic curves demonstrated that LASr (area under the curve, 0.83) had similar diagnostic performance as exercise E/e' (area under the curve, 0.79;
P
=0.20 on DeLong test). A model combining LASr and clinical metrics showed robust association with metabolic equivalents achieved in patients with CKD.

Conclusions
LASr, a marker of decreased LA compliance is an independent correlate of exercise capacity in patients with stage 3 and 4 CKD, with similar diagnostic value to exercise E/e'. Thus, LASr may serve as a resting biomarker of functional capacity in this population.
New Cardiomyokine Reduces Myocardial Ischemia/Reperfusion Injury by PI3K‐AKT Pathway Via a Putative KDEL‐Receptor Binding
Authors: Maciel Leonardo , de Oliveira Dahienne Ferreira , Mesquita Fernanda , Souza Hercules Antônio da Silva , Oliveira Leandro , Christie Michelle Lopes Araújo , Palhano Fernando L. , Campos de Carvalho Antônio Carlos , Nascimento José Hamilton Matheus , Foguel Debora 
Published: December 2020

Background
CDNF (cerebral dopamine neurotrophic factor) belongs to a new family of neurotrophic factors that exert systemic beneficial effects beyond the brain. Little is known about the role of CDNF in the cardiac context. Herein we investigated the effects of CDNF under endoplasmic reticulum‐stress conditions using cardiomyocytes (humans and mice) and isolated rat hearts, as well as in rats subjected to ischemia/reperfusion (I/R).

Methods and Results
We showed that CDNF is secreted by cardiomyocytes stressed by thapsigargin and by isolated hearts subjected to I/R. Recombinant CDNF (exoCDNF) protected human and mouse cardiomyocytes against endoplasmic reticulum stress and restored the calcium transient. In isolated hearts subjected to I/R, exoCDNF avoided mitochondrial impairment and reduced the infarct area to 19% when administered before ischemia and to 25% when administered at the beginning of reperfusion, compared with an infarct area of 42% in the untreated I/R group. This protection was completely abrogated by AKT (protein kinase B) inhibitor. Heptapeptides containing the KDEL sequence, which binds to the KDEL‐R (KDEL receptor), abolished exoCDNF beneficial effects, suggesting the participation of KDEL‐R in this cardioprotection. CDNF administered intraperitoneally to rats decreased the infarct area in an in vivo model of I/R (from an infarct area of ≈44% in the I/R group to an infarct area of ≈27%). Moreover, a shorter version of CDNF, which lacks the last 4 residues (CDNF‐ΔKTEL) and thus allows CDNF binding to KDEL‐R, presented no cardioprotective activity in isolated hearts.

Conclusions
This is the first study to propose CDNF as a new cardiomyokine that induces cardioprotection via KDEL receptor binding and PI3K/AKT activation.
Greening Faith and Herbology in Pentecostalism in Zimbabwe
Authors: Sande Nomatter 
Published: December 2020

Abstract
The role of religion in ecological discourse has gained ground in the quest to improve people’s lives in society. Herbal medicine is known to treat complex diseases. However, there are complexities in protecting the environment since herbal medicine entails having an in-depth understanding of traditional knowledge systems, beliefs, and practices. Pentecostal churches in Zimbabwe such as the Apostolic Faith Mission (AFM) have remained impervious to the widespread campaign promoting the use of herbs as an effective healing treatment. Divine healing is central to the AFM, and thus they view traditional herbal medicines as originating from evil spirits, despite scriptures referring to herbs as both food and medicine. Accordingly, developing a theology of ‘greening faith’ in the AFM will foster a constructive attitude toward the use of traditional herbal medicines. This article examines the position of the AFM on traditional herbal medicine and utilises ecotheology as its theoretical framework together with data gathered through in-depth interviews. The article concludes that the AFM should consciously use faith to protect the environment and promote the health and well-being of its believers.
Horizontal and Vertical Dimensions in Zambian Sermons about the COVID-19 Pandemic
Authors: Kroesbergen-Kamps Johanneke 
Published: December 2020

Abstract
In the contemporary literature about the relationship between religion and COVID-19, vertical as well as horizontal responses can be distinguished. Much of the current literature is based on personal reflection or on quantitative research. This article adds a qualitative research perspective and offers a preliminary analysis of the religious frameworks used by pastors in the Reformed Church in Zambia. Although the pastors acknowledge the need for communal action, their livestreamed services show an emphasis on the vertical dimension, i.e., the relation with God. As this article argues, this can be understood from an African worldview. There is also evidence that the initial vertical dimension of the services shifts to more horizontal concerns as the pandemic progresses.