bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast Connectivity Minimization on Large-Scale Networks
Authors: Chen Chen , Peng Ruiyue , Ying Lei , Tong Hanghang
Published: May 2021

The connectivity of networks has been widely studied in many high-impact applications, ranging from immunization, critical infrastructure analysis, social network mining, to bioinformatic system studies. Regardless of the end application domains, connectivity minimization has always been a fundamental task to effectively control the functioning of the underlying system. The combinatorial nature of the connectivity minimization problem imposes an exponential computational complexity to find the optimal solution, which is intractable in large systems. To tackle the computational barrier, greedy algorithm is extensively used to ensure a near-optimal solution by exploiting the diminishing returns property of the problem. Despite the empirical success, the theoretical and algorithmic challenges of the problems still remain wide open. On the theoretical side, the intrinsic hardness and the approximability of the general connectivity minimization problem are still unknown except for a few special cases. On the algorithmic side, existing algorithms are hard to balance between the optimization quality and computational efficiency. In this article, we address the two challenges by (1) proving that the general connectivity minimization problem is NP-hard and

is the best approximation ratio for any polynomial algorithms, and (2) proposing the algorithm
CONTAIN
and its variant
CONTAIN
+ that can well balance optimization effectiveness and computational efficiency for eigen-function based connectivity minimization problems in large networks.
Design of Enterprise Management System Based on Edge Computing Architecture
Authors: Yang Yongzhong , Mei Zheng , Zheng Benxia , Qiu Shuoli
Published: May 2021

In the current enterprise management system, the coupling relationship between enterprise management and operation and maintenance database is not considered, which leads to many system vulnerabilities, slow running speed, and long response time. An enterprise management system based on edge computing architecture is designed. According to the characteristics of mobile edge computing, we design the architecture of the edge computing platform, integrate the MEC virtualization infrastructure layer, MEC platform layer, and MEC application layer, construct the edge computing model, reflect the coupling relationship between enterprise management and operation and maintenance database, calculate the delay vector of the enterprise management server, and complete the parameter calculation of enterprise management and operation and maintenance system. This paper analyzes the feasibility, objectives, and users and functional requirements of the enterprise management system, designs the functional structure of the system, realizes the design of the public module, function menu module, and login module, adopts the SQL database management system, and designs the database and data table, so as to realize the design of the enterprise management system based on edge computing architecture. Experimental results show that the proposed method has fewer system vulnerabilities and can effectively speed up the system operation speed and shorten the system response time.
Clinical and Radiological Findings in Patients with Newly Diagnosed Graves’ Ophthalmopathy
Authors: Cevik Yakup , Taylan Sekeroglu Hande , Ozgen Burce , Erkan Turan Kadriye , Sanac Ali Sefik
Published: May 2021

Background. Graves’ ophthalmopathy is the most common extrathyroidal manifestation of Graves’ disease. The objective of this study was to investigate the clinical ophthalmological and MRI findings in newly diagnosed Graves’ ophthalmopathy. Methods. This study included 36 newly diagnosed Graves’ disease patients and 23 control participants. Patients and control participants underwent detailed ophthalmologic examination. In addition, all subjects underwent orbital MRI examination; and sizes, cross-sectional areas, and signal intensities of extraocular muscles were also measured. Results. Based on MRI measurements, the mean exophthalmos in the left eye was significantly higher in the patient group when compared to those of controls (2.04 ± 0.29 vs. 1.85 ± 0.15 cm,

p

 = 0.003). The mean long diameter of inferior oblique muscle in both the right and left eyes were significantly shorter in patients when compared to those of controls (

p

 = 0.001,

p

 = 0.002, resp.); however, the mean long diameter of superior oblique in the left eye was longer in patients than those of controls (

p

 = 0.001). Patients had significantly higher superior oblique muscle signal intensity than those of controls in the right eye (

p

 = 0.01). There was no significant difference for the other parameters between the patient and control groups. Conclusion. Our findings suggest that there is no obvious change in MRI examination despite clinical ophthalmological findings in patients with newly diagnosed Graves’ ophthalmopathy. Unnecessary MRI examination should be avoided in this patient group due to unsatisfactory cost-effectiveness.
A Validated Study of a Modified Shallow Water Model for Strong Cyclonic Motions and Their Structures in a Rotating Tank
Authors: Chen Hung-Cheng , Leu Jai-Houng , Liu Yong , Xie He-Sheng , Chen Qiang
Published: May 2021

A joint theoretical and numerical study was carried out to investigate the fluid dynamical aspect of the motion of a vortex generated in a rotating tank with a sloping bottom. This study aims at understanding the evolution of strong cyclonic motions on a β-plane in the Northern Hemisphere. The strong cyclonic vortices were characterized by four nondimensional parameters which were derived through a scale analysis of the depth variations of fluid. By simplifying the model flow field and the prototype flow field, respectively, through the conservation of potential vorticity, two sets of dynamic similarity conditions are derived. This study proposed a sophisticated modified shallow water model (MSWM) to investigate the flow features of such strong vortices. A detailed numerical calculation adopted by multidimensional positive definite advection transport algorithm (MPDATA) was carried out to validate those effects considered in the MSWM model, including sloping bottom, parabolic free surface deformation, and viscous dissipation. Close agreements were found between the experimental and numerical results, including the streamlines patterns and the vortex trajectory. Comprehensive simulations for strong cyclonic vortices over different sloping bottoms were investigated to understand the impact of planetary β effect on vortex. The results calculated by MSWM demonstrate a variety of flow features of interactions between the primary vortex and induced secondary Rossby wave wakes that were essential and prominent in environmental geophysical flows.
Hemorrhagic Shock after Neonatal Circumcision: Severe Congenital Factor XIII Deficiency
Authors: Cohen Erin L. , Millikan Samantha E. , Morocco Perry C. , de Jong Jill L. O.
Published: May 2021

A Caucasian male infant born full term via normal spontaneous vaginal delivery was given vitamin K after birth, circumcised on day of life (DOL) 1, and discharged from the nursery on DOL 2. At the time of circumcision, oozing from the surgical site was noted and initially resolved with silver nitrate. Over the next two days, he presented to local emergency rooms multiple times for recurrent bleeding, eventually developing hemorrhagic shock resulting in admission to the neonatal intensive care unit. After extensive work up, he was ultimately diagnosed with severe congenital factor XIII deficiency. Congenital factor XIII deficiency is a rare bleeding disorder characterized by normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) coagulation labs on routine screening, and has a high risk of complications, such as spontaneous intracranial hemorrhage. Although uncommon, when caring for a child with bleeding, physicians must have a high index of suspicion to make this diagnosis in order to initiate proper treatment and start prophylaxis given the risk of morbidity and mortality in untreated patients.
The Mathematical Model for the Tippe Top Inversion
Authors: Usubamatov R. , Bergander M. , Kapayeva S.
Published: May 2021

The dynamics of rotating objects is an area of classical mechanics that has many unsolved problems. Among these problems are the gyroscopic effects manifested by the spinning objects of different forms. One of them is the Tippe top designed as the truncated sphere which is fitted with a short, cylindrical rod for rotation. The unexplainable gyroscopic effect of the Tippe top is manifested by its inversion towards the support surface. Researchers tried to describe this gyroscopic effect for two centuries, but all modelings were on the level of assumptions. It is natural because the Tippe top has a more complex design than the simple spinning disc, which gyroscopic effects did not have an analytical solution until recent time. The latest research, in the area of gyroscopic effects, reveals the action of the system of several interrelated inertial torques on any spinning object. The gyroscopic inertial torques are generated by their rotating mass. These inertial torques and the variable ratio of the angular velocities of the spinning object around axes of rotations constitute the fundamental principles of gyroscope theory. These physical principles of dynamics of rotating objects enable to description and compute of any gyroscopic effects and also the Tippe top inversion.
Effects of High-Intensity Interval Training Protocols on Liver Enzymes and Wellness in Women
Authors: Rengers Timothy A. , Orr Samantha C. , Marks Charles R. C. , Hew-Butler Tamara , Choi Myung D. , Butcher Scotty J. , Drignei Dorin , Brown Elise C.
Published: May 2021

Background. Single-modality, high-intensity interval training (HIIT) using traditional cardiorespiratory exercise selection has been found to provide similar and sometimes superior cardiometabolic effects compared with moderate-intensity continuous training. However, little is known regarding the cardiometabolic and psychosocial effects of HIIT using resistance training modalities. Therefore, this study aims to compare the effects of HIIT using rowing (R-HIIT) and multimodal HIIT (MM-HIIT) using resistance training on liver enzymes, cardiometabolic risk factors, and psychosocial outcomes. Method. Recreationally active females with a body mass index <30 kg/m2 (N = 16, 23.0 ± 5.9 years) were randomized into a MM-HIIT or R-HIIT group and completed a 12-week HIIT intervention (ClinicalTrials.gov registration number: https://clinicaltrials.gov/ct2/show/NCT03093441) using principles of social cognitive theory (SCT). Participants completed pre- and postintervention measurements on anthropometrics, resting heart rate, blood pressure, blood measures (lipids, liver enzymes, and glucose), exercise self-efficacy, and perceived wellness. Analysis of covariance was used to examine differences in postintervention measures between groups after controlling for baseline values, waist circumference, and waist-to-height ratio. Results. R-HIIT group had significantly decreased alanine aminotransferase (mean difference = 13.16,

P
=
0.013

, effect size (ES) = 0.44, confidence interval (CI) = 3.40 to 22.92) and aspartate aminotransferase (mean difference = 10.79,

P
=
0.024

, ES = 0.38, CI = 1.67 to 19.90) levels compared with the M-HIIT group, and the whole group had improved wellness scores (14.72 ± 2.6 to 16.89 ± 2.76,

P
=
0.002

). Conclusion. R-HIIT may be an effective preventative method for improving liver health in females without obesity. When using principles of SCT, HIIT may enhance overall well-being.
GTSE1 Facilitates the Malignant Phenotype of Lung Cancer Cells via Activating AKT/mTOR Signaling
Authors: Zhang Fan , Meng Jingfei , Jiang Hong , Feng Xing , Wei Dongshan , Meng Wen
Published: May 2021

The expression of G2 and S phase-expressed-1 (GTSE1) was upregulated in human cancer. However, its expression and roles in lung cancer have not been identified yet. In our study, we reported that GTSE1 expression was statistically higher in lung tissues than in the adjacent noncancerous tissues which might be a consequence of hypomethylation of the GTSE1 promoter. The upregulated expression of GTSE1 mRNA predicted the poorer survival of the lung patients. Ectopic expression of GTSE1 in lung cancer cells significantly increased while knockdown of GTSE1 decreased cell proliferation, cell migration, and cell invasion in H460 and A549 cells. Furthermore, knockdown of GTSE1 regulated the cell cycle and promoted cell apoptosis in H460 and A549 cells. Finally, we presented that GTSE1 was able to activate AKT/mTOR signaling in H460 and A549 cells. In conclusion, these results indicated that the overexpressed GTSE1 was involved in the progress of lung cancer by promoting proliferation migration and invasion and inhibiting apoptosis of lung cancer cells via activating AKT/mTOR signaling.
Probability Error Bounds for Approximation of Functions in Reproducing Kernel Hilbert Spaces
Authors: Aydın Ata Deniz , Gheondea Aurelian
Published: May 2021

We find probability error bounds for approximations of functions

f

in a separable reproducing kernel Hilbert space

H

with reproducing kernel

K

on a base space

X

, firstly in terms of finite linear combinations of functions of type

K

x

i

and then in terms of the projection

π

x

n

on

span

K

x

i

i
=
1

n

, for random sequences of points

x
=

x

i

i

in

X

. Given a probability measure

P

, letting

P

K

be the measure defined by

d

P

K

x

=
K

x
,
x

d
P

x

,

x
∈
X

, our approach is based on the nonexpansive operator

L

2

X
;

P

K

∋
λ
↦

L

P
,
K

λ
≔

∫

X

λ

x

K

x

d
P

x

∈
H
,

where the integral exists in the Bochner sense. Using this operator, we then define a new reproducing kernel Hilbert space, denoted by

H

P

, that is the operator range of

L

P
,
K

. Our main result establishes bounds, in terms of the operator

L

P
,
K

, on the probability that the Hilbert space distance between an arbitrary function

f

in

H

and linear combinations of functions of type

K

x

i

, for

x

i

i

sampled independently from

P

, falls below a given threshold. For sequences of points

x

i

i
=
1

∞

constituting a so-called uniqueness set, the orthogonal projections

π

x

n

to

span

K

x

i

i
=
1

n

converge in the strong operator topology to the identity operator. We prove that, under the assumption that

H

P

is dense in

H

, any sequence of points sampled independently from

P

yields a uniqueness set with probability 1. This result improves on previous error bounds in weaker norms, such as uniform or

L

p

norms, which yield only convergence in probability and not almost certain convergence. Two examples that show the applicability of this result to a uniform distribution on a compact interval and to the Hardy space

H

2

D

are presented as well.
“This Is Not the Original Timeline”: A Case Report of an Extended Dissociative Episode in a Healthy Young Male Accompanied with Severe Decline in Mental State
Authors: Tong Godwin , Groom Kieran , Ward Louisa , Naeem Muhammad
Published: May 2021

Dissociation is a disconnection between a person’s thoughts, memories, feelings, actions, or sense of who he or she is. Dissociative disorders can be described and understood using the combination of five core symptoms: amnesia, depersonalisation, derealisation, identity confusion, or identity alteration. They are frequently associated with previous experience of trauma. The challenge in diagnosis and the lifetime prevalence of approximately 10% in the general population and clinical psychiatric setting ensures the relevance of this case. We write about a 21-year-old gentleman with history of autism and obsessive compulsive disorder, but no significant medical history was presented to the emergency department with increased anxiety, subsequently progressing to agitation, pacing, and becoming nonverbal. No significant findings were uncovered on laboratory blood testing (other than prolactin 737 mu/L and phosphate 0.35 mmol/L), lumbar puncture, or brain imaging. Consequently, he was admitted to a psychiatric unit for assessment. The patient continued to present with severe disorientation, limited speech, and altered state of consciousness with occasional spastic-like movements. Antipsychotic and benzodiazepine medication was initiated, with no significant change in presentation. The patient continued to be witnessed wandering and having incoherent speech. First signs of improvement came 21 days postadmission with brief conversation and lucidity. This continued to improve over the next 7 days where he was reported to be at his baseline mental state. Environmental stressors including university examinations, the COVID-19 pandemic, and recent contact with his estranged father were possible precipitants to the episode. The patient reported almost complete unawareness of the psychiatric admission. A diagnosis of dissociative disorder, unspecified, was given. This case shows the management and diagnostic challenges of patients presenting with the aforementioned symptoms. There are no formal guidelines for the management of treating dissociative episodes, and this case report suggests the possible benefits of a drug-free period of watchful waiting upon admission.
ECG Heartbeat Classification Based on an Improved ResNet-18 Model
Authors: Jing Enbiao , Zhang Haiyang , Li ZhiGang , Liu Yazhi , Ji Zhanlin , Ganchev Ivan
Published: May 2021

Based on a convolutional neural network (CNN) approach, this article proposes an improved ResNet-18 model for heartbeat classification of electrocardiogram (ECG) signals through appropriate model training and parameter adjustment. Due to the unique residual structure of the model, the utilized CNN layered structure can be deepened in order to achieve better classification performance. The results of applying the proposed model to the MIT-BIH arrhythmia database demonstrate that the model achieves higher accuracy (96.50%) compared to other state-of-the-art classification models, while specifically for the ventricular ectopic heartbeat class, its sensitivity is 93.83% and the precision is 97.44%.
15q Duplication Syndrome: Report on the First Patient from Ecuador with an Unusual Clinical Presentation
Authors: Ortiz-Prado Esteban , Iturralde Ana Lucía , Simbaña-Rivera Katherine , Gómez-Barreno Lenin , Hidalgo Iván , Rubio-Neira Mario , Espinosa Nicolás , Izquierdo-Condoy Juan , Arteaga-Espinosa María Emilia , Lister Alex , López-Cortés Andrés , Cabrera-Andrade Alejandro
Published: May 2021

Background. The 15q11.1-13.1 duplication, also known as Dup15q syndrome, is a rare congenital disease affecting 1 in 30,000 to 1 in 60,000 children worldwide. This condition is characterized by the presence of at least one extra copy of genetical material within the Prader-Willi/Angelman Critical Region (PWACR) of the referred 15q11.2-q13.1 chromosome. Case Report. Our study presents the clinical and genetical features of the first patient with a denovo 15q11.2 interstitial duplication on the maternal allele (inv Dup15q) that mimics a milder Prader-Willi syndrome probably due to an atypical disruption of the SNHG14 gene. Methylation-specific MLPA analysis has confirmed the presence of a very unlikely duplication that lies between breakpoint 1 (BP1) and the middle of BP2 and BP3 (BP3). This atypical alteration might be linked to the milder patient’s clinical phenotype. Conclusions. This is the first Dup15q patient reported in Ecuador and of the very few in South America. This aberration has never been described in a patient with Dup15q, and the unusual clinical presentation is probably due to the atypical distal breakpoint occurring within the gene SNHG14 which lies between BP2 and BP3 and does not therefore contain the whole PWACR. If the duplication disrupted the gene, then it is possible that it is the cause of, or contributing to, the patient’s clinical phenotype.
Analysis of Environmental Factors for Mobile Software Development Focused on Korean Companies
Authors: Song Kwang Yoon , Chang In Hong , Pham Hoang
Published: May 2021

Software should be a product that can be used easily and accurately by the user and should be improved quickly and accurately when problems arise. In many software development projects, software requirements are frequently modified during the design or development phase, which tests the development of specific designers’ or developers’ capabilities. Software development environmental factors (SDEFs), such as differences in mutual work recognition among users, developers, and testers or knowledge differences, can hinder communication, which may lead to faulty development owing to erroneous job definition. Because the exact size and scope of the software cannot be calculated, the risk of excessive requirements, such as schedule, cost, and manpower, may increase. This study aims to investigate 32 SDEFs to examine the influence of factors affecting the reliability of software developed by Korean companies to identify factors with high influence and compare differences with previous studies. Moreover, we found whether any new SDEFs from the top 10 rankings only affected Korean companies, and also US companies included in previous studies. A factor analysis revealed several potential factors to identify the mutually independent characteristics of the factors. Through statistical analysis methods, the difference between the group means and the impact on improving the software reliability were found in Korean companies. These findings can provide useful benefits to software developers and managers working in countries with different or similar cultures and help increase working efficiency, i.e., work versus time investment and software reliability improvement.
Factors Associated with Condom Knowledge, Attitude, and Use among Black Heterosexual Men in Ontario, Canada
Authors: Etowa Josephine , Ghose Bishwajit , Loemba Hughes , Etowa Egbe B. , Husbands Winston , Omorodion Francisca , Luginaah Isaac , Wong Josephine Pui-Hing
Published: May 2021

African, Caribbean, and Black (ACB) men living in Canada share a heightened risk of HIV infection and the associated risk factors such as suboptimal use of family planning services such as condom use. In this study, we assessed the factors associated with knowledge, attitude, and condom use among ACB men in Ontario. Methods. This was a cross-sectional study that surveyed heterosexual ACB men regardless of their residency status living in Ontario (n = 430). This is a part of a larger mixed methods study informed by critical race theory, intersectionality, and community-based participatory research (CBPR). Outcome variables were knowledge of condom use, attitude towards condom use, and actual use of condom during the last 12 months. Results. Of 430 participants, 77.70% has good knowledge of condom use as a protection against HIV transmission, 31.77% had positive attitude towards condom use, and 62.43% reported using condom regularly with casual partners during the last 12 months. Men who were currently married had more positive attitude towards condom use compared with their unmarried counterparts (odds ratio = 1.46, 95% CI = 1.20, 1.78). Canadian residents were found to have higher odds of having correct knowledge of condom (odds ratio = 1.31, 95% CI = 1.11, 1.55), and positive attitude towards condom use (odds ratio = 1.44, 95%CI = 1.09, 1.92). Men who visited sexual health clinics showed a positive association with having correct knowledge of condom (odds ratio = 1.78, 95% CI = 1.30, 2.44) and reported experiences of difficulty in accessing sexual health. This showed a negative association towards condom use (odds ratio = 0.45, 95% CI = 0.21, 0.97]. Conclusion. A considerable percentage of heterosexual ACB men did not have correct knowledge regarding the protective effect of condom use against HIV and positive attitude towards the use of condom. Several sociodemographic and healthcare-related factors were significantly associated with knowledge, attitude, and use of condom.
Transcranial Sonography of the Substantia Nigra for the Differential Diagnosis of Parkinson’s Disease and Other Movement Disorders: A Meta-Analysis
Authors: Mei Yan-Liang , Yang Jing , Wu Zheng-Rong , Yang Ying , Xu Yu-Ming
Published: May 2021

This meta-analysis aimed to evaluate the accuracy of hyperechogenicity of the substantia nigra (SN) for the differential diagnosis of Parkinson’s disease (PD) and other movement disorders. We systematically searched the PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases for relevant studies published between January 2015 and May 2020. Eligible articles comparing the echogenicity of the SN between patients with PD and those with other movement disorders were screened, and two independent reviewers extracted data according to the inclusion and exclusion criteria. Statistical analyses were conducted using STATA (version 15.0) (Stata Corporation, College Station, TX, USA), Review Manager 5.3 (Cochrane Collaboration), and Meta-DiSc1.4 to assess the pooled diagnostic value of transcranial sonography (TCS) for PD. Nine studies with a total of 1046 participants, including 669 patients with PD, were included in the final meta-analysis. Our meta-analysis demonstrated that hyperechogenicity of the SN had a pooled sensitivity and specificity of 0.85 (0.82, 0.87) and 0.71 (0.66, 0.75), respectively, for distinguishing idiopathic Parkinson’s disease from other movement disorders. Furthermore, the area under the curve of the summary receiver operating characteristic was 0.94. Transcranial sonography of the SN is a valuable tool for the differential diagnosis of PD and other movement disorders.
Kannan Contraction Operator on the Domain of
r

.

-Cesàro Matrix in

ℓ

t

.

and Related Prequasi Ideal with an Application of Nonlinear Difference Equations
Authors: Bakery Awad A. , El Dewaik M. H.
Published: May 2021

In this article, the sequence space

Ξ

r
,
t

υ

has been built by the domain of

r

l

-Cesàro matrix in Nakano sequence space

ℓ

t

l

, where

t
=

t

l

and

r
=

r

l

are sequences of positive reals with

1
≤

t

l

<
∞

, and

υ

f

=

∑

l
=
0

∞

∑

z
=
0

l

r

z

f

z

/

∑

z
=
0

l

r

z

t

l

, with

f
=

f

z

∈
Ξ

r
,
t

. Some topological and geometric behavior of

Ξ

r
,
t

υ

, the multiplication maps acting on

Ξ

r
,
t

υ

, and the eigenvalues distribution of operator ideal constructed by

Ξ

r
,
t

υ

and

s

-numbers have been examined. The existence of a fixed point of Kannan prequasi norm contraction mapping on this sequence space and on its prequasi operator ideal are investigated. Moreover, we indicate our results by some explanative examples and actions to the existence of solutions of nonlinear difference equations.
Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation
Authors: Heckler Max , Ali Lestat R. , Clancy-Thompson Eleanor , Qiang Li , Ventre Katherine S. , Lenehan Patrick , Roehle Kevin , Luoma Adrienne , Boelaars Kelly , Peters Vera , McCreary Julia , Boschert Tamara , Wang Eric S. , Suo Shengbao , Marangoni Francesco , Mempel Thorsten R. , Long Henry W. , Wucherpfennig Kai W. , Dougan Michael , Gray Nathanael S. , Yuan Guo-Cheng , Goel Shom , Tolaney Sara M. , Dougan Stephanie K.
Published: May 2021

CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8+ T cells during early stages of activation. Mice receiving tumor-specific CD8+ T cells treated with CDK4/6 inhibitors displayed increased T-cell persistence and immunologic memory. CDK4/6 inhibition upregulated MXD4, a negative regulator of MYC, in both mouse and human CD8+ T cells. Silencing of Mxd4 or Myc in mouse CD8+ T cells demonstrated the importance of this axis for memory formation. We used single-cell transcriptional profiling and T-cell receptor clonotype tracking to evaluate recently activated human CD8+ T cells in patients with breast cancer before and during treatment with either palbociclib or abemaciclib. CDK4/6 inhibitor therapy in humans increases the frequency of CD8+ memory precursors and downregulates their expression of MYC target genes, suggesting that CDK4/6 inhibitors in patients with cancer may augment long-term protective immunity.

Significance:

CDK4/6 inhibition skews newly activated CD8+ T cells toward a memory phenotype in mice and humans with breast cancer. CDK4/6 inhibitors may have broad utility outside breast cancer, particularly in the neoadjuvant setting to augment CD8+ T-cell priming to tumor antigens prior to dosing with checkpoint blockade.

This article is highlighted in the In This Issue feature, p. 2355
Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab
Authors: Filho Otto Metzger , Viale Giuseppe , Stein Shayna , Trippa Lorenzo , Yardley Denise A. , Mayer Ingrid A. , Abramson Vandana G. , Arteaga Carlos L. , Spring Laura M. , Waks Adrienne G. , Wrabel Eileen , DeMeo Michelle K. , Bardia Aditya , Dell'Orto Patrizia , Russo Leila , King Tari A. , Polyak Kornelia , Michor Franziska , Winer Eric P. , Krop Ian E.
Published: May 2021

Intratumor heterogeneity is postulated to cause therapeutic resistance. To prospectively assess the impact of HER2 (ERBB2) heterogeneity on response to HER2-targeted therapy, we treated 164 patients with centrally confirmed HER2-positive early-stage breast cancer with neoadjuvant trastuzumab emtansine plus pertuzumab. HER2 heterogeneity was assessed on pretreatment biopsies from two locations of each tumor. HER2 heterogeneity, defined as an area with ERBB2 amplification in >5% but <50% of tumor cells, or a HER2-negative area by FISH, was detected in 10% (16/157) of evaluable cases. The pathologic complete response rate was 55% in the nonheterogeneous subgroup and 0% in the heterogeneous group (P < 0.0001, adjusted for hormone receptor status). Single-cell ERBB2 FISH analysis of cellular heterogeneity identified the fraction of ERBB2 nonamplified cells as a driver of therapeutic resistance. These data suggest HER2 heterogeneity is associated with resistance to HER2-targeted therapy and should be considered in efforts to optimize treatment strategies.

Significance:

HER2-targeted therapies improve cure rates in HER2-positive breast cancer, suggesting chemotherapy can be avoided in a subset of patients. We show that HER2 heterogeneity, particularly the fraction of ERBB2 nonamplified cancer cells, is a strong predictor of resistance to HER2 therapies and could potentially be used to optimize treatment selection.

See related commentary by Okines and Turner, p. 2369.

This article is highlighted in the In This Issue feature, p. 2355
Large Breast Tumor Ulceration and Quality of Life in an 80-Year-Old Woman
Authors: Yamaguchi Kei , Matsunuma Ryoichi , Hayami Ryosuke , Tsuneizumi Michiko
Published: May 2021

Advanced breast cancer with skin ulceration, bleeding, and odor is associated with impaired quality of life (QoL). In patients with metastatic breast cancer, treatment aims to relieve symptoms, improve QoL, and slow the progression of cancer. Occasionally, it is extremely difficult to alleviate symptoms and improve QoL in patients with breast cancer and skin ulceration, especially elderly patients. Since patient age, patient preferences, and the expected survival benefit from treatment are factors that influence the selection of therapy, physicians should provide an optimal treatment for patients with metastatic disease depending on the situation. In this study, we report the case of an elderly patient with metastatic breast cancer who had substantial skin ulceration. In this patient, multidisciplinary treatment including chemotherapy, radiotherapy, and surgery resulted in significantly improved QoL.
Escolares migrantes y profesorado: reflejos de la opresión en la escuela chilena actual
Authors: Mora-Olate María Loreto
Published: May 2021

(analítico)El artículo, derivado de una investigación cualitativa, analiza críticamente la tesis referida a la condición de opresión compartida entre los docentes y alumnado migrante que está arribando sostenidamente a la escuela chilena. Ambos actores oprimidos, en el sentido freiriano, son analizados en el espacio escolar, a través de una revisión documental, retomando conceptos claves de la teoría de la reproducción de Bourdieu y Passeron y de los planteamientos de Althusser, que significan la escuela en su función ideológica y represora. La condición de opresión prevalece a las diferencias culturales, siendo los docentes también migrantes en la escuela tensionada por la diversidad cultural. Se concluye que un primer paso para la liberación radica en la toma de conciencia de dicha circunstancia, emergiendo como esperanza liberadora la construcción de una Pedagogía crítica latinoamericana.
Palabras clave: Migrante, docente, escuela, opresión.
De Borges a Lou Reed: una aproximación semiótica a la creencia
Authors: Núñez Alberca Alejandro
Published: May 2021

El presente ensayo toma a su cargo el análisis de dos textos con orígenes muy distintos. El primero, el cuento Los dos reyes y los dos laberintos del escritor argentino Jorge Luis Borges; el segundo, la letra de la canción Dime Store Mystery del cantautor neoyorquino Lou Reed. El análisis emplea instrumentos metodológicos provenientes de la semiótica francesa y, en específico, los aportes de la hipótesis tensiva, los cuales permiten una aproximación metódica a la función de la afectividad en el ámbito de la semiosis. A través de ambos discursos, la dicotomía entre lo divino y lo humano se impone como categoría semántica primigenia del universo de sentido, siendo la creencia el resorte fundamental de las variaciones de las magnitudes tensivas que afectan y transforman el cuerpo del actante.
Semiótica discursiva e Educação básica: um diálogo possível e necessário
Authors: Lima Eliane Soares de
Published: May 2021

Com base em uma problematização de questões envolvidas na formação profissional de professores, propomos discutir as contribuições que a Semiótica Discursiva tem a oferecer à eficiência qualitativa da ação docente no contexto atual. Trataremos tanto do que se refere à competencialização no domínio de conhecimentos específicos do ensino de língua materna, quanto da preparação didática para isso, procurando mostrar que, por aumentar a competência de análise dos diferentes tipos de texto, a proposta teórico-metodológica da Semiótica favorece um modo eficaz de trabalhá-los em sala de aula. A atenção ao processo de formação docente e ao que se pode trazer para essa etapa como alguma colaboração importa, sobretudo, quando constatamos que o professor é a peça-chave no processo de transposição didática, ponto de articulação entre os saberes aí em jogo: o saber acadêmico-científico de referência, o saber a ensinar e o saber ensinado.
Leituras e escrituras em tempos de pandemia. Quarentenas, Quarenteninhas e Quaquarentenas, de Torero e Minkovicius
Authors: Silva Luiza Helena Oliveira da
Published: May 2021

Este trabalho analisa produções de três séries de pequenas crônicas escritas por José Roberto Torero Fernandes Junior e ilustradas por Ivo Minkovicius, publicadas diariamente no Facebook, ao longo de 2020, cobrindo o que pode ser compreendido como três momentos de percepção da pandemia provocada pelo Covid-19 no Brasil, ao menos no que diz respeito à sua experiência nas metrópoles. Intitulam-se respectivamente como Quarentenas, Quarenteninhas e Quaquarentenas. Mobilizando reflexões produzidas pelos estudos da literatura de testemunho e da semiótica, são analisadas, a partir da leitura de uma literatura vinculada ao cotidiano, as “traduções” da experiência de viver e sentir o acontecimento. À medida que se vivencia a duração da pandemia, muito além das previsões mais pessimistas, observa-se a atenuação do sentir o efeito inicialmente impactante de sua aparição, caminhando para uma anestesia que concorre para a indiferença quanto aos seus efeitos. Escrever, contudo, é ainda insistir no sentido sentido.
O contágio na semiótica brasileira: uma questão semio-historiográfica
Authors: Moreira Patricia Veronica , Portela Jean Cristtus
Published: May 2021

Neste trabalho, buscamos entender o conceito de “sensível”, mais especificamente a questão do contágio, na semiótica, pela abordagem semio-historiográfica (SANTOS, 2020), contextualizando, primeiramente, sua emergência. Depois, nos estudos de semioticistas franceses e brasileiros, recuperados por meio dos grupos de especialidades de semiótica - institucionalizados em diferentes universidades do território internacional e brasileiro - segundo as ideias de Murray (1994, 1998) e de Moreira (2019). Esses grupos de especialidades, compreendidos nos períodos que chamamos de greimasiano e pós-greimasiano, são a recepção da teoria semiótica francesa a partir do discurso fundador encontrado nos trabalhos de A. J. Greimas e a sua continuidade com seus colaboradores, sobretudo nos trabalhos de Fontanille, Landowski e Zilberberg. Aliando os princípios semiótico-historiográficos definidos por Portela (2018), Koerner (1996, 2014), Swiggers (2009, 2015), Moreira (2019), Santos (2020) e Auroux (2008) ao conceito de “sensível” em sua rede conceitual, investigamos na recepção brasileira, em que medida o contágio aparece na retórica e/ou na imanência dos trabalhos analisados. Por fim, a partir dessas primeiras reflexões, conseguimos definir provisoriamente o lugar histórico-epistemológico que o sensível (contágio) ocupa na semiótica brasileira, para explorar não apenas as continuidades teórico-metodológicas, mas também as rupturas existentes.
Apresentação: Semiótica e vida social
Authors: Schwartzmann Matheus Nogueira , Sousa Silvia Maria de
Published: May 2021

A semiótica brasileira, que hoje pode até mesmo ser reconhecida como uma “escola” de pensamento independente, tem sido exercida “com inteligência, sensibilidade, emoção e gosto particulares” (Schwartzmann; Portela, 2017, p. 65), não se limitando a objetos clássicos, mostrando-se sempre receptiva e aberta ao diálogo interdisciplinar com outras correntes linguísticas e com outras áreas do conhecimento. Reconhecendo justamente essa tendência na semiótica brasileira, e buscando contribuir com o avanço dessas reflexões entre semiótica e vida social, o Grupo de Trabalho de Semiótica da ANPOLL elegeu esse tema para nortear o biênio 2018-2020. No âmbito do Grupo de Trabalho, foram gestados os artigos que aqui se apresentam. Pudemos reunir cinco eixos  de discussão da semiótica contemporânea, como tem sido desenvolvida no Brasil, os quais fazem avançar questões que nos são próprias, seja de um ponto de vista teórico, seja do ponto de vista dos objetos que continuam a desafiar a teoria: (1) os discursos políticos;  (2) o diálogo entre semiótica e ensino;  (3) a historiografia semiótica; (4) os discursos nas redes digitais e sociais; e (5) as práticas de inscrição urbana. Esses cinco eixos temáticos podem ser tomados como diferentes faces da vida social, que podem ser descritas e explicadas por meio da semiótica.
O duplo condicionamento tensivo e retórico das estruturas elementares da significação
Authors: Zilberberg Claude
Published: May 2021

Tendo por referência o modelo do "percurso gerativo do sentido" (A. J. Greimas), este artigo discute, em primeiro lugar, a possibilidade de reinterpretar suas chamadas "estruturas elementares" não apenas em termos de uma inspiração "lógica", na continuidade da tradição aristotélica, nem tampouco de uma inspiração "fonológica", apoiada nos trabalhos do Círculo linguístico de Praga, mas, radicalizando as intuições dos linguistas dinamarqueses, em uma direção topologizante, que (i) concede aos termos confrontados a deformabilidade que lhes falta nas interpretações anteriores, e (ii) dando a primazia epistemológica ao complexo, leva a repensar os valores como posições em um fluxo, havendo "menores" ou "maiores" intervalos a separá-los. Tais cifras infracategoriais de "menos" e "mais" são lidas, enfim, como um convite à retorização da semiótica, pois a retórica tropológica, que sempre trabalhou sobre a dimensão do discurso e sempre se interessou pelas intensificações de seus efeitos, pode trazer ricos esclarecimentos a esse ponto teórico.
Comparative Analysis Following Implementation of Two Types of Y‐Composite Multiarterial Revascularization Strategies at a Single Academic Institution
Authors: Gharibeh Lara , Hosoyama Katsuhiro , Glineur David , Shaw Richard E. , Lapierre Harry , Ruel Marc , Grau Juan B.
Published: May 2021

Background

We compared early outcomes, at a single academic institution, of implementing full coronary revascularization in coronary artery bypass grafting using multiarterial Y‐composite grafts with multiple sequential anastomoses.

Methods and Results

Clinical records of 425 consecutive patients who underwent coronary artery bypass grafting using Y‐grafting with left internal mammary artery and radial artery (Y‐RA group) or right internal mammary artery (Y‐RIMA group) from 2015 to 2019, were reviewed. These were compared with the institutional experience of isolated coronary artery bypass grafting cases (in situ on pump/off pump) for the same period of time. When comparing the 4 groups, the Y‐RIMA/RA groups revealed a higher number of distal anastomosis than the in situ on‐ or off‐pump groups. When the number of distal arterial anastomosis was analyzed, there was a superiority of using the Y‐configuration compared with the in situ approach. Moreover, there were no significant differences among groups for mortality and/or major adverse cardiac and cerebrovascular events in hospital or at 30‐day follow‐up. A subanalysis comparing the Y‐RIMA group with the Y‐RA group showed that complementary grafts to the Y‐construct were required to accomplish full revascularization more frequently in the Y‐RIMA group. Full‐arterial revascularization was achieved in 92.2% of the Y‐RA group and 72.0% of the Y‐RIMA group (
P
<0.001). In 82.8% of the Y‐RA group and 30.8% of the Y‐RIMA group, revascularization was completed as an anaortic procedure (
P
<0.001).

Conclusions

The 2 types of arterial Y‐composite grafting were able to be introduced in the routine practice of our institution showing comparable results to the established institutional practice. This procedure allowed for more arterial distal anastomosis to be performed safely without compromising outcomes.
Decrypting the Signs of Regulatory Competition in Regulating Cryptoassets
Authors: Chiu Iris H-Y
Published: May 2021

The icos market has challenged financial regulators in terms of determining fit with existing regimes and consideration for regulatory reform. Regulatory divergences have emerged in a number of jurisdictions and we discuss three dominant approaches in relation to hegemonic, self-regulatory and enabling regimes. These reflect different assumptions and regulators’ understandings of the cryptoasset industry, and we argue that the ‘terms for competition’ in relation to supply and demand side needs are still being discovered and are incomplete. This provides a unique opportunity for regulators to jettison familiar assumptions in relation to corporatized securities issuers or institutional investors in order to discover what governance needs are truly at stake. This may pose challenges for coherence with existing regulation but coherence should not itself be an obstacle for learning and potentially, reform. We also argue that signs of international regulatory coordination in relation to the Libra project are not necessarily reflective of a wider trend for the cryptoasset industry. This is because regulators can apply existing and familiar financial regulation paradigms more easily to the Libra Association, in particular its leading founding member Facebook. The cryptoasset market is still likely to give rise to diversity and should facilitate the discovery of new bases for regulatory thinking and policy, uncoordinated or otherwise.
Ensemble Oscillation Correction (EnOC): Leveraging oscillatory modes to improve forecasts of chaotic systems
Authors: Bach Eviatar , Mote Safa , Krishnamurthy V. , Sharma A. Surjalal , Ghil Michael , Kalnay Eugenia
Published: May 2021

Oscillatory modes of the climate system are among its most predictable features, especially at intraseasonal time scales. These oscillations can be predicted well with data-driven methods, often with better skill than dynamical models. However, since the oscillations only represent a portion of the total variance, a method for beneficially combining oscillation forecasts with dynamical forecasts of the full system was not previously known. We introduce Ensemble Oscillation Correction (EnOC), a general method to correct oscillatory modes in ensemble forecasts from dynamical models. We compute the ensemble mean—or the ensemble probability distribution—with only the best ensemble members, as determined by their discrepancy from a data-driven forecast of the oscillatory modes. We also present an alternate method which uses ensemble data assimilation to combine the oscillation forecasts with an ensemble of dynamical forecasts of the system (EnOCDA). The oscillatory modes are extracted with a time-series analysis method called multi-channel singular spectrum analysis (M-SSA), and forecast using an analog method. We test these two methods using chaotic toy models with significant oscillatory components, and show that they robustly reduce error compared to the uncorrected ensemble. We discuss the applications of this method to improve prediction of monsoons as well as other parts of the climate system.
Skillful Subseasonal Prediction of United States Extreme Warm Days and Standardized Precipitation Index in Boreal Summer
Authors: Miller Douglas E. , Wang Zhuo , Li Bo , Harnos Daniel S. , Ford Trent
Published: May 2021

Skillful subseasonal prediction of extreme heat and precipitation greatly benefits multiple sectors, including water management, public health, and agriculture, in mitigating the impact of extreme events. A statistical model is developed to predict the weekly frequency of extreme warm days and 14-day standardized precipitation index (SPI) during boreal summer in the United States (US). We use a leading principal component of US soil moisture and an index based on the North Pacific sea surface temperature (SST) as predictors. The model outperforms the NCEP’s Climate Forecast System version 2 (CFSv2) at weeks 3-4 in the eastern US. It is found that the North Pacific SST anomalies persist several weeks and are associated with a persistent wave train pattern (WTZ500), which leads to increased occurrences of blocking and extreme temperature over the eastern US. Extreme dry soil moisture conditions persist into week 4 and are associated with an increase in sensible heat flux and decrease in latent heat flux, which may help maintain the overlying anticyclone. The clear sky conditions associated with blocking anticyclones further decrease soil moisture conditions and increase the frequency of extreme warm days. This skillful statistical model has the potential to aid in irrigation scheduling, crop planning, reservoir operation, and provide mitigation of impacts from extreme heat events.