bluuebunny/crossref_metadata_2025 huggingface dataset:
The Monocyte-to-Lymphocyte Ratio at Hospital Admission Is a Novel Predictor for Acute Traumatic Intraparenchymal Hemorrhage Expansion after Cerebral Contusion
Authors: Sheng Jiangtao , Li Tian , Zhuang Dongzhou , Cai Shirong , Yang Jinhua , Ding Faxiu , Chen Xiaoxuan , Tian Fei , Huang Mindong , Li Lianjie , Li Kangsheng , Chen Weiqiang
Published: December 2020

Purpose. To explore the potential of monocyte-to-lymphocyte ratio (MLR) at hospital admission for predicting acute traumatic intraparenchymal hematoma (tICH) expansion in patients with cerebral contusion. Patients and Methods. This multicenter, observational study included patients with available at-hospital admission (baseline) and follow-up computed tomography for volumetric analysis (retrospective development cohort: 1146 patients; prospective validation cohort: 207 patients). Semiautomated software assessed tICH expansion (defined as ≥33% or 5 mL absolute growth). MLR was acquired from routine blood tests upon admission. We constructed two predictive models: basic combined model of clinical and imaging variables and MLR combined model of both MLR and other variables in the basic model. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were used to estimate the performance of MLR for predicting acute tICH expansion. Results. MLR was significantly larger in patients with acute tICH expansion compared to those without acute tICH expansion (mean [SD], 1.08 [1.05] vs. 0.59 [0.37],

P
<
0.001

). A nonlinear positive relationship between MLR and the incidence of acute tICH expansion was observed. Multivariate logistic regression indicated MLR as an independent risk factor for acute tICH expansion (odds ratio (OR), 5.88; 95% confidence interval (CI), 4.02-8.61). The power of the multivariate model for predicting acute tICH expansion was substantially improved with the inclusion of MLR (AUC 0.86 vs. AUC 0.74,

P
<
0.001

), as was also observed in an external validation cohort (AUC 0.83 vs. AUC 0.71,

P
<
0.001

). The net benefit of MLR model was higher between threshold probabilities of 20-100% in DCA. For clinical application, a nomogram derived from the multivariate model with MLR was introduced. In addition, MLR was positively associated with 6-month unfavorable outcome. Conclusion. MLR is a novel predictor for traumatic parenchymatous hematoma expansion. A nomogram derived from the MLR model may provide an easy-to-use tool for predicting acute tICH expansion and promoting the individualized treatment of patients with hemorrhagic cerebral contusion. MLR is associated with long-term outcome after cerebral contusion.
Current Physical Therapy Practice in the Intensive Care Unit in Saudi Arabia: A Multicentre Cross-Sectional Survey
Authors: Alqahtani Mazen , Kashoo Faizan , Alzhrani Msaad , Ahmad Fuzail , Seyam Mohammed K. , Ahmad Mehrunnisha , Alhusaini Adel A. , Melam Ganeswara Rao , Buragadda Syamala
Published: December 2020

Background. Early mobilisation of patients in the intensive care unit (ICU) is associated with positive health benefits. Research literature lacks insight into the current status of ICU physical therapy (PT) practice in the Kingdom of Saudi Arabia. Aim. To determine the current standard of ICU PT practice, attitude, and barriers. Methods. A questionnaire was e-mailed to physiotherapists (PTs) working in the hospital. The questions pertained to experience, qualification, barriers, and most frequently encountered case scenarios in the ICU. Results. The response rate was 28.1% (124/442). Frequent cases referred to the PTs were traumatic paraplegia (n = 111, 89%) and stroke (n = 102, 82.3%) as compared to congestive heart failure (n = 20, 16.1%) and pulmonary infections (n = 7, 5.6%). The preferred treatment of choice among PTs was chest physiotherapy (n = 102, 82.2%) and positioning (n = 73, 58.8%), whereas functional electrical stimulation (n = 12, 9.6%) was least preferred irrespective of the condition. Perceived barriers in the ICU PT management were of low confidence in managing cases (n = 89, 71.7%) followed by inadequate training (n = 53, 42.7%), and the least quoted barrier was a communication gap between the critical care team members (n = 8, 6.4%). Conclusion. PTs reported significant variation in the choice of treatment for different clinical cases inside ICU. The main barriers in the ICU setting were low confidence and inadequate training.
Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: A Bidirectional Relationship
Authors: Muzica Cristina M. , Sfarti Catalin , Trifan Anca , Zenovia Sebastian , Cuciureanu Tudor , Nastasa Robert , Huiban Laura , Cojocariu Camelia , Singeap Ana-Maria , Girleanu Irina , Chiriac Stefan , Stanciu Carol
Published: December 2020

Worldwide, the leading cause of chronic liver disease is represented by nonalcoholic fatty liver disease (NAFLD) which has now become a global epidemic of the 21st century, affecting 1 in 4 adults, and which appears to be associated with the steadily increasing rates of metabolic syndrome and its components (obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia). NAFLD has been reported to be associated with extrahepatic manifestations such as cardiovascular disease, T2DM, chronic kidney disease, extrahepatic malignancies (e.g., colorectal cancer), endocrine diseases (e.g., hypothyroidism, polycystic ovarian syndrome, psoriasis, and osteoporosis), obstructive sleep apnea, and iron overload. The prevalence of NAFLD is very high, affecting 25–30% of the world population and encloses two steps: (1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and (2) nonalcoholic steatohepatitis (NASH) defined by the presence of steatosis and inflammation with hepatocyte ballooning, with or without fibrosis which can progress to liver fibrosis, hepatocellular carcinoma, and liver transplantation. Current data define a more complex relationship between NAFLD and T2DM than was previously believed, underlining a bidirectional and mutual association between the two entities. This review aims to summarize the current literature regarding the incidence of T2DM among patients with NAFLD and also the prevalence of NAFLD in T2DM patients, highlighting the recent key studies. Clinicians should screen, diagnose, and treat T2DM in patients with NAFLD in order to avoid short- and long-term complications.
Is there a Role of Intravenous Immunoglobulin in Immunologic Recurrent Pregnancy Loss?
Authors: Yang Xiuhua , Meng Tao
Published: December 2020

Recurrent pregnancy loss (RPL) commonly refers to three or more miscarriages that occur before 20 weeks of pregnancy. The immunological cause of RPL could be either an auto- or alloimmune-related event or both. Because of the discovery of immunological abnormalities in RPL patients in clinical practice, several immunomodulatory therapies were introduced to maintain the immune balance at the maternal-fetal interface. Intravenous immunoglobulin (IVIg) is one of the immunomodulators. In recent years, several studies have analyzed the therapeutic effect of IVIg on RPL patients with antiphospholipid syndrome (APS) or unexplained RPL. However, their results are controversial. IVIg can be used in RPL patients with APS who have previously failed in other treatments. It is recommended that IVIg infusion could be considered used before conception in RPL patients who have cellular immune abnormalities such as increased natural killer (NK) cell counts, NK cell cytotoxicity, or increased T helper (Th)1/Th2 ratio, depending on the cut-off values of each hospital. The aim of this review was to summarize the mechanisms, efficacy, pharmacokinetics, and side effects associated with passive immunization using IVIg in immunologic RPL, according to the literature published in recent years. We hope that more obstetricians will be able to understand the timing and indication of IVIg properly in immunologic RPL patients and effectively enhance pregnancy outcomes for mothers and neonates.
Changes in Functional Connectivity of Specific Cerebral Regions in Patients with Toothache: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Wu Shi-Nan , Zhang Meng-Yao , Shu Hui-Ye , Liang Rong-Bin , Ge Qian-Ming , Pan Yi-Cong , Zhang Li-Juan , Li Qiu-Yu , Shao Yi
Published: December 2020

Objective. In order to further study the changes of cerebral functional connectivity in patients with toothache (TA), this study used the resting-state functional magnetic resonance imaging (rs-fMRI) technique and degree centrality (DC) analysis method. Methods. Eighteen TA patients (8 males, 10 females) and 18 healthy individuals of similar age, sex, and educational levels were recruited as healthy controls (HCs) to take part in the study, and all underwent rs-fMRI examination. And DC technology was used to compare the state of their cerebral spontaneous functional activity. In order to compare the average DC values of the TA group and HC group, we used independent two-sample

t

-test and receiver operating characteristic (ROC) curve to compare the difference of DC values between the two groups, so as to distinguish the accuracy of TA diagnosis. Finally, we also carry out Pearson’s linear regression analysis. Results. The TA group showed higher DC values in the right lingual gyrus (RLG), right precentral gyrus, and left middle temporal gyrus (LMTG) than HCs. Moreover, ROC curve analysis indicated that the area under the curve (AUC) of each cerebral region studied had high accuracy. In addition, linear analysis indicated that the DC values of the RLG were positively correlated with the Hospital Anxiety and Depression Scale (HADS) (

r
=
0.844

,

p
<
0.001

), and the DC values of the LMTG were positively correlated with the visual analogue scale (VAS) (

r
=
0.723

,

p
<
0.001

). Conclusion. TA generates abnormal changes in the intrinsic activity patterns of pain-related and vision-related areas of the cerebral cortex, which will be beneficial to reveal the underlying neuropathic mechanisms.
Enabling Sector Scheduling for 5G-CPE Dense Networks
Authors: Yang Jie , Feng Li , Jin Tong , Liang Hong , Xu Fangxin , Tian Liwei
Published: December 2020

5G customer premise equipment (5G-CPE) is an IoT gateway technology that integrates 5G and Wi-Fi and therefore can provide Wi-Fi connection for IoT devices and meanwhile benefit from the advantages of 5G. With the increasing number of IoT devices, transmission collisions and hidden/exposed terminal problems on the Wi-Fi connection side become more and more serious. Conventional mechanisms cannot solve these problems well. In this paper, we propose a Wi-Fi sector (Wi-FiS) design, which is compatible with Wi-Fi, to solve them fundamentally. Wi-FiS divides the whole coverage area of Wi-Fi into multiple sectors and utilizes beamforming technology and sector-based scheduling to improve system performance of Wi-Fi dense networks. For a single-cell network, Wi-FiS differentiates uplink and downlink operations and totally excludes collision in downlink. For a multicell network, Wi-FiS can avoid hidden and exposed terminal problems, while enabling parallel transmissions among multiple cells. We then develop a theoretical model to analyze Wi-FiS’s throughput. Extensive simulations verify that our theoretical model is very accurate and Wi-FiS can improve system throughput of Wi-Fi dense networks significantly.
Footprint of the COVID-19 Pandemic in India: A Study of Immune Landscape and Other Factors Shielding Mortality
Authors: Al-Dayan Noura , Venugopal Divya , Dhanasekaran Sugapriya
Published: December 2020

The impact of the SARS-CoV-2 pandemic has significantly affected global health and created a world crisis. The exponentially increasing numbers of infection and mortality have made preventive measures challenging. India being a highly populated nation has so far effectively counteracted the pandemic outbreak with a significantly lower rate of mortality despite the high infection rates. The genetic architecture of the immune response genes in the Indian population, BCG vaccination, the predominantly young age group of people, and their traditional food habits might contribute to the lower rate of mortality. Human leukocyte antigens (HLA) play a vital role in triggering T cells, and natural killer (NK) cells can immediately react to eliminate infected cells. Activation of virus-specific CD4+ T cells and CD8+ cytotoxic T cells selectively targets the infected cells and strengthens the immunoregulatory system. The checkpoint for NK cell function is the engagement of killer Ig-like receptors (KIR) molecules with their respective HLA ligands overexpressed or expressed on the compromised virus-infected cells which have shown polymorphism among different ethnic groups. Here, we explore if certain KIR-HLA motifs grant Indians a survival advantage in terms of the low rate of mortality. Additionally, enhanced immunity through BCG vaccination may favor fruitful eradication of SARS-CoV-2 and provide the way out as in therapeutic intervention and vaccination strategies.
Sudden Odynophagia and Globus—A Unique Presentation of a Nonsecreting Parathyroid Adenoma: A Case Report and Literature Review
Authors: Srikantha Luxman , Amjad Esmael H. , Beydoun Rafic
Published: December 2020

Parathyroid adenomas are most commonly diagnosed when symptoms consistent with primary hyperparathyroidism arise. However, certain parathyroid glands may enlarge without such symptoms. Described here is a case in which a patient presented with acute signs of unilateral cervical point tenderness, dysphagia, and odynophagia. Calcium and parathyroid hormone levels tested within normal range. Imaging revealed an enlarged right-sided mass, with compression of the trachea-esophageal groove and potentially the right recurrent laryngeal nerve. Surgical excision was performed, and final pathology revealed an infarcted parathyroid adenoma. Clinical symptoms promptly resolved thereafter. Current NIH criteria for parathyroidectomy include various symptoms of hyperparathyroidism but do not include the above findings. Nonsecreting parathyroid adenomas rarely cause laryngeal symptoms, as this has only been documented once before.
Overexpression of PRDX4 Modulates Tumor Microenvironment and Promotes Urethane-Induced Lung Tumorigenesis
Authors: Zheng Jianbo , Guo Xin , Nakamura Yuka , Zhou Xiaolei , Yamaguchi Reimon , Zhang Jing , Ishigaki Yasuhito , Uramoto Hidetaka , Yamada Sohsuke
Published: December 2020

Peroxiredoxin 4 (PRDX4), initially reported as an antioxidant, is overexpressed in lung cancer and participates in its progression. However, its role in the urethane-induced lung tumor model is undetermined. The aim of this study was to investigate the effect of PRDX4 overexpression on carcinogen-induced lung tumor development. Human PRDX4 overexpression transgenic (Tg) mice (hPRDX4+/+) and non-Tg mice were intraperitoneally injected with urethane to induce lung tumor. After 6 months, tumor formation was compared between groups and possible mechanisms for the difference in tumor development were investigated. The serum and lung PRDX4 expressions were enhanced after urethane stimulation in Tg mice. Both the average number of tumors (≥0.5 mm) and tumor diameter per mouse in the Tg group were significantly larger than in non-Tg controls, while body weight was lower in the Tg group. Compared with non-Tg controls, tumor cell proliferation was enhanced, while tumor cell apoptosis was suppressed in Tg mice. Systemic oxidative stress and oxidative stress in lung tumors were inhibited by PRDX4 overexpression. The balance of prooxidant enzymes and antioxidant enzymes was also shifted to a decreased level in Tg tumor. In lung tumor tissue, the density of microvessel penetrated into tumor was higher in the Tg group; macrophage infiltration was enhanced in Tg tumors, while there was no difference in T lymphocyte infiltration; the expressions of cytokines, including interleukin-1 beta (IL-1β) and matrix metallopeptidase 9 (MMP9), were elevated in Tg tumors, which resulted from enhanced phosphorylation of nuclear factor-κB p65 (NF-κB p65) and c-Jun, respectively. In conclusion, PRDX4 overexpression modulated tumor microenvironment and promoted tumor development in the mouse urethane-induced lung cancer model.
Development of an Immunoassay for the Detection of Amyloid Beta 1-42 and Its Application in Urine Samples
Authors: Wongta Anurak , Hongsibsong Surat , Chantara Somporn , Pattarawarapan Mookda , Sapbamrer Ratana , Sringarm Korawan , Xu Zhen-Lin , Wang Hong
Published: December 2020

Amyloid beta peptides (Aβ1-42) have been found to be associated with the cause of Alzheimer’s disease (AD) and dementia. Currently, methods for detecting Aβ1-42 are complicated and expensive. The present study is aimed at developing an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) to detect Aβ1-42 by using a polyclonal antibody from alpaca, an application used in urine samples. The serum was collected from the alpaca after immunizing it with Aβ1-42 at 500 μg/injection 5 times. The ic-ELISA was developed and showed a half-maximal inhibitory concentration (

I

C

50

) of 103.20 ng/ml. The limit of detection (LOD) was 0.39 ng/100 μl. The cross-reactivity was tested with Aβ1-40 and 8 synthesized peptides that had sequence similarities to parts of Aβ1-42. The cross-reactivity of Aβ1-40 and peptide 1 (DAEFRHDSGYE) was 55% and 69.4%, respectively. The ic-ELISA was applied to analyze Aβ1-42 in the urine and precipitated protein urine samples. This method can be used for detecting a normal level of total soluble Aβ (approximately 1 ng in 5 mg of precipitated urine protein) and can be used for detecting the early stages of AD. It is considered to be an easy and inexpensive method for monitoring and diagnosing AD.
Efficacy of Venetoclax and Dexamethasone in Refractory IgM Primary Plasma Cell Leukemia with t(11;14) and TP53 Mutation: A Case Report and Literature Review
Authors: Valliani Salimah , Ali Mir , Mahmoo Omar , Hinduja Sanjay , Chen Calvin K. , Damon Lloyd , Abdulhaq Haifaa
Published: December 2020

Primary plasma cell leukemia (pPCL) is an uncommon disease. IgM multiple myeloma (MM) is an infrequent subtype that accounts for less than 1 percent of MM cases. IgM pPCL is quite rare with only a few cases published to date. We describe a case of a patient with IgM pPCL who initially presented with hyperviscosity syndrome requiring urgent plasma exchange. His bone marrow biopsy demonstrated t(11;14). He progressed on proteasome inhibitors, immunomodulating agents, and other chemotherapy medications but later achieved very good partial response (VGPR) to venetoclax and dexamethasone. Given the poor prognosis of pPCL, further studies using venetoclax alone or in combination with other novel agents as first-line treatment options are warranted particularly in patients with t(11;14).
An Intelligent IoT Based Healthcare System Using Fuzzy Neural Networks
Authors: Hameed Kashif , Bajwa Imran Sarwar , Ramzan Shabana , Anwar Waheed , Khan Akmal
Published: December 2020

Healthcare facilities in modern age are key challenge especially in developing countries where remote areas face lack of high-quality hospitals and medical experts. As artificial intelligence has revolutionized various fields of life, health has also benefited from it. The existing architecture of store-and-forward method of conventional telemedicine is facing some problems, some of which are the need for a local health center with dedicated staff, need for medical equipment to prepare patient reports, time constraint of 24–48 hours in receiving diagnosis and medication details from a medical expert in a main hospital, cost of local health centers, and need for Wi-Fi connection. In this paper, we introduce a novel and intelligent healthcare system that is based on modern technologies like Internet of things (IoT) and machine learning. This system is intelligent enough to sense and process a patient’s data through a medical decision support system. This system is low-cost solution for the people of remote areas; they can use it to find out whether they are suffering from a serious health issue and cure it accordingly by contacting near hospitals. The results of the experiments also show that the proposed system is efficient and intelligent enough to provide health facilities. The results presented in this paper are the proof of the concept.
Ligand-Activated Peroxisome Proliferator-Activated Receptor β/δ Facilitates Cell Proliferation in Human Cholesteatoma Keratinocytes
Authors: Zhang Chen , Liu Yang-Wenyi , Chi Zhangcai , Chen Bing
Published: December 2020

Cholesteatoma is characterized by both the overgrowth of hyperkeratinized squamous epithelium and bone erosion. However, the exact mechanism underlying the hyperproliferative ability of cholesteatoma remains unknown. In this study, we investigated PPAR β/δ expression in human surgical specimens of cholesteatoma and analyzed its functional role as a regulator of epithelial keratinocyte hyperproliferation. We found that the expression of PPAR β/δ was significantly upregulated in cholesteatoma and ligand-activated PPAR β/δ markedly promoted the proliferation of cholesteatoma keratinocytes. Furthermore, we showed that PPAR β/δ activation increased PDK1 expression and decreased PTEN generation, which led to increased phosphorylation of AKT and GSK3β and increased the expression level of Cyclin D1. Overall, our data suggested that the proliferating effect of PPAR β/δ on the cholesteatoma keratinocytes was mediated by the positive regulation of the PDK1/PTEN/AKT/GSK3β/Cyclin D1 pathway. These findings warranted further investigation of PPAR β/δ as a therapeutic target for recurrent or residual cholesteatoma.
Regularity of Semigroups of Transformations Whose Characters Form the Semigroup of a
Δ
-Structure
Authors: Rakbud Jittisak , Chaiya Malinee
Published: December 2020

In this paper, we make use of the notion of the character of a transformation on a fixed set

X

, provided by Purisang and Rakbud in 2016, and the notion of a

Δ

-structure on

X

, provided by Magill Jr. and Subbiah in 1974, to define a sub-semigroup of the full-transformation semigroup

T

X

. We also define a sub-semigroup of that semigroup. The regularity of those two semigroups is also studied.
Plasmablastic Lymphoma Associated with Adjacent Mature Plasma Cell Population Exhibiting Opposite Light Chain Restriction
Authors: Furlan Karina , Miller Ira , Mahon Brett , Ocampo Gonzalez Fernando A. , Ward Nicholas
Published: December 2020

Plasmablastic lymphoma (PBL) is an aggressive high-grade B cell lymphoma, considered a variant of diffuse large B cell lymphoma with approximately 75% mortality within 6-7 months. We describe an unusual case of PBL arising as a maxillary mass in an HIV-negative, nontransplanted 78-year-old female. Histologic examination revealed a diffuse infiltrate of anaplastic appearing cells exhibiting plasmablastic morphology with an adjacent contiguous infiltrate of mature appearing plasma cells. The PBL and mature plasma cell components both demonstrated an immunophenotype of CD20(-), CD38(+), and CD138(+). The two populations differed by the PBL featuring a high proliferation rate by Ki-67 (~95%) with coexpression of both c-MYC and EBV, while the mature plasma cell component featured a low proliferation rate by Ki-67 (~5%) without coexpression of c-MYC or EBV. Kappa/lambda staining demonstrated lambda light chain restriction involving the PBL, while the mature plasma cell infiltrate revealed kappa light chain restriction. Our findings describe the rare association of PBL with a synchronous distinct population of mature plasma cells exhibiting opposite light chain restriction.
Application of KLE-PEM for Random Dynamic Analysis of Nonlinear Train-Track-Bridge System
Authors: Jiang Lizhong , Liu Xiang , Zhou Tuo , Xiang Ping , Chen Yuanjun , Feng Yulin , Lai Zhipeng , Cao Shanshan
Published: December 2020

A nonlinear train-track-bridge system (TTBS) considering the random track irregularity and mass of train is discussed. Based on the Karhunen–Loéve theory, the track irregularity is expressed and input into the TTBS, and the result of random response is calculated using the point estimation method. Two cases are used to compare and validate the applicability of the proposed method, which show that the proposed method has a high precision and efficiency. Then, taking a 7-span bridge and a high-speed train as an example, the calculation results of random response of the nonlinear and linear wheel-rail model are compared, and the results show that for the bridge and rail response, the nonlinear and linear models are almost the same. Finally, comparing the calculated probability distribution results with the test results, it shows that the method can be applied to the prediction of actual response range.
Relativistic Rotating Electromagnetic Fields
Authors: Vargas-Rodríguez H. , Gallegos A. , Muñiz-Torres M. A. , Rosu H. C. , Domínguez P. J.
Published: December 2020

In this work, we consider axially symmetric stationary electromagnetic fields in the framework of special relativity. These fields have an angular momentum density in the reference frame at rest with respect to the axis of symmetry; their Poynting vector form closed integral lines around the symmetry axis. In order to describe the state of motion of the electromagnetic field, two sets of observers are introduced: the inertial set, whose members are at rest with the symmetry axis; and the noninertial set, whose members are rotating around the symmetry axis. The rotating observers measure no Poynting vector, and they are considered as comoving with the electromagnetic field. Using explicit calculations in the covariant

3
+
1

splitting formalism, the velocity field of the rotating observers is determined and interpreted as that of the electromagnetic field. The considerations of the rotating observers split in two cases, for pure fields and impure fields, respectively. Moreover, in each case, each family of rotating observers splits in two subcases, due to regions where the electromagnetic field rotates with the speed of light. These regions are generalizations of the light cylinders found around magnetized neutron stars. In both cases, we give the explicit expressions for the corresponding velocity fields. Several examples of relevance in astrophysics and cosmology are presented, such as the rotating point magnetic dipoles and a superposition of a Coulomb electric field with the field of a point magnetic dipole.
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.
Aprendizaje de la seguridad asistencial en medicina intensiva
Authors: Ruiz Balart Carolina , Zúñiga Parada Denisse
Published: December 2020

Introducción: la seguridad asistencial (SA) es una competencia especialmente relevante en las Unidades de Cuidados Intensivos (UCI), ya que la gravedad de los pacientes y los tratamientos que reciben, generan situaciones de riesgo para eventos adversos (EA). Se presenta una revisión narrativa de los conceptos más importantes de SA, con énfasis en su enseñanza-aprendizaje en medicina intensiva (MI). Además, se describen los resultados de una experiencia piloto sobre formación en SA, para residentes de MI de la Pontificia Universidad Católica de Chile (UC). Métodos: para la revisión narrativa se utilizó una estrategia de búsqueda amplia en Pubmed, considerando artículos clínicos y de educación. También se revisó la literatura nacional, incluyendo libros de resúmenes de congresos. La experiencia piloto consistió en un taller de cinco sesiones, basado en aprendizaje en pequeño grupo. Resultados: iniciativas internacionales han tratado de estandarizar el aprendizaje de la SA. Para una atención de salud segura deben considerarse competencias como comunicación, liderazgo y trabajo en equipo; pues, 20-30% de los EAs están relacionados con estas. Al término del taller de formación en SA, se encontró que la adquisición de conocimientos fue adecuada; sin embargo, no hubo mejoría en la percepción de la importancia de esta competencia. Conclusión: la SA es fundamental para cualquier actividad clínica, siendo indispensable la capacitación de los intensivistas en esta competencia. La próxima versión del dispositivo de formación en SA para residentes de la subespecialidad de MI de la UC se optimizará, agregando un módulo de aprendizaje en el lugar de trabajo en la UCI.
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

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

One 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

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 >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.
Aplicações da fabricação digital em arquitetura, design e construção: processos de apropriação tecnológica e adequação sociotécnica em experimentos na América do Sul
Authors: Scheeren Rodrigo , Sperling David Moreno
Published: December 2020

O artigo apresenta uma taxonomia de projetos relacionados à aplicação das tecnologias de fabricação digital na arquitetura, design e construção, desenvolvidos no contexto da América do Sul. Como parte de uma pesquisa em andamento, o material remete aos temas da apropriação tecnológica, adequação sociotécnica e inovação social. O objetivo é elencar alguns dos experimentos projetuais identificados durante a pesquisa, para apresentar uma perspectiva local das estratégias de produção. Os métodos utilizados englobam a revisão da literatura e revisão sistemática, mapeamento, questionário e estudos de caso. O contexto recente de instalação dos laboratórios de fabricação digital, iniciado em 2007, foi se ampliando nas instituições por meio do ensino e pesquisa, além da consolidação do modelo Fab Lab. Os resultados práticos são muito heterogêneos, ainda limitados em escala e fortemente baseados na articulação híbrida entre o analógico e o digital, devido aos materiais disponíveis, tipo de maquinário acessível e da especialização técnica necessária para produzi-los, mas já direcionados às dinâmicas de solução de problemas no aspecto social.
Organização compositiva e lumínica de uma fachada fractal
Authors: Mariano Pedro Oscar Pizzetti , Pereira Alice Theresinha Cybis
Published: December 2020

Este trabalho descreve o desenvolvimento e avaliação compositiva de um processo de projeto paramétrico que permite organizar elementos de fachada, com características da geometria fractal, conforme as necessidades do partido arquitetônico ou por meio do consequente comportamento da luz natural diurna. Para isso elementos de proteção baseados em fractais lineares foram criados, e por intermédio desses elementos é possível formar e controlar arranjos compositivos conforme a radiação solar incidente sob fachada. Os resultados desses arranjos são avaliados de modo quantitativo através de simulações dinâmicas da luz natural, e de modo qualitativo por intermédio de modelos renderizados e de uma maquete física, construída com o auxílio de uma cortadora a laser. Para se desenvolver o processo paramétrico uma sequência de ações foi elaborada dentro de um software de programação visual, sendo os principais módulos: a criação de um ambiente urbano; a formação de um elemento de fachada; e componentes de avaliação para o processo. Como conclusão foi possível identificar que os resultados e meios de avaliação disponibilizados pelo processo paramétrico possibilitam ampliar a tomada de decisão do projetista, podendo hierarquizar suas escolhas. Essas decisões ainda podem ser potencializadas com o auxílio de maquetes físicas, pois possibilitam identificar características pontuais que podem alterar as definições compositivas já identificadas em análises quantitativas e visualizações bidimensionais.
Escola e laço fraterno
Authors: Souto Luís Adriano Salles , Moschen Simone Zanon
Published: December 2020

Este artigo recupera algumas das características civilizatórias que marcaram o advento das sociedades da modernidade democrática e destaca aquele que seria o traço distintivo da escola republicana. A identificação desse traço permite confrontar as reivindicações de movimentos que atualmente afirmam a prioridade da educação familiar sobre a educação escolar e interrogar alguns dos pressupostos dos ideólogos de uma “educação para a sociabilidade democrática”, que muitas vezes desconsideram que uma educação escolar comprometida com promoção da experiência democrática passa, antes de tudo, pela afirmação da escola como instituição implicada com a produção de uma filiação simbólica comum. É essa afirmação que nos permitirá vislumbrar, por fim, o limite da família no processo da transmissão simbólica que balizará o acontecimento de um sujeito interpelado na modernidade como indivíduo e como cidadão.
Transferência, desejo e ato em um caso de inclusão escolar
Authors: Rocha Eduardo Vallejos da
Published: December 2020

Trata-se de um caso acompanhado em uma escola, no qual uma professora e o assistente de práticas inclusivas manejaram as violências e autoagressões de uma criança pela via da transferência, do desejo e do ato. Por violências, entendemos os atos do sujeito articulados à satisfação da pulsão de morte. Os operadores conceituais da psicanálise de orientação lacaniana foram tomados como norteadores para a condução do caso e para a leitura crítica da instituição, que mostrou dificuldade em incluir o inesperado e disruptivo das violências e autoagressões como objetos potentes para o trabalho. Verificou-se que o desejo e o ato provocaram, por contingências distintas, uma mudança de posição subjetiva da educadora, do assistente e, em seguida, a tomada da palavra pela criança. Evidenciou-se a maior preocupação da instituição, encarnada na figura da assessora de práticas inclusivas, em avaliar o que era produzido por cada educadora em sala de aula, do ponto de vista da confecção e adaptação de atividades para os alunos em situação de inclusão, em detrimento da escuta dos impasses da equipe. Nesse caso, o conceito lacaniano de extimidade pode orientar o trabalho do profissional junto às instituições que se pretendem inclusivas. Seja contratado pela família como acompanhante terapêutico ou, especialmente, pela escola como assistente de práticas inclusivas, o desafio é estabelecer um vínculo com a instituição sem necessariamente responder a todas as suas demandas, que porventura podem impedir a escuta da criança que urge. Para tanto, o profissional deve estar aberto às contingências dos encontros, permitindo que algo novo possa se inscrever na experiência escolar do aluno.
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.