bluuebunny/crossref_metadata_2025 huggingface dataset:
Advertising Strategies of Hyundai Motors In Indian Market
Authors: Reddy L. Sudershan , P V Ranjith , Sabnis Saili , Ganatra Varsha , Shastry Kailash , Elviona Anastasya , Sin Liem Gai , Chee Yaw Nee , Kee Daisy Mui Hung , Kerof Chareeya A/P Perak , Qianya Wang , Jiaze Wei
Published: March 2021

India’s leading passenger car exporter which is Hyundai Motors India Limited has a market share of India’s total car exports about 26 % in 2019. The term strategy is intended a lot for all business entities in today's competitive marketplace. When a company has a distinctive and distinct benefit, it must be inventive with its marketing strategy. Hyundai has introduced and embraced numerous strategies for securing the overall demand for brand placement. This study attempts to investigate traditional and digital advertising conducted by Hyundai Motors Company which will enhance the success of the company in terms of creating the brand and facilitating user engagement. Close-ended questionnaire is used to collect the data for this study. The data was collected from individuals with different income ranges in India through a non-probability purposive convenience sampling method. The result of this study showed that generation nowadays know more about the products through broadcast advertising such as TV and digital media rather than print media such as newspaper and magazine. Therefore, Hyundai Motors should invest more marketing strategy in broadcast and digital advertising.
Analytical Comparison of Structure with Reinforced Concrete Wall Against Lateral Load
Authors: Bhavsar Mehul J. , Pastagia Digant A.
Published: March 2021

Buildings are generally designed to withstand against gravity load for expected life and resist extent of lateral loads by satisfying the codal provision. Main objective of structural elements is to transfer the load safely to the ground, which depends on structural system adopted. Generally, structural system can be adopted depending on the demand of client/building needs/use of structure, environmental condition, performance optimization, economic condition etc. For high rise building moment resisting frame system, structural wall systems, dual system, flat slab-structural wall systems can be employed. A residential ground with ten upper floors high rise building situated in zone-III has been taken under reference, where MRF with RC structural wall system is used. Structural parameters are compared in the study for various location and orientation of RC wall. Linear static and dynamic analysis is performed on the structure based on the IS 1893 Part-I on ETABS software.
Osteonecrose dos Maxilares Induzida por Bisfosfonatos: Relato de Caso Clínico
Authors: Caldas Rogério Jardim , Pontes José Roberto de Menezes , Antunes Héliton Spíndola
Published: March 2021

A osteonecrose dos maxilares induzida por bisfosfonatos é a primeira complicação tardia da terapia com bisfosfonatos descrita na literatura científica. Essa é definida como o desenvolvimento de osso necrótico na cavidade oral de um paciente que esteja recebendo tratamento com bisfosfonatos e não tenha recebido radioterapia em região de cabeça e pescoço. Clinicamente, as lesões se caracterizam como ulcerações da mucosa oral, frequentemente muito dolorosas, que expõem o osso subjacente. O objetivo deste trabalho é relatar um caso clínico de osteonecrose induzida por bisfosfonatos de surgimento espontâneo, com difícil resposta a tratamento conservador, alcançando a cura com cirurgia.
Avaliação do Nível de Genotoxicidade através do Ensaio Cometa em Manipuladores de Quimioterápicos em Serviços de Oncologia
Authors: Rombaldi Fernanda , Cassini Carina , Pesamosca Luciana Garlet , Salvador Mirian , Saffi Jenifer , Erdtmann Bernardo
Published: March 2021

Introdução: é crescente a preocupação sobre o efeito mutagênico e carcinogênico de agentes genotóxicos em populações expostas ocupacionalmente. Entre os diferentes agentes de risco ocupacional, destacam-se as drogas antineoplásicas. Objetivo: este trabalho avaliou o risco ocupacional dos profissionais que manipulam quimioterápicos em hospitais e clínicas de Caxias do Sul (RS), Brasil. Metodologia: vinte farmacêuticos e enfermeiros que manipulam quimioterápicos foram monitorados durante uma semana de trabalho, tendo sido coletadas seis amostras de sangue: segunda-feira pela manhã (antes de iniciar o trabalho) e à tarde, e terça a sexta-feira à tarde. Foi avaliada a genotoxicidade, através do ensaio cometa que identifica dano ao DNA; e, por ser simples, rápido e de baixo custo, tem sido recomendado para avaliação rotineira de trabalhadores em risco com agentes genotóxicos. Resultados: neste trabalho, os indivíduos expostos apresentaram um aumento no dano ao DNA pelo teste cometa em relação aos controles em todas as amostras, exceto na segunda-feira de manhã (p=0,000 e p=0,143, respectivamente), mostrando assim a importância do descanso do final de semana. Os resultados do ensaio cometa também mostraram uma correlação positiva com os dias da semana e com o consumo de álcool (r=0,228, p=0,014). Conclusão: o monitoramento de profissionais em risco ocupacional de forma mais prolongada, como neste estudo, durante uma semana, é extremamente relevante, pois pode apresentar novos aspectos do comportamento de risco, cujos resultados podem complementar o controle do risco de genotoxicidade.
Determinan Kepuasan Pengguna Sistem Aplikasi Keuangan Tingkat Instansi dan Pengaruhnya Terhadap Individu dan Organisasi
Authors: Nasrudin Edy , Widagdo Ari Kuncara
Published: March 2021

Penelitian ini bertujuan untuk memberikan bukti empiris bahwa ekspektasi kinerja, ekspektasi usaha, kondisi yang memfasilitasi, kualitas informasi, kualitas sistem dan sikap pada penggunaan berpengaruh terhadap kepuasan pengguna sistem aplikasi keuangan negara yang bernama Sistem Aplikasi Keuangan Tingkat Instansi (SAKTI). Selain itu, penelitian ini juga memberikan bukti pengaruh tak langsung ekspektasi kinerja dan usaha terhadap kepuasan pengguna SAKTI dimediasi variabel sikap pada penggunaan serta pengaruh kepuasan pengguna terhadap dampak individu dan organisasi. Responden yang digunakan dalam penelitian adalah user SAKTI. Sampel yang digunakan sebanyak 282 responden. Data dianalisis menggunakan Partial Least Square (PLS) Smart 3.2.6. Hasil pengujian hipotesis menunjukkan bahwa ekspektasi kinerja, ekspektasi usaha, kondisi yang memfasilitasi, kualitas informasi, kualitas sistem dan sikap pada penggunaan berpengaruh terhadap kepuasan pengguna SAKTI. Demikian halnya, ekspektasi kinerja, ekspektasi usaha berpengaruh terhadap kepuasan pengguna SAKTI melalui sikap pada penggunaan. Lebih lanjut, kepuasan pengguna berpengaruh terhadap dampak individu dan organisasi.
Producción de fracciones antioxidantes de sangre bovina
Authors: Figueroa Omar , Ospino Karen , Mejía Emil , Peñaloza Sandy , Morales Jesús
Published: March 2021

En este trabajo se analizó el efecto del grado de hidrolisis (GH) de hidrolizados enzimáticos de fracciones de sangre bovina (Plasma y fracción globular) con Alcalasa 2.4L, sobre la actividad antioxidante de fracciones peptídicas. A las condiciones óptimas se produjeron hidrolizados en tres tiempos de hidrólisis para evaluar la capacidad antioxidante, con los métodos ORAC, ABTS y FRAP, alcanzando en general, mayor capacidad antioxidante en el tiempo de 2 horas, salvo para el caso de la capacidad en los agentes antioxidantes de la fracción globular medidos con la técnica ABTS, donde resulta suficiente hidrolizar 30 min y obtener hidrolizados intermedios para favorecer la mayor capacidad antioxidante, siendo esta estadísticamente igual a las fracciones con alto GH.
Diagnóstico geológico minero ambiental de las canteras de caliza en el departamento del Cesar
Authors: Mendoza Castro Martha Lucia , Urbina Garrido Islem Issela
Published: March 2021

El presente diagnóstico fue elaborado con el fin de brindar un soporte a las canteras, para mejorar y analizar las dificultades que estas han estado presentando en la parte geológica, minera y ambiental. Para lo anterior, es necesario conocer si en la minería a mediana escala se están haciendo los estudios geológicos pertinentes, además, comparar los métodos de explotación de la caliza y determinar los impactos ambientales generados; cabe resaltar que esta investigación es cuantitativa y se rige bajo la correlación bibliográfica y empleo de lista de chequeo. Ahora bien, las canteras no realizan estudios geoquímicos por el tipo de roca, sin embargo realizan análisis químicos y de calidad donde se usa para cemento, base de construcción, hormigón, y para procesos químicos de cal viva. Los métodos de explotación se clasifican en banco escalonado ascendente y banco escalonado descendente. Por último, a nivel ambiental se logró determinar impactos de polución, desforestación, alteración paisajística. En conclusión las canteras emplean los estudios geológicos de acuerdo a su necesidad, además que el método de explotación más recomendado es el de banco escalonado descendente. Así mismo se identificó a partir de la correlación con la matriz de Leopold (1971), que en la etapa donde se presenta más impacto es en la de Construcción y montaje.
Medición multidimensional de la pobreza del corregimiento de Caracolí
Authors: Duran Barón Ricardo
Published: March 2021

La pobreza es un fenómeno multidimensional, por esa razón una persona pobre se reconoce como aquella que tiene necesidades insatisfechas, que carece de ingresos, de protección social que hace que su presente se degrade y su futuro sea inseguro, y de un conjunto multidimensional de bienes y servicios deseables que se restringe y se hace ajeno. El objetivo de este estudio consistió en determinar el índice de pobreza del corregimiento de Caracolí basado en un censo a la población y la metodología de análisis multidimensional. El análisis permite concluir que el índice de calidad de vida es deficiente pues en todos los factores hay variables críticas que hacen pensar en que esta es una población pobre y alguna parte de ella en extrema pobreza con empleos de mala calidad cuyos ingresos no alcanzan para cubrir los gastos mínimos de la familia, los servicios públicos son deficientes teniendo agua no potable, sin servicio de alcantarillado, deficiencia y poco acceso a la educación.
Optimización económica de los camiones asignados en la operación Dragalinas/Apron Feeder en una empresa minera de carbón en el departamento del Cesar
Authors: Molina Sandra , Hernández Mary
Published: March 2021

En el ámbito de la minería para que exista una óptima producción depende de muchos factores, en la operación Dragalina/Apron Feeder depende directamente del factor de camiones asignados, la cual tiene un gran impacto en la producción y costos de la operación. Mediante este artículo se busca determinar la saturación de la asignación de camiones proporcionado por la tasa de producción óptima al menor costo por metro cúbico banco. Además, se determinará el número mínimo de camiones asignados, lo que produce un costo por metro cúbico banco por debajo del objetivo de corte de la empresa, desarrollando un modelo de costos a partir de los datos históricos y costos de producción en la Mina utilizando Excel para analizar el impacto que genera una buena asignación de Camiones.
TINJAUAN PENGGUNAAN ABU SISA PEMBAKARAN BATU BARA PABRIK DILEM TERHADAP KUAT TEKAN BETON
Authors: Wiyanti Dwi Sri , Laksono Taufik Dwi , Barkah Atiyah
Published: March 2021

Banyak penelitian beton menggunakan substitusi material pengganti berupa abu terbang (fly ash) yang berasal dari abu sisa pembakaran batu bara dari Industri PLTU. Penggunaan batu bara juga dimanfaatkan industri pengolahan daun Dilem di PT. SCI di daerah Purbalingga. Untuk pemanfaatan limbah abu sisa pembakaran Industri Daun Dilem dilakukan penelitian tentang kuat tekan beton menggunakan abu sisa pembakaran batubara dari PT. SCI . Tujuan dari penelitian adalah mengetahui pengaruh penggunaan abu sisa pembakaran batu bara terhadap kuat tekan beton dan mengetahui selisih kuat tekan beton yang dihasilkan dengan prosentase abu sisa pembakaran batu bara 10%, 12,5%, 15%, dan 17,5% terhadap berat semen. Penggunaan abu sisa pembakaran batubara mempengaruhi kuat tekan beton yang dihasilkan, dengan prosentase abu sisa pembakaran batubara sebesar 12,5% sebagai substitusi semen memberikan kuat tekan beton paling maksimal sebesar 23,0 Mpa.Kata Kunci : Beton, Kuat tekan beton, Abu Terbang, Abu Sisa Pembakaran batu bara.
THERAPEUTIC PARTICULARITIES OF CHRONIC SUPPURATED CHOLESTEATOMATOUS OTOMASTOIDITIS
Authors: Stan C. , Enachi Andreea Mihaela , Vesa Doina
Published: March 2021

Chronic suppurated otomastoiditis is a chronic inflammatory damage of the middle ear and mastoid process that exceeds 12 weeks and which leads to the permanent perforation of the eardrum’s membrane. There is local damage such as osteitis, osteonecrosis and cholesteatoma, while a general view reveals an  asymptomatic evolution, with a good general state, otorrhea being the only local symptom. This paper brings to light a case resulting from the thorough analysis of case studies run by the ENT Clinic of the Emergency County Hospital "Sf. Apostol Andrei” of Galaţi, through the fact that otomastoiditis progresses given the presence of a congenital hemangioma located on the left half of the cephalic extremity, at a cervical, thoracic and abdominal level. The patient, aged 41, has been suffering from this disease since childhood and has undergone numerous surgeries up to this moment, but none has proven to be adequate for the extent of the lesion due to the malformation and the difficulty in providing general anesthesia with orotracheal intubation, the hemangioma being present in the oropharynx, hypopharynx and larynx. Given the overlapping of the two disorders, the surgical-medical approach to the ear damage has proven insufficient in time due to the risk of massive bleeding, taking into account the fact that the hemangioma was extended to the left ear duct, pharynx and larynx. For this reason, the disease has progressed, leading to extended erosive cholesteatoma with left otomastoiditis. The particularities of the therapeutic approach are presented along with anesthesiologic and surgical problems involved by the hemangioma. Although the risk of hemorrhaging was great, approaching the condition by choosing to provide general anesthesia and making the incisions only with the help of an electric scalpel, the case was eventually solved successfully from a surgical point of view.
NEW THERAPIES IN UNRESECTABLE PANCREATIC NEUROENDOCRINE TUMORS
Authors: Berescu Ana Georgiana , Stoica Andreea Mihaela , Bolocan Alexandra
Published: March 2021

Until recently, the main form of treatment for the pancreatic neuroendocrine tumors was the surgical resection (the Whipple operation). Due to technological advances, which resulted in more frequent diagnosis, attempts were made to discover other less radical forms of treatment, including limited surgical resection and multiple forms of chemotherapy. Surgical resection has shown benefit only on small lesions with no metastases. According to the recent studies chemotherapeutic agents have shown substantial benefits in terms of survival and disease progression, especially sunitinib and everolimus.
AN UNEXPECTED COMPLICATION OF APPENDICITIS
Authors: Popescu Mihaela , Miron A. , Nădrăgea M. , Ghilencea L. , Dumitrescu Doina
Published: March 2021

Appendicitis is quite a common pathology and is usually followed by a simple surgical procedure. This was not the case for a 24-year-old patient that initially presented with abdominal pain and diarrhea. The diagnosis of appendicitis was not apparent at first and after a few days of bed rest with malaise and fever, he starts having shortness of breath. The next examination deems his symptoms as a case of pneumonia. He is treated with antibiotics; he shows no signs of improvement and also develops hypoxia and tachycardia. He is referred to our cardiology clinic where the diagnosis of bilateral massive thromboembolism is established, along with the discovery of a large retroperitoneal abscess. Because the patient was septic, the surgery cannot be postponed. A ruptured retroceccal appendix is confirmed as the cause of the abscess. Later, the Doppler examination shows left popliteal vein thrombosis and also the laboratory results confirm that the patient has thrombophilia. This case illustrates an unfortunate association between an unknown thrombophilia, a long standing infection and massive thromboembolism. This combined pathology transformed a simple intervention for appendicitis into a high risk one.
HEMIARTHROPLASTY IN FOUR-PART DISPLACED FRACTURES
Authors: Tudor G. M. , Cristea S.
Published: March 2021

The hemiarthroplasty is the choice of election in the four-part humeral fracture when the glenoid surface is good. It is a relative easy procedure with a short operating time and can be revised to a total shoulder arthroplasty later if necessary. For hemiarthroplasty there are used unconstrained prostheses which are designed to closely replicate the normal anatomy. The general idea is to replace the avascular humeral head with a metal ball in condition of normal glenoid surface.
TOTALLY MINIMALLY INVASIVE ESOPHAGECTOMY 3D HD FOR THORACIC ESOPHAGEAL CANCER AFTER NEOADJUVANT CHEMORADIOTHERAPY
Authors: Achim F. , Gheorghe M. , Constantin A. , Hoara P. , Popa C. , Alkadour A. , Vergu Iuliana , Birceanu Adelina , Constantinoiu S.
Published: March 2021

Esophagectomy is a major surgical procedure with morbidity, and mortality related to the patient'scondition, stage of the disease at the moment of diagnosis, complementary treatments and surgicalexperience of the surgeon. Minimally invasive esophagectomy (MIE) may lead to a reduction inperioperative morbidity and mortality with an acceptable quality of life and similar oncologic resultsto an open approach. We present an experience of the Center of Excellence in Esophageal Surgeryregarding totally MIE through thoracolaparoscopic modified McKeown triple approach, followedby esophageal reconstruction by gastric intrathoracic pull-up and cervical esophagogastricanastomosis and feeding jejunostomy in a patient with thoracic esophageal cancer who underwentpreoperative neoadjuvant chemoradiotherapy. The short-term outcomes of the totally minimallyinvasive esophagectomy procedure were very encouraging. The overall operative times were:thoracoscopic - 120 minutes, laparoscopic - 130 minutes and cervical - 50 minutes with a total of360 minutes. The intraoperative blood loss was 200 ml. The postoperative outcome was favorablewith early feeding on the jejunostomy. The control of cervical anastomosis was performed in the 6thday postoperative and the patient was discharged in the 10th day postoperative without anysymptomatology. At the first and third-month follow-up was not reported any postoperativecomplications. The totally minimally invasive approach using advanced technology of endoscopicsurgery allowed for this patient a simple postoperative evolution, no major complications and agood recovery after extensive surgery. The solid experience in open esophageal surgery ofUpper Gastro-Intestinal surgeons provides a fast learning curve of complex minimally invasivesurgical procedures with reduced perioperative morbidity. Long-term follow-up can confirm theresults from the literature regarding the survival, which is expected to be for these patients atleast equivalent with outcomes after open esophagectomy.
TUMOR MARKERS IN OVARIAN CANCER
Authors: Nenciu Adina-Elena , Nenciu C. G. , Fodoroiu R. , Șandru Florica , Dumitrașcu M.C.
Published: March 2021

Even if today’s society is rapidly evolving there is still much that can be done. This applies in theoncological field. One of the main female health problems worldwide is represented by thegynecological cancers. Ovarian cancer is the main cause of mortality among women withgynecological cancers. Although its prevalence is lover compared to breast, uterine or cervicalcancer, the mortality and morbidity rates are significantly higher. The first step in the managementof ovarian cancer is represented by regular screening and rapid diagnosis. One of the most importanttolls is represented by serological markers dosage in order to estimate the type of tumor before thegynecological specific intervention. There is a real need to identify correctly the ovarian cancer asearly as possible in order to obtain the favorable prognosis that comes with the diagnosis in earlystage. Most of the ovarian cancers (above 90%) are represented by carcinomas which are frequentlydiagnosed in advanced stages. The roles of the biomarkers are to indicate the malignancy of anovarian tumor and to predict the relapse risk. The aim of this paper is to update the indicationsregarding the usage of serological markers in ovarian cancers and the importance of using them forour patients.
DEVELOPMENT OF COD (CHEMICAL OXYGEN DEMAND) ANALYSIS METHOD IN WASTE WATER USING SPECTRODIRECT
Authors: Mulyati Ade Heri , Heliawati Leny , . Sutanto , Hasanah Uswatun , Widiastuti Diana , Warnasih Siti , Syahputri Yulian
Published: March 2021

Increased human activities will cause various problems, one of which is water pollution in water sources because it receives a pollution load that exceeds its carrying capacity. In the context of environmental conservation, the government has set quality standards for liquid waste produced by various industries and other activities in a Decree of the State Minister for the Environment. COD (Chemical Oxygen Demand) is one of the most important parameters in wastewater quality standards. This study aims to validate the COD analysis method which refers to COD Thermoreactor System (LOVIBOND brand) at Pakuan University Service Laboratory, to ensure the validity of COD analysis results at Pakuan University Service Laboratory. Spectrodirect COD analysis method provides results that meet the requirements of accuracy, precision, LOD, and LOQ which is quite good. The results of the Coefficient of Variation give good results with a value of 1.8841% indicating the accuracy of the analysis method is good. The accuracy parameter also gives good results and meets the requirements with a% recovery value of 98.70351%. Overall, it can be stated that the spectrodirect analysis method tested is an accurate, precise, simple, and economical method for determining COD levels
Budaya Sosial Masyarakat Postkolonial Jawa pada Masa Orde Baru dalam Novel Entrok Karya Okky Madasari
Authors: Fitri Nurul Afni Fitri Nurul Afni
Published: March 2021

Masyararakat postkolonial Jawa memiliki budaya sosial yang menjadi kebiasaan masyarakat sebagai hasil dari percampuran budaya dari bangsa-bangsa kolonial maupun budaya asli masyarakat yang tidak berubah. Masyarakat postkolonial dalam novel Entrok berlatar masa Orde Baru yang menunjukan cerminan kebudayaan masyarakat Indonesia, khususnya masyarakat postkoloial Jawa. Artikel ini bertujuan untuk mengdentifikasi bentuk budaya sosial pada masyarakat postkolonial Jawa pada masa Orde baru dalam novel Entrok karya Okky Madasari sebagai refleksi dari kehidupan masyarakat Jawa setelah mengalami penjajahan oleh bangsa Barat. Fokus masalah dalam artikel ini yaitu kebudayaan atau kebisaan sosial yang dilakukan masyarakat postkolonial Jawa dalam novel Entrok. Metodologi penelitian pada atikel ini menggunakan pendekatan kualitatif yaitun metode deskriptif, menggunakan teknik pengumpulan data berupa teknik studi pustaka. Teknik analisis data pada artikel ini berupa reduksi data, penyajian data, dan kesimpulan. Hasil artikel ini menemukan berbagai budaya sosial masyarakat postkolonial Jawa dalam novel Entrok berupa kelas sosial, ketidaksetaraan gender, diskriminasi, kebebasan berpendapat, pemerasan, dan kesewenang-wenangan.
How Can Termites Achieve Their Unparalleled Postembryonic Developmental Plasticity? A Test for the Role of Intermolt-Specific High Juvenile Hormone Titers
Authors: Korb Judith , Greiner Carolin , Foget Marion , Geiler Adrian
Published: March 2021

Termites are “social cockroaches” and amongst the most phenotypically plastic insects. The different castes (i.e., two types of reproductives, workers, and soldiers) within termite societies are all encoded by a single genome and present the result of differential postembryonic development. Besides the default progressive development into winged sexuals of solitary hemimetabolous insects, termites have two postembryonic, non-terminal molts (stationary and regressive; i.e., molts associated, respectively, with no change or reduction of size/morphological differentiation) which allow them to retain workers, and two terminal developmental types to become soldiers and replacement reproductives. Despite this unique plasticity, especially the mechanisms underlying the non-terminal development are poorly understood. In 1982, Nijhout and Wheeler proposed a model how this diversity might have evolved. They proposed that varying juvenile hormone (JH) titers at the start, mid-phase, and end of each intermolt period account for the developmental diversity. We tested this rarely addressed model in the lower termiteCryptotermes secundususing phase-specific pharmacological manipulations of JH titers. Our results partially support the Nijhout and Wheeler model. These data are supplemented with gene expression studies of JH-related genes that characterize different postembryonic developmental trajectories. Our study provides new insights into the evolution of the unique postembryonic developmental plasticity of termites that constitutes the foundation of their social life.
Epitope Mapping of Exposed Tegument and Alimentary Tract Proteins Identifies Putative Antigenic Targets of the Attenuated Schistosome Vaccine
Authors: Farias Leonardo P. , Vance Gillian M. , Coulson Patricia S. , Vitoriano-Souza Juliana , Neto Almiro Pires da Silva , Wangwiwatsin Arporn , Neves Leandro Xavier , Castro-Borges William , McNicholas Stuart , Wilson Keith S. , Leite Luciana C. C. , Wilson R. Alan
Published: March 2021

The radiation-attenuated cercarial vaccine remains the gold standard for the induction of protective immunity againstSchistosoma mansoni. Furthermore, the protection can be passively transferred to naïve recipient mice from multiply vaccinated donors, especially IFNgR KO mice. We have used such sera versus day 28 infection serum, to screen peptide arrays and identify likely epitopes that mediate the protection. The arrays encompassed 55 secreted or exposed proteins from the alimentary tract and tegument, the principal interfaces with the host bloodstream. The proteins were printed onto glass slides as overlapping 15mer peptides, reacted with primary and secondary antibodies, and reactive regions detected using an Agilent array scanner. Pep Slide Analyzer software provided a numerical value above background for each peptide from which an aggregate score could be derived for a putative epitope. The reactive regions of 26 proteins were mapped onto crystal structures using the CCP4 molecular graphics, to aid selection of peptides with the greatest accessibility and reactivity, prioritizing vaccine over infection serum. A further eight MEG proteins were mapped to regions conserved between family members. The result is a list of priority peptides from 44 proteins for further investigation in multiepitope vaccine constructs and as targets of monoclonal antibodies.
Decoy Receptor 3 Inhibits Monosodium Urate-Induced NLRP3 Inflammasome Activation via Reduction of Reactive Oxygen Species Production and Lysosomal Rupture
Authors: Pan Yi-Gen , Huang Ming-Ting , Sekar Ponarulselvam , Huang Duen-Yi , Lin Wan-Wan , Hsieh Shie-Liang
Published: March 2021

Gout is a common inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in the joints. This activates the macrophages into a proinflammatory state by inducing NLRP3-dependent interleukin-1β (IL-1β) secretion, resulting in neutrophil recruitment. Soluble decoy receptor 3 (DcR3) is an immune modulator and can exert biological functions via decoy and non-decoy actions. Previously, we showed that DcR3 suppresses lipopolysaccharides (LPS)- and virus-induced inflammatory responses in the macrophages and promotes the macrophages into the M2 phenotype. In this study, we clarified the actions of DcR3 and its non-decoy action motif heparin sulfate proteoglycan (HSPG) binding domain (HBD) in the MSU crystal-induced NLRP3 inflammasome activation in the macrophages and in mice. In bone marrow-derived macrophages, THP-1 and U937 cells, we found that the MSU crystal-induced secretion of IL-1β and activation of NLRP3 were suppressed by both DcR3.Fc and HBD.Fc. The suppression of the MSU-induced NLRP3 inflammasome activation is accompanied by the inhibition of lysosomal rupture, mitochondrial production of the reactive oxygen species (ROS), expression of cathepsins, and activity of cathepsin B, without affecting the crystal uptake and the expression of NLRP3 or pro-IL-1β. In the air pouch mice model of gout, MSU induced less amounts of IL-1β and chemokines secretion, an increased M2/M1 macrophage ratio, and a reduction of neutrophil recruitment in DcR3-transgenic mice, which expresses DcR3 in myeloid cells. Similarly, the mice intravenously treated with DcR3.Fc or HBD.Fc displayed less inflammation response. These findings indicate that HBD of DcR3 can reduce MSU crystal-induced NLRP3 inflammasome activation via modulation of mitochondrial and lysosomal functions. Therefore, we, for the first time, demonstrate a new therapeutic potential of DcR3 for the treatment of gout.
Exploiting Common Aspects of Obesity and Alzheimer’s Disease
Authors: Tabassum Sidra , Misrani Afzal , Yang Li
Published: March 2021

Alzheimer’s disease (AD) is an example of age-related dementia, and there are still no known preventive or curative measures for this disease. Obesity and associated metabolic changes are widely accepted as risk factors of age-related cognitive decline. Insulin is the prime mediator of metabolic homeostasis, which is impaired in obesity, and this impairment potentiates amyloid-β (Aβ) accumulation and the formation of neurofibrillary tangles (NFTs). Obesity is also linked with functional and morphological alterations in brain mitochondria leading to brain insulin resistance (IR) and memory deficits associated with AD. Also, increased peripheral inflammation and oxidative stress due to obesity are the main drivers that increase an individual’s susceptibility to cognitive deficits, thus doubling the risk of AD. This enhanced risk of AD is alarming in the context of a rapidly increasing global incidence of obesity and overweight in the general population. In this review, we summarize the risk factors that link obesity with AD and emphasize the point that the treatment and management of obesity may also provide a way to prevent AD.
Deciphering the Pharmacological Mechanisms of Guizhi-Fuling Capsule on Primary Dysmenorrhea Through Network Pharmacology
Authors: Zhang Siqin , Lai Xinxing , Wang Xin , Liu Gang , Wang Zhenzhong , Cao Liang , Zhang Xinzhuang , Xiao Wei , Li Shao
Published: March 2021

Guizhi-Fuling capsule (GZFLC), originated from a classical traditional Chinese herbal formula Guizhi-Fuling Wan, has been clinically used for primary dysmenorrhea in China. Nonetheless, the underlying pharmacological mechanisms of GZFLC remain unclear. The integration of computational and experimental methods of network pharmacology might be a promising way to decipher the mechanisms. In this study, the target profiles of 51 representative compounds of GZFLC were first predicted by a high-accuracy algorithm, drugCIPHER-CS, and the network target of GZFLC was identified. Then, potential functional modules of GZFLC on primary dysmenorrhea were investigated using functional enrichment analysis. Potential bioactive compounds were recognized by hierarchical clustering analysis of GZFLC compounds and first-line anti-dysmenorrhea drugs. Furthermore, the potential anti-dysmenorrhea mechanisms of GZFLC were verified through enzyme activity assays and immunofluorescence tests. Moreover, effects of GZFLC on primary dysmenorrhea were evaluated in oxytocin-induced dysmenorrhea murine model. In the network target analysis, GZFLC may act on five functional modules of pain, inflammation, endocrine, blood circulation and energy metabolism. Integrating computational and experimental approaches, we found that GZFLC significantly inhibited the writhing response and reduced the degree of uterine lesions in oxytocin-induced dysmenorrhea murine model. Furthermore, GZFLC may partially alleviate primary dysmenorrhea by inhibiting cyclooxygenase 2 (COX2) and downregulating MAPK signaling pathway. Consequently, GZFLC presented pain relief and sustained benefits for primary dysmenorrhea. This study could provide a scientific approach for deciphering pharmacological mechanisms of herbal formulae through network pharmacology.
High Fat Diet Dysbiotic Mechanism of Decreased Gingival Blood Flow
Authors: Stanisic Dragana , Jeremic Nevena , Majumder Suravi , Pushpakumar Sathnur , George Akash , Singh Mahavir , Tyagi Suresh C.
Published: March 2021

The gut microbiome has a very important role in human health and its influence on the development of numerous diseases is well known. In this study, we investigated the effect of high fat diet (HFD) on the onset of dysbiosis, gingival blood flow decreases, and the periodontal matrix remodeling. We established a dysbiosis model (HFD group) and probiotic model by Lactobacillus rhamnosus GG (LGG) treatment for 12weeks. Fecal samples were collected 24h before mice sacrificing, while short chain fatty acids (SCFA) analysis, DNA extraction, and sequencing for metagenomic analysis were performed afterwards. After sacrificing the animals, we collected periodontal tissues and conducted comprehensive morphological and genetic analyses. While HFD reduced Bacteroidetes, SCFA, and gingival blood flow, this type of diet increased Firmicutes, lipopolysaccharide (LPS) binding protein, TLR4, pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), matrix metalloproteinases (MMP-2 and MMP-9) expression, and also altered markers of bone resorption (OPG and RANKL). However, LGG treatment mitigated these effects. Thus, it was observed that HFD increased molecular remodeling via inflammation, matrix degradation, and functional remodeling and consequently cause reduced gingival blood flow. All of these changes may lead to the alveolar bone loss and the development of periodontal disease.
Smoking Is Correlated With the Prognosis of Coronavirus Disease 2019 (COVID-19) Patients: An Observational Study
Authors: Peng Fei , Lei Si , Zhang Quan , Zhong Yanjun , Wu Shangjie
Published: March 2021

Background

Cigarette smoking has been proven to be a risk factor in the development of many diseases. However, it remains controversial with respect to the relationship of smoking with COVID-19. The purpose of this study was to explore the role of smoking in COVID-19.

Methods

A total of 622 patients with COVID-19 in China were enrolled in the study. Corresponding clinical and laboratory data were collected and analyzed. Meanwhile, Kaplan-Meier curve and Cox regression analysis were employed to analyze the association of smoking with survival in patients with COVID-19.

Results

Smoking was statistically significant comparing non-survivors and survivors of patients with COVID-19 (P= 0.007). Males had higher proportion of smoking than females (91.9% vs. 8.1%,P< 0.001). Compared with the non-smoker, there was significant statistical difference in the incidence of cerebrovascular disease in smoking patients with COVID-19 (9.7% vs. 3.4%,P= 0.017). White blood cell count (6.3 vs. 5.4;P= 0.037), hemoglobin level (139.0 vs. 127.0;P< 0.001), and creatinine level (77.3 vs. 61.0;P< 0.001) were significantly increased in COVID-19 patients who smoked. Moreover, smoking patients showed a worse survival compared with non-smoking patients (Log RankP= 0.045). After adjustment for age, gender and underlying diseases, patients with smoking still had higher risk of mortality than that of non-smoking patients (hazard ratio[HR] 1.897, 95% confidence interval [CI]1.058–3.402,P= 0.032).

Conclusion

Smoking was thought to be a risk factor in predicting the prognosis of COVID-19 and smoking patients might have a higher risk of mortality than that of the non-smoking patients.
ZMK1 Is Involved in K+ Uptake and Regulated by Protein Kinase ZmCIPK23 in Zea mays
Authors: Han Wu , Ji Yun , Wu Wei , Cheng Jin-Kui , Feng Han-Qian , Wang Yi
Published: March 2021

Potassium (K+) is one of essential mineral elements for plant growth and development. K+ channels, especially AKT1-like channels, play crucial roles in K+ uptake in plant roots. Maize is one of important crops; however, the K+ uptake mechanism in maize is little known. Here, we report the physiological functions of K+ channel ZMK1 in K+ uptake and homeostasis in maize. ZMK1 is a homolog of Arabidopsis AKT1 channel in maize, and mainly expressed in maize root. Yeast complementation experiments and electrophysiological characterization in Xenopus oocytes indicated that ZMK1 could mediate K+ uptake. ZMK1 rescued the low-K+-sensitive phenotype of akt1 mutant and enhanced K+ uptake in Arabidopsis. Overexpression of ZMK1 also significantly increased K+ uptake activity in maize, but led to an oversensitive phenotype. Similar to AKT1 regulation, the protein kinase ZmCIPK23 interacted with ZMK1 and phosphorylated the cytosolic region of ZMK1, activating ZMK1-mediated K+ uptake. ZmCIPK23 could also complement the low-K+-sensitive phenotype of Arabidopsis cipk23/lks1 mutant. These findings demonstrate that ZMK1 together with ZmCIPK23 plays important roles in K+ uptake and homeostasis in maize.
Fine Mapping of Leaf Trichome Density Revealed a 747-kb Region on Chromosome 1 in Cold-Hardy Hybrid Wine Grape Populations
Authors: Yin Lu , Karn Avinash , Cadle-Davidson Lance , Zou Cheng , Underhill Anna , Atkins Paul , Treiber Erin , Voytas Daniel , Clark Matthew
Published: March 2021

Segregation for leaf trichome density was observed in a cold-hardy hybrid grape population GE1025 (N= ∼125, MN1264 × MN1246) that was previously used to detect a quantitative trait locus (QTL) underlying foliar phylloxera resistance on chromosome 14. Our hypothesis was that high trichome density was associated with resistance to phylloxera. Existing literature found trichome density QTL on chromosomes 1 and 15 using a hybrid grape population of “Horizon” × Illinois 547-1 and suggested a few candidate genes. To validate the reported QTL and our hypothesis, interval mapping was conducted in GE1025 with previous genotyping-by-sequencing (GBS) single nucleotide polymorphism (SNP) genotype data and phenotypic scores collected using a 0–6 trichome density scale at several leaf positions. Evaluations were done on replicated forced dormant cuttings in 2 years and on field-grown leaves in 1 year. There was no strong relationship between trichome density and phylloxera resistance except for a Pearson’s correlation (r) of about -0.2 between a few trichome density traits and phylloxera severity traits at 2 and 3 weeks after infestation. Two genetic regions were repeatedly detected for multiple trichome density traits: from 10 to 20.7 Mbp (∼10 Mbp) on chromosome 1 for ribbon and simple density traits and from 2.4 to 8.9 Mbp on chromosome 10 for ribbon density traits, explaining 12.1–48.2 and 12.6–27.5% of phenotypic variation, respectively. To fine map, we genotyped a larger population, GE1783 (N= ∼1,023, MN1264 × MN1246), with conserved rhAmpSeq haplotype markers across multipleVitisspecies and phenotyped 233 selected potential recombinants. Evaluations were conducted on field-grown leaves in a single year. The QTL for ribbon trichome density on adaxial vein and adaxial leaf and simple density on abaxial vein was fine mapped to 12.63–13.38 Mbp (747 kb) on chromosome 1. We found variations of MN1264 and MN1246 at candidate genes NAC transcription factor 29, EF-hand protein, and MYB140 in this region and three other surrounding candidate genes proposed previously. Even though no strong relationship between foliar phylloxera resistance and trichome density was found, this study validated and fine mapped a major QTL for trichome density using a cold-hardy hybrid grape population and shed light on a few candidate genes that have implications for different breeding programs.
Verticillium dahliae Inoculation and in vitro Propagation Modify the Xylem Microbiome and Disease Reaction to Verticillium Wilt in a Wild Olive Genotype
Authors: Anguita-Maeso Manuel , Trapero-Casas José Luis , Olivares-García Concepción , Ruano-Rosa David , Palomo-Ríos Elena , Jiménez-Díaz Rafael M. , Navas-Cortés Juan A. , Landa Blanca B.
Published: March 2021

Host resistance is the most practical, long-term, and economically efficient disease control measure for Verticillium wilt in olive caused by the xylem-invading fungus Verticillium dahliae (Vd), and it is at the core of the integrated disease management. Plant’s microbiome at the site of infection may have an influence on the host reaction to pathogens; however, the role of xylem microbial communities in the olive resistance to Vd has been overlooked and remains unexplored to date. This research was focused on elucidating whether in vitro olive propagation may alter the diversity and composition of the xylem-inhabiting microbiome and if those changes may modify the resistance response that a wild olive clone shows to the highly virulent defoliating (D) pathotype of Vd. Results indicated that although there were differences in microbial communities among the different propagation methodologies, most substantial changes occurred when plants were inoculated with Vd, regardless of whether the infection process took place, with a significant increase in the diversity of bacterial communities when the pathogen was present in the soil. Furthermore, it was noticeable that olive plants multiplied under in vitro conditions developed a susceptible reaction to D Vd, characterized by severe wilting symptoms and 100% vascular infection. Moreover, those in vitro propagated plants showed an altered xylem microbiome with a decrease in total OTU numbers as compared to that of plants multiplied under non-aseptic conditions. Overall, 10 keystone bacterial genera were detected in olive xylem regardless of infection by Vd and the propagation procedure of plants (in vitro vs nursery), with Cutibacterium (36.85%), Pseudomonas (20.93%), Anoxybacillus (6.28%), Staphylococcus (4.95%), Methylobacterium-Methylorubrum (3.91%), and Bradyrhizobium (3.54%) being the most abundant. Pseudomonas spp. appeared as the most predominant bacterial group in micropropagated plants and Anoxybacillus appeared as a keystone bacterium in Vd-inoculated plants irrespective of their propagation process. Our results are the first to show a breakdown of resistance to Vd in a wild olive that potentially may be related to a modification of its xylem microbiome and will help to expand our knowledge of the role of indigenous xylem microbiome on host resistance, which can be of use to fight against main vascular diseases of olive.
Is Mindfulness Linked to Life Satisfaction? Testing Savoring Positive Experiences and Gratitude as Mediators
Authors: Cheung Rebecca Y. M. , Lau Elsa Ngar-Sze
Published: March 2021

Grounded in Mindfulness-to-Meaning Theory, this study examined the relation between dispositional mindfulness and life satisfaction through mediating mechanisms including savoring positive experiences and gratitude. A total of 133 Chinese mindfulness practitioners at 20–72 years old were recruited from a 3-day transnational meditation event in Hong Kong. Findings based on structural equation modeling indicated that controlling for sex, age, education, family income, number of hours of mindfulness practice per week, and type of administration, dispositional mindfulness was associated with satisfaction with life through savoring positive experiences and gratitude as mediators. The findings provided initial evidence for these processes between mindfulness and life satisfaction in the Chinese context. To promote life satisfaction, researchers and mental health practitioners should recognize the chain of mechanisms related to mindfulness.
Framing a Phenomenological Mixed Method: From Inspiration to Guidance
Authors: Martiny Kristian Moltke , Toro Juan , Høffding Simon
Published: March 2021

Despite a long history of researchers who combine phenomenology with qualitative or quantitative methods, there are only few examples of working with a phenomenological mixed method—a method where phenomenology informs both qualitative and quantitative data generation, analysis, and interpretation. Researchers have argued that in working with a phenomenological mixed method, there should be mutual constraint and enlightenment between the qualitative (first-person, subjective) and quantitative (third-person, objective) methods for studying consciousness. In this article, we discuss what a framework for phenomenological mixed methods could look like and we aim to provide guidance of how to work within such framework. We are inspired by resources coming from research in mixed methods and existing examples of phenomenological mixed-method research. We also present three cases of phenomenological mixed methods where we study complex social phenomena and discuss the process of how we conducted the studies. From both the research inspiration and our own studies, we depict the landscape of possibilities available for those interested in mixing phenomenology with qualitative and quantitative methods, as well as the challenges and common pitfalls that researchers face. To navigate in this landscape, we develop a three-fold structure, focusing on (1) the phenomenological frame, (2) the phenomenologically informed generation of qualitative and quantitative data (tier one), and (3) the phenomenologically informed analysis and interpretation of data (tier two).
Inhibition of the Growth of Breast Cancer-Associated Brain Tumors by the Osteocyte-Derived Conditioned Medium
Authors: Sano Tomohiko , Sun Xun , Feng Yan , Liu Shengzhi , Hase Misato , Fan Yao , Zha Rongrong , Wu Di , Aryal Uma K. , Li Bai-Yan , Sudo Akihiro , Yokota Hiroki
Published: March 2021

The brain is a common site of metastasis from advanced breast cancer but few effective treatments are available. We examined a therapeutic option with a conditioned medium (CM), focusing on the role of Lrp5 and β-catenin in Wnt signaling, and IL1ra in osteocytes. Osteocytes presented the innate anti-tumor effect and the overexpression of the above genes strengthened their action. In a mouse model, the injection of their CM inhibited mammary tumors and tumor-driven osteolysis. Importantly, Lrp5- and/or IL1ra-overexpressing osteocytes or the local administration of β-catenin-overexpressing CM markedly inhibited brain tumors. In the transport analysis, tumor-suppressing factors in CM were shown to diffuse through the skull. Mechanistically, the CM with overexpression of the above genes downregulated oncogenic genes such as MMP9, Runx2, TGFβ, and Snail in breast cancer cells. Also, the CM with β-catenin overexpression downregulated CXCL1 and CXCL5 and upregulated tumor suppressors such as LIMA1, DSP, p53, and TRAIL in breast cancer cells. Notably, whole-genome proteomics revealed that histone H4 was enriched in CM and acted as an atypical tumor suppressor. Lrp5-overexpressing MSCs were also shown to act as anti-tumor agents. Collectively, this study demonstrated the therapeutic role of engineered CM in brain tumors and the tumor-suppressing action of extracellular histone H4. The result sheds light on the potential CM-based therapy for breast cancer-associated brain metastases in a minimally invasive manner.
Plasma Proteins and Cancer
Authors: Enroth Stefan
Published: March 2021

The human plasma comes into contact with virtually all the cells in the human body and can be easily sampled through phlebotomy [...]