bluuebunny/crossref_metadata_2025_split huggingface dataset:
La selección de la variable principal y su relación con el tamaño de la muestra en los ensayos clínicos de biomateriales
Authors: Pérez Alvarez Mayra , Guerra Bretaña Rosa Mayelín 
Published: August 2020

La eficacia y la seguridad en la utilización de un biomaterial se demuestran, finalmente, en ensayos
clínicos controlados, ya que la utilización de un grupo control es la única forma de evaluar realmente
el efecto del nuevo tratamiento respecto a la regresión espontánea o en relación con un tratamiento ya
establecido.
El cálculo del número de sujetos necesario dependerá de la variable principal escogida para
evaluar el tratamiento, debido a que su selección incide directamente en la eficacia y el beneficio d
esperado con el nuevo tratamiento. El tamaño de la muestra depende, además, del riesgo de concluir
una diferencia que no existe (a) y del riesgo de no poner en evidencia un beneficio al menos
igual d aunque él exista (b).
La inclusión de una cantidad excesiva de pacientes en un ensayo trae un alargamiento innecesario
del periodo de inclusión, gasto excesivo de materiales y puede involucrar hasta problemas éticos.
Por el contrario, una cantidad insuficiente puede traer como resultado la imposibilidad de
demostrar científicamente la hipótesis planteada.
En este trabajo se observa como, la selección adecuada de la variable principal permite demostrar
estadísticamente la superioridad del adhesivo tisular TISUACRYL, respecto a la sutura en dos
ensayos clínicos en Cirugía Bucal, con la inclusión del mínimo número de pacientes.
Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences
Authors: Zaheer Tahreem , Waseem Maaz , Waqar Walifa , Dar Hamza Arshad , Shehroz Muhammad , Naz Kanwal , Ishaq Zaara , Ahmad Tahir , Ullah Nimat , Bakhtiar Syeda Marriam , Muhammad Syed Aun , Ali Amjad 
Published: August 2020

Background
The coronavirus SARS-CoV-2 is a member of the Coronaviridae family that has caused a global public health emergency. Currently, there is no approved treatment or vaccine available against it. The current study aimed to cover the diversity of SARS-CoV-2 strains reported from all over the world and to design a broad-spectrum multi-epitope vaccine using an immunoinformatics approach.

Methods
For this purpose, all available complete genomes were retrieved from GISAID and NGDC followed by genome multiple alignments to develop a global consensus sequence to compare with the reference genome. Fortunately, comparative genomics and phylogeny revealed a significantly high level of conservation between the viral strains. All the Open Reading Frames (ORFs) of the reference sequence NC_045512.2 were subjected to epitope mapping using CTLpred and HLApred, respectively. The predicted CTL epitopes were then screened for antigenicity, immunogenicity and strong binding affinity with HLA superfamily alleles. HTL predicted epitopes were screened for antigenicity, interferon induction potential, overlapping B cell epitopes and strong HLA DR binding potential. The shortlisted epitopes were arranged into two multi-epitope sequences, Cov-I-Vac and Cov-II-Vac, and molecular docking was performed with Toll-Like Receptor 8 (TLR8).

Results
The designed multi-epitopes were found to be antigenic and non-allergenic. Both multi-epitopes were stable and predicted to be soluble in an Escherichia coli expression system. The molecular docking with TLR8 also demonstrated that they have a strong binding affinity and immunogenic potential. These in silico analyses suggest that the proposed multi-epitope vaccine can effectively evoke an immune response.
Genome‐wide identification of CpG island methylator phenotype related gene signature as a novel prognostic biomarker of gastric cancer
Authors: Zeng Zhuo , Xie Daxing , Gong Jianping 
Published: July 2020

BackgroundGastric cancer (GC) is one of the most fatal cancers in the world. Results of previous studies on the association of the CpG island methylator phenotype (CIMP) with GC prognosis are conflicting and mainly based on selected CIMP markers. The current study attempted to comprehensively assess the association between CIMP status and GC survival and to develop a CIMP-related prognostic gene signature of GC.MethodsWe used a hierarchical clustering method based on 2,082 GC-related methylation sites to stratify GC patients from the cancer genome atlas into three different CIMP subgroups according to the CIMP status. Gene set enrichment analysis, tumor-infiltrating immune cells, and DNA somatic mutations analysis were conducted to reveal the genomic characteristics in different CIMP-related patients. Cox regression analysis and the least absolute shrinkage and selection operator were performed to develop a CIMP-related prognostic signature. Analyses involving a time-dependent receiver operating characteristic (ROC) curve and calibration plot were adopted to assess the performance of the prognostic signature.ResultsWe found a positive relationship between CIMP and prognosis in GC. Gene set enrichment analysis indicated that cancer-progression-related pathways were enriched in the CIMP-L group. High abundances of CD8+ T cells and M1 macrophages were found in the CIMP-H group, meanwhile more plasma cells, regulatory T cells and CD4+ memory resting T cells were detected in the CIMP-L group. The CIMP-H group showed higher tumor mutation burden, more microsatellite instability-H, less lymph node metastasis, and more somatic mutations favoring survival. We then established a CIMP-related prognostic gene signature comprising six genes (CST6, SLC7A2, RAB3B, IGFBP1, VSTM2LandEVX2). The signature was capable of classifying patients into high‐and low‐risk groups with significant difference in overall survival (OS;p< 0.0001). To assess performance of the prognostic signature, the area under the ROC curve (AUC) for OS was calculated as 0.664 at 1 year, 0.704 at 3 years and 0.667 at 5 years. When compared with previously published gene-based signatures, our CIMP-related signature was comparable or better at predicting prognosis. A multivariate Cox regression analysis indicated the CIMP-related prognostic gene signature was an independent prognostic indicator of GC. In addition, Gene ontology analysis indicated that keratinocyte differentiation and epidermis development were enriched in the high-risk group.ConclusionCollectively, we described a positive association between CIMP status and prognosis in GC and proposed a CIMP-related gene signature as a promising prognostic biomarker for GC.
GTP and guanosine synergistically enhance NGF‐induced neurite outgrowth from PC12 cells
Authors: Gysbers J.W. , Rathbone M.P. 
Published: July 2002

AbstractSix per cent of rat pheochromocytoma (PC12) cells extended neurites (processes greater than one cell diameter in length) in the presence of 300 μM extracellular GTP or 300 μM guanosine for 48 hr, compared to only 2.5% of cells in control cultures. In the presence of 40 ng/ml of 2.5S NGF, about 20–35% of PC12 cells had neurites after 48 hr, and the addition of 300 μM guanosine or GTP together with NGF synergistically increased the proportion of cells with neurites to 40–65%. GTP and guanosine also increased the average number of branches per neurite, from 0.6 in NGF‐treated cultures to 1.2 (guanosine) or 1.5 (GTP). Neurites formed after exposure to NGF alone had axonal characteristics as determined by immunocytochemistry with antibody, SMI‐31, against axonal‐specific polyphosphorylated neurofilament epitopes. Neurites generated with the addition of both guanosine or GTP had the same characteristics.GTP probably did not exert its effects via the P2X or P2Y purinoceptors because the adenine nucleotides ATP, ATPγS, ADPβS, and ADP, which are all agonists of these receptors, inhibited rather than enhanced, NGF‐induced neurite outgrowth. UTP also enhanced the proportion of cells with neurites, although not to the same degree as did GTP. This may indicate activity through a P2U‐like nucleotide receptor. However, the response profile obtained, GTP > UTP ≫ ATP, does not fit the profile of any known P2Y, P2X or P2U receptor. The poorly hydrolyzable GTP analogues, GTPγS and GDPβs were also unable to enhance the proportion of cells with neurites. This implied that GTP may produce its effects through a GTP‐specific ectoenzyme or kinase. This idea was supported by results showing that another poorly hydrolyzable analogue, GMP‐PCP, competitively inhibited the effects of GTP on neurite outgrowth. GTP did not exert its effects after hydrolysis to guanosine since the metabolic intermediates GDP and GMP were also ineffective in enhancing the proportion of cells with neurites. Moreover, the effects of GTP and guanosine were mutually additive, implying that these two purines utilized different signal transduction mechanisms.The effects of guanosine were not affected by the nucleoside uptake inhibitors nitrobenzylthioinosine (NBTI) and dipyridamole, indicating that a transport mechanism was not involved. Guanosine also did not activate the purinergic P1 receptors, because the A2 receptor antagonists, 1, 3‐dipropyl‐7‐methylxanthine (DPMX) or CGS15943, and the At receptor antagonist, 1, 3‐dipropyl‐8‐(2‐amino‐4‐chloro)xanthine (PACPX) did not inhibit its reaction. Therefore guanosine enhanced neurite outgrowth by a signal transduction mechanism that does not include the activation of the Pt purinoceptors.The enhancement of the neuritogenic effects of NGF by GTP and guanosine may have physiological implications in sprouting and functional recovery after neuronal injury in the CNS, due to the high levels of nucleosides and nucleotides released from dead or injured cells.
Antidepressant effect of 5-methoxypsoralen: the melatonin synchronizer hypothesis
Authors: Darcourt G , Feuillade P , Bistagnin Y , Robert P , Pringuey D , Touari M , Merdji Y , Bensmaïl B 
Published: July 2002

Summary5-methoxypsoralen (5-MOP) stimulates pineal melatonin secretion, and a decrease in dark phase melatonin levels has been described in major depression. As exogenous melatonin has shown synchronizer properties, authors hypothesized that giving 5-MOP would have antidepressant properties.Twenty-six inpatients meeting the criteria of major depressive disorders were enrolled in a four-week, double blind trial of 5-MOP versus amitriptyline. Clinical improvement was identical in both treatment groups but biological changes were different in each group: 5-MOP patients showed an early nocturnal surge of melatonin levels that was maintained at the fourth treatment week, while melatonin levels remained unchanged in patients treated with amitriptyline.
Evaluation of chemical tests for fetal bleeding from vasa previa
Authors: Odunsi K. , Bullough C.H.W. , Henzel J. , Polanska A. 
Published: July 2002

AbstractObjectives: To evaluate different alkaline denaturation tests and compare with hemoglobin electrophoresis and the Kleihauer test, and to identify the simplest and most sensitive test that may help to rapidly show the presence of fetal hemoglobin and establish the diagnosis of fetal bleeding from vasa previa. Methods: Maternal and fetal cord blood were obtained from 20 women with uncomplicated deliveries and the samples were mixed in known concentrations ranging from 0–100% fetal blood. Further samples were prepared in which maternal and fetal blood mixtures were diluted with amniotic fluid so that the final concentration of fetal hemoglobin similarly ranged from 0–100%. Alkaline denaturation tests (Apt, Ogita, Loendersloot), hemoglobin electrophoresis and Kleihauer tests were performed on all 40 samples. Results: The Apt and Loendersloot tests were clearly positive at 60% concentrations of fetal blood. It took approximately 7 and 4 min, respectively, to complete the tests. The Ogita test was positive from fetal blood concentrations of 20% and took ~ 5 min. Hemoglobin electrophoresis took ~ 1 h to complete and the Hb‐F band was present even at 0% concentration of fetal blood and the band became more marked with increasing fetal blood concentration. The Kleihauer test was negative at 0% but positive from 0.01% fetal blood concentration. The test took ~ 45 min to perform. Conclusions: The Ogita test is the best all round alkaline denaturation test that may help to rapidly identify the presence of fetal hemoglobin and so establish the need to expedite delivery when there is fetal bleeding from vasa previa. It is simple to perform, does not require sophisticated equipment, unlikely to give false positive results, and takes only 5 min. The simplicity of the test makes it attractive for routine use on the labor ward.
Fertility and pregnancy in inflammatory bowel disease
Authors: Hudson M. , Flett G. , Sinclair T.S. , Brunt P.W. , Templeton A. , Mowat N.A.G. 
Published: July 2002

AbstractObjective: A retrospective study of women with inflammatory bowel disease, aged 16–45 years during the 20‐year period 1967–1986, was carried out in North East Scotland. Method: Five‐hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. Results: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. Conclusions: Overall, at conception women with active disease were as likely to have a normal full‐term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.
Safety and efficacy of stripping of membranes at term
Authors: Gupta R , Vasishta K , Sawhney H , Ray P 
Published: July 2002

AbstractObjectives: To assess the efficacy of stripping of membranes in initiation of labor and to study its effect on maternal and perinatal morbidity. Method: One‐hundred primigravidae with certain gestational dates were randomized at 38 weeks gestation to either receive stripping of membranes or only gentle cervical examination. Cervical swabs were taken before pelvic examination at 38 weeks and again at the onset of labor. Placental membranes were sent for bacteriological study after delivery in all patients. Results: The mean gestational age, parity and Bishop score were similar in both groups at recruitment. Gestational age at delivery was lower in the study group (38.70±0.63) compared to the control group. Seventy‐two percent of the study group and 8% of the control group had spontaneous onset of labor within 7 days of examination. Labor was induced in one patient (2%) of the study group and 16 patients (32%) of the control group. No statistically significant difference was noted in incidence of premature rupture of membranes (PROM), mode of delivery, intrapartum events and perinatal outcome. No increase in neonatal morbidity was seen in association with this procedure. No patient in the study group had clinical evidence of chorioamnionitis. There was no statistically significant difference in the microbiological flora of both groups. Conclusion: Stripping of the fetal membranes is a safe and efficacious procedure for induction of labor. It decreases the incidence of induction of labor with no increase in incidence of maternal and neonatal morbidity.
Preeclampsia, labor duration and mode of delivery
Authors: Edwards C. , Witter F.R. 
Published: July 2002

AbstractObjective: To determine if there is a difference in the length of labor, and method of delivery between preeclamptic and normotensive patients. Methods: A retrospective case control study was performed using a perinatal database. Study subjects included nulliparous patients diagnosed with preeclampsia, and were compared with normotensive nulliparous patients. Results: There were 1454 controls and 727 subjects identified. There was no difference between groups with regard to duration of total labor. There was a statistically but not clinically significant increase in the duration of the second stage in preeclamptics (35 vs. 27 min, P = 0.003). Preeclamptics had a consistently higher risk of cesarean delivery, even when controlled for confounding variables. Conclusion: The clinical belief that preeclamptic patients have more rapid labors is not supported. Preeclamptics do seem to have a higher risk of cesarean delivery.
The effects of systemic hormonal replacement therapy on the skin of postmenopausal women
Authors: Sauerbronn A.V.D , Fonseca A.M , Bagnoli V.R , Saldiva P.H , Pinotti J.A 
Published: July 2002

AbstractObjective: The aim of this study was to determine the effects of hormonal replacement therapy on the skin of postmenopausal women. Method: Forty‐one postmenopausal women were randomly allocated to receive either hormonal replacement (valerate estradiol — 2 mg/day for 21 days and cyproterone acetate — 1 mg/day for 10 days) or placebo, both in a cyclic scheme for 6 months. Neither patients nor investigators were aware of the group allocation. Histologic changes were evaluated by skin biopsy of the left upper arm at baseline and after 6 months of treatment, utilizing computerized image analysis to assess the ratio area of epidermis/basement membrane length (AE/BML), ratio area of keratin/basement membrane length (AK/BML) and collagen and elastic fibers content. Result: Collagen content of the left upper arm increased after 6 months of treatment only in the hormonal group (+6.49%; P<0.05). Other parameters did not present any significant alteration after treatment in both groups. Conclusion: Hormonal replacement for climacterics increases skin collagen content.
A novel approach to studying the migratory morphology of embryonic mesenchymal cells
Authors: Harkin Damien G. , Bianco John I. , Collins Natalie 
Published: July 2002

A polarized morphology, defined by extension of an anterior pseudopod, is essential for the amoeboid migration of embryonic mesenchymal cells. Leukocytes adopt a similar morphology immediately following suspension in simple buffers containing chemotactic factors. Polarization in suspension therefore provides a rapid and sensitive screening assay for putative regulators of leukocyte migration. The aim of the present study was to investigate whether this assay might also be used to study the motile behaviour of embryonic mesenchymal cells. Primary cultures of mesenchymal cells were established from explants of stage 28 chick embryo corneal‐limbal stroma. Serum‐starved, subconfluent cultures were harvested using ethylene‐diamine tetra‐acetic acid and resuspended in Hanks’ solution for up to 15 min at 37 °C. A variety of cell shapes, including spherical cells, blebbed cells, and cells with either non‐polarized or polarized pseudopodia were observed. The proportions of cells with pseudopodia increased significantly over time. Treatment of cells with the chemotactic mitogen platelet derived growth factor‐BB (PDGF‐BB, homodimer isoform) suppressed blebbing and increased both pseudopod formation and polarization. Optimal polarization occurred in concentrations of PDGF‐BB that are similar to those required for optimal chemotaxis (10 ng·mL–1). The polarization observed in the absence of PDGF‐BB suggests that the migration of cells examined in this study might be controlled at least in part by some intrinsic mechanism. In addition, the strong polarization response to PDGF‐BB confirms the role for this growth factor during corneal development. Observations of mesenchymal cell morphology in suspension, therefore provide novel data regarding the motile behaviour of embryonic cells.
New service development: areas for exploitation and exploration
Authors: Menor Larry J. , Tatikonda Mohan V. , Sampson Scott E. 
Published: July 2002

AbstractThe management of new service development (NSD) has become an important competitive concern in many service industries. However, NSD remains among the least studied and understood topics in the service management literature. As a result, our current understanding of the critical resources and activities to develop new services is inadequate given NSD’s importance as a service competitiveness driver. Until recently, the generally accepted principle behind NSD was that “new services happen” rather than occurring through formal development processes. Recent efforts to address this debate have been inconclusive. Thus, additional research is needed to validate or discredit the belief that new services happen as a result of intuition, flair, and luck. Relying upon the general distinctions between research exploitation and exploration, this paper describes areas in NSD research that deserve further leveraging and refinement (i.e. exploitation) and identifies areas requiring discovery or new study (i.e. exploration). We discuss the critical substantive and research design issues facing NSD scholars such as defining new services, choice in focusing on the NSD process or performance (or both), and specification of unit of analysis. We also examine what can be exploited from the study of new product development to further understanding of NSD. Finally, we explore one important area for future NSD research exploration: the impact of the Internet on the design and development of services. We offer research opportunities and research challenges in the study of NSD throughout the paper.
Age‐ and gender‐related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors
Authors: Muschler George F. , Nitto Hironori , Boehm Cynthia A. , Easley Kirk A. 
Published: July 2002

AbstractBone marrow harvested by aspiration contains connective tissue progenitor cells which can be induced to express a bone phenotype in vitro. The number of osteoblastic progenitors can be estimated by counting the colony‐forming units which express alkaline phosphatase (CFU‐APs). This study was undertaken to test the hypothesis that human aging is associated with a significant change in the number or prevalence of osteoblastic progenitors in the bone marrow. Four 2‐ml bone marrow aspirates were harvested bilaterally from the anterior iliac crest of 57 patients, 31 men (age 15–83) and 26 women (age 13–79). A mean of 64 million nucleated cells was harvested per aspirate. The mean prevalence of CFU‐APs was found to be 55 per million nucleated cells. These data revealed a significant age‐related decline in the number of nucleated cells harvested per aspirate for both men and women (P = 0.002). The number of CFU‐APs harvested per aspirate also decreased significantly with age for women (P = 0.02), but not for men (P = 0.3). These findings are relevant to the harvest of bone marrow derived connective tissue progenitors for bone grafting and other tissue engineering applications, and may also be relevant to the pathophysiology of age‐related bone loss and post‐menopausal osteoporosis. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.