Miracle-dz/UniFAR-FTUs huggingface dataset:
Ado-trastuzumab emtansine (T-DM1) in HER2+ advanced breast cancer patients: does pretreatment with pertuzumab matter?

AIM We evaluated the outcomes of patients treated with ado-trastuzumab emantasine (T-DM1) after first-line pertuzumab/trastuzumab, compared with those receiving a trastuzumab-only-based regimen. PATIENTS & METHODS Patients who received second-line T-DM1 after pertuzumab/trastuzumab (n = 34) were compared with those who received only trastuzumab (n = 73). RESULTS Overall response rate was 33.3% in patients with prior pertuzumab and 57.1% in the remaining subjects. Disease control rate was 47 and 43%, respectively, and the clinical benefit rate was 43.3 and 71.1%, respectively. Median progression-free survival was 5.0 and 11.0 months, respectively (hazard ratio: 2.02; 95% CI: 1.14-3.58; p = 0.01). CONCLUSION Patients treated with T-DM1 who previously received pertuzumab present poorer clinical outcomes compared with those receiving a trastuzumab-only-based regimen in the first-line setting.
Diagnosis-to-treatment interval and control of locoregionally advanced head and neck cancer.

OBJECTIVE To assess the impact of prolonged diagnosis-to-treatment interval (DTI) that falls in the time frame associated with the increasing complexity of planning treatment for patients with locoregionally advanced head and neck cancer (LAHNC). DESIGN Retrospective study. SETTING The University of Alabama at Birmingham. PATIENTS An institutional database was searched for all patients with LAHNC who were treated with radiotherapy between 1995 and 2007 at the University of Alabama at Birmingham. After patients with prior treatment for head and neck cancer (including surgery or neoadjuvant chemotherapy), patients younger than 18 years, and patients with stage I or II tumors were excluded, 427 patients remained for analysis. MAIN OUTCOME MEASURES The DTI was defined as the time in days between the date that a biopsy specimen showing malignancy was obtained and the first day of radiotherapy. RESULTS The median DTI was 34 days (range, 7-441 days). A longer DTI was not significantly associated with locoregional control (P = .11), distant metastases-free survival (P = .32), or overall survival (P = .07). CONCLUSION A prolonged DTI did not appear to adversely affect outcomes in this cohort of patients with LAHNC.
he sensing of respiratory gases in fish : Mechanisms and signalling athways

Chemoreception in fish is critical for sensing changes in the chemical composition of the external and internal environments and is often the first step in a cascade of events leading to cardiorespiratory and metabolic adjustments. Of paramount importance is the ability to sense changes in the levels of the three respiratory gases, oxygen (O2), carbon dioxide (CO2) and ammonia (NH3). In this review, we discuss the role of piscine neuroepithelial cells (NEC), putative peripheral chemoreceptors, as tri-modal sensors of O2, CO2 and NH3. Where possible, we elaborate on the signalling pathways linking NEC stimulation to afferent responses, the potential role of neurotransmitters in activating downstream neuronal pathways and the impact of altered levels of the respiratory gases on NEC structure and function. Although serotonin, the
Enhancement of cisplatin cytotoxicity in combination with herniarin in vitro

Abstract Combinatorial chemotherapy is a valuable route, which can be conducted by different approaches. Use of cisplatin has been approved by the U.S. Food and Drug Administration for different kinds of cancers including bladder cancer. Herniarin is a member of simple coumarins, which are a group of common secondary metabolites in plants. In this study, the enhancing effects of herniarin on cisplatin cytotoxicity were investigated. Cytotoxicity of herniarin on transitional cell carcinoma (TCC) cells was first investigated in comparison with umbelliferone, the parent compound for a large number of coumarins including herniarin, by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. In order to test the effects of herniarin on cisplatin cytotoxicity, TCC cells were also treated with various combining concentrations of herniarin and cisplatin. In these experiments same amounts of dimethyl sulfoxide were used as controls. After 24, 48 and 72 h of treatments, the effects of herniarin on cisplatin cytotoxicity were evaluated by MTT assay. The level of chromatin condensation which represents the apoptotic morphology was also investigated by 4′,6-diamidino-2-phenylindole (DAPI) staining. Results indicated that unlike umbelliferone, its methoxy analog, herniarin, had no significant cytotoxicity on TCC cells. On the other hand, the combination of 80 µg/mL herniarin with 5 µg/mL cisplatin, significantly enhanced the cytotoxicity of cisplatin. Furtheremore, DAPI staining revealed that combining concentrations of herniarin and cisplatin resulted in increased chromatin condensation in comparison with controls. This study is another confirmation for bioactivity of herniarin and shows that it might be a good candidate for further experiments investigating its mechanism of action.
Comparación entre síntomas de estrés según el curso

Los efectos del estres academico estan mediados por factores, que pueden actuar como protectores o facilitadores del estres, como son las variables sociodemograficas y socioeducativas, sexo del estudiante y curso academico. Se plantea que hombres y mujeres comparten muchas influencias ambientales pero tambien que son socializados de acuerdo a diferentes patrones que pueden afectar a la forma en que se situan frente a las experiencias estresantes y a las respuestas que generan ante el. Ademas, existen evidencias de que los estudiantes noveles y de ultimo curso padecen mayores niveles de estres. Con el fin de averiguar si existen diferencias de genero en el padecimiento sintomas de estres en funcion del curso academico se realizo este estudio observacional en una poblacion de 264 estudiantes. Los resultados muestran que el estres se percibe de manera diferente segun el curso academico, aumentando la aparicion de los sintomas de estres en los primeros cursos y disminuyendo su aparicion el ultimo curso de la titulacion. Ademas, se evidencia una distribucion muy homogenea de las respuestas de estres por parte de las mujeres que muestran valores superiores con respecto al experimentado en los hombres, lo que refleja un peor manejo del estres de la poblacion femenina.
Detection of piluslike structures on clinical and environmental isolates of Vibrio vulnificus

Twenty clinical isolates of Vibrio vulnificus were compared with 10 environmental strains by using electron microscopy and agglutination assays with human erythrocytes, guinea pig erythrocytes, and Saccharomyces cerevisiae. In addition, the isolates were tested for ability to adhere to the human epithelial cell lines HEp-2 and A549. When examined by electron microscopy, 16 (80%) of the 20 clinical isolates demonstrated the presence of piluslike structures; the composition of the bacterial populations ranged from 0 to 68% piliated cells. In contrast, only 3 (30%) of the 10 environmental isolates were piliated, with a range from 0 to 16% piliated cells. A significant association between the presence of piliated cells and the isolate source was found (P less than 0.05). None of the 30 strains agglutinated erythrocytes or yeast cells. V. vulnificus adherence results obtained with HEp-2 cells showed 10 (50%) of 20 clinical isolates and 0 (0%) of 10 environmental isolates with averages of greater than 10 adherent bacteria per cell, demonstrating a correlation between attachment and the isolate source (P less than 0.05). Selected strains were tested to determine whether methyl alpha-D-mannopyranoside, fructose, or alpha-L-(-)-fucose would inhibit bacterial adherence to HEp-2 cells. Multiple patterns of adherence inhibition were observed. Adherence to A549 cells showed 8 (40%) of 20 clinical isolates and 0 (0%) of 10 environmental strains with averages of greater than 10 adherent bacteria per cell. A statistical association between attachment and the isolate source was demonstrated (P less than 0.05). These data suggest that the presence of piluslike structures and the ability to adhere to human epithelial cell lines may be more closely associated with V. vulnificus isolates from clinical specimens than with environmental strains.
Complicações e impacto da remoção de terceiros molares na qualidade de vida relacionada à saúde bucal de jovens e adultos

remocao dos terceiros molares pode ser seguida de complicacoes pos-operatorias. Dor, edema, hemorragia e infeccao sao os principais problemas relatados apos o procedimento cirurgico. Tais condicoes causam relativo desconforto aos individuos, afetando sua rotina diaria. O objetivo desta tese foi avaliar a prevalencia de complicacoes pos-operatorias em individuos que realizaram a extracao dos terceiros molares nas clinicas de cirurgia do Curso de Odontologia da Universidade Federal de Santa Maria dos anos 2000 a 2015. Assim como, avaliar o impacto na qualidade de vida relacionada a saude bucal (QVRSB) dos individuos da remocao no pos-operatorio de sete e 30 dias. Um total de 3657 terceiros molares foram extraidos ao longo de 15 anos. Os dados foram tabulados e a analise descritiva realizada obtendo-se a prevalencia de qualquer complicacao pos-operatoria. A avaliacao das complicacoes com fatores associados foi verficada atraves da analise de regressao. Para a avaliacao do impacto na QVRSB, 75 pacientes responderam ao questionario OHIP-14 antes do procedimento cirurgico. Outras duas avaliacoes foram realizadas sete e trinta dias apos a extracao do terceiro molar. Os pacientes tambem indicaram a ocorrencia de dor e edema durante este periodo. A analise descritiva foi calculdada para as variaveis clinicas e demograficas e para dados clinicos pre- e pos-operatorios. Media e desvio-padrao foram obtidos para cada item do questionario OHIP-14 e a diferenca de media entre os escores pre- e pos-operatorios foi avaliada usando o teste de Wilcoxon. O tamanho do efeito foi realizado para avaliar a diferenca entre os dominios e os escores total do OHIP-14 no pre-operatorio, pos-operatorio de 7 dias e pos-operatorio de 30 dias. Complicacoes pos-operatorias foram observadas em 1108 (30,33%) dos individuos. Individuos do sexo feminino, que extrairam terceiros molares inferiores inclusos/semi-inclusos e que fizeram uso de medicacao antibiotica e anti-inflamatoria apresentaram maior probabilidade de apresentar alguma complicacao pos-operatoria. Quanto ao impacto na qualidade de vida, a media dos escores do OHIP-14 aumentou ao longo de 7 dias pos-operatorio, demonstrando impacto negativo na qualidade de vida dos individuos. Ao longo do periodo de trinta dias, porem, retornaram a niveis inferiores ao pre-operatorio. Em funcao da alta prevalencia de complicacoes e do impacto negativo na qualidade de vida dos individuos nos primeiros sete dias apos o procedimento cirurgico concluimos dessa forma que tais condicoes devem ser considerados durante a tomada de decisao do paciente e profissional pela remocao dos terceiros molares.
Dendritic Cells from Mice Neonatally Vaccinated with Modified Vaccinia Virus Ankara Transfer Resistance against Herpes Simplex Virus Type I to Naive One-Week-Old Mice1

Modified vaccinia Ankara (MVA) is an attenuated virus. MVA induces the production of IFN and Flt3-L (FL), which results in the expansion of dendritic cells (DC) and enhanced resistance against viral infections. We report on the interplay among IFN, FL, and DC in the resistance against heterologous virus after injection of neonatal mice with MVA. The induction of serum FL was tested on day 2, and the expansion of DC was tested 1 wk after treatment with MVA. At this time point the resistance against infection with heterologous virus was also determined. After MVA treatment, serum FL was enhanced, and DC, including plasmacytoid cells in spleen, were increased in number. Mice that lacked functional IFN type I and II systems failed to increase both the concentration of FL and the number of DC. Treatment with MVA enhanced resistance against HSV-1 in wild-type animals 100-fold, but animals without a functional IFN system were not protected. Transfer of CD11c+ cells from MVA-treated mice into naive animals protected against lethal infection with HSV-1. Thus, although the increased resistance could be largely attributed to the increase in activation of IFN-producing plasmacytoid cells, this, in turn, depends on a complex interplay between the DC and T cell systems involving both FL and IFNs.
Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND Previous studies have shown that high fiber intake is associated with lower mortality. However, little is known about the association of dietary fiber with specific causes of death other than cardiovascular disease (CVD). OBJECTIVE The aim of this study was to assess the relation between fiber intake, mortality, and cause-specific mortality in a large European prospective study of 452,717 men and women. DESIGN HRs and 95% CIs were estimated by using Cox proportional hazards models, stratified by age, sex, and center and adjusted for education, smoking, alcohol consumption, BMI, physical activity, total energy intake, and, in women, ever use of menopausal hormone therapy. RESULTS During a mean follow-up of 12.7 y, a total of 23,582 deaths were recorded. Fiber intake was inversely associated with total mortality (HR(per 10-g/d increase): 0.90; 95% CI: 0.88, 0.92); with mortality from circulatory (HR(per 10-g/d increase): 0.90 and 0.88 for men and women, respectively), digestive (HR: 0.61 and 0.64), respiratory (HR: 0.77 and 0.62), and non-CVD noncancer inflammatory (HR: 0.85 and 0.80) diseases; and with smoking-related cancers (HR: 0.86 and 0.89) but not with non-smoking-related cancers (HR: 1.05 and 0.97). The associations were more evident for fiber from cereals and vegetables than from fruit. The associations were similar across BMI and physical activity categories but were stronger in smokers and participants who consumed >18 g alcohol/d. CONCLUSIONS Higher fiber intake is associated with lower mortality, particularly from circulatory, digestive, and non-CVD noncancer inflammatory diseases. Our results support current recommendations of high dietary fiber intake for health maintenance.
Mucopolysaccharidoses: autoradiographic study of sulphate‐35S uptake by cultured fibroblasts

Hurler syndrome and Morquio disease are inborn errors of metabolism which result in an accumulation of acid mucopolysaccharides (AMPS) in various tissues of the body. Danes & Bearn (1965, 1966) demonstrated the persistence of metachromatic granules due to the presence of AMPS in the cytoplasm of cultured fibroblasts from the skin of patients with Hurler’s syndrome, and Matalon & Dorfman (1 966) showed that incorporation of ~u lpha te -~~S by cultured fibroblasts from Hurler’s patients is distinctly higher than that by normal cells. In a previous note (Fraccaro et al. 1967) we described the persistence of metachromasia also in cultured fibroblasts from Morquio patients, a finding concurrently discovered by Danes & Bearn (1967a) on much larger material. We report here on an autoradiographic study of the uptake and distribution of 35S04 in cultured fibroblasts from Morquio and Hurler patients. The main purpose of this investigation was to convince ourselves of a correspondence between the histochemical demonstration of metachromatic granules and location of the autoradiographic grains resulting from the incorporation into AMPS of the radioactive sulphate. In the course of the investigation, however, we found that cultured fibroblasts from two sisters with Morquio’s disease were consistently negative for metachromasia and for uptake of radioactive sulphate. The significance of this negative finding will be also discussed.
Omsorgsinriktat lärande : en studie om lärande i hemtjänsten

Studien ar utford i tva norrlandskommuner i 6 olika hemtjanstgrupper. Syftet med studien har varit studera larandets forutsattningar och villkor i hemtjansten. Metoden som anvants ar en etnografisk .
Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats.

Glucagon-like peptide-1 (GLP-1) is an incretin, which induces glucose-dependent insulin secretion. GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. We investigated whether DPPIV-deficient F344/DuCrj rats show improved glucose tolerance when compared with DPPIV-positive F344/Jcl rats. Oral glucose tolerance test indicated improved glucose tolerance in F344/DuCrj rats, but blood glucose levels of the two strains were almost the same 120 min after the glucose bolus. Valine-pyrrolidide, a DPPIV inhibitor, had no effect on the glucose tolerance of F344/DuCrj rats, but improved that of F344/Jcl rats. Enhanced insulin secretion and high plasma active GLP-1 levels were detected in an intraduodenal glucose tolerance test. Glucose tolerance is improved in DPPIV-deficient F344/DuCrj rats via enhanced insulin release mediated by high active GLP-1 levels. Our results suggest that DPPIV inhibition is a rational strategy to treat diabetic patients by improving glucose tolerance with low risk of hypoglycemia.
EFFECT OF IMMUNOSUPPRESSIVE DRUGS (AZATHIOPRINE)

For more than 18 years, we have been treating myasthenic patients with cytostatic drugs. We began with 6-mercaptopurin, actinomycin and ametopterin but we were forced to discontinue routine usage when serious side effects became evident. For the last 1 1 years, we have been using azathioprine at a dosage of 150-200 mg daily and have published our experiences with the drug at various times, mainly in German journals.l, * In 1978 we were able to report our results with azathioprine at the Plasmapheresis Conference in San Francisco; 5 , since then, many myasthenia clinics have accepted azathioprine usage; however, mostly in connection with plasmaphere~is. ~-T Little new data have been uncovered during the last years concerning azathioprine treatment. First impressions about cytostatic drugs in myasthenia were published originally by Mertens in 1969; the experiences of other European authors O-I2 and our own multicenter-study results in 1976 2, have been mainly affirmed.
Does Ischemia Time Affect the Outcome of Free Fibula Flaps for Head and Neck Reconstruction? A Review of 116 Cases

Background: The fibula osteoseptocutaneous flap is an excellent option for the reconstruction of segmental mandibular defects. This study was conducted to investigate the relationship between ischemia time and outcome of the fibula flap, thus establishing the critical ischemia time for this procedure. Methods: Between February of 2003 and March of 2005, 114 patients who underwent 116 fibular osteoseptocutaneous flaps for head and neck reconstruction were reviewed retrospectively. Complications were classified as acute, subacute, or chronic based on the time at which they were detected postoperatively. Outcomes among different ischemia time groups were evaluated: group A, less than 3 hours; group B, 3 to 4 hours; group C, 4 to 5 hours; and group D, 5 to 7 hours. Results: The mean success rate of the fibula osteoseptocutaneous flap was 98.3 percent. Mean flap ischemia time was 3.6 ± 0.97 hours. Sixty-six patients (56.9 percent) experienced one or more complications at different stages (86 complications total). There were no statistically significant differences in acute, subacute, and chronic complications among the four groups (p = 0.6, p = 0.6, and p = 0.2, chi-square test). The overall complication rate was significantly higher in group D (81.8 percent) (p = 0.03, chi-square test). The partial flap loss rate was also statistically higher in group D (45.5 percent) compared with the other three groups (12.1, 12.2, and 8.7 percent) (p = 0.02, chi-square test). Conclusions: Using the fibula osteoseptocutaneous flap for head and neck reconstruction, ischemia times less than 5 hours do not increase complication rates in different postoperative stages. However, the critical ischemia time of the fibula osteoseptocutaneous flap should be limited to 5 hours to reduce partial skin paddle loss and overall complications.
Effects of international health electives on medical student learning and career choice: results of a systematic literature review.

BACKGROUND AND OBJECTIVES The present study reviewed the published literature to examine the effects of international health electives (IHEs) on medical student learning and career choice. METHODS A systematic literature review was conducted to identify key English-language articles on IHEs, using PubMed journal databases for the period 1990--2009. Article inclusion for this review was vetted by a rigorous evaluation of each article's study methods, content, and data quality. Pooled or aggregate information from 11 key articles, including information on type and duration of IHE, study and comparison group characteristics, and measured outcomes such as self-reported changes in cultural competency, clinical skills, and specialty choice, were extracted and summarized. RESULTS Findings suggest that having IHE experiences contributed to a more well-rounded training for medical students; students reported being more culturally competent and were more likely to choose a primary care specialty and/or a public service career. CONCLUSIONS Although IHE experiences appear to have educational benefits, the quality and availability of these electives vary by institution. Barriers to ensuring that students attain a safe and rich experience include the lack of consistent categorical funding, safety concerns when traveling, and limited faculty experience and resources to support and guide students during their rotations abroad.
Expression and function of B7‐1 and B7‐2 in hapten‐induced contact sensitivity

We analyzed the expression and function of the co‐stimulatory molecules B7‐1 (CD80) and B7‐2 (CD86) during contact sensitivity reactions induced by the hapten 2,4‐dinitrofluorobenzene (DNFB). In the normal skin, only a few epidermal Langerhans cells or dermal dendritic cells express B7‐2. In contrast, following challenge with DNFB, expression of B7‐2 is up‐regulated in both epidermis and dermis. Importantly, B7‐1 is induced later and at lower levels compared to B7‐2. Intravenous injections of anti‐B7‐2 mAb, but not anti‐B7‐1 mAb partially inhibit the hapten‐induced contact sensitivity reaction. Experiments in which mice are injected differentially with anti‐B7‐2 mAb, either before the afferent or before the efferent phase of the contact sensitivity response, suggest that B7‐2 is important for successful antigen priming.
p-Akt and its relationship with clinicopathological features and survival in oral squamous cell carcinoma: an immunohistochemical study.

BACKGROUND The aim of this study was to evaluate, through immunohistochemical reaction in samples of oral squamous cell carcinoma, the correlation between the expression status of protein kinase B (p-Akt) and patient survival as well as histological grade and some clinicopathological features. METHODS Samples were collected from 46 patients with oral squamous cell carcinoma. The immunohistochemical expression of p-Akt was analysed, as were clinicopathological features including the use of tobacco, tumour stage, size and infiltration of metastatic lymph nodes. The association of immunostaining with histological grade was analysed in 40 patients. The associations were examined for statistical significance using a chi-square test. Overall survival rates were estimated by the Kaplan-Meier method and compared using a log rank test (P > 0.05). RESULTS The results indicated a statistically significant association with p-Akt immunostaining for the variables lymph node metastasis (P = 0.006), tumour size (P = 0.044) and survival rate (P = 0.0298). CONCLUSION From these results, the present study suggests that high p-Akt expression found in oral squamous cell carcinoma patients may contribute to tumour growth, metastasis to regional lymph nodes and shorter survival time.