Miracle-dz/UniFAR-FTUs huggingface dataset:
Resective surgery for medically refractory epilepsy using intraoperative MRI and functional neuronavigation: the Erlangen experience of 415 patients.

OBJECTIVE Intraoperative overestimation of resection volume in epilepsy surgery is a well-known problem that can lead to an unfavorable seizure outcome. Intraoperative MRI (iMRI) combined with neuronavigation may help surgeons avoid this pitfall and facilitate visualization and targeting of sometimes ill-defined heterogeneous lesions or epileptogenic zones and may increase the number of complete resections and improve seizure outcome. METHODS To investigate this hypothesis, the authors conducted a retrospective clinical study of consecutive surgical procedures performed during a 10-year period for epilepsy in which they used neuronavigation combined with iMRI and functional imaging (functional MRI for speech and motor areas; diffusion tensor imaging for pyramidal, speech, and visual tracts; and magnetoencephalography and electrocorticography for spike detection). Altogether, there were 415 patients (192 female and 223 male, mean age 37.2 years; 41% left-sided lesions and 84.9% temporal epileptogenic zones). The mean preoperative duration of epilepsy was 17.5 years. The most common epilepsy-associated pathologies included hippocampal sclerosis (n = 146 [35.2%]), long-term epilepsy-associated tumor (LEAT) (n = 67 [16.1%]), cavernoma (n = 45 [10.8%]), focal cortical dysplasia (n = 31 [7.5%]), and epilepsy caused by scar tissue (n = 23 [5.5%]). RESULTS In 11.8% (n = 49) of the surgeries, an intraoperative second-look surgery (SLS) after incomplete resection verified by iMRI had to be performed. Of those incomplete resections, LEATs were involved most often (40.8% of intraoperative SLSs, 29.9% of patients with LEAT). In addition, 37.5% (6 of 16) of patients in the diffuse glioma group and 12.9% of the patients with focal cortical dysplasia underwent an SLS. Moreover, iMRI provided additional advantages during implantation of grid, strip, and depth electrodes and enabled intraoperative correction of electrode position in 13.0% (3 of 23) of the cases. Altogether, an excellent seizure outcome (Engel Class I) was found in 72.7% of the patients during a mean follow-up of 36 months (range 3 months to 10.8 years). The greatest likelihood of an Engel Class I outcome was found in patients with cavernoma (83.7%), hippocampal sclerosis (78.8%), and LEAT (75.8%). Operative revisions that resulted from infection occurred in 0.3% of the patients, from hematomas in 1.6%, and from hydrocephalus in 0.8%. Severe visual field defects were found in 5.2% of the patients, aphasia in 5.7%, and hemiparesis in 2.7%, and the total mortality rate was 0%. CONCLUSIONS Neuronavigation combined with iMRI was beneficial during surgical procedures for epilepsy and led to favorable seizure outcome with few specific complications. A significantly higher resection volume associated with a higher chance of favorable seizure outcome was found, especially in lesional epilepsy involving LEAT or diffuse glioma.
Assistência à saúde dos homens: um desafio para os serviços de atenção primária

O texto discute como os servicos de atencao primaria podem contribuir para uma pratica saudavel por parte da populacao masculina. Tal objetivo implica a discussao de estrategias que envolvem os homens como sujeitos confrontados com as diferentes dimensoes da vida; os servicos na maneira como eles se organizam para atender os usuarios considerando suas particularidades; e os vinculos estabelecidos entre os homens e os servicos e vice-versa. Como fundamentacao teorica, prevalecem os conceitos de genero e de necessidade em saude. Esses conceitos sao relacionados a experiencia pratica desenvolvida no Centro de Saude Escola Samuel B. Pessoa, localizado no bairro do Butanta, na cidade de Sao Paulo.
A Survey of Intravenous Sodium Bicarbonate in Neonatal Asphyxia among European Neonatologists: Gaps between Scientific Evidence and Clinical Practice

Background: Birth asphyxia is characterized by intermittent periods of hypoxia/ischemia leading to metabolic acidosis. The use of intravenous sodium bicarbonate (IVSB) is still a matter of controversy in clinical practice. Objective: To assess the use of IVSB in birth asphyxia by attending neonatologists in European hospitals. Design/Methods: Survey using a questionnaire administered to neonatologists in Europe whose electronic addresses were provided by the national councils of neonatology of each participating country. The questionnaire consisted of a brief theoretical introduction followed by demographic questions related to the respondent’s professional qualification. This was followed by a clinical case of an asphyxiated term neonate with severe combined metabolic and respiratory acidosis and case-specific questions related to the perceived indication for administration of IVSB and use of additional therapies to address the clinical situation. Descriptive statistics and χ2 analysis were performed. Results: The questionnaire was answered by 259 neonatologists from 17 countries. IVSB was believed to be indicated by 109 (42.2%) of the respondents in this clinical scenario. Results differed significantly between countries, with IVSB use varying from as high as 68% in Portugal and <5% in Scandinavian countries. However, there were no differences in the choice of other therapeutic measures. Conclusions: Although scientific evidence suggests that IVSB is not effective in asphyxiated newborns and current guidelines do not recommend its use, 42.2% of the consulted neonatologists in Europe would use it, with significant differences between but not within countries. There were no differences regarding additional measures to overcome asphyxia. Strategies to implement use of internationally accepted guidelines are needed.
Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction

Background: Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. Methods: We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. Results: The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1–2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. Conclusions: Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT00526474.
Helping Adolescents Achieve Positive Mental Health: Implications for Social Marketing

This study sought to explore barriers to achieving positive mental health in adolescence from the perspectives of adolescents and their carers. In-depth interviews with male and female adolescents aged 15-17 years and school psychologists practicing in government and private schools provided insight into the mental health problems experienced by adolescents and the most effective ways to resolve these problems. The study found that current levels of community knowledge about mental health problems, the need to maintain a positive self-image, and the use of non-ideal coping skills may be the primary reasons for a reluctance among adolescents to seek help when afflicted with a mental health problem. The findings from this study provide insight for public policy makers and health promotion organisations by suggesting specific social marketing recommendations. In addition, practical information and recommendations are directed towards educators, parents, and adolescents.
Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity

Background Altered regulation of many transcription factors has been shown to be important in the development of leukemia. TWIST2 modulates the activity of a number of important transcription factors and is known to be a regulator of hematopoietic differentiation. Here, we investigated the significance of epigenetic regulation of TWIST2 in the control of cell growth and survival and in response to cytotoxic agents in acute lymphoblastic leukemia. Design and Methods TWIST2 promoter methylation status was assessed quantitatively, by combined bisulfite and restriction analysis (COBRA) and pyrosequencing assays, in multiple types of leukemia and TWIST2 expression was determined by quantitative reverse transcriptase polymerase chain reaction analysis. The functional role of TWIST2 in cell proliferation, survival and response to chemotherapy was assessed in transient and stable expression systems. Results We found that TWIST2 was inactivated in more than 50% of cases of childhood and adult acute lymphoblastic leukemia through promoter hypermethylation and that this epigenetic regulation was especially prevalent in RUNX1-ETV6-driven cases. Re-expression of TWIST2 in cell lines resulted in a dramatic reduction in cell growth and induction of apoptosis in the Reh cell line. Furthermore, re-expression of TWIST2 resulted in increased sensitivity to the chemotherapeutic agents etoposide, daunorubicin and dexamethasone and TWIST2 hypermethylation was almost invariably found in relapsed adult acute lymphoblastic leukemia (91% of samples hypermethylated). Conclusions This study suggests a dual role for epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia, initially through altering cell growth and survival properties and subsequently by increasing resistance to chemotherapy.
Chronic Akt1 Deficiency Attenuates Adverse Remodeling and Enhances Angiogenesis After Myocardial Infarction

Background—Akt1 is a key signaling molecule in multiple cell types, including endothelial cells. Accordingly, Akt1 was proposed as a therapeutic target for ischemic injury in the context of myocardial infarction (MI). The aim of this study was to use multimodal in vivo imaging to investigate the impact of systemic Akt1 deficiency on cardiac function and angiogenesis before and after MI. Methods and Results—In vivo cardiac MRI was performed before and at days 1, 8, 15, and 29 to 30 after MI induction for wild-type, heterozygous, and Akt1-deficient mice. Noninfarcted hearts were imaged using ex vivo stereomicroscopy and microcomputed tomography. Histological examination was performed for noninfarcted hearts and for hearts at days 8 and 29 to 30 after MI. MRI revealed mildly decreased baseline cardiac function in Akt1 null mice, whereas ex vivo stereomicroscopy and microcomputed tomography revealed substantially reduced coronary macrovasculature. After MI, Akt1–/– mice demonstrated significantly attenuated ventricular remodeling and a smaller decrease in ejection fraction. At 8 days after MI, a larger functional capillary network at the remote and border zone, accompanied by reduced scar extension, preserved cardiac function, and enhanced border zone wall thickening, was observed in Akt1–/– mice when compared with littermate controls. Conclusions—Using multimodal imaging to probe the role of Akt1 in cardiac function and remodeling after MI, this study revealed reduced adverse remodeling in Akt1-deficient mice after MI. Augmented myocardial angiogenesis coupled with a more functional myocardial capillary network may facilitate revascularization and therefore be responsible for preservation of infarcted myocardium.
Cytotoxic evaluation of fluvastatin and rosuvastatin and effect of fluvastatin in the hela cell cycle

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, were originally designed to reduce cholesterol biosynthesis and have been extensively used as prevention drugs against hyperlipidemia and cardiovascular conditions. Recently, these compounds have been shown to display chemopreventive activity against cancer. However, the effects of statins on cancer are not completely understood. For this reason, we have studied the cytotoxic effect of rosuvastatin and fluvastatin on three cell tumoral lines: human larynx carcinoma (HEp-2), human nasopharyngeal carcinoma (KB), and human epithelial carcinoma (HeLa). We have found that only fluvastatin has relevant activity against the tumoral cell lines assayed and the capacity to arrest G1-phase, whereas a significant decline was observed in the S-phase percentage. Fluvastatin IC50 were 2.43±0.56 μg/mL (HEp-2), 2.29±0.19 μg/mL (KB), and 5.02±1.52 μg/mL (HeLa), whereas rosuvastatin showed poor activity. These results indicate that the cytotoxic effect of fluvastatin may not depend directly on HMG-CoA reductase inhibition. The antitumor statins effect needs further investigation.
The Effect of Consanguinity on Neonatal Outcomes and Health

Consanguineous marriages constitute a significant fraction of marriages worldwide and confer a major public health concern on newborns. In addition to the risk of acquiring a recessive genetic disease, the offspring of consanguineous parents are plausibly at an increased risk of preterm birth, decreased anthropometric measurements, congenital defects and mortality. How consanguinity confers such an increased risk is still largely unknown. In this review, we discuss the effect of consanguinity on selected gestational outcomes by delineating the different studies that have led to such findings. We also investigate the different conclusions that have emerged regarding the effect of consanguinity on gestational outcomes.
No Signal Intensity Increase in the Dentate Nucleus on Unenhanced T1-weighted MR Images after more than 20 Serial Injections of Macrocyclic Gadolinium-Based Contrast Agents

Purpose To determine the effect of more than 20 serial injections of macrocyclic gadolinium-based contrast agents (GBCAs) on the signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance (MR) images. Materials and Methods In this retrospective, institutional review board-approved study, 33 patients who underwent at least 20 consecutive MR imaging examinations (plus an additional MR imaging for reference) with the exclusive use of macrocyclic GBCAs gadoterate meglumine and gadobutrol were analyzed. SI ratio differences were calculated for DN-to-pons and DN-to-middle cerebellar peduncle (MCP) ratios by subtracting the SI ratio at the first MR imaging examination from the SI ratio at the last MR imaging examination. One-sample t tests were used to examine if the SI ratio differences differed from 0, and Bayes factors were calculated to quantify the strength of evidence for each test. Results Patients underwent a mean of 23.03 ± (standard deviation) 4.20 GBCA administrations (mean accumulated dose, 491.21 mL ± 87.04 of a 0.5 M GBCA solution) with an average of 12.09 weeks ± 2.16 between every administration. Both ratio differences did not differ significantly from 0 (DN-to-pons ratio: -0.0032 ± 0.0154, P = .248; DN-to-MCP ratio: -0.0011 ± 0.0093, P = .521), and one-sided Bayes factors provided substantial to strong evidence against an SI ratio increase (Bayes factor for DN-to-pons ratio = 0.09 and that for DN-to-MCP ratio = 0.12). Conclusion The study indicates that 20 or more serial injections of macrocyclic GBCAs administered with on average 3 months between each injection are not associated with an SI increase in the DN. © RSNA, 2016.
Immunotoxicologic effects of cyclosporine on tumor progression in models of squamous cell carcinoma and B-cell lymphoma in C3H mice

Many immunosuppressive drugs are associated with an increased risk of neoplasia, principally non-melanoma skin cancers and B-cell lymphomas. However, only 6 of the 13 immunosuppressive drugs tested in 2 year bioassays increased the incidence of neoplasia. For example, the 2-year bioassays conducted with cyclosporine (CSA), an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, were negative. The purpose of these investigations was to use transplanted tumor models in immunocompetent, syngeneic mice to gain insight into the failure of the 2-year bioassay to show an increased incidence of neoplasia with CSA. C3H HeN mice were used in a battery of assays with a transplanted squamous cell carcinoma (SCC VII cells) or a B-cell, lymphoma (38C13 cells) cells to study effects of CSA on local growth and metastases, experimental metastases, and progression of established metastases. Mice received CSA twice weekly by subcutaneous (SC) injection at doses of 0.5, 5, or 50 mg/kg; controls received the CSA vehicle. CSA had a modest inhibitory effect on SC tumors initiated by 38C13 cells and on intramuscular tumors initiated by SCC VII cells. CSA also decreased the number of lung colonies and decreased the size, growth fraction and vascularity of established lung metastases initiated by SCC VII cells. In contrast, CSA increased progressive growth of metastases to the sentinel lymph node from an intramuscular SCC VII tumor, but had no effect cellular traffic to the node. In conclusion, CSA at doses up to 50 mg/kg did not facilitate tumor progression and it partially inhibited tumor growth, suggesting that suppression of tumor progression may partially explain the failure of CSA to act as a carcinogen in 2 year bioassays.
Rational Selection of Syngeneic Preclinical Tumor Models for Immunotherapeutic Drug Discovery

Murine syngeneic tumor models are used to study responses to antitumor immunotherapies. To rationalize model selection, the underlying genetic and immunologic biology of the models was analyzed, allowing parallels to be drawn between models and human disease phenotypes. Murine syngeneic tumor models are critical to novel immuno-based therapy development, but the molecular and immunologic features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We used array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles. We identified strong differential gene expression in immune-related pathways and changes in immune cell–specific genes that suggested differences in tumor immune infiltrates between models. Further investigation using flow cytometry showed differences in both the composition and magnitude of the tumor immune infiltrates, identifying models that harbor “inflamed” and “non-inflamed” tumor immune infiltrate phenotypes. We also found that immunosuppressive cell types predominated in syngeneic mouse tumor models that did not respond to immune-checkpoint blockade, whereas cytotoxic effector immune cells were enriched in responsive models. A cytotoxic cell–rich tumor immune infiltrate has been correlated with increased efficacy of immunotherapies in the clinic, and these differences could underlie the varying response profiles to immunotherapy between the syngeneic models. This characterization highlighted the importance of extensive profiling and will enable investigators to select appropriate models to interrogate the activity of immunotherapies as well as combinations with targeted therapies in vivo. Cancer Immunol Res; 5(1); 29–41. ©2016 AACR.
Characterization of Lung Cancer: A 10-Year Experience from a Tertiary Hospital in Yaounde, Cameroon

The incidence rate of lung cancer in Africa is low. However, there are few studies reporting clinical characteristics of lung cancer in African countries. We did a study of lung cancer at the Medical Oncology Service of the Yaounde General Hospital, Cameroon, from January 1998 to December 2007. Out of the 2,355 cancer patients seen at this hospital over a 10-year period, 48 patients (28 men and 20 women) were diagnosed with lung cancer. The average age (SD) of patients was 53 (13) years and ranged from 25 to 80 years. Seven patients were cigarette smokers. The median duration from initial symptoms to visiting doctors was 5 months (interquartile range: 3-11 months). The most common histology types were squamous cell carcinomas (31, 65%), followed by adenocarcinomas (8, 17%), large cell carcinomas (4, 8%), small cell carcinomas (4, 8%), and fibrosarcoma (1, 2%). Of the 19 patients with stage classification, 8 had stage IV and 11 had stage III disease. Only 14 patients reported having received treatment, including chemotherapy, radiotherapy, and/or surgery. In conclusion, lung cancer was uncommon in Yaounde, Cameroon, but most of patients presented with advanced stage due to long delay in seeking diagnosis. Less than half of the patients received chemotherapy, radiotherapy, or surgery.
Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

Background/Aims: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63) and gastric cancer (SGC7901) cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.