vgaraujov/thesis-chile huggingface dataset:
Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimerâ€™s disease

Abstract Background Stable and non-toxic fluorescent markers are gaining attention in molecular diagnostics as powerful tools for enabling long and reliable biological studies. Such markers should not only have a long half-life under several assay conditions showing no photo bleaching or blinking but also, they must allow for their conjugation or functionalization as a crucial step for numerous applications such as cellular tracking, biomarker detection and drug delivery. Results We report the functionalization of stable fluorescent markers based on nanodiamonds (NDs) with a bifunctional peptide. This peptide is made of a cell penetrating peptide and a six amino acids long β-sheet breaker peptide that is able to recognize amyloid β (Aβ) aggregates, a biomarker for the Alzheimer disease. Our results indicate that functionalized NDs (fNDs) are not cytotoxic and can be internalized by the cells. The fNDs allow ultrasensitive detection (at picomolar concentrations of NDs) of in vitro amyloid fibrils and amyloid aggregates in AD mice brains. Conclusions The fluorescence of functionalized NDs is more stable than that of fluorescent markers commonly used to stain Aβ aggregates such as Thioflavin T. These results pave the way for performing ultrasensitive and reliable detection of Aβ aggregates involved in the pathogenesis of the Alzheimer disease.
Different Array CGH profiles within hereditary breast cancer tumors associated to BRCA1 expression and overall survival

Abstract Background Array CGH analysis of breast tumors has contributed to the identification of different genomic profiles in these tumors. Loss of DNA repair by BRCA1 functional deficiency in breast cancer has been proposed as a relevant contribution to breast cancer progression for tumors with no germline mutation. Identifying the genomic alterations taking place in BRCA1 not expressing tumors will lead us to a better understanding of the cellular functions affected in this heterogeneous disease. Moreover, specific genomic alterations may contribute to the identification of potential therapeutic targets and offer a more personalized treatment to breast cancer patients. Methods Forty seven tumors from hereditary breast cancer cases, previously analyzed for BRCA1 expression, and screened for germline BRCA1 and 2 mutations, were analyzed by Array based Comparative Genomic Hybridization (aCGH) using Agilent 4x44K arrays. Overall survival was established for tumors in different clusters using Log-rank (Mantel-Cox) Test. Gene lists obtained from aCGH analysis were analyzed for Gene Ontology enrichment using GOrilla and DAVID tools. Results Genomic profiling of the tumors showed specific alterations associated to BRCA1 or 2 mutation status, and BRCA1 expression in the tumors, affecting relevant cellular processes. Similar cellular functions were found affected in BRCA1 not expressing and BRCA1 or 2 mutated tumors. Hierarchical clustering classified hereditary breast tumors in four major, groups according to the type and amount of genomic alterations, showing one group with a significantly poor overall survival (p = 0.0221). Within this cluster, deletion of PLEKHO1, GDF11, DARC, DAG1 and CD63 may be associated to the worse outcome of the patients. Conclusions These results support the fact that BRCA1 lack of expression in tumors should be used as a marker for BRCAness and to select these patients for synthetic lethality approaches such as treatment with PARP inhibitors. In addition, the identification of specific alterations in breast tumors associated with poor survival, immune response or with a BRCAness phenotype will allow the use of a more personalized treatment in these patients.
Geomagnetic disturbances driven by solar activity enhance total and cardiovascular mortality risk in 263 U.S. cities

Abstract Background Short-term geomagnetic disturbances (GMD) driven by the quasi-periodic 11-year cycle of solar activity have been linked to a broad range of adverse health effects, including cardiovascular diseases (CVD) and total deaths. We conducted a large epidemiological study in 263 U.S. cities to assess the effects of GMD on daily deaths of total, CVD, myocardial infarction (MI), and stroke. Methods We employed a two-step meta-analysis approach, in which we estimated city-specific and season-stratified mortality risk associated with a GMD parameter (Kp index) in 263 U.S. cities. In addition, sensitivity analysis was performed to assess whether effect modification of particulate matter (PM2.5) in the prior day changed Kp index effects on daily deaths after adjusting for confounders. Results We found significant association between daily GMD and total, CVD, and MI deaths. The effects were even stronger when we adjusted the models for 24-h PM2.5 for different seasons. For example, in the winter and fall one standard deviation of z-score Kp index increase was associated with a 0.13 and 0.31% increase in total deaths, respectively (Winter: p = 0.01, 95% CI: 0.02 to 0.24; Fall: p = 0.00001; 95% CI: 0.23 to 0.4), without adjusting for PM2.5. The effects of GMD on total deaths were also observed in spring and summer in the models without PM2.5 (p = 0.00001). When the models were adjusted for PM2.5 the total deaths increased 0.47% in winter (p = 0.00001, 95% CI: 0.3 to 0.65) and by 0.23% in fall (p = 0.001, 95% CI: 0.09 to 0.37). The effects of GMD were also significant associated with MI deaths and CVD. No positive significant association were found between Kp and stroke. The GMD effects on deaths were higher than for 24 h-PM2.5 alone, especially in spring and fall. Conclusion Our results suggest that GMD is associated with total, CVD and MI deaths in 263 U. S cities. Increased mortality in the general population during GMD should be further investigated to determine whether those human physiological dynamics driven by variations in solar activity can be related to daily clinical cardiovascular observations.
Health equity: evidence synthesis and knowledge translation methods

Abstract Background At the Rio Summit in 2011 on Social Determinants of Health, the global community recognized a pressing need to take action on reducing health inequities. This requires an improved evidence base on the effects of national and international policies on health inequities. Although systematic reviews are recognized as an important source for evidence-informed policy, they have been criticized for failing to assess effects on health equity. Methods This article summarizes guidance on both conducting systematic reviews with a focus on health equity and on methods to translate their findings to different audiences. This guidance was developed based on a series of methodology meetings, previous guidance, a recently developed reporting guideline for equity-focused systematic reviews (PRISMA-Equity 2012) and a systematic review of methods to assess health equity in systematic reviews. Results We make ten recommendations for conducting equity-focused systematic reviews; and five considerations for knowledge translation. Illustrative examples of equity-focused reviews are provided where these methods have been used. Conclusions Implementation of the recommendations in this article is one step toward monitoring the impact of national and international policies and programs on health equity, as recommended by the 2011 World Conference on Social Determinants of Health.Abstract Background At the Rio Summit in 2011 on Social Determinants of Health, the global community recognized a pressing need to take action on reducing health inequities. This requires an improved evidence base on the effects of national and international policies on health inequities. Although systematic reviews are recognized as an important source for evidence-informed policy, they have been criticized for failing to assess effects on health equity. Methods This article summarizes guidance on both conducting systematic reviews with a focus on health equity and on methods to translate their findings to different audiences. This guidance was developed based on a series of methodology meetings, previous guidance, a recently developed reporting guideline for equity-focused systematic reviews (PRISMA-Equity 2012) and a systematic review of methods to assess health equity in systematic reviews. Results We make ten recommendations for conducting equity-focused systematic reviews; and five considerations for knowledge translation. Illustrative examples of equity-focused reviews are provided where these methods have been used. Conclusions Implementation of the recommendations in this article is one step toward monitoring the impact of national and international policies and programs on health equity, as recommended by the 2011 World Conference on Social Determinants of Health.
Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders

Abstract Background Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism. Methods The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot. Results We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider. Conclusions People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.
High density lipoprotein cholesterol and proteome in SR-B1 KO mice: lost in precipitation

Abstract Scavenger receptor class B type 1 (SR-B1) plays an essential role in high density lipoprotein (HDL) metabolism. SR-B1 deficient (SR-B1 KO) mice are prone to atherosclerosis and exhibit abnormally large, cholesterol-rich, dysfunctional HDL. In a recent issue of J Transl Med, Cao et al. described results of proteomics analyses of HDL isolated from wild-type (WT) and SR-B1 KO mice using precipitation of large lipoproteins with polyethylene glycol (PEG). They report abnormalities in SR-B1 KO HDL protein components that correlate with HDL function. In this commentary, we describe and discuss the differences in the results published by Cao et al. and those obtained in a recent study from our laboratory using shotgun proteomics of HDL of SR-B1 KO mice isolated by ultracentrifugation. We propose that different HDL purification procedures used may account for the discrepancies observed. We show that SR-B1 KO HDL purification using either PEG or dextran sulfate precipitation results in enrichment of small HDL subclasses, and may therefore underestimate alterations in lipoprotein composition or function. Compared to HDL obtained by ultracentrifugation, HDL isolated by PEG precipitation show a lower ApoE/ApoA-I proportion and reduced cholesterol content. HDL protein components described by Cao et al. or our laboratory are mostly inconsistent: only 33 HDL proteins were detected in both datasets, whereas a significant number of proteins were only identified by Cao et al. (n = 43) or Contreras-Duarte et al. (n = 26) datasets. The relative abundance of HDL-associated peptide and protein levels in WT vs SR-B1 HDL were also highly different in both datasets. This study indicates that caution must be taken when interpreting results from HDL isolated by chemical precipitation.
Highlights from the 1st ISCB Latin American Student Council Symposium 2014

Abstract This report summarizes the scientific content and activities of the first edition of the Latin American Symposium organized by the Student Council of the International Society for Computational Biology (ISCB), held in conjunction with the Third Latin American conference from the International Society for Computational Biology (ISCB-LA 2014) in Belo Horizonte, Brazil, on October 27, 2014.Abstract This report summarizes the scientific content and activities of the first edition of the Latin American Symposium organized by the Student Council of the International Society for Computational Biology (ISCB), held in conjunction with the Third Latin American conference from the International Society for Computational Biology (ISCB-LA 2014) in Belo Horizonte, Brazil, on October 27, 2014.
High-risk HPV infection after five years in a population-based cohort of Chilean women

Abstract Background The need to review cervical cancer prevention strategies has been triggered by the availability of new prevention tools linked to human papillomavirus (HPV): vaccines and screening tests. To consider these innovations, information on HPV type distribution and natural history is necessary. This is a five-year follow-up study of gynecological high-risk (HR) HPV infection among a Chilean population-based cohort of women. Findings A population-based random sample of 969 women from Santiago, Chile aged 17 years or older was enrolled in 2001 and revisited in 2006. At both visits they answered a survey on demographics and sexual history and provided a cervical sample for HPV DNA detection (GP5+/6+ primer-mediated PCR and Reverse line blot genotyping). Follow-up was completed by 576 (59.4%) women; 45 (4.6%) refused participation; most losses to follow-up were women who were unreachable, no longer eligible or had missing samples. HR-HPV prevalence increased by 43%. Incidence was highest in women < 20 years of age (19.4%) and lowest in women > 70 (0%); it was three times higher among women HR-HPV positive versus HPV negative at baseline (25.5% and 8.3%; OR 3.8, 95% CI 1.8-8.0). Type-specific persistence was 35.3%; it increased with age, from 0% in women < 30 years of age to 100% in women > 70. An enrollment Pap result ASCUS or worse was the only risk factor for being HR-HPV positive at both visits. Conclusions HR-HPV prevalence increased in the study population. All HR-HPV infections in women < 30 years old cleared, supporting the current recommendation of HR-HPV screening for women > 30 years.
Disagreements between central clinical events committee and site investigator assessments of myocardial infarction end-points in an international clinical trial : review of the PURSUIT study

Abstract Background Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and those adjudicated by a central clinical events committee (CEC) to determine the reasons for differences in event rates. Methods The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. The primary end-point was death or post-enrolment MI at 30 days as assessed by the CEC; this end-point was also constructed using site-reported events. The CEC identified suspected MIs by systematic review of clinical, cardiac enzyme, and electrocardiographic data. Results The CEC identified 5005 (46%) suspected events, of which 1415 (28%) were adjudicated as MI. The site investigator and CEC assessments of whether a MI had occurred disagreed in 983 (20%) of the 5005 patients with suspected MI, mostly reflecting site misclassification of post-enrolment MIs (as enrolment MIs) or underreported periprocedural MIs. Patients for whom the CEC and site investigator agreed that no end-point MI had occurred had the lowest mortality at 30 days and between 30 days and 6 months, and those with agreement that a MI had occurred had the highest mortality. Conclusion CEC adjudication provides a standard, systematic, independent, and unbiased assessment of end-points, particularly for trials that span geographic regions and clinical practice settings. Understanding the review process and reasons for disagreement between CEC and site investigator assessments of MI is important to design future trials and interpret event rates between trials.
Does anatomic single-bundle ACL reconstruction using hamstring autograft produce anterolateral meniscal root tearing?

Abstract Background To determine if tibial tunnel reaming during anatomic single-bundle anterior cruciate ligament (ACL) reconstruction using hamstring autograft can result in anterolateral meniscal root injury, as diagnosed by magnetic resonance imaging (MRI). Methods A case series of 104 primary anatomic single-bundle ACL reconstructions using hamstring autograft was retrospectively reviewed. Pre- and post-operative (>1 year) MRIs were radiologically evaluated for each patient, with a lateral meniscus extrusion > 3 mm at the level of the medial collateral ligament midportion on a coronal MRI, to establish anterolateral meniscal root injury. Results No patients presented radiological findings of anterolateral meniscal root injury in this case series. Conclusions Examining a single-bundle ACL reconstruction technique using hamstring autograft that considered tibial tunnel positioning in the center of the tibial footprint, this case series found no evidence of anterolateral meniscal root injury in patient MRIs, even more than 1-year post-operation.Abstract Background To determine if tibial tunnel reaming during anatomic single-bundle anterior cruciate ligament (ACL) reconstruction using hamstring autograft can result in anterolateral meniscal root injury, as diagnosed by magnetic resonance imaging (MRI). Methods A case series of 104 primary anatomic single-bundle ACL reconstructions using hamstring autograft was retrospectively reviewed. Pre- and post-operative (>1 year) MRIs were radiologically evaluated for each patient, with a lateral meniscus extrusion > 3 mm at the level of the medial collateral ligament midportion on a coronal MRI, to establish anterolateral meniscal root injury. Results No patients presented radiological findings of anterolateral meniscal root injury in this case series. Conclusions Examining a single-bundle ACL reconstruction technique using hamstring autograft that considered tibial tunnel positioning in the center of the tibial footprint, this case series found no evidence of anterolateral meniscal root injury in patient MRIs, even more than 1-year post-operation.
Draft genome sequences of Cylindrospermopsis raciborskii strains CS-508 and MVCC14, isolated from freshwater bloom events in Australia and Uruguay

Abstract Members of the genus Cylindrospermopsis represent an important environmental and health concern. Strains CS-508 and MVCC14 of C. raciborskii were isolated from freshwater reservoirs located in Australia and Uruguay, respectively. While CS-508 has been reported as non-toxic, MVCC14 is a saxitoxin (STX) producer. We annotated the draft genomes of these C. raciborskii strains using the assembly of reads obtained from Illumina MiSeq sequencing. The final assemblies resulted in genome sizes close to 3.6 Mbp for both strains and included 3202 ORFs for CS-508 (in 163 contigs) and 3560 ORFs for MVCC14 (in 99 contigs). Finally, both the average nucleotide identity (ANI) and the similarity of gene content indicate that these two genomes should be considered as strains of the C. raciborskii species.
Human papillomavirus and Epstein-Barr virus infections in breast cancer from chile

Abstract Background Human papillomavirus (HPV) and Epstein Barr virus (EBV) have been found in breast carcinomas (BCs) around the world. In this study, fifty-five BCs from Chile were analyzed for HPV and EBV presence. In addition, HPV-16 viral load/physical status and E6/E7 expressions were determined. Results The amplification of a housekeeping gene showed that 46/55 samples (84%) had amplifiable DNA. HPV-16 was detected in 4/46 BCs (8.7%) and EBV was detected in 3/46 (6.5%) BCs. The analysis of HPV-16 physical status showed that this virus was integrated in all of the tumors with a relatively low viral load (range: 0.14 to 33.8 copies/cell). E6 and E7 transcripts, however, were not detected in any HPV-16 positive specimens. Using a Cox-regression model, we found a statistically significant association between EBV presence and poor survival (p = 0.013). Conclusions The findings in this study suggest that it is unlikely that HPV and/or EBV play a direct role in the etiology of BC.Abstract Background Human papillomavirus (HPV) and Epstein Barr virus (EBV) have been found in breast carcinomas (BCs) around the world. In this study, fifty-five BCs from Chile were analyzed for HPV and EBV presence. In addition, HPV-16 viral load/physical status and E6/E7 expressions were determined. Results The amplification of a housekeeping gene showed that 46/55 samples (84%) had amplifiable DNA. HPV-16 was detected in 4/46 BCs (8.7%) and EBV was detected in 3/46 (6.5%) BCs. The analysis of HPV-16 physical status showed that this virus was integrated in all of the tumors with a relatively low viral load (range: 0.14 to 33.8 copies/cell). E6 and E7 transcripts, however, were not detected in any HPV-16 positive specimens. Using a Cox-regression model, we found a statistically significant association between EBV presence and poor survival (p = 0.013). Conclusions The findings in this study suggest that it is unlikely that HPV and/or EBV play a direct role in the etiology of BC.
Novel treatments for complications after bariatric surgery

Abstract Bariatric surgery has been considered one of best treatments for obesity. As every surgical procedure—and any medical intervention, it is not exempt of complications, among which leaks, strictures, acute hemorrhages and fistulae highlight. Leaks are more common in the gastro-jejunal anastomosis (GJA) in the case of Roux-en-y Gastric Bypass (RYGB), while in Sleeve Gastrectomy (LSG) they locate in the stapler line. Stenosis can be seen in the gastro-jejunostomy in the RYGB and in the gastric tube in case of the LSG. For each of these complications, many innovative solutions have been developed, including new surgical devices. In spite of promising good results, evidence regarding utility and safeness of these technologies is still scarce. Self-expandable endoscopic stents have been used to treat leaks, with an overall success rate of 80–90 % and a migration rate of 15–35 %. The bear trap-like over-the-scope (Ovesco) clips have been used to treat GI hemorrhages, leaks and even fistulae, with a 70–80 % success rate, although more endoscopic sessions may be needed. Overstitch, an endosurgical suture devices, have been used to treat leaks, fistulae and perforations. Overall, technical success achievement approaches to 90 %, while clinical success ranges from 80 to 90 %, except for leaks closure, where a lower success rate has been observed. Despite of all of these advances, early diagnosis and treatment remains the main strategy to achieve success. In summary, novel therapies for complication management can be very useful, though further studies with larger series are still needed in order to confirm their efficacy and safeness.