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IL-10 and IL-6/IL-10 as predictive biomarkers for treatment response in non-infectious uveitis
(Frontiers Media SA, 2025-05-13)
Rodrigo A. Valenzuela
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Fabian Vega-Tapia
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Nathaly Elizalde
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Ivan Flores
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Felipe M. Rojas
Uveitis, a group of heterogeneous diseases causing ocular inflammation, is a major contributor to vision loss globally. While systemic corticosteroids (CS) are the mainstay treatment, identifying CS-refractory patients remains a significant challenge. This study aimed to explore cytokine expression and Glucocorticoid Receptor (GR) levels as biomarkers for the early detection of CS-refractory cases in non-infectious uveitis. We assayed blood samples from 19 patients with non-infectious uveitis, for the expression of IL-6, IL-17A, TNF-α, IL-10 and GRα. The cohort included 11 refractory and 8 sensitive patients, categorized based on their clinical response to corticosteroids (prednisone 1 mg/kg/day). Blood draws were conducted at three time points (at baseline, day 7- and day 14 after CS initiation), and peripheral blood mononuclear cells (PBMCs) were isolated to measure cytokine and GRα transcript levels via real-time PCR. The expression levels of GRα and cytokines IL-6, IL-17A and TNF-α did not show significant changes between CS-sensitive and CS-refractory patients on the different days of treatment. However, IL-10 expression levels as the day14-to-day7 ratio were significantly higher in patients sensitive to CS therapy. A higher day14-to-day7 ratio was also found for the IL-6/IL-10, IL-17A/IL-10 and GRα/IL-10 ratios. ROC curve analysis demonstrated a robust predictive performance of IL-10 mRNA expression and the IL-6/IL-10 ratio for identifying CS-refractory patients. In conclusion, the expression of IL-10 and the IL-6/IL-10 ratio hold promise as early predictive biomarkers for CS treatment refractoriness in patients with non-infectious uveitis. These findings offer valuable insights into personalized treatment strategies, potentially leading to improved clinical outcomes.
Scopus© Citations 6 1
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Ethnic disparities in the association between maternal socioeconomic status and childhood anemia in Peru: a nationwide multiyear cross-sectional study
(Elsevier BV, 2025-07)
Ali Al-kassab-Córdova
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Claudio Intimayta-Escalante
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Pamela Robles-Valcarcel
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Diego Urrunaga-Pastor
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CABIESES VALDES, BALTICA BEATRIZ
1
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Chronic dizziness in older adults: Disrupted sensorimotor EEG beta oscillations during postural instability
(Elsevier BV, 2025-06)
Toby J. Ellmers
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Richard Ibitoye
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CASTRO ABARCA, PATRICIA BERNARDITA
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Elmar C. Kal
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Diego Kaski
Scopus© Citations 2 1
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Early high-sensitivity troponin elevation and short-term mortality in sepsis: a systematic review with meta-analysis
(Springer Science and Business Media LLC, 2025-02-14)
Abraham I. J. Gajardo
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Santiago Ferrière-Steinert
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Joaquín Valenzuela Jiménez
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Sebastián Heskia Araya
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Thomas Kouyoumdjian Carvajal
Abstract Background Serum cardiac troponin (cTn) elevation is a well-established phenomenon in sepsis. However, the clinical signifcance of this phenomenon with high-sensitivity (hs) assays and the current sepsis defnition needs to be settled. Research Question What is the association between early serum cTn levels measured by hs-assays and the risk of short-term mortality in septic patients? Study Design and Methods We conducted a systematic review using a comprehensive PubMed, Scopus, and Embase search. Studies were eligible if they reported association data on early hs-cTn and mortality in an adult sample with sepsis that met the Sepsis-3 defnition. For the synthesis of the efect of hs-cTn on mortality, we applied random efect models on the pooled unadjusted and adjusted odds ratio (OR and aOR, respectively) of elevated vs. normal hs-cTn serum values, and on the crude standardized mean diference (SMD) of hs-cTn between survivors and non-survivors. Results In total, 6242 patients from 17 studies were included, with short-term mortality rates ranging from 16.9% to 53.8%. Using a crude analysis, non-survivor patients showed higher hs-cTn than survivors (SMD of 0.87, 95%CI: 0.41–1.33). Elevated hs-cTn was associated with increased mortality (OR=1.78, 95% CI: 1.41–2.25). However, this prognostic efect was absent in studies that adjusted for diferent confounders (aOR=1.06, 95% CI: 0.99–1.14). Discussion and Conclusions Non-survivors of sepsis exhibited signifcantly elevated hs-cTn levels. While elevated hs-cTn levels are associated with an increased risk of mortality, they are not independently associated with this outcome in sepsis
1Scopus© Citations 19
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Advances in machine learning for tumour classification in cancer of unknown primary: A mini-review
(2025)
Karen Oróstica
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Felipe Mardones
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Yanara A. Bernal
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Samuel Molina
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Marcos Orchard
Scopus© Citations 3 8
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Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation
(2024)
Bruno Dubois
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Nicolas Villain
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Lon Schneider
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Nick Fox
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Noll Campbell
<jats:sec id="ab-nsc240001-1"><jats:title>Importance</jats:title><jats:p>Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer’s Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations.</jats:p></jats:sec><jats:sec id="ab-nsc240001-2"><jats:title>Objective</jats:title><jats:p>To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states.</jats:p></jats:sec><jats:sec id="ab-nsc240001-3"><jats:title>Evidence Review</jats:title><jats:p>PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms “biomarker” OR “amyloid” OR “tau” OR “neurodegeneration” OR “preclinical” OR “CSF” OR “PET” OR “plasma” AND “Alzheimer’s disease.” The references of relevant articles were also searched.</jats:p></jats:sec><jats:sec id="ab-nsc240001-4"><jats:title>Findings</jats:title><jats:p>In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease.</jats:p></jats:sec><jats:sec id="ab-nsc240001-5"><jats:title>Conclusions and Relevance</jats:title><jats:p>The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.</jats:p></jats:sec>
Scopus© Citations 73 2
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Early high-sensitivity troponin elevation in predicting short-term mortality in sepsis: A protocol for a systematic review with meta-analysis
(2024)
Santiago Ferrière-Steinert
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Joaquín Valenzuela Jiménez
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Sebastián Heskia Araya
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Thomas Kouyoumdjian
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José Ramos-Rojas
<jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>Sepsis is a common admission diagnosis in the intensive care unit (ICU). The Sepsis-3 consensus associates sepsis diagnosis with acute organ dysfunction. In these patients troponin elevation is a well-established phenomenon, but its clinical significance is not settled, as no systematic review has addressed the prognostic significance of the increasingly prevalent high-sensitivity troponin assays in acute organ dysfunction setting.</jats:p> <jats:p>This study aims to clarify the association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>We will systematically search PubMed, Scopus and Embase for original articles; additionally, a manual search will be carried out through relevant literature. Generally, studies will be deemed eligible for inclusion if they evaluate the association between high-sensitivity troponin in the first 24 hours of admission and ICU, 30-days, or In-hospital mortality; in patients with septic shock or sepsis related to acute organ dysfunction. Two reviewers will independently select studies and extract the data. A meta-analysis for mortality outcome will be performed for comparative data regarding two effect measures: Odd ratios and Standardized Mean differences.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Discussion</jats:title> <jats:p>This study will provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients; potentially helping to guide further research and yielding valuable information for patient assessment.</jats:p> <jats:p>Conclusion about the certainty of evidence will be presented in a ´Summary of findings´ table.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Trial registration</jats:title> <jats:p>PROSPERO registration:</jats:p> <jats:p>(<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024468883" xlink:type="simple">CRD42024468883</jats:ext-link>).</jats:p> </jats:sec>
8Scopus© Citations 3
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Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine
(2023)
Macarena Las Heras
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Benjamín Szenfeld
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Rami A. Ballout
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Emanuele Buratti
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Silvana Zanlungo
<jats:title>Abstract</jats:title><jats:p>Niemann-Pick type C (NPC) disease is a lysosomal storage disease (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss of function mutations in the <jats:italic>NPC1</jats:italic> and <jats:italic>NPC2</jats:italic> genes. NPC patients can present with a broad phenotypic spectrum, with differences at the age of onset, rate of progression, severity, organs involved, effects on the central nervous system, and even response to pharmacological treatments. This article reviews the phenotypic variation of NPC and discusses its possible causes, such as the remaining function of the defective protein, modifier genes, sex, environmental cues, and splicing factors, among others. We propose that these factors should be considered when designing or repurposing treatments for this disease. Despite its seeming complexity, this proposition is not far-fetched, considering the expanding interest in precision medicine and easier access to multi-omics technologies.</jats:p>
Scopus© Citations 7 2
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Network anatomy in logopenic variant of primary progressive aphasia
(2023)
Maria Luisa Mandelli
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Diego L. Lorca‐Puls
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Sladjana Lukic
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Maxime Montembeault
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GAJARDO VIDAL, ANDREA ELIZABETH
<jats:title>Abstract</jats:title><jats:p>The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through predetermined networks. First, we used cross‐sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface‐based approach paired with an anatomically fine‐grained parcellation of the cortical surface (i.e., HCP‐MMP1.0 atlas). Second, we combined cross‐sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter‐seeded resting‐state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically‐intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporoparietal junction regions, predominantly follows at least two partially nonoverlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis.</jats:p>
Scopus© Citations 10 2
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Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function
(2023)
Macarena Ortiz
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Francisca Sánchez
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Daniela Álvarez
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Cristian Flores
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Francisca Salas-Pérez
7Scopus© Citations 5

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