Publications by authors named "Miguel Hernandez"

Cladribine is an immune reconstitution therapy for multiple sclerosis (MS) that selectively produces long-term reductions in highly pathological memory B cells, with temporary reductions in other B- and T-cell subsets, thereby restoring immune function close to baseline levels in the short term. Here, we describe two cases of relapsing MS (RMS) treated with a second course of cladribine. Both patients were initially diagnosed with clinically isolated syndrome and later enrolled in the ORACLE-MS and CLASSIC-MS studies.

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This study examines the impact of cytogenetic abnormalities and their co-segregation on the prognosis of newly diagnosed multiple myeloma patients. The analysis included 1304 patients from four different GEM-PETHEMA clinical trials. Genetic alterations, such as t(4;14), t(14;16), del(17p), +1q, and del(1p), were investigated using FISH on CD38 purified plasma cells.

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Objective: To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing-remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response.

Methods: Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology.

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Sequence-specific endonucleases have been key to the study of the mechanisms and control of DNA double-strand break (DSB) repair and recombination, and the availability of CRISPR-Cas nucleases over the last decade has driven rapid progress in the understanding and application of targeted recombination in many organisms, including plants. We present here an analysis of recombination at targeted chromosomal 5' overhang DSB generated by the FnCas12a endonuclease in the plant, . The much-studied Cas9 nuclease cleaves DNA to generate blunt-ended DSBs, but relatively less is known about the repair of other types of breaks, such as those with 5'-overhanging ends.

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Article Synopsis
  • The study assessed outcomes, resource use, and costs related to Chronic Obstructive Pulmonary Disease (COPD) by analyzing a cohort of patients who visited the emergency department in 2018.
  • In a sample of 2,384 COPD patients, the study found high mortality rates—23.4% within one year—and significant readmission rates, with costs totaling approximately €14.6 million.
  • The findings highlight the need for specialized programs to improve care for COPD patients due to their high mortality, readmission rates, and substantial economic burden on the healthcare system.
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  • - The report discusses a case of fatal canine visceral leishmaniasis (VL) in a 2-year-old pug from Brazil, which was imported to French Guiana, a region not typically associated with this disease.
  • - The dog initially showed a skin issue that healed, but later developed serious symptoms, leading to suspicion of VL, which was confirmed posthumously by testing for L. infantum.
  • - This case highlights the rarity of canine VL in French Guiana and suggests a need for increased local surveillance to monitor potential transmission routes of the parasite.
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Purpose: Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM.

Methods: Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years.

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The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have, therefore, investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by next-generation flow cytometry (NGF) identified cases with a significantly shorter median progression-free survival (mPFS) (MS: not reached vs.

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Retinoblastoma protein is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. Immunostaining and biochemical evidence demonstrated that during interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize in vivo in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions.

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Article Synopsis
  • Using a large language model (LLM) for complex tasks in biomedicine can be tough due to issues like generating false information or being swayed by bad data, which affects accuracy and reliability.
  • KRAGEN is a new tool that combines knowledge graphs and advanced techniques to effectively break down and solve complex problems by reducing inaccuracies and hallucinations in the responses it generates.
  • KRAGEN is an open-source tool that can be deployed using custom Docker containers and is available on GitHub for anyone to use.
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Introduction: Although depression is common in primary care, challenges to timely intervention exist, particularly for communities of color and lower socioeconomic status. Our objective was to understand barriers and facilitators to mental healthcare access among a sample of patients receiving care at a federally qualified health center (FQHC) in Minnesota, United States.

Methods: We qualitatively interviewed 34 patients of an urban FQHC, purposively sampled on race/ethnicity, insurance status, language, and depression symptom status (based on Patient Health Questionnaire-9 responses).

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The growing environmental consequences caused by plastic pollution highlight the need for a better understanding of plastic polymer cycles and their associated additives. We present a novel, comprehensive top-down method using inflow-driven dynamic probabilistic material flow analysis (DPMFA) to map the plastic cycle in coastal countries. For the first time, we covered the progressive leaching of microplastics to the environment during the use phase of products and modeled the presence of 232 plastic additives.

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For people with HIV (PWH) who have psychological comorbidities, effective management of mental health issues is crucial to achieving and maintaining viral suppression. Care coordination programs (CCPs) have been shown to improve outcomes across the HIV care continuum, but little research has focused on the role of care coordination in supporting the mental health of PWH. This study reports qualitative findings from the Program Refinements to Optimize Model Impact and Scalability based on Evidence (PROMISE) study, which evaluated a revised version of an HIV CCP for Ryan White Part A clients in New York City.

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Background: Despite substantial progress in AI research for healthcare, translating research achievements to AI systems in clinical settings is challenging and, in many cases, unsatisfactory. As a result, many AI investments have stalled at the prototype level, never reaching clinical settings.

Objective: To improve the chances of future AI implementation projects succeeding, we analyzed the experiences of clinical AI system implementers to better understand the challenges and success factors in their implementations.

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The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase II study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM).

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Introduction: Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations.

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Objective: Providing the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM.

Methods: An integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04).

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Introduction: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression.

Methods: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks.

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Motivation: Biomedical and healthcare domains generate vast amounts of complex data that can be challenging to analyze using machine learning tools, especially for researchers without computer science training.

Results: Aliro is an open-source software package designed to automate machine learning analysis through a clean web interface. By infusing the power of large language models, the user can interact with their data by seamlessly retrieving and executing code pulled from the large language model, accelerating automated discovery of new insights from data.

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Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10).

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From November 2014 to May 2017, 332 patients homogeneously treated with bortezomib, lenalidomide, and dexamethasone (VRD) induction, autologous stem cell transplant, and VRD consolidation were randomly assigned to receive maintenance therapy with lenalidomide and dexamethasone (RD; 161 patients) vs RD plus ixazomib (IRD; 171 patients). RD consisted of lenalidomide 15 mg/d from days 1 to 21 plus dexamethasone 20 mg/d on days 1 to 4 and 9 to 12 at 4-week intervals, whereas in the IRD arm, oral ixazomib at a dose of 4 mg on days 1, 8, and 15 was added. Therapy for patients with negative measurable residual disease (MRD) after 24 cycles was discontinued, whereas those who tested positive for MRD remained on maintenance with RD for 36 more cycles.

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In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone (KCd) was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PL). One hundred and ninety-seven patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred.

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There are little data on pentamidine as a treatment for paediatric cutaneous leishmaniasis (CL). The objective of this study was to describe the effectiveness and safety of pentamidine over a 10-year period. Every child seen in French Guiana between 2010 and 2020 with proven CL and treated with pentamidine was included.

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Tandem ASCT has been suggested as a valid approach to improve the prognosis of patients with MM and HR cytogenetic. In this observational, retrospective study, 213 patients with newly diagnosed MM and HR cytogenetic in 35 hospitals from the Spanish Myeloma Group underwent single or tandem ASCT between January 2015 and December 2019 after induction with VTD/VRD. HR cytogenetic was defined as having ≥1 of the following: del17p, (4;14), (14;16) or gain 1q21.

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