Publications by authors named "Pablo Martinez"

Background: Tarlatamab binds to delta-like ligand 3 on cancer cells and cluster of differentiation-3 on T cells, leading to T-cell-mediated tumor lysis, and has demonstrated a promising safety and efficacy profile in patients with previously treated small-cell lung cancer (SCLC). Here, we present pharmacokinetic results from DeLLphi-300 (NCT03319940), an ongoing international, open-label, first-in-human study in previously treated adult patients with SCLC.

Methods: Multiple escalating doses of tarlatamab were administered every 2 weeks (Q2W; 0.

View Article and Find Full Text PDF

What Is This Summary About?: This is a summary of a phase 2 clinical study called DeLLphi-301. The study looked at how effective and safe a medicine called tarlatamab was in participants with small cell lung cancer (SCLC). Participants previously received at least two other treatments for their SCLC.

View Article and Find Full Text PDF

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons (MNs), and despite progress, there is no effective treatment. A large body of evidence shows that astrocytes expressing ALS-linked mutant proteins cause non-cell autonomous toxicity of MNs. Although MNs innervate muscle fibers and ALS is characterized by the early disruption of the neuromuscular junction (NMJ) and axon degeneration, there are controversies about whether muscle contributes to non-cell-autonomous toxicity to MNs.

View Article and Find Full Text PDF

Unlabelled: Eighty percent of depressed patients in Primary Health Care (PHC) have a comorbidity. It is essential to contribute local evidence on the characteristics of patients with physical and psychiatric comorbidities to better address clinical practice.

Aim: To characterize depressed patients from the cardiovascular program (PCV) of eight family health centers (CESFAM) in two communes of the Metropolitan Region.

View Article and Find Full Text PDF

This study aims to develop methods to design the complete magnetic system for a truly portable MRI scanner for neurological and musculoskeletal (MSK) applications, optimized for field homogeneity, field of view (FoV), and gradient performance compared to existing low-weight configurations. We explore optimal elliptic-bore Halbach configurations based on discrete arrays of permanent magnets. In this way, we seek to improve the field homogeneity and remove constraints to the extent of the gradient coils typical of Halbach magnets.

View Article and Find Full Text PDF
Article Synopsis
  • - This study examines treatment patterns and real-world overall survival (rwOS) in patients with extensive-stage small cell lung cancer (ES-SCLC) after the introduction of anti-PD-L1 therapies in 2019 and 2020.
  • - Researchers analyzed a nationwide database, focusing on patients who received systemic therapy from 2013 to 2021, finding that etoposide plus platinum chemotherapy was the most common first-line treatment.
  • - Despite the use of anti-PD-L1 therapies, the median overall survival rates for patients were relatively low: 8.3 months for those treated with 1L anti-PD-L1 compared to 8.0 months for those who were not, indicating ongoing challenges
View Article and Find Full Text PDF
Article Synopsis
  • Snakebite envenoming is a major global public health issue, especially in Brazil, where Bothrops snakes cause most incidents, leading to complications and fatalities.
  • A study from 2015-2021 analyzed data from various Brazilian municipalities to discover factors influencing snakebite incidence, utilizing Species Distribution Models and examining variables like precipitation, temperatures, and land use.
  • Results showed that higher snakebite rates were primarily in northern Brazil, with increased incidents linked to extensive forests, historical forest loss, higher temperatures, and precipitation, suggesting a correlation with snake activity and human interactions.
View Article and Find Full Text PDF
Article Synopsis
  • - Prostate cancer is the most common cancer in men, with over 52,000 new cases each year, and robotic-assisted radical prostatectomy (RARP) has become a popular treatment method with a focus on achieving the "trifecta" of cancer control, urinary continence, and erectile function.
  • - A study analyzing 1,790 RARP procedures from 2008 to 2023 indicated low complication rates, with 23.8% of patients experiencing biochemical recurrence and a 97.9% overall survival rate over 10 years.
  • - The findings show that after 15 years of using RARP, the procedure is effective for handling localized prostate cancer, comparable to international results, enabling patients to
View Article and Find Full Text PDF
Article Synopsis
  • - CXCR4 is a chemokine receptor that plays key roles in immune cell movement, organ development, and various diseases, including cancer and HIV-1 infection, with only one blocker, plerixafor, currently used clinically.
  • - Recent research shows that when activated by CXCL12, CXCR4 changes its structure, reducing membrane-bound units and forming larger immobile clusters necessary for cells to respond to chemical signals.
  • - Using molecular modeling, scientists discovered a compound, AGR1.137, that disrupts these CXCR4 clusters without interfering with CXCL12 binding, effectively blocking cellular response to chemical gradients in laboratory settings.
View Article and Find Full Text PDF

Pathological aggregation and propagation of hyperphosphorylated and aberrant forms of tau are critical features of the clinical progression of Alzheimer's disease and other tauopathies. To better understand the correlation between these pathological tau species and disease progression, we profiled the temporal progression of tau seeding activity and the levels of various phospho- and conformational tau species in the brains of two mouse models of human tauopathies. Our findings indicate that tau seeding is an early event that occurs well before the appearance of AT8-positive NFT.

View Article and Find Full Text PDF
Article Synopsis
  • Tarlatamab, an immunotherapy targeting delta-like ligand 3, shows promising anticancer effects in small cell lung cancer (SCLC) based on the DeLLphi-300 and DeLLphi-301 trials, with manageable safety profiles.
  • In the extended follow-up of DeLLphi-300, the overall response rate was 25%, with a median duration of response of 11.2 months and a median overall survival of 17.5 months across 152 patients.
  • Among those receiving a specific dose regimen (10 mg every two weeks), 35.3% experienced a response, and notable intracranial tumor shrinkage was found in patients with existing brain lesions, highlighting tarlatam
View Article and Find Full Text PDF
Article Synopsis
  • The study investigates how psychiatrists and psychologists diagnose adjustment disorder (AD) and distinguish it from major depressive episode (MDE) using a grounded theory approach that included interviews with professionals in Colombia.
  • Key findings reveal that clinicians face challenges in discussing stressful events without medicalizing them, emphasize that while diagnoses are essential, they are not infallible, and view AD as a valid diagnosis reflecting varying responses to stress.
  • The research suggests that recognizing AD can help prevent the overdiagnosis of MDE, and highlights the importance of considering AD similarly to MDE in treatment strategies, focusing on coping and interventions related to stressors.
View Article and Find Full Text PDF
Article Synopsis
  • Asymptomatic Alzheimer's disease (AsymAD) is characterized by the presence of Alzheimer's-related brain pathology without cognitive decline, allowing researchers to study brain resilience mechanisms.
  • The study of AsymAD brains revealed unique features like higher core plaque levels, more active microglia, and less tau aggregation compared to typical Alzheimer's brains.
  • Key findings indicate that efficient actin-based motility in microglia and reduced tau seeding could help protect against the harmful effects of amyloid-beta, potentially slowing the progression of Alzheimer's disease.
View Article and Find Full Text PDF

The aggregation and spreading of "tau-seeds" are key for the development and progression of tauopathies, including Alzheimer's disease. Here we describe the steps to isolate and analyze biochemically active tau-seeds from human, mouse, and cell origin. We detail the procedure to isolate soluble tau-seeds by size exclusion chromatography and seeding assay.

View Article and Find Full Text PDF

Neuroinflammation is a prominent feature of Alzheimer's disease (AD). Activated microglia undergo a reprogramming of cellular metabolism necessary to power their cellular activities during disease. Thus, selective targeting of microglial immunometabolism might be of therapeutic benefit for treating AD.

View Article and Find Full Text PDF

Background And Aims: Public health concerns regarding pregnant women's health after the enactment of the Cannabis Act in Canada (CAC) (a law that allowed non-medical cannabis use), and the potential impact of the COVID-19 pandemic, call for a contemporary assessment of these two events. Our study measured associations between the CAC, the COVID-19 pandemic and the monthly prevalence rates of cannabis-, all drug- and alcohol-related diagnosed disorders among pregnant women in the province of Quebec.

Design, Setting And Participants: This was a quasi-experimental design applying an interrupted time-series methodology in the province of Quebec, Canada.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the impact of the Canadian Cannabis Act (implemented in 2018) and the COVID-19 pandemic on cannabis-related disorder (CRD) diagnoses in Québec from January 2010 to March 2022.
  • It uses time-series analysis of health data to evaluate changes in diagnosis rates, revealing that the average rates nearly doubled during the pandemic compared to the pre-legalization period.
  • Findings indicate significant monthly increases in CRD diagnoses for both general and male populations post-CCA and during the pandemic, with females also showing notable rises in diagnosis rates.
View Article and Find Full Text PDF
Article Synopsis
  • The study investigates treatment patterns and outcomes for real-world SCLC patients in the US who underwent three or more lines of therapy, highlighting the complexities of their care.
  • It analyzed a group of 326 patients, revealing median overall survival of 5.3 months and a progression-free survival of 2.5 months after receiving three lines of treatment.
  • The findings emphasize the poor efficacy of current therapies for advanced SCLC and highlight the urgent need for new treatment options.
View Article and Find Full Text PDF
Article Synopsis
  • ALS is a deadly neurodegenerative disease marked by the harmful loss of motoneurons, and currently, no effective treatment exists despite research efforts.
  • The study examines how muscle cells (myotubes) from ALS mice with a specific mutant protein (mutSOD1) can harm motoneurons, suggesting these muscle cells can contribute to the disease's progression.
  • Findings reveal that substances released from these mutSOD1 myotubes cause significant damage to motoneurons, affecting their functioning and ultimately leading to cell death.
View Article and Find Full Text PDF

Background: In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified.

Objectives: To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied.

View Article and Find Full Text PDF

Objective: To assess the impact of tobacco control regulations and policy implementation on smoking cessation tendencies in cigarette users born between 1982 and 1991 in Chile.

Design: Longitudinal cross-sectional study.

Setting: National level.

View Article and Find Full Text PDF

Background: In Chile, Laws 19366 and 20000, implemented in 1995 and 2005 respectively, regulated and sanctioned cannabis' personal use, cultivation and trafficking.

Methods: We use thirteen biannual cross-sectional national surveys data from 1994 to 2018 to examine the effect of Laws 19366 and 20000-using the rate of individuals incarcerated per 100000 population due to drug-related crimes as proxy-on the age of onset of cannabis use over time. We estimate the effect of these policies using a mixed proportional hazards framework that models the transition to first cannabis use in 47,832 individuals aged 12-21.

View Article and Find Full Text PDF

Background: Climate change is expected to have profound effects on the distribution of venomous snake species, including reductions in biodiversity and changes in patterns of envenomation of humans and domestic animals. We estimated the effect of future climate change on the distribution of venomous snake species and potential knock-on effects on biodiversity and public health.

Methods: We built species distribution models based on the geographical distribution of 209 medically relevant venomous snake species (WHO categories 1 and 2) and present climatic variables, and used these models to project the potential distribution of species in 2070.

View Article and Find Full Text PDF

A material recovery facility (MRF) can transform municipal solid waste (MSW) into a valued commodity called refuse-derived fuel (RDF) as a promising solution to waste-to-energy conversion. The quality of the produced RDF significantly relies on the composition of in-feed waste and waste characterization method applied for auditing purposes, a process that is both time-consuming and fraught with potential hazards. This study focuses to enhance the workflow of the waste characterization process at an MRF.

View Article and Find Full Text PDF
Article Synopsis
  • Incomplete species inventories in Antarctica hinder ecological research and conservation efforts, with notable gaps in understanding species interactions, population dynamics, and overall biodiversity.
  • A new living database called terrANTALife has been developed, compiling and revising inventories of eukaryotic species in Antarctic terrestrial and freshwater ecosystems, including significant contributions from various groups of microorganisms.
  • The comprehensive checklists now include 470 animal species, 306 plant species, 997 fungal species, and 434 protists, marking a significant step toward understanding and preserving Antarctic biodiversity.
View Article and Find Full Text PDF