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Therapeutic strategies targeting non-adaptive immune cells are currently in clinical development. γδT cells are a small subtype of T cells (1-10% of total T cells) that mediate their effector function without the necessity of the antigen presenting machinery, and also share functional properties with innate cells. Among the different γδT subtypes, antibodies against Vγ9Vδ2T have reported signs of clinical efficacy in early clinical studies. In this review we describe the biology of this subtype of non-conventional T cells and provide insights into the mechanism of action of novel antibodies that activate these cells. We will focus on antibodies targeting the BTN3A ligand and bi-specific γδT cell engagers. We will review in detail the advantages of these strategies including the potential for overcoming mechanisms of resistance to check point inhibitors, or the much more adequate safety profile compared with agents activating classical T cells. Limitations identified during the first studies in humans and strategies to overcome them will be revised and discussed. Finally, clinical options for future clinical development will be suggested.
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Receptores de Antígenos de Linfocitos T gamma-delta , Humanos , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Animales , Butirofilinas/inmunología , Activación de Linfocitos/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Inmunoterapia/métodos , Linfocitos Intraepiteliales/inmunología , Antígenos CDRESUMEN
Colorectal cancer (CRC) is the third most common cancer worldwide. Recent experiments suggest that CDK12 can be a good therapeutic target in CRC, and therefore, novel inhibitors targeting this protein are currently in preclinical development. Lipid-based formulations of chemical entities have demonstrated the ability to enhance activity while improving the safety profile. In the present work, we explore the antitumor activity of a new CDK12 inhibitor (CDK12-IN-E9, CDK12i) and its lipid-based formulation (LP-CDK12i) in CRC models, to increase efficacy. SW620, SW480 and HCT116 CRC cell lines were used to evaluate the inhibitor and the liposomal formulation using MTT proliferation assay, 3D invasion cultures, flow cytometry, Western blotting and immunofluorescence experiments. Free-cholesterol liposomal formulations of CDK12i (LP-CDK12i) were obtained by solvent injection method and fully characterized by size, shape, polydispersity, encapsulation efficiency, and release profile and stability assessments. LP-CDK12i induced a higher antiproliferative effect compared with CDK12i as a free agent. The IC50 value was lower across all cell lines tested, leading to a reduction in cell proliferation and the formation of 3D structures. Evaluation of apoptosis revealed an increase in cell death, while biochemical studies demonstrated modifications of apoptosis and DNA damage components. In conclusion, we confirm the role of targeting CDK12 for the treatment of CRC and describe, for the first time, a liposomal formulation of a CDK12i with higher antiproliferative activity compared with the free compound.
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OBJECTIVES: To develop a decalogue of self-care competencies to manage educational intervention during Cardiac Rehabilitation (CR) programs in Heart Failure with preserved Ejection Fraction (HFpEF) patients through multidisciplinary consensus. DESIGN: 3-round e-Delphi study using an initial questionnaire of 23 competencies based on the main recommendations of the CR and self-care guidelines. SITE: It was framed under the ethics of a randomised clinical trial developed at the Regional Hospital of Malaga. The survey was designed and disseminated as an online questionnaire. PARTICIPANTS: The expert panel comprised two patients with HFpEF and 13 healthcare professionals from Internal Medicine (n=3), Cardiology (n=2), Physiotherapy (n=3), Nursing (n=3) and Occupational Therapy (n=2). METHOD: The analysis of results included the content validity index, the percentage of agreement, and the concordance using Fleiss Kappa and Krippendorff's alpha. RESULTS: After the third round, 20 self-care competencies were identified, grouped into 12 domains, with sufficient consensus for their inclusion in the decalogue. CONCLUSIONS: The decalogue of self-care competencies generated from the multidisciplinary consensus guides education in patients with HFpEF, systematically addressing educational content tailored to patients for clinical practice in CR programs.
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This paper introduces Art_GenEvalGPT, a novel dataset of synthetic dialogues centered on art generated through ChatGPT. Unlike existing datasets focused on conventional art-related tasks, Art_GenEvalGPT delves into nuanced conversations about art, encompassing a wide variety of artworks, artists, and genres, and incorporating emotional interventions, integrating speakers' subjective opinions and different roles for the conversational agents (e.g., teacher-student, expert guide, anthropic behavior or handling toxic users). Generation and evaluation stages of GenEvalGPT platform are used to create the dataset, which includes 13,870 synthetic dialogues, covering 799 distinct artworks, 378 different artists, and 26 art styles. Automatic and manual assessment proof the high quality of the synthetic dialogues generated. For the profile recovery, promising lexical and semantic metrics for objective and factual attributes are offered. For subjective attributes, the evaluation for detecting emotions or subjectivity in the interventions achieves 92% of accuracy using LLM-self assessment metrics.
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Patients hospitalized with COVID-19 have low levels of vitamins and trace elements. This could lead to a post-acute COVID-19 condition (PCC) that can worsen a patient's quality of life. We aimed to study the baseline micronutrient status of patients and assess whether a multiple micronutrient supplement (MMS) taken for 2 weeks at the first sign of COVID-19 symptoms would be able to reduce the incidence of PCC. This double-blind, placebo-controlled, randomized clinical trial was conducted in adult outpatients with acute COVID-19, recruited between 2021 and 2023 in Spain. Of the 285 patients assessed for eligibility, 267 were randomized and 246 were included in the intent-to-treat population. The mean age was 46.8 years, and 68% were female. Overall, 54.6% had micronutrient deficiencies in the acute phase of COVID-19 at baseline, and 26.2% had PCC after 180 days of follow-up (D180). The most frequently recorded PCC symptoms were neurological (14.1%), with 24% patients scoring worse in the cognitive tests compared to their baseline status. The rate of PCC at D180 was similar between the placebo (25.0%) and intervention (27.7%) groups, without significant differences (p = 0.785). Age over 50 years was the most relevant risk factor for developing PCC, followed by female sex. The most important protective factor against PCC was SARS-CoV-2 vaccination. In this population of predominantly middle-aged, white women with acute COVID-19 not requiring hospital admission, MMS intake for 14 days at symptom onset did not prevent PCC nor improve their micronutrient status at D180.
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COVID-19 , Suplementos Dietéticos , Micronutrientes , SARS-CoV-2 , Humanos , Femenino , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/complicaciones , Masculino , Método Doble Ciego , Persona de Mediana Edad , Micronutrientes/administración & dosificación , Adulto , España/epidemiología , Síndrome Post Agudo de COVID-19 , Anciano , BetacoronavirusRESUMEN
The placement of endotracheal prostheses is a procedure used to treat tracheal lesions when no other surgical options are available. Unfortunately, this technique remains controversial. Both silicon and metallic stents are used with unpredictable success rates, as they have advantages but also disadvantages. Typical side effects include restenosis due to epithelial hyperplasia, obstruction and granuloma formation. Repeat interventions are often required. Biodegradable stents are promising in the field of cardiovascular biomechanics but are not yet approved for use in the respiratory system. The aim of the present study is to summarize important information and to evaluate the role of different geometrical features for the fabrication of a new tracheo-bronchial prosthesis prototype, which should be biodegradable, adaptable to the patient's lesion and producible by 3D printing. A parametric design and subsequent computational analysis using the finite element method is carried out. Two different stent designs are parameterized and analyzed. The biodegradable material chosen for simulations is polylactic acid. Experimental tests are conducted for assessing its mechanical properties. The role of the key design parameters on the radial force of the biodegradable prosthesis is investigated. The computational results allow us to elucidate the role of the pitch angle, the wire thickness and the number of cells or units, among other parameters, on the radial force. This work may be useful for the design of ad hoc airway stents according to the patient and type of lesion.
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INTRODUCION: The concept of a window of opportunity in hidradenitis suppurativa (HS) management suggests that early initiation of biological therapy leads to better outcomes, though its timing remains uncertain. METHODS: We conducted a retrospective observational multicenter study, including consecutive patients with moderate to severe HS who initiated secukinumab treatment following prior failure with systemic antibiotics or adalimumab. Therapeutic burden was defined as the sum of previous systemic treatment cycles and previous major surgical interventions for HS. Patients were followed up for 24 weeks. Main outcomes were safety and effectiveness, assessed through the proportion of patients achieving HS Clinical Response (HiSCR) and a 55% reduction in International HS Severity Score System (IHS4-55). Additionally, potential predictors of response to secukinumab were studied. Analysis was performed on an intention-to-treat basis. RESULTS: A total of 67 patients (33 men, 34 women) were included, with a mean age of 41.55 (11.94) years and a mean baseline IHS4 of 17.88 (11.13). The mean therapeutic burden was 6.06 (3.49). At week 24, 10.45% (7/67) of patients experienced adverse events, with three leading to treatment discontinuation. At week 24, 41.79% (28/67) of patients achieved HiSCR, and 44.78% (30/67) of patients achieved IHS4-55. HiSCR could not be calculated in 12 patients with a baseline AN count < 3. A lower therapeutic burden was significantly associated with a higher likelihood of achieving HiSCR and IHS4-55 at week 24. CONCLUSIONS: Secukinumab showed safety and efficacy in real-world patients with HS, and the inverse correlation found between therapeutic burden and treatment response supports the concept of a window of opportunity, offering insights into its timing.
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The maturation of B cells is a complex, multi-step process. During B cell differentiation, errors can occur, leading to the emergence of aberrant versions of B cells that, finally, constitute a malignant tumor. These B cell malignancies are classified into three main groups: leukemias, myelomas, and lymphomas, the latter being the most heterogeneous type. Since their discovery, multiple biological studies have been performed to characterize these diseases, aiming to define their specific features and determine potential biomarkers for diagnosis, stratification, and prognosis. The rise of advanced -omics approaches has significantly contributed to this end. Notably, proteomics strategies appear as promising tools to comprehensively profile the final molecular effector of these cells. In this narrative review, we first introduce the main B cell malignancies together with the most relevant proteomics approaches. Then, we describe the core studies conducted in the field and their main findings and, finally, we evaluate the advantages and drawbacks of flow cytometry, mass cytometry, and mass spectrometry for the profiling of human B cell disorders.
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Linfocitos B , Neoplasias Hematológicas , Proteómica , Humanos , Proteómica/métodos , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/patología , Linfocitos B/metabolismo , Biomarcadores de Tumor/metabolismo , Espectrometría de Masas/métodos , Citometría de Flujo/métodosRESUMEN
Trachoma is targeted for elimination as a public health problem worldwide by 2030. In Nigeria, elimination activities are implemented at the local government area (LGA) level. They started in 2002 by conducting baseline population-based prevalence surveys (PBPSs), which continued in a systematic manner with engagement from the Global Trachoma Mapping Project in 2013, and subsequently Tropical Data. The results led to the development of Nigeria's first trachoma action plan and its subsequent revision with additional information. Following 449 baseline PBPSs, 122 LGAs had an active trachoma prevalence above the elimination threshold, requiring interventions, while 231 LGAs required community-based interventions for trichiasis management. By 2021, >34 million antibiotic treatments had been provided in 104 LGAs, with 89 LGAs eliminating active trachoma. Nationally, water and sanitation coverages increased by 3% and 18%, respectively, in 7 y. Systematic trichiasis case finding and management were carried out in 231 LGAs, resulting in the management of 102 527 people. Fifty-four LGAs decreased trichiasis prevalence unknown to the health system to <0.2% in persons ≥15 y of age. Where this elimination prevalence threshold was reached, trichiasis services were transitioned to routine eye/healthcare systems. Such progress relied on strong leadership and coordination from the national trachoma program and tremendous support provided by partners. Attaining elimination of trachoma as a public health problem in Nigeria by 2030 is feasible if funding support is sustained.
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Canola protein obtained from canola meal, a byproduct of the canola industry, is an economical biopolymer with promising film-forming properties. It has significant potential for use as a food packaging material, though it possesses some functional limitations that need improvement. Incorporating nanomaterials is an option to enhance functional properties. This study aims to produce canola protein films by integrating GO exfoliated at several oxidation times and weight ratios to optimize mechanical, thermal, and barrier properties. Oxidation alters the C/O ratio and adds functional groups that bond with the amino/carboxyl groups of protein, enhancing the film properties. Significant improvement was obtained in GO at 60 and 120 min oxidation time and 3% addition level. Tensile strength and elastic modulus increased 200% and 481.72%, respectively, compared to control. Control films showed a 37.57 × 10-3 cm3m/m2/day/Pa oxygen permeability, and it was significantly reduced to 5.65 × 10-3 cm3m/m2/day/Pa representing a 665% reduction.
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Embalaje de Alimentos , Grafito , Nanopartículas , Proteínas de Plantas , Resistencia a la Tracción , Embalaje de Alimentos/instrumentación , Grafito/química , Nanopartículas/química , Proteínas de Plantas/química , Brassica napus/química , Permeabilidad , Oxidación-ReducciónRESUMEN
Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.
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Protocolos de Quimioterapia Combinada Antineoplásica , ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Neoplasia Residual , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Neoplasia Residual/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Biopsia Líquida/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Tomografía Computarizada por Tomografía de Emisión de Positrones , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Biomarcadores de Tumor/sangre , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Pronóstico , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Secuenciación de Nucleótidos de Alto Rendimiento , Prednisona/uso terapéutico , Prednisona/administración & dosificaciónRESUMEN
The identification of targets that are expressed on the cell membrane is a main goal in cancer research. The Lymphocyte Antigen 6 Family Member G6D (LY6G6D) gene codes for a protein that is mainly present on the surface of colorectal cancer (CRC) cells. Therapeutic strategies against this protein like the development of T cell engagers (TCE) are currently in the early clinical stage. In the present work, we interrogated public genomic datasets including TCGA to evaluate the genomic and immunologic cell profile present in tumors with high expression of LY6G6D. We used data from TCGA, among others, and the Tumor Immune Estimation Resource (TIMER2.0) platform for immune cell estimations and Spearman correlation tests. LY6G6D expression was exclusively present in CRC, particularly in the microsatellite stable (MSS) subtype, and was associated with left-side tumors and the canonical genomic subgroup. Tumors with mutations of APC and p53 expressed elevated levels of LY6G6D. This protein was expressed in tumors with an inert immune microenvironment with an absence of immune cells and co-inhibitory molecules. In conclusion, we described clinical, genomic and immune-pathologic characteristics that can be used to optimize the clinical development of agents against this target. Future studies should be performed to confirm these findings and potentially explore the suggested clinical development options.
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Neoplasias Colorrectales , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Femenino , Masculino , Proteína de la Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Regulación Neoplásica de la Expresión Génica , Mutación , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/genética , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Antígenos Ly/metabolismo , Antígenos Ly/genética , Antígenos B7/genética , Antígenos B7/metabolismoRESUMEN
Immuno-oncology has gained momentum with the approval of antibodies with clinical activities in different indications. Unfortunately, for anti-PD (L)1 agents in monotherapy, only half of the treated population achieves a clinical response. For other agents, such as anti-CTLA4 antibodies, no biomarkers exist, and tolerability can limit administration. In this study, using publicly available genomic datasets, we evaluated the expression of the macrophage scavenger receptor-A (SR-A) (MSR1) and its association with a response to check-point inhibitors (CPI). MSR1 was associated with the presence of macrophages, dendritic cells (DCs) and neutrophils in most of the studied indications. The presence of MSR1 was associated with macrophages with a pro-tumoral phenotype and correlated with TIM3 expression. MSR1 predicted favorable overall survival in patients treated with anti-PD1 (HR: 0.56, FDR: 1%, p = 2.6 × 10-5), anti PD-L1 (HR: 0.66, FDR: 20%, p = 0.00098) and anti-CTLA4 (HR: 0.37, FDR: 1%, p = 4.8 × 10-5). When specifically studying skin cutaneous melanoma (SKCM), we observed similar effects for anti-PD1 (HR: 0.65, FDR: 50%, p = 0.0072) and anti-CTLA4 (HR: 0.35, FDR: 1%, p = 4.1 × 10-5). In a different dataset of SKCM patients, the expression of MSR1 predicted a clinical response to anti-CTLA4 (AUC: 0.61, p = 2.9 × 10-2). Here, we describe the expression of MSR1 in some solid tumors and its association with innate cells and M2 phenotype macrophages. Of note, the presence of MSR1 predicted a response to CPI and, particularly, anti-CTLA4 therapies in different cohorts of patients. Future studies should prospectively explore the association of MSR1 expression and the response to anti-CTLA4 strategies in solid tumors.
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Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Perfilación de la Expresión Génica , Transcriptoma , Oncología Médica , Receptores Depuradores de Clase ARESUMEN
Fusarium graminearum causes destructive ear rot diseases in maize and wheat. New antifungals are essential to combat this pathogen, and aerial parts of Justicia species (Acanthaceae) are a potential source. We investigated the antifungal activity of extracts from stems and leaves of five Justicia species native to Northwest Argentina. The aerial parts were subjected to sequential extractions with dichloromethane, ethyl acetate, and methanol. The resulting extracts were tested by the disc diffusion method against F. graminearum strains. Only the leaf and stem extracts from J. xylosteoides displayed inhibitory effects, with the dichloromethane leaf extract as the most active. The compounds involved were identified as the lignans hinokinin, savinin, and isohibalactone. Both the dichloromethane extract and hinokinin synergised with tebuconazole, and inhibited deoxynivalenol biosynthesis. The identified compounds warrant further research as additives to azole fungicides for F. graminearum control.
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The identification of surfaceome proteins is a main goal in cancer research to design antibody-based therapeutic strategies. T cell engagers based on KLK2, a kallikrein specifically expressed in prostate cancer (PRAD), are currently in early clinical development. Using genomic information from different sources, we evaluated the immune microenvironment and genomic profile of prostate tumors with high expression of KLK2. KLK2 was specifically expressed in PRAD but it was not significant associated with Gleason score. Additionally, KLK2 expression did not associate with the presence of any immune cell population and T cell activating markers. A mild correlation between the high expression of KLK2 and the deletion of TMPRSS2 was identified. KLK2 expression associated with high levels of surface proteins linked with a detrimental response to immune checkpoint inhibitors (ICIs) including CHRNA2, FAM174B, OR51E2, TSPAN1, PTPRN2, and the non-surface protein TRPM4. However, no association of these genes with an outcome in PRAD was observed. Finally, the expression of these genes in PRAD did not associate with an outcome in PRAD and any immune populations. We describe the immunologic microenvironment on PRAD tumors with a high expression of KLK2, including a gene signature linked with an inert immune microenvironment, that predicts the response to ICIs in other tumor types. Strategies targeting KLK2 with T cell engagers or antibody-drug conjugates will define whether T cell mobilization or antigen release and stimulation of immune cell death are sufficient effects to induce clinical activity.
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Calicreínas , Neoplasias de la Próstata , Receptores Odorantes , Humanos , Masculino , Genómica , Calicreínas/genética , Calicreínas/inmunología , Calicreínas/metabolismo , Proteínas de Neoplasias , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/metabolismo , Tetraspaninas , Microambiente Tumoral/genéticaRESUMEN
AIMS: This paper aims to assess kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test (6MWT) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: A cross-sectional study was conducted in which adults 70 years or older with HFpEF were voluntarily recruited between April 2019 and March 2020. An inertial sensor was placed at the L3-L4 level and another on the sternum to assess kinematic parameters. The 6MWT was divided into two 3-min phases. Leg fatigue and breathlessness, assessed by the Borg scale, the heart rate (HR), and the oxygen saturation (SpO2), were measured at the beginning and the end of the 6MWT. The difference in kinematic parameters between the 6MWT two 3-min phases was also calculated. Bivariate Pearson correlations and subsequent multivariate linear regression analysis were performed. Seventy older adults with HFpEF (mean = 80.74 years old) were included. Kinematic parameters explained 81.00% of the functional capacity, 45.50% of the leg fatigue and 66.10% of the breathlessness variance. Moreover, kinematic parameters could explain 30.90% of the SpO2 variance at the end of the 6MWT. Kinematic parameters also explained 33.10% of the SpO2 difference between the beginning and end of 6MWT. Kinematic parameters explained neither the HR variance at the end of 6MWT nor the HR difference between the beginning and end. CONCLUSION: Gait kinematics from L3-L4 and sternum explain a part of the variance in subjective outcomes, assessed by the Borg scale, and objective outcomes such as functional capacity and SpO2. The kinematic assessment allows clinicians to quantify fatigue and breathlessness through objective parameters related to the patient's functional capacity. REGISTRATION: ClinicalTrials.gov NCT03909919.
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Insuficiencia Cardíaca , Humanos , Anciano , Anciano de 80 o más Años , Prueba de Paso/métodos , Estudios Transversales , Insuficiencia Cardíaca/complicaciones , Volumen Sistólico/fisiología , Fenómenos Biomecánicos , Disnea , Fatiga , Prueba de Esfuerzo/métodosRESUMEN
BACKGROUND: Photography could be used to train individuals to diagnose trachomatous inflammation-follicular (TF) as trachoma prevalence decreases and to ensure accurate field TF grading in trachoma prevalence surveys. We compared photograph and field TF grading and determined the acceptability and feasibility of eyelid photography to community members and trachoma survey trainers. METHODS: A total of 100 children ages 1-9 y were examined for TF in two Maasai villages in Tanzania. Two images of the right everted superior tarsal conjunctiva of each child were taken with a smartphone and a digital single-lens reflex (DSLR) camera. Two graders independently graded all photos. Focus group discussions (FGDs) were conducted with community members and Tropical Data trainers. RESULTS: Of 391 photos, one-fifth were discarded as ungradable. Compared with field grading, photo grading consistently underdiagnosed TF. Compared with field grading, DSLR photo grading resulted in a higher prevalence and sensitivity than smartphone photo grading. FGDs indicated that communities and trainers found photography acceptable and preferred smartphones to DSLR in terms of practicalities, but image quality was of paramount importance for trainers. CONCLUSIONS: Photography is acceptable and feasible, but further work is needed to ensure high-quality images that enable accurate and consistent grading before being routinely implemented in trachoma surveys.
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Estudios de Factibilidad , Fotograbar , Tracoma , Humanos , Tracoma/diagnóstico , Tracoma/epidemiología , Tanzanía/epidemiología , Fotograbar/métodos , Preescolar , Niño , Lactante , Femenino , Masculino , Grupos Focales , Prevalencia , Teléfono InteligenteRESUMEN
PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.
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Tracoma , Humanos , Lactante , Tracoma/epidemiología , Tracoma/prevención & control , Prevalencia , Salud Pública , Manejo de Datos , Organización Mundial de la SaludRESUMEN
Antibody-drug conjugates (ADCs) have emerged as a novel therapeutic strategy that has successfully reached patient treatment in different clinical scenarios. ADCs are formed by an antibody against a specific tumor-associated antigen (TAA), a cytotoxic payload, and a chemical linker that binds both. To this regard, most efforts have been focused on target identification, antibody design and linker optimization, but other relevant aspects for clinical development have not received the necessary attention. In this article using data from approved ADCs, we evaluated all characteristics of these agents, including payload physicochemical properties, in vitro potency, drug antibody ratio (DAR), exposure-response relationships, and clinical development strategies. We suggest that compounds with best options for clinical development include those with optimal payload physicochemical properties and cleavable linkers that would lead to a bystander effect. These modalities can facilitate the development of ADCs in indications with low expression of the TAA. Early clinical development strategies including changes in the schedule of administration with more frequent doses are also discussed in the context of an efficient strategy. In conclusion, we highlight relevant aspects that are needed for the optimal development of ADCs in cancer, proposing options for improvement.