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1.
Hematol Oncol ; 42(3): e3278, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38726682

RESUMEN

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma. Circulating lymphoma (CL) cells can be seen at diagnosis in some FL patients, however, previous studies evaluating this have shown mixed results. Therefore, we sought to evaluate the impact of CL at diagnosis on outcomes in patients with newly diagnosed FL using data from a single center. Patients were divided into CL+ and CL- based on immunophenotyping via peripheral blood (PB) flow cytometry. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of FL. The primary endpoint was progression-free survival (PFS) after first-line treatment and secondary endpoints included overall response rate (ORR), overall survival (OS), diagnosis to treatment interval (DTI), progression of disease within 2 years of diagnosis (POD24), and cumulative incidence of transformation between the two groups. Among the 541 patients with FL, 204 had PB flow cytometry performed at diagnosis, and after excluding patients not meeting the eligibility criteria, 147 cases remained with 24 (16%) CL+ at diagnosis. Patients in the CL+ group were younger (53 vs. 58 years, p = 0.02), had more extranodal involvement (83% vs. 44%, p < 0.01), follicular lymphoma international prognostic index 3-5 (55% vs. 31%, p = 0.01), and a higher proportion received first-line immunochemotherapy (75% vs. 43%, p = 0.01) compared to the CL-group. The median PFS was not significantly different between CL+ (6.27 years, 95% CI = 3.61-NR) and CL- (6.61 years, 95% CI = 5.10-9.82) cohorts regardless of the first-line treatment or level of absolute PB CL cells. There was no significant difference in ORR, median OS, DTI, POD24, and cumulative incidence of transformation between the two groups. In our study, we found that the presence of CL cells at diagnosis in FL in the contemporary era did not impact outcomes and survival.


Asunto(s)
Linfoma Folicular , Células Neoplásicas Circulantes , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidad , Linfoma Folicular/patología , Linfoma Folicular/sangre , Persona de Mediana Edad , Femenino , Masculino , Pronóstico , Anciano , Adulto , Células Neoplásicas Circulantes/patología , Inmunofenotipificación , Tasa de Supervivencia , Anciano de 80 o más Años
2.
JTCVS Open ; 18: 360-368, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38690416

RESUMEN

Objective: There is limited clinical evidence to support any specific parenchymal air leak resolution criteria when using digital pleural drainage devices following lung resection. The aim of this study is to determine an optimal air leak resolution criteria, where duration of chest tube drainage is minimized while avoiding complications from premature chest tube removal. Methods: Airflow data averaged at 10-minute intervals was collected prospectively using a digital pleural drainage device (Thopaz; Medela) in 400 patients from 2015 to 2019. All permutations of air leak resolution criteria from <10 to 100 mL/minute for 4 to 12 hours were applied retrospectively to the pleural drainage data to determine air leak duration, and air leak recurrence frequency and volume. Air leak recurrence indicates potential for rather than occurrence of adverse events. Descriptive statistics were used to identify the optimal criteria based on patient safety (low frequency and volume of air leak recurrences), and efficiency (shortest initial air leak duration). Results: The majority of the 400 patients underwent lobectomy (57% [227 out of 400]), wedge resections (29% [115 out of 400]), or segmentectomies (8% [32 out of 400]) for lung cancer (90% [360 out of 400]). An airflow threshold <50 mL/minute resulted in longer air leak duration before meeting the criteria for air leak resolution (P < .0001). Air leak recurrence frequency and volume were greater in patients with a monitoring period <8 consecutive hours (P < .0001). Conclusions: When using a digital pleural drainage device, a postoperative air leak resolution criteria <50 mL/minute for 8 consecutive hours was associated with the best safety and efficiency profile.

3.
bioRxiv ; 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38712065

RESUMEN

Single-cell spatial transcriptomics promises a highly detailed view of a cell's transcriptional state and microenvironment, yet inaccurate cell segmentation can render this data murky by misattributing large numbers of transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio cell simulation to rapidly infer morphologically plausible cell boundaries that preserve cell type heterogeneity. Benchmarking applied to datasets generated by three commercial platforms show superior performance and computational efficiency of this approach compared with existing methods. We show that improved accuracy in cell segmentation aids greatly in detection of difficult to accurately segment tumor infiltrating immune cells such as neutrophils and T cells. Lastly, through improvements in our ability to delineate subsets of tumor infiltrating T cells, we show that CXCL13-expressing CD8+ T cells tend to be more closely associated with tumor cells than their CXCL13-negative counterparts in data generated from renal cell carcinoma patient samples. Proseg is available under at open source license at https://github.com/dcjones/proseg .

4.
Geobiology ; 22(3): e12594, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38700397

RESUMEN

Lehman Caves is an extensively decorated high desert cave that represents one of the main tourist attractions in Great Basin National Park, Nevada. Although traditionally considered a water table cave, recent studies identified abundant speleogenetic features consistent with a hypogenic and, potentially, sulfuric acid origin. Here, we characterized white mineral deposits in the Gypsum Annex (GA) passage to determine whether these secondary deposits represent biogenic minerals formed during sulfuric acid corrosion and explored microbial communities associated with these and other mineral deposits throughout the cave. Powder X-ray diffraction (pXRD), scanning electron microscopy with electron dispersive spectroscopy (SEM-EDS), and electron microprobe analyses (EPMA) showed that, while most white mineral deposits from the GA contain gypsum, they also contain abundant calcite, silica, and other phases. Gypsum and carbonate-associated sulfate isotopic values of these deposits are variable, with δ34SV-CDT between +9.7‰ and +26.1‰, and do not reflect depleted values typically associated with replacement gypsum formed during sulfuric acid speleogenesis. Petrographic observations show that the sulfates likely co-precipitated with carbonate and SiO2 phases. Taken together, these data suggest that the deposits resulted from later-stage meteoric events and not during an initial episode of sulfuric acid speleogenesis. Most sedimentary and mineral deposits in Lehman Caves have very low microbial biomass, with the exception of select areas along the main tour route that have been impacted by tourist traffic. High-throughput 16S rRNA gene amplicon sequencing showed that microbial communities in GA sediments are distinct from those in other parts of the cave. The microbial communities that inhabit these oligotrophic secondary mineral deposits include OTUs related to known ammonia-oxidizing Nitrosococcales and Thaumarchaeota, as well as common soil taxa such as Acidobacteriota and Proteobacteria. This study reveals microbial and mineralogical diversity in a previously understudied cave and expands our understanding of the geomicrobiology of desert hypogene cave systems.


Asunto(s)
Bacterias , Cuevas , Minerales , Cuevas/microbiología , Minerales/análisis , Bacterias/clasificación , Bacterias/metabolismo , Nevada , Archaea/metabolismo , Sedimentos Geológicos/microbiología , Sedimentos Geológicos/química , Parques Recreativos , ARN Ribosómico 16S/genética , Ácidos Sulfúricos , Filogenia , Microbiota , Sulfato de Calcio/química , Microscopía Electrónica de Rastreo
6.
mBio ; 15(5): e0075124, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38591890

RESUMEN

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly, BA.2.87.1 is more resistant to neutralization by XBB.1.5-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines. IMPORTANCE: This study investigates the recently emerged SARS-CoV-2 variants, BA.2.87.1 and JN.1, in comparison to earlier variants and the parental D614G. Varied infectivity and cell-cell fusion activity among these variants suggest potential disparities in their ability to infect target cells and possibly pathogenesis. BA.2.87.1 exhibits lower nAb escape from bivalent mRNA vaccinee and BA.2.86/JN.1-infected sera than JN.1 but is relatively resistance to XBB.1.5-vaccinated hamster sera, revealing distinct properties in immune reason and underscoring the significance of continuing surveillance of variants and reformulation of vaccines. Antigenic differences between BA.2.87.1 and other earlier variants yield critical information not only for antibody evasion but also for viral evolution. In conclusion, this study furnishes timely insights into the spike biology and immune escape of the emerging variants BA.2.87.1 and JN.1, thus guiding effective vaccine development and informing public health interventions.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Fusión Celular , Evasión Inmune , SARS-CoV-2 , Animales , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , COVID-19/inmunología , COVID-19/virología , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Cricetinae , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas contra la COVID-19/inmunología
7.
J Strength Cond Res ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38662946

RESUMEN

ABSTRACT: Witte, BC, Schouten, TC, Westphal, JA, VanZile, AW, Jones, DD, Widenhoefer, TL, Dobbs, WC, Jagim, AR, Luedke, JA, and Almonroeder, TG. The modified reactive strength index is a valid measure of lower-body explosiveness in male and female high school athletes. J Strength Cond Res XX(X): 000-000, 2024-The modified reactive strength index (mRSI) is a commonly used metric to quantify lower-body explosiveness during countermovement jump (CMJ) performance. However, few studies have attempted to examine its validity as a measure of explosiveness, particularly among high school athletes. The purpose of this study was to examine the validity of the mRSI as a measure of lower-body explosiveness among a relatively large sample of male and female high school athletes from various sports. As part of this study, male (n = 132) and female (n = 43) high school athletes performed CMJs, while ground reaction forces were recorded using a force platform. The vertical ground reaction force data collected during the CMJs were used to derive the following variables: peak force (PF), peak power, time to PF, time to take-off, peak rate of force development, and the mRSI. Principal component analysis was applied and reduced these variables into 2 components related to "force" and "speed." The mRSI loaded on both the force (loading = 0.82) and speed (loading = -0.46) components, indicating that it incorporates elements of both force and speed, although it loaded more strongly on the force component than the speed component. The observed pattern of cross-loading suggests that the mRSI is generally a valid measure of lower-body explosiveness for male and female high school athletes.

9.
Cell Chem Biol ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38608683

RESUMEN

Adhesion G protein-coupled receptor (aGPCR) signaling influences development and homeostasis in a wide range of tissues. In the current model for aGPCR signaling, ligand binding liberates a conserved sequence that acts as an intramolecular, tethered agonist (TA), yet this model has not been evaluated systematically for all aGPCRs. Here, we assessed the TA-dependent activities of all 33 aGPCRs in a suite of transcriptional reporter, G protein activation, and ß-arrestin recruitment assays using a new fusion protein platform. Strikingly, only ∼50% of aGPCRs exhibited robust TA-dependent activation, and unlike other GPCR families, aGPCRs showed a notable preference for G12/13 signaling. AlphaFold2 predictions assessing TA engagement in the predicted intramolecular binding pocket aligned with the TA dependence of the cellular responses. This dataset provides a comprehensive resource to inform the investigation of all human aGPCRs and for targeting aGPCRs therapeutically.

10.
bioRxiv ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38559216

RESUMEN

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly. BA.2.87.1 is more resistant to neutralization by XBB.15-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.

11.
Eur Heart J ; 45(18): 1647-1658, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38513060

RESUMEN

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. METHODS: NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. RESULTS: Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. CONCLUSIONS: In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.


Asunto(s)
Síndrome Coronario Agudo , Lesión Renal Aguda , Medios de Contraste , Angiografía Coronaria , Nitratos , Humanos , Angiografía Coronaria/efectos adversos , Angiografía Coronaria/métodos , Medios de Contraste/efectos adversos , Masculino , Femenino , Método Doble Ciego , Nitratos/administración & dosificación , Nitratos/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Anciano , Persona de Mediana Edad , Tasa de Filtración Glomerular/efectos de los fármacos , Compuestos de Potasio/administración & dosificación , Compuestos de Potasio/uso terapéutico
12.
J Cardiovasc Comput Tomogr ; 18(3): 291-296, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38462389

RESUMEN

BACKGROUND: Computed tomography cardiac angiography (CTCA) is recommended for the evaluation of patients with prior coronary artery bypass graft (CABG) surgery. The BYPASS-CTCA study demonstrated that CTCA prior to invasive coronary angiography (ICA) in CABG patients leads to significant reductions in procedure time and contrast-induced nephropathy (CIN), alongside improved patient satisfaction. However, whether CTCA information was used to facilitate selective graft cannulation at ICA was not protocol mandated. In this post-hoc analysis we investigated the influence of CTCA facilitated selective graft assessment on angiographic parameters and study endpoints. METHODS: BYPASS-CTCA was a randomized controlled trial in which patients with previous CABG referred for ICA were randomized to undergo CTCA prior to ICA, or ICA alone. In this post-hoc analysis we assessed the impact of selective ICA (grafts not invasively cannulated based on the CTCA result) following CTCA versus non-selective ICA (imaging all grafts irrespective of CTCA findings). The primary endpoints were ICA procedural duration, incidence of CIN, and patient satisfaction post-ICA. Secondary endpoints included the incidence of procedural complications and 1-year major adverse cardiac events. RESULTS: In the CTCA cohort (n â€‹= â€‹343), 214 (62.4%) patients had selective coronary angiography performed, whereas 129 (37.6%) patients had non-selective ICA. Procedure times were significantly reduced in the selective CTCA â€‹+ â€‹ICA group compared to the non-selective CTCA â€‹+ â€‹ICA group (-5.82min, 95% CI -7.99 to -3.65, p â€‹< â€‹0.001) along with reduction of CIN (1.5% vs 5.8%, OR 0.26, 95% CI 0.10 to 0.98). No difference was seen in patient satisfaction with the ICA, however procedural complications (0.9% vs 4.7%, OR 0.21, 95% CI 0.09-0.87) and 1-year major adverse cardiac events (13.1% vs 20.9%, HR 0.55, 95% CI 0.32-0.96) were significantly lower in the selective group. CONCLUSIONS: In patients with prior CABG, CTCA guided selective angiographic assessment of bypass grafts is associated with improved procedural parameters, lower complication rates and better 12-month outcomes. Taken in addition to the main findings of the BYPASS-CTCA trial, these results suggest a synergistic approach between CTCA and ICA should be considered in this patient group. REGISTRATION: ClinicalTrials.gov, NCT03736018.


Asunto(s)
Angiografía por Tomografía Computarizada , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria , Valor Predictivo de las Pruebas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/cirugía , Resultado del Tratamiento , Puente de Arteria Coronaria/efectos adversos , Factores de Tiempo , Factores de Riesgo , Satisfacción del Paciente , Vasos Coronarios/diagnóstico por imagen , Enfermedades Renales/diagnóstico por imagen , Tempo Operativo , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos
13.
J Natl Compr Canc Netw ; 22(3)2024 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-38479107

RESUMEN

Mutations in BRAF are present in 4% of non-small cell lung cancer (NSCLC), of which half are well-characterized activating variants affecting codon 600 (classified as class I). These mutations, most commonly BRAF V600E, have been associated with response to BRAF/MEK-directed small molecule kinase inhibitors. NSCLC with kinase-activating BRAF mutations occurring at other codons (class II variants) represent a substantial portion of BRAF-mutated NSCLC, but use of targeted therapy in these tumors is still under investigation. Class II mutations have been described in other tumor types and have been associated with response to BRAF/MEK-targeted agents, although optimal treatment strategies for these patients are lacking. This report presents a case of a woman with metastatic NSCLC harboring a class II BRAF p.N486_P490del variant who had a sustained clinical response to combination therapy with dabrafenib and trametinib. This first report of the use of BRAF/MEK-targeted therapy for this variant in NSCLC supports consideration of such treatment for tumors with class II BRAF variants.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Imidazoles , Neoplasias Pulmonares , Piridonas , Pirimidinonas , Femenino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas B-raf/genética , Oximas/uso terapéutico , Quinasas Quinasa Quinasa PAM , Mutación , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética
14.
Appl Opt ; 63(7): 1736, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437274

RESUMEN

This erratum corrects an error in Appl. Opt.62, 3932 (2023)APOPAI0003-693510.1364/AO.488653. The correction does not affect the results and conclusions of the original paper.

15.
Circulation ; 149(12): e964-e985, 2024 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-38344851

RESUMEN

In 1924, the founders of the American Heart Association (AHA) envisioned an international society focused on the heart and aimed at facilitating research, disseminating information, increasing public awareness, and developing public health policy related to heart disease. This presidential advisory provides a comprehensive review of the past century of cardiovascular and stroke science, with a focus on the AHA's contributions, as well as informed speculation about the future of cardiovascular science into the next century of the organization's history. The AHA is a leader in fundamental, translational, clinical, and population science, and it promotes the concept of the "learning health system," in which a continuous cycle of evidence-based practice leads to practice-based evidence, permitting an iterative refinement in clinical evidence and care. This advisory presents the AHA's journey over the past century from instituting professional membership to establishing extraordinary research funding programs; translating evidence to practice through clinical practice guidelines; affecting systems of care through quality programs, certification, and implementation; leading important advocacy efforts at the federal, state and local levels; and building global coalitions around cardiovascular and stroke science and public health. Recognizing an exciting potential future for science and medicine, the advisory offers a vision for even greater impact for the AHA's second century in its continued mission to be a relentless force for longer, healthier lives.


Asunto(s)
Enfermedades Cardiovasculares , Cardiopatías , Accidente Cerebrovascular , Estados Unidos , Humanos , American Heart Association , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/epidemiología , Práctica Clínica Basada en la Evidencia , Mediastino , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/epidemiología
17.
Appl Plant Sci ; 12(1): e11568, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38369976

RESUMEN

Premise: A family-specific probe set for sunflowers, Compositae-1061, enables family-wide phylogenomic studies and investigations at lower taxonomic levels, but may lack resolution at genus to species levels, especially in groups complicated by polyploidy and hybridization. Methods: We developed a Hyb-Seq probe set, Compositae-ParaLoss-1272, that targets orthologous loci in Asteraceae. We tested its efficiency across the family by simulating target enrichment sequencing in silico. Additionally, we tested its effectiveness at lower taxonomic levels in the historically complex genus Packera. We performed Hyb-Seq with Compositae-ParaLoss-1272 for 19 Packera taxa that were previously studied using Compositae-1061. The resulting sequences from each probe set, plus a combination of both, were used to generate phylogenies, compare topologies, and assess node support. Results: We report that Compositae-ParaLoss-1272 captured loci across all tested Asteraceae members, had less gene tree discordance, and retained longer loci than Compositae-1061. Most notably, Compositae-ParaLoss-1272 recovered substantially fewer paralogous sequences than Compositae-1061, with only ~5% of the recovered loci reporting as paralogous, compared to ~59% with Compositae-1061. Discussion: Given the complexity of plant evolutionary histories, assigning orthology for phylogenomic analyses will continue to be challenging. However, we anticipate Compositae-ParaLoss-1272 will provide improved resolution and utility for studies of complex groups and lower taxonomic levels in the sunflower family.

18.
NEJM Evid ; 3(2): EVIDoa2300286, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38320489

RESUMEN

Dapagliflozin in Myocardial InfarctionA total of 4017 patients with acute myocardial infarction, but no diabetes or chronic heart failure, were randomly assigned 10 mg of dapagliflozin or placebo. The primary outcome was a composite of death, hospitalization for heart failure, and five cardiometabolic outcomes analyzed using the win ratio method. There were significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval, 1.20 to 1.50), which was driven by the cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure was not different between the two groups.


Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Insuficiencia Cardíaca , Infarto del Miocardio , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico
19.
Int J Drug Policy ; 124: 104329, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38232437

RESUMEN

BACKGROUND: Buprenorphine is a gold-standard treatment for opioid use disorders, but most people with these disorders do not access it. Barriers to treatment access may be diminished by low-threshold mobile treatment programs but concern regarding their impact on local public safety challenges their adoption. METHODS: This quasi-experimental study uses difference-in-differences analyses to measure the impact of four mobile buprenorphine clinics in Pittsburgh on neighborhood arrest rates. The study period spans 2018 to 2022, with a pre-intervention period of 11 to 12 quarters and a post-intervention period of 7 to 8 quarters (dependent on neighborhood). A treatment group of 84 census block groups in the areas surrounding clinics during the time period after their establishment were compared to a control group of city census blocks not within one mile of a clinic plus treated block groups in the two years prior to clinic establishment. Outcome variables include drug, non-drug, and total arrests, measured quarterly per 100 in population. RESULTS: Compared to block groups further than 1 mile from a clinic, arrests fell by 34.13 % (b = -0.358, 95 % CI = -0.557, -0.158), drug arrests by 33.85 % (b = -0.087, 95 % CI = -0.151, -0.023), and non-drug related arrests by 22.29 % (b = -0.179, 95 % CI = -0.302, -0.057). Drug arrests declined significantly on days when the clinics were not present (b = -0.015, 95 % CI = -0.025, -0.006), with no significant change on clinic operational days (b = -0.002, 95 % CI = -0.016, -0.013). Total arrests declined significantly on days when clinics were and were not present (b = -0.045, 95 % CI = -0.078, -0.012; and b = -0.052, CI = -0.082, -0.023, respectively). CONCLUSIONS: Mobile clinics providing medication for opioid use disorders were associated with reduced neighborhood arrest rates. Expansion of mobile services could promote health equity and public safety.


Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Reducción del Daño , Promoción de la Salud , Buprenorfina/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Combinación Buprenorfina y Naloxona/uso terapéutico
20.
J Interpers Violence ; : 8862605231225518, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38197396

RESUMEN

Religion has had a mixed impact on society, with some followers engaging in violent behavior. It remains unclear why some followers perpetrate violence and others are peaceful. We argue that religious overclaiming is one facet of religion to be considered when trying to understand the relationship between religion and violence. Across two studies (N = 551), we tested the hypothesis that a higher tendency to overclaim knowledge of the Christian Bible would be associated with higher perpetration of intimate partner violence (IPV). We also tested the hypotheses that men who overclaim would be most likely to engage in the perpetration of IPV, and that higher religiosity would attenuate the effects of religious overclaiming. In both studies, participants completed a measure of religious overclaiming, reported on their perpetration of IPV, and reported their religiosity. Our findings across both studies indicated that Bible overclaiming was associated with greater perpetration of IPV. Further, Study 1 found that those high in Bible overclaiming (especially men) engaged in the most perpetration of IPV. However, this gender-based finding did not replicate in Study 2. Both studies found that religiosity was unassociated with the perpetration of IPV. Our results provide evidence that Bible overclaiming is related to the perpetration of IPV. Specifically, individuals who claim to know religious concepts that do not exist are associated with a higher risk for IPV.

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