Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Robust metabolic transcriptional components in 34,494 patient-derived cancer-related samples and cell lines

BACKGROUND: Patient-derived bulk expression profiles of cancers can provide insight into the transcriptional changes that underlie reprogrammed metabolism in cancer. These profiles represent the average expression pattern of all heterogeneous tumor and non-tumor cells present in biopsies of tumor lesions. Hence, subtle transcriptional footprints of metabolic processes can be concealed by other biological processes and experimental artifacts. However, consensus independent component analyses (c-ICA) can capture statistically independent transcriptional footprints of both subtle and more pronounced metabolic processes. METHODS: We performed c-ICA with 34,494 bulk expression profiles of patient-derived tumor biopsies, non-cancer tissues, and cell lines. Gene set enrichment analysis with 608 gene sets that describe metabolic processes was performed to identify the transcriptional components enriched for metabolic processes (mTCs). The activity of these mTCs was determined in all samples to create a metabolic transcriptional landscape. RESULTS: A set of 555 mTCs was identified of which many were robust across different datasets, platforms, and patient-derived tissues and cell lines. We demonstrate how the metabolic transcriptional landscape defined by the activity of these mTCs in samples can be used to explore the associations between the metabolic transcriptome and drug sensitivities, patient outcomes, and the composition of the immune tumor microenvironment. CONCLUSIONS: To facilitate the use of our transcriptional metabolic landscape, we have provided access to all data via a web portal (www.themetaboliclandscapeofcancer.com). We believe this resource will contribute to the formulation of new hypotheses on how to metabolically engage the tumor or its (immune) microenvironment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-021-00272-7

Ischemia and reperfusion of the soleus muscle of rats with pentoxifylline

BACKGROUND: Reperfusion of the skeletal muscle worsens existing lesions during ischemia, since the production of reactive oxygen species, associated with intense participation of neutrophils, increases the inflammatory reaction that induces tissue changes. OBJECTIVE: To evaluate the morphological and immunohistochemical changes of the skeletal (soleus) muscle of rats submitted to ischemia and reperfusion with pentoxifylline. METHODS: Sixty rats were submitted to ischemia of the pelvic limb for 6 hours induced by clamping the left common iliac artery. After ischemia, group A animals (n = 30) were observed for 4 hours and group B animals (n = 30) for 24 hours. Six animals constituted the sham group. Pentoxifylline was applied only in the reperfusion period A2 (n = 10) and B2 (n = 10), and in ischemia and reperfusion periods in A3 (n = 10) and B3 (n = 10). The soleus muscle was evaluated by histological (fiber disruption, leukocyte infiltrate, necrosis) and immunohistochemical (apoptosis through caspase-3 expression) analysis. The non-parametric tests Kruskal-Wallis and Mann-Whitney (p < 0.05) were applied. RESULTS: The changes were more intense in group B1, with fiber disruption mean scores of 2.16±0.14; neutrophilic infiltrate of 2.05±0.10; and caspase-3 expression in the perivascular area of 4.30±0.79; and less intense in group A3, with means of 0.76±0.16; 0.92±0.10; 0.67±0,15, respectively (p < 0.05). Caspase-3 was more expressive in group B1 in the perivascular area, with mean of 4.30±0.79 when compared with group B1 in the perinuclear area, with mean of 0.91±0.32 (p < 0.05) CONCLUSIONS: The lesions were more intense when observation time was longer after reperfusion, and pentoxifylline attenuated these lesions, above all when used in the beginning of ischemia and reperfusion phases.CONTEXTO: A reperfusão de músculo esquelético piora as lesões já presentes no período de isquemia, pois a produção de espécies reativas de oxigênio, associadas à intensa participação de neutrófilos, amplia a reação inflamatória que induz alterações teciduais. OBJETIVO: Avaliar as alterações morfológicas e imuno-histoquímicas de músculo esquelético (sóleo) de ratos submetidos a isquemia e reperfusão com pentoxifilina. MÉTODOS: Sessenta ratos foram submetidos a isquemia do membro pélvico, por 6 horas, pelo clampeamento da artéria ilíaca comum esquerda. Após isquemia, os animais do grupo A (n = 30) foram observados por 4 horas, e os do grupo B (n = 30), por 24 horas. Seis animais constituíram o grupo simulado. Administrou-se pentoxifilina apenas no período de reperfusão em A2 (n = 10) e B2 (n = 10) e nos períodos de isquemia e reperfusão em A3 (n = 10) e B3 (n = 10). O músculo sóleo foi avaliado por análise histológica (dissociação de fibras, infiltrado leucocitário, necrose) e imuno-histoquímica (apoptose pela expressão da caspase-3). Foram aplicados os testes não-paramétricos de Kruskal-Wallis e Mann-Whitney (p < 0,05). RESULTADOS: As alterações foram mais intensas no grupo B1, com médias de escore da dissociação de fibras musculares de 2,16 ± 0,14, infiltrado neutrofílico de 2,05 ± 0,10 e expressão da caspase-3 na área perivascular de 4,30 ± 0,79; e menos intensas no grupo A3, com respectivas médias de 0,76 ± 0,16, 0,92 ± 0,10 e 0,67 ± 0,15 (p < 0,05). A caspase-3 mostrou-se mais expressiva no grupo B1 na área perivascular, com média de 4,30 ± 0,79, em comparação com o grupo B1 na área perinuclear, com média de 0,91 ± 0,32 (p < 0,05). CONCLUSÕES: As lesões são mais intensas quando o tempo de observação é maior após a reperfusão, e a pentoxifilina atenua essas lesões, sobretudo quando usada no início das fases de isquemia e de reperfusão.SBACVUniversidade Federal de Mato Grosso do Sul Hospital UniversitárioUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUFMSUNIFESP-EPM Departamento de PatologiaUFMS Departamento de Clínica CirúrgicaUFMS Hospital Universitário Comissão de Residência MédicaUNIFESP, EPM, Depto. de PatologiaSciEL

Usefulness of preclinical models for assessing the efficacy of late-life interventions for sarcopenia

Caloric restriction and physical exercise have proven beneficial against age-associated changes in body composition and declining physical performance; however, little is known regarding what benefit these interventions might have when initiated late in life. The study of mimetics of diet and exercise and the combination thereof may provide additional treatments for a vulnerable elderly population; however, how and when to initiate such interventions requires consideration in developing the most safe and efficacious treatment strategies. In this review, we focus on preclinical late-life intervention studies, which assess the relationship between physical function, sarcopenia, and body composition. We provide a conceptual framework for the ever-changing definition of sarcopenia and a rationale for the use of an appropriate rodent model of this condition. We finish by providing our perspective regarding the implications of this body of work and future areas of research that may also contribute to the ultimate goal of extending healthspan. © 2011 The Author

Comparison of highest and overall percentage Gleason pattern 4 in prostate cancer biopsies

Current guidelines recommend pathologists to report percentage Gleason pattern 4 (GP4%) in Gleason score (GS) 7 prostate cancer (PCa) biopsies. However, it is unspecified whether the highest or overall GP4% should be reported. This study aims to clarify which quantification method correlates best with radical prostatectomy (RP) pathology. This study included 308 men with the highest GS 3 + 4 = 7, 4 + 3 = 7, or 4 + 4 = 8 on centrally revised systematic and/or targeted biopsies who underwent RP between 2018 and 2022. The highest and overall biopsy GP4% were compared with RP GP4% using Spearman’s rank correlation coefficient and adverse pathology (AP) (pT-stage ≥ T3, GS ≥ 4 + 3 = 7 and/or pN1) using multivariable logistic regression models adjusted for clinical tumor stage, prostate specific antigen (PSA), percentage of tumor positive biopsies, biopsy modality (systematic/targeted/both), and cribriform pattern. Both quantification methods correlated with RP GP4% (both rho = 0.59), and no significant difference was found between them (p = 0.78). On multivariable analyses, both GP4% quantification methods were significantly associated with AP (per 10% increase, highest GP4% odds ratio [OR] 1.26 [95% CI 1.14–1.39], overall GP4% OR 1.38 [95% CI 1.22–1.58], both p &lt; 0.001). The area under the curve (AUC) was slightly better for overall (0.78 [95% CI 0.73–0.83]) than the highest GP4% (0.76 [95% CI 0.71–0.81], p = 0.041). This study found that the highest and overall biopsy GP4% both correlated with RP GP4%. Although the discriminative performance of the highest and overall GP4% was comparable with respect to AP at RP, the overall GP4% statistically slightly outperformed the highest GP4%. Including the overall GP4% may have added value in risk stratification and clinical decision-making in a subset of PCa patients.</p

Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors

Background: Sepsis survivors often develop chronic critical illness (CCI) and demonstrate the persistent inflammation, immunosuppression, and catabolism syndrome predisposing them to long-term functional limitations and higher mortality. There is a need to identify biomarkers that can predict long-term worsening of physical function to be able to act early and prevent mobility loss. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-accepted biomarker of cardiac overload, but it has also been shown to be associated with long-term physical function decline. We explored whether NT-proBNP blood levels in the acute phase of sepsis are associated with physical function and muscle strength impairment at 6 and 12 months after sepsis onset. Methods: This is a retrospective analysis conducted in 196 sepsis patients (aged 18-86 years old) as part of the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) who consented to participate in the 12-month follow-up study. NT-proBNP was measured at 24 h after sepsis onset. Patients were followed to determine physical function by short physical performance battery (SPPB) test score (scale 0 to12-higher score corresponds with better physical function) and upper limb muscle strength by hand grip strength test (kilograms) at 6 and 12 months. We used a multivariate linear regression model to test an association between NT-proBNP levels, SPPB, and hand grip strength scores. Missing follow-up data or absence due to death was accounted for by using inverse probability weighting based on concurrent health performance status scores. Statistical significance was set at p ≤ 0.05. Results: After adjusting for covariates (age, gender, race, Charlson comorbidity index, APACHE II score, and presence of CCI condition), higher levels of NT-proBNP at 24 h after sepsis onset were associated with lower SPPB scores at 12 months (p &lt; 0.05) and lower hand grip strength at 6-month (p &lt; 0.001) and 12-month follow-up (p &lt; 0.05). Conclusions: NT-proBNP levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors

Improving gene function predictions using independent transcriptional components

The interpretation of high throughput sequencing data is limited by our incomplete functional understanding of coding and non-coding transcripts. Reliably predicting the function of such transcripts can overcome this limitation. Here we report the use of a consensus independent component analysis and guilt-by-association approach to predict over 23,000 functional groups comprised of over 55,000 coding and non-coding transcripts using publicly available transcriptomic profiles. We show that, compared to using Principal Component Analysis, Independent Component Analysis-derived transcriptional components enable more confident functionality predictions, improve predictions when new members are added to the gene sets, and are less affected by gene multi-functionality. Predictions generated using human or mouse transcriptomic data are made available for exploration in a publicly available web portal. Our understanding of the function of many transcripts is still incomplete, limiting the interpretability of transcriptomic data. Here the authors use consensus-independent component analysis, together with a guilt-by-association approach, to improve the prediction of gene function