A comparison of immunohistochemical assays and FISH in detecting the ALK translocation in diagnostic histological and cytological lung tumor material.

Introduction:Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives.Methods:Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification.Results:All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene.Conclusions:IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein

Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) : Gender-specific changes in the microRNA expression profiling in ME/CFS

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state. Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge. The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS. The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post-exertional malaise in ME/CFS. We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects' metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements. The identification of gender-based miRNAs importantly provides new insights into gender-specific ME/CFS susceptibility and demands exploration of sex-suited ME/CFS therapeutics

Patterns and predictors of co-morbidities in Tuberculosis: A cross-sectional study in the Philippines.

Diabetes and undernutrition are common risk factors for TB, associated with poor treatment outcomes and exacerbated by TB. We aimed to assess non-communicable multimorbidity (co-occurrence of two or more medical conditions) in Filipino TB outpatients, focusing on malnutrition and diabetes. In a cross-sectional study, 637 adults (70% male) from clinics in urban Metro Manila (N = 338) and rural Negros Occidental (N = 299) were enrolled. Diabetes was defined as HbA1c of ≥6.5% and/or current diabetes medication. Study-specific HIV screening was conducted. The prevalence of diabetes was 9.2% (54/589, 95%CI: 7.0-11.8%) with 52% newly diagnosed. Moderate/severe undernutrition (body mass index (BMI) <17 kg/2) was 20.5% (130/634, 95%CI: 17.4-23.9%). Forty percent of participants had at least one co-morbidity (diabetes, moderate/severe undernutrition or moderate/severe anaemia (haemoglobin <11 g/dL)). HIV infection (24.4%, 74/303) was not associated with other co-morbidities (but high refusal in rural clinics). Central obesity assessed by waist-to-hip ratio was more strongly associated with diabetes (Adjusted Odds Ratio (AOR) = 6.16, 95%CI: 3.15-12.0) than BMI. Undernutrition was less common in men (AOR = 0.44, 95%CI: 0.28-0.70), and associated with previous history of TB (AOR = 1.97, 95%CI: 1.28-3.04) and recent reduced food intake. The prevalence of multimorbidity was high demonstrating a significant unmet need. HIV was not a risk factor for increased non-communicable multimorbidity

ESTUDO DA UTILIZAÇÃO DE NUTRIÇÃO PARENTERAL EM PACIENTES PEDIÁTRICOS / STUDY OF PARENTERAL NUTRITION IN PEDIATRIC PATIENTS

Introdução. A nutrição parenteral utilizada em adultos e crianças é constituída por uma associação de substâncias que são manipuladas pela farmácia hospitalar e prescritas de acordo com a necessidade de cada paciente. Objetivo. Avaliar a utilização de nutrição parenteral em pacientes pediátricos. Métodos. Este trabalho analisou 669 prescrições de 159 crianças internadas na Unidade Materno Infantil do Hospital Universitário de São Luís, no período de setembro de 2008 a fevereiro de 2009. Resultados. A maioria das prescrições manipuladas neste período foram destinadas à lactentes de 1 a 2 Kg. Houve predominância do diagnóstico prematuridade para se justificar a indicação da terapia nutricional. Conclusão. A maioria dos pacientes recebeu suporte nutricional parenteral por até 3 dias.Palavras-chave: Nutrição parenteral. Pediatria. Farmácia hospitalar.AbstractIntroduction. Parenteral nutrition used in adults and children consists of a combination of substances that are handled by the hospital pharmacy and prescribed according to the needs of each patient. Objective. To evaluate the utilization of parenteral nutrition in pediatric patients. Methods. This study analyzed 669 medical prescriptions of 159 children admitted to the University hospital of São luís - Materno Infantil unit, from September 2008 to February 2009. Results. Most prescriptions examined during the research were directed to nurslings whose weights were 1-2 kg. Prematurity was the most common diagnosis that justified the indication for nutritional therapy. Conclusion. Most patients received parenteral nutrition support for up to three days.  Keywords: Parenteral nutrition. Pediatrics. Hospital pharmacy

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Evaluating the utility of combining high resolution thermal, multispectral and 3D imagery from unmanned aerial vehicles to monitor water stress in vineyards

30 Pág.Purpose: High resolution imagery from unmanned aerial vehicles (UAVs) has been established as an important source of information to perform precise irrigation practices, notably relevant for high value crops often present in semi-arid regions such as vineyards. Many studies have shown the utility of thermal infrared (TIR) sensors to estimate canopy temperature to inform on vine physiological status, while visible-near infrared (VNIR) imagery and 3D point clouds derived from red–green–blue (RGB) photogrammetry have also shown great promise to better monitor within-field canopy traits to support agronomic practices. Indeed, grapevines react to water stress through a series of physiological and growth responses, which may occur at different spatio-temporal scales. As such, this study aimed to evaluate the application of TIR, VNIR and RGB sensors onboard UAVs to track vine water stress over various phenological periods in an experimental vineyard imposed with three different irrigation regimes. Methods: A total of twelve UAV overpasses were performed in 2022 and 2023 where in situ physiological proxies, such as stomatal conductance (gs), leaf (Ψleaf) and stem (Ψstem) water potential, and canopy traits, such as LAI, were collected during each UAV overpass. Linear and non-linear models were trained and evaluated against in-situ measurements. Results: Results revealed the importance of TIR variables to estimate physiological proxies (gs, Ψleaf, Ψstem) while VNIR and 3D variables were critical to estimate LAI. Both VNIR and 3D variables were largely uncorrelated to water stress proxies and demonstrated less importance in the trained empirical models. However, models using all three variable types (TIR, VNIR, 3D) were consistently the most effective to track water stress, highlighting the advantage of combining vine characteristics related to physiology, structure and growth to monitor vegetation water status throughout the vine growth period. Conclusion: This study highlights the utility of combining such UAV-based variables to establish empirical models that correlated well with field-level water stress proxies, demonstrating large potential to support agronomic practices or even to be ingested in physically-based models to estimate vine water demand and transpiration.This research was supported by the DATI project (PCI2021-121932) from the Spanish Ministry of Science and Innovation (AEI/https://doi.org/10.13039/501100011033) and the PRIMA EU program. This work was also supported by the EO4WUE research project (TED2021-129814B-I00) funded by MCIN/AEI/https://doi.org/10.13039/501100011033 and by the European Union NextGenerationEU/PRTR. The authors VBL and IBS were financed by the grant FJC2021-047273-I and FJC2021-047687-1, respectively, funded by MCIN/AEI/https://doi.org/10.13039/501100011033 and European Union NextGenerationEU/PRTR, while the authors GMR has been a beneficiary of a FPI fellowship by the Spanish Ministry of Education and Professional Training (PRE2018-083227).Peer reviewe

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin