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We carry out a theoretical investigation about quantum noise in coherent mixtures of states with different statistics. On the one hand, we investigate the dependence between the behavior wave-particle and associated noise. On the other hand, we are interested in studying the persistence of chaotic behavior in mixtures of states with quantum and classical behavior. For this, we perform mixtures of single photons with coherent states of different averages. We find that the noise associated with quantum chaos depends on the proportion of the quantum–classical mixture and that quantum wave states are more efficient than classical wave states in terms of their randomness properties.

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and usually requires the administration of adjuvant chemotherapy after surgery but even with this treatment many patients still suffer from a relapse. The main objective of this study was to identify proteomics-based biomarkers that predict the response to standard adjuvant chemotherapy, so that patients at are not going to benefit from it can be offered therapeutic alternatives. We analyzed the proteome of a retrospective series of formalin-fixed, paraffin-embedded TNBC tissue applying high-throughput label-free quantitative proteomics. We identified several protein signatures with predictive value, which were validated with quantitative targeted proteomics in an independent cohort of patients and further evaluated in publicly available transcriptomics data. Using univariate Cox analysis, a panel of 18 proteins was significantly associated with distant metastasis-free survival of patients (p<0.01). A reduced 5-protein profile with prognostic value was identified and its prediction performance was assessed in an independent targeted proteomics experiment and a publicly available transcriptomics dataset. Predictor P5 including peptides from proteins RAC2, RAB6A, BIEA and IPYR was the best performance protein combination in predicting relapse after adjuvant chemotherapy in TNBC patients. This study identified a protein combination signature that complements histopathological prognostic factors in TNBC treated with adjuvant chemotherapy. The protein signature can be used in paraffin-embedded samples, and after a prospective validation in independent series, it could be used as predictive clinical test in order to recommend participation in clinical trials or a more exhaustive follow-up.

Renal cell carcinoma comprises a variety of entities, the most common being the clear-cell, papillary and chromophobe subtypes. These subtypes are related to different clinical evolution; however, most therapies have been developed for clear-cell carcinoma and there is not a specific treatment based on different subtypes. In this study, one hundred and sixty-four paraffin samples from primary nephrectomies for localized tumors were analyzed. MiRNAs were isolated and measured by microRNA arrays. Significance Analysis of Microarrays and Consensus Cluster algorithm were used to characterize different renal subtypes. The analyses showed that chromophobe renal tumors are a homogeneous group characterized by an overexpression of miR 1229, miR 10a, miR 182, miR 1208, miR 222, miR 221, miR 891b, miR 629-5p and miR 221-5p. On the other hand, clear cell renal carcinomas presented two different groups inside this histological subtype, with differences in miRNAs that regulate focal adhesion, transcription, apoptosis and angiogenesis processes. Specifically, one of the defined groups had an overexpression of proangiogenic microRNAs miR185, miR126 and miR130a. In conclusion, differences in miRNA expression profiles between histological renal subtypes were established. In addition, clear cell renal carcinomas had different expression of proangiogenic miRNAs. With the emergence of antiangiogenic drugs, these differences could be used as therapeutic targets in the future or as a selection method for tailoring personalized treatments.

Background Rollout designs, which include stepped wedge designs, are defined by staggered implementation of new or alternative programs or services. Critiques of stepped wedge and other rollout designs have raised concerns regarding the confounding of true implementation or program effects with unrelated, global changes in service delivery, with some recommending they only be used when traditional parallel-group designs are not practicable. However, rollout designs may sometimes be more suitable than traditional parallel group designs for ethical, scientific, or practical reasons. Results As investigators involved in several recent rollout trials, we define and provide rationale for and examples of stepped wedge and the larger class of rollout designs, in which all participating units receive a new program or service implementation. Staged implementation in a rollout design may be necessary when denying, rather than delaying, implementation of a known effective service is ethically unacceptable. Scientifically, stepped wedge has increased statistical power relative to an equivalent parallel group design, and some rollout designs have the capability to compare different phases of implementation and sustainment. A rollout design may be practically necessary either because of limited resources and other logistical challenges or community requirements that no site serve as a control. Examples of completed and ongoing rollout trials illustrate how these ethical, scientific, and practical considerations influenced trial designs. Conclusions Stepped wedge and other rollout trial designs may be well suited to evaluation of implementation strategies or policy changes. In implementation trials, rollout designs may be necessary for practical reasons, may be required for ethical reasons, and may be preferred for scientific reasons. We summarize when such rollout designs have advantages and drawbacks.

This manuscript describes the rationale and design of a family-based, Hispanic sexual minority youth (HSMY) specific preventive intervention, Familias con Orgullo (Families with Pride). HSMY ( N = 306) and their primary caregivers will be recruited in South Florida and be randomized to Familias con Orgullo or prevention as usual. The intervention will be delivered by trained study facilitators. Outcomes will be measured at baseline and 6-, 18-, and 30-months post-baseline. The goals of this study are to evaluate whether the Familias con Orgullo intervention, compared to community practice, is effective in reducing drug use and depressive symptoms through the improvement of parent support for the youth, parent acceptance, family functioning, youth stress, and sexual minority stress. Additionally, we will explore whether gender and baseline levels of parent support for the youth, parent acceptance, family functioning, youth stress, and sexual minority stress moderate intervention effects on the youth outcomes. ClinicalTrials.gov identifier: NCT06057337 , First posted September 28, 2023.

This article focuses on the rationale, design and methods of an effectiveness-implementation hybrid type I randomized trial of eHealth Familias Unidas Mental Health , a family-based, online delivered intervention for Hispanic families to prevent/reduce depressive and anxious symptoms, suicide ideation/behaviors, and drug use in Hispanic youth. Utilizing a rollout design with 18 pediatric primary care clinics and 468 families, this study addresses intervention effectiveness, implementation research questions, and intervention sustainment, to begin bridging the gap between research and practice in eliminating mental health and drug use disparities among Hispanic youth. Further, we will examine whether intervention effects are partially mediated by improved family communication and reduced externalizing behaviors, including drug use, and moderated by parental depression. Finally, we will explore whether the intervention’s impact on mental health and drug use, as well as sustainment of the intervention in clinics, varies by quality of implementation at clinic and clinician levels. Trail registration: ClinicalTrials.gov Identifier: NCT05426057 , First posted June 21, 2022.

Background Behavioral Interventions are needed to prevent HIV in substance users, which is associated with higher risk for contracting HIV via unprotected sexual intercourse or syringe-based exposure. We reviewed universal HIV prevention interventions targeting intravenous drug users (IDUs) and non-IDUs (NIDUs) to identify which prevention interventions are the most effective at reducing HIV transmission risk among IDU’s and NIDU’s and identify gaps in the literature. Methods A PubMed literature review (1998–2017), limiting studies to universal HIV prevention interventions targeting adult HIV-negative substance users. Interventions were compared across sample sizes, sociodemographic, intervention setting, study design, use of theoretical models, and intervention effects. Results Of 1455 studies identified, 19 targeted IDUs ( n  = 9) and NIDUs ( n  = 10). Both IDU and NIDU studies were conducted in substance use treatment centers and included both group (44% vs. 73%) and individual-based (56% vs. 27%) methods; only one NIDU study used a couple-based intervention. All IDU, and 89% of NIDU, studies used explanatory and behavior-change theoretical models to guide selection of intervention mechanisms. Reduction in frequency of risky sexual behaviors were observed in 33% IDU and 64% NIDU studies, where 56% of IDU studies effectively increased drug use-related hygiene and 67% decreased frequency of injections. Eight studies included start-of-study HIV testing and five examined HIV seroconversion. Conclusion The interventions reviewed demonstrate promising results for decreasing risky sexual practices for NIDUs and reducing high-risk drug practices for IDUs, thereby reducing HIV transmission risk. Future studies should include HIV testing and measurement of HIV seroconversion to fully elucidate intervention effects.

Background Metabolomics has a great potential in the development of new biomarkers in cancer and it has experiment recent technical advances. Methods In this study, metabolomics and gene expression data from 67 localized (stage I to IIIB) breast cancer tumor samples were analyzed, using (1) probabilistic graphical models to define associations using quantitative data without other a priori information; and (2) Flux Balance Analysis and flux activities to characterize differences in metabolic pathways. Results On the one hand, both analyses highlighted the importance of glutamine in breast cancer. Moreover, cell experiments showed that treating breast cancer cells with drugs targeting glutamine metabolism significantly affects cell viability. On the other hand, these computational methods suggested some hypotheses and have demonstrated their utility in the analysis of metabolomics data and in associating metabolomics with patient’s clinical outcome. Conclusions Computational analyses applied to metabolomics data suggested that glutamine metabolism is a relevant process in breast cancer. Cell experiments confirmed this hypothesis. In addition, these computational analyses allow associating metabolomics data with patient prognosis.

Background Muscle-invasive bladder tumors are associated with a high risk of relapse and metastasis even after neoadjuvant chemotherapy and radical cystectomy. Therefore, further therapeutic options are needed and molecular characterization of the disease may help to identify new targets. The aim of this study was to characterize muscle-invasive bladder tumors at the molecular level using computational analyses. Methods The TCGA cohort of muscle-invasive bladder cancer patients was used to describe these tumors. Probabilistic graphical models, layer analyses based on sparse k-means coupled with Consensus Cluster, and Flux Balance Analysis were applied to characterize muscle-invasive bladder tumors at a functional level. Results Luminal and Basal groups were identified, and an immune molecular layer with independent value was also described. Luminal tumors showed decreased activity in the nodes of epidermis development and extracellular matrix, and increased activity in the node of steroid metabolism leading to a higher expression of the androgen receptor. This fact points to the androgen receptor as a therapeutic target in this group. Basal tumors were highly proliferative according to Flux Balance Analysis, which makes these tumors good candidates for neoadjuvant chemotherapy. The Immune-high group showed a higher degree of expression of immune biomarkers, suggesting that this group may benefit from immune therapy. Conclusions Our approach, based on layer analyses, established a Luminal group candidate for therapy with androgen receptor inhibitors, a proliferative Basal group which seems to be a good candidate for chemotherapy, and an immune-high group candidate for immunotherapy.