Substance Use and Its Relationship With Attachment and Early Maladaptive Schemes in Adolescents in Ecuador.

Given the scarcity of studies addressing substance consumption and its relationship with attachment styles and early maladaptive schemas in adolescents, the present study is proposed. Aims of this study are to analyze the relationship among attachment styles, early maladaptive schemas, and substance use; test the predictive role of attachment styles on substance use; and observe the mediating role of early maladaptive schemas in the relationship between attachment and substance use. The sample consisted of 1533 adolescents from Ecuador (53.9% males) aged between 14 and 18 years (M = 15.76; SD = 1.25). The attachment styles of security, value to parental authority, parental permissiveness, parental interference, self-sufficiency and resentment against parents, childhood trauma, and family concern predict substance use (tobacco, alcohol, tranquilizers/sedatives or sleeping pills, hashish or marijuana, cocaine, GHB or liquid ecstasy, ecstasy, amphetamines/speed, hallucinogens, heroin, inhalants/volatiles), and the mediating role of early maladaptive schemas is confirmed (explained variance up to 33.33%). Identifying risk or vulnerability factors, such as attachment and early maladaptive schemas related to substance consumption, is especially relevant for designing and implementing preventive interventions in the adolescent population.

Identification of a Proteomic Signature for Predicting Immunotherapy Response in Patients With Metastatic Non-Small Cell Lung Cancer.

Immunotherapy has improved survival rates in patients with cancer, but identifying those who will respond to treatment remains a challenge. Advances in proteomic technologies have enabled the identification and quantification of nearly all expressed proteins in a single experiment. Integrating mass spectrometry with high-throughput technologies has facilitated comprehensive analysis of the plasma proteome in cancer, facilitating early diagnosis and personalized treatment. In this context, our study aimed to investigate the predictive and prognostic value of plasma proteome analysis using the SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) strategy in newly diagnosed patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab therapy. We enrolled 64 newly diagnosed patients with advanced NSCLC treated with pembrolizumab. Blood samples were collected from all patients before and during therapy. A total of 171 blood samples were analyzed using the SWATH-MS strategy. Plasma protein expression in metastatic NSCLC patients prior to receiving pembrolizumab was analyzed. A first cohort (discovery cohort) was employed to identify a proteomic signature predicting immunotherapy response. Thus, 324 differentially expressed proteins between responder and non-responder patients were identified. In addition, we developed a predictive model and found a combination of seven proteins, including ATG9A, DCDC2, HPS5, FIL1L, LZTL1, PGTA, and SPTN2, with stronger predictive value than PD-L1 expression alone. Additionally, survival analyses showed an association between the levels of ATG9A, DCDC2, SPTN2 and HPS5 with progression-free survival (PFS) and/or overall survival (OS). Our findings highlight the potential of proteomic technologies to detect predictive biomarkers in blood samples from NSCLC patients, emphasizing the correlation between immunotherapy response and the idenfied protein set.

The role of resilience and coping strategies as predictors of well-being in breast cancer patients.

PURPOSE: This study investigated the role of resilience and coping strategies on breast cancer patients' well-being using a structural equation model. To achieve this objective, a model previously developed by Mayordomo's group was partially replicated using a longitudinal study design in an oncological sample. METHODS: The study was a longitudinal observational survey. Patients with breast cancer were recruited (N = 166). Resilience was measured with the Mexican Resilience Measurement Scale, coping strategies with the Forms of Coping and Dimensions Scale and perception of the psychological well-being with a short-form of Ryff's Scales of Psychological Well-Being at the start and end of adjuvant chemotherapy (T1 and T2 respectively). RESULTS: The results showed stability in the variables over time and revealed differences with respect to Mayordomo's model. The best predictor of well-being at T2 was well-being at T1. In addition, the model indicated that resilience had a direct impact on well-being through problem-focused coping. Indeed, resilience and problem-focused coping best explained well-being at T2. CONCLUSIONS: Both at the start and end of adjuvant chemotherapy for breast cancer, problem-focused coping positively predicted resilience, which in turn was a positive predictor of well-being. On the other hand, emotion-focused coping showed no association with resilience or well-being. As part of the multidisciplinary cancer team, oncology nurses have a key role to play in promoting resilience and problem-focused coping as an important goal of psychosocial interventions in breast cancer patients.

Resilience in Newly Diagnosed Breast Cancer Women: The Predictive Role of Diurnal Cortisol and Social Support.

BACKGROUND: Breast cancer is currently the most prevalent malignancy among women. Psychological resilience is an important factor that diminishes the stress-related emotional and psychosocial disturbances triggered when receiving the diagnosis. Furthermore, resilience appears to be associated with cortisol, the hormonal end-product of the hypothalamic-pituitary-adrenal axis; however, further studies are needed due to the mixed results reported. Thus, we aim to examine the predictive role of social support and cortisol in resilience among breast cancer patients. METHODS: A total of 132 women with primary breast cancer completed the Medical Outcomes Study-Social Support Survey (MOS-SSS) and the Resilience Scale (RS-14) and provided four salivary samples for the estimation of participants' total daily cortisol production, for which the formula of the area under the curve with respect to the ground (AUCg) was applied. Moderation analyses were performed to study the influence of social support and AUCg on psychological resilience levels. RESULTS: The regression analyses showed a direct significant effect for the emotional support subscale of MOS-SSS on resilience and the interaction between emotional support and AUCg was also found to be statistically significant. Specifically, the conditional effect of emotional support on resilience was found to be significant at middle (M = 3.08; p < .05) and low levels (M = .59; p < .001) of AUCg. CONCLUSIONS: Our results suggest that newly diagnosed breast cancer women with middle and low diurnal cortisol profiles may benefit more from emotional support based-interventions while women with high diurnal cortisol may need more individualized therapies.

Binding of exogenous cyanide reveals new active-site states in [FeFe] hydrogenases.

[FeFe] hydrogenases are highly efficient metalloenyzmes for hydrogen conversion. Their active site cofactor (the H-cluster) is composed of a canonical [4Fe-4S] cluster ([4Fe-4S]H) linked to a unique organometallic di-iron subcluster ([2Fe]H). In [2Fe]H the two Fe ions are coordinated by a bridging 2-azapropane-1,3-dithiolate (ADT) ligand, three CO and two CN- ligands, leaving an open coordination site on one Fe where substrates (H2 and H+) as well as inhibitors (e.g. O2, CO, H2S) may bind. Here, we investigate two new active site states that accumulate in [FeFe] hydrogenase variants where the cysteine (Cys) in the proton transfer pathway is mutated to alanine (Ala). Our experimental data, including atomic resolution crystal structures and supported by calculations, suggest that in these two states a third CN- ligand is bound to the apical position of [2Fe]H. These states can be generated both by "cannibalization" of CN- from damaged [2Fe]H subclusters as well as by addition of exogenous CN-. This is the first detailed spectroscopic and computational characterisation of the interaction of exogenous CN- with [FeFe] hydrogenases. Similar CN--bound states can also be generated in wild-type hydrogenases, but do not form as readily as with the Cys to Ala variants. These results highlight how the interaction between the first amino acid in the proton transfer pathway and the active site tunes ligand binding to the open coordination site and affects the electronic structure of the H-cluster.

Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients.

Background: Lack of biomarkers for treatment selection and monitoring in small cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC. Methods: We quantified cfDNA in 46 SCLC patients at different times during first-line of chemotherapy or chemo-immunotherapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch® system. The possible association between both biomarkers and patients' outcomes was investigated in order to develop a prognostic model. Results: High cfDNA levels before therapy were associated with shorter progression-free survival (PFS) and overall survival (OS). Furthermore, cfDNA levels at 3 weeks and at progression disease were also associated with patients' outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender and baseline cfDNA levels was associated with a higher risk of progression and death. Conclusions: We confirmed the prognostic utility of cfDNA quantitative analysis in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.

Bioelectrocatalytic CO2 Reduction by Redox Polymer-Wired Carbon Monoxide Dehydrogenase Gas Diffusion Electrodes.

The development of electrodes for efficient CO2 reduction while forming valuable compounds is critical. The use of enzymes as catalysts provides the advantage of high catalytic activity in combination with highly selective transformations. We describe the electrical wiring of a carbon monoxide dehydrogenase II from Carboxydothermus hydrogenoformans (ChCODH II) using a cobaltocene-based low-potential redox polymer for the selective reduction of CO2 to CO over gas diffusion electrodes. High catalytic current densities of up to -5.5 mA cm-2 are achieved, exceeding the performance of previously reported bioelectrodes for CO2 reduction based on either carbon monoxide dehydrogenases or formate dehydrogenases. The proposed bioelectrode reveals considerable stability with a half-life of more than 20 h of continuous operation. Product quantification using gas chromatography confirmed the selective transformation of CO2 into CO without any parasitic co-reactions at the applied potentials.

Comparative analysis of capture methods for genomic profiling of circulating tumor cells in colorectal cancer.

The genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. Here, we contrasted the genomic profiles of CTC pools recovered from metastatic colorectal cancer (mCRC) patients using different enrichment strategies (CellSearch, Parsortix, and FACS). Mutations inferred in the CTC pools differed depending on the enrichment strategy and, in all cases, represented a subset of the mutations detected in the matched primary tumor samples. However, the CTC pools from Parsortix, and in part, CellSearch, showed diversity estimates, mutational signatures, and drug-suitability scores remarkably close to those found in matching primary tumor samples. In addition, FACS CTC pools were enriched in apparent sequencing artifacts, leading to much higher genomic diversity estimates. Our results highlight the utility of CTCs to assess the genomic heterogeneity of individual tumors and help clinicians prioritize drugs in mCRC.

A global health model integrating psychological variables involved in cancer through a longitudinal study.

Objective: The literature has shown the relevance of certain psychological variables in adjustment to cancer. However, there is a great variability, and these features could be modified through the disease process. The aim of this study is to provide an integrated and global perspective of the importance of variables such as coping, resilience, emotional control, social support, affect, and others in cancer patients through a longitudinal study, with the objective of exploring their associations and underlying interactions. Methods: The sample was composed of 71 people diagnosed with cancer who were attending psychological support at the Spanish Association Against Cancer (Biscay). We assessed the following variables in two periods of 6 months: perceived stress (PSS), emotional control (CECS), resilience (CD-RISC), coping strategies (CERQ), personality (NEOFFI), social support (MOSS), affect (PANAS), emotional distress (GHQ), quality of life (SF-12) and visual-analogic scales (EVA). Results: Results showed predictive effects of perceived stress on physical health perception (ß = -0.22; t = -3.26; p = 0.002). Mental health perception was influenced by almost all the psychological variables. Consciousness at baseline (ßCo = 0.15; p = 0.003), change in Extraversion (ßEx = 0.16; p = 0.001) and Resilience (ßRe = 0.15; p = 0.002) had significant effects on perceived mental health. Conclusion: This study provides a global health model that integrates and explores associations between psychological variables related to cancer disease. This information could be useful for guiding personalized psychotherapeutic interventions, with the aim of increasing adjustment to disease.

Methods for the Detection of Circulating Biomarkers in Cancer Patients.

Liquid biopsy has emerged as one of the main pillars for personalized oncology. The term englobes body-fluid samples which contain tumor-derived material such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating extracellular vesicles (cEVs). Potential clinical application of liquid biopsy analyses includes cancer screening, detection of minimal residual disease and recurrence, therapy selection, and evaluation of acquired resistance. Despite the great developments of technology focused on circulating biomarkers characterization only cfDNA testing is nowadays implemented for the therapy selection in some advanced tumors. This can be partially explained by the fact that there is still a lack of global standardization of procedures both in the pre-analytical and analytical steps. In the present chapter, we summarize the different strategies for addressing the study of liquid biopsy taking into account their pros and cons to be applied in a clinical context and we also discuss the main technical and clinical challenges in the field of circulating biomarkers and personalized oncology.

Stability of the H-cluster under whole-cell conditions-formation of an Htrans-like state and its reactivity towards oxygen.

Hydrogenases are metalloenzymes that catalyze the reversible oxidation of molecular hydrogen into protons and electrons. For this purpose, [FeFe]-hydrogenases utilize a hexanuclear iron cofactor, the H-cluster. This biologically unique cofactor provides the enzyme with outstanding catalytic activities, but it is also highly oxygen sensitive. Under in vitro conditions, oxygen stable forms of the H-cluster denoted Htrans and Hinact can be generated via treatment with sulfide under oxidizing conditions. Herein, we show that an Htrans-like species forms spontaneously under intracellular conditions on a time scale of hours, concurrent with the cells ceasing H2 production. Addition of cysteine or sulfide during the maturation promotes the formation of this H-cluster state. Moreover, it is found that formation of the observed Htrans-like species is influenced by both steric factors and proton transfer, underscoring the importance of outer coordination sphere effects on H-cluster reactivity.

Role of resilience and emotional control in relation to mental health in people with cancer.

This study explored the relationship between emotional control, resilience, and mental health in cancer. Patients with cancer were recruited (n = 170). Courtauld Scale of Emotional Control, Connor-Davidson Resilience Scale, and the General Health Questionnaire were selected. Assuming the absence of interaction among the variables, they were analyzed separately. Four groups resulted, finding statistically significant differences (F(4, 165) = 18.03; p < 0.001). High resilience and low emotional control seem to be protective attributes, and high emotional control has demonstrated to be a risk factor for mental health. Considering differences in cancer-related psychological variables could derive in personalized psychotherapeutic interventions.

Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non-small-cell lung cancer treated with pembrolizumab.

Immune checkpoint inhibitors, such as pembrolizumab, are revolutionizing therapeutic strategies for different cancer types, including non-small-cell lung cancer (NSCLC). However, only a subset of patients benefits from this therapy, and new biomarkers are needed to select better candidates. In this study, we explored the value of liquid biopsy analyses, including circulating free DNA (cfDNA) and circulating tumour cells (CTCs), as a prognostic or predictive tool to guide pembrolizumab therapy. For this purpose, a total of 109 blood samples were collected from 50 patients with advanced NSCLC prior to treatment onset and at 6 and 12 weeks after the initiation of pembrolizumab. Plasma cfDNA was measured using hTERT quantitative PCR assay. The CTC levels at baseline were also analysed using two enrichment technologies (CellSearch® and Parsortix systems) to evaluate the efficacy of both approaches at detecting the presence of programmed cell death ligand 1 on CTCs. Notably, patients with high baseline hTERT cfDNA levels had significantly shorter progression-free survival (PFS) and overall survival (OS) than those with low baseline levels. Moreover, patients with unfavourable changes in the hTERT cfDNA levels from baseline to 12 weeks showed a higher risk of disease progression. Additionally, patients in whom CTCs were detected using the CellSearch® system had significantly shorter PFS and OS than patients who had no CTCs. Finally, multivariate regression analyses confirmed the value of the combination of CTCs and cfDNA levels as an early independent predictor of disease progression, identifying a subgroup of patients who were negative for CTCs, who presented low levels of cfDNA and who particularly benefited from the treatment.

Resilience and coping strategies in relation to mental health outcomes in people with cancer.

Considering the importance of psychological variables on health-related processes, this study investigated the role of resilience and coping strategies in relation to health. The aim of this research was to explore the underlying association between these aspects for the better understanding of the effect of psychosocial variables on mental health in cancer. This information could lead to the design of adapted psychological interventions in cancer. Participants with different diagnosis of cancer were recruited (N = 170). They came from the Spanish Association Against Cancer of Biscay. Resilience was measured with the 10 items Connor-Davidson Resilience Scale, coping with the Cognitive Emotion Regulation Questionnaire and mental health was measured as a global indicator through the SF-12 and the GHQ-12. A structural equation model (SEM) was conducted to test the effects between the constructs. Results showed that resilience and coping were significantly associated. Results reflected an absence of significant correlation between adaptive and disadaptive coping strategies. Resilience was the factor that most correlated with health outcomes (ß = -.45, p < .001). However, disadaptive coping strategies did not correlate with resilience or mental health indicators. Findings in this study underscore the positive contribution of high levels of resilience and an adaptive coping on participants´ level of health. Disadaptive coping strategies did not reflect any positive relation with resilience or health indicators. Thus, promoting resilience and adaptive coping could be a significant goal for psychosocial and educational interventions in people with cancer.

Circulating Free DNA and Its Emerging Role in Autoimmune Diseases.

Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid biopsy, we found clinical application in nontumour pathologies, including autoimmune diseases. Since the discovery of the presence of high levels of cfDNA in patients with systemic lupus erythaematosus (SLE) in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and its association with disease activity. However, with technological advancements and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity, interest in cfDNA and autoimmune diseases has not expanded until recently. In this review, we provide an overview of the basic biology of cfDNA in the context of autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response. We discuss and integrate available information about these important aspects.

Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer.

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

Immunotherapy in nonsmall-cell lung cancer: current status and future prospects for liquid biopsy.

Immunotherapy has been one of the great advances in the recent years for the treatment of advanced tumors, with nonsmall-cell lung cancer (NSCLC) being one of the cancers that has benefited most from this approach. Currently, the only validated companion diagnostic test for first-line immunotherapy in metastatic NSCLC patients is testing for programmed death ligand 1 (PD-L1) expression in tumor tissues. However, not all patients experience an effective response with the established selection criteria and immune checkpoint inhibitors (ICIs). Liquid biopsy offers a noninvasive opportunity to monitor disease in patients with cancer and identify those who would benefit the most from immunotherapy. This review focuses on the use of liquid biopsy in immunotherapy treatment of NSCLC patients. Circulating tumor cells (CTCs), cell-free DNA (cfDNA) and exosomes are promising tools for developing new biomarkers. We discuss the current application and future implementation of these parameters to improve therapeutic decision-making and identify the patients who will benefit most from immunotherapy.

Design and evaluation of a positive intervention to cultivate mental health: preliminary findings

Abstract The past two decades have witnessed a proliferation of positive psychological interventions for clinical and nonclinical populations, and recent research, including meta-analyses, is providing evidence of its effectiveness. Most interventions have focused on increasing life satisfaction, positive affect, and psychological well-being. Manualized, multi-component interventions based on a comprehensive theory are scarce. Keyes' concept of mental health and flourishing (subjective, psychological, and social well-being) is an overarching theoretical framework to guide the design of a multi-component psychological intervention to cultivate well-being and personal development. Therefore, the purpose of this study was to design a theory-driven positive intervention and to pilot test the intervention. The manual presents an 8-week group program that includes homework activities. A sample of 56 young adults completed the intervention. Participants were assessed at base line, after termination, and at a 6-month follow-up session. Standardized instruments were used to assess the dimensions of mental health proposed by Keyes. Pre- and post-test measures of subjective, psychological, and social well-being showed significant differences, as did the total mental health scores. At 6-month follow-up, differences remained in subjective and psychological well-being and in positive mental health, with smaller effect sizes. Limitations of these preliminary findings as well as future lines of research and improvements in this manualized intervention are proposed in the light of current research on positive interventions.