Machine learning-aided design and screening of an emergent protein function in synthetic cells.

Recently, utilization of Machine Learning (ML) has led to astonishing progress in computational protein design, bringing into reach the targeted engineering of proteins for industrial and biomedical applications. However, the design of proteins for emergent functions of core relevance to cells, such as the ability to spatiotemporally self-organize and thereby structure the cellular space, is still extremely challenging. While on the generative side conditional generative models and multi-state design are on the rise, for emergent functions there is a lack of tailored screening methods as typically needed in a protein design project, both computational and experimental. Here we describe a proof-of-principle of how such screening, in silico and in vitro, can be achieved for ML-generated variants of a protein that forms intracellular spatiotemporal patterns. For computational screening we use a structure-based divide-and-conquer approach to find the most promising candidates, while for the subsequent in vitro screening we use synthetic cell-mimics as established by Bottom-Up Synthetic Biology. We then show that the best screened candidate can indeed completely substitute the wildtype gene in Escherichia coli. These results raise great hopes for the next level of synthetic biology, where ML-designed synthetic proteins will be used to engineer cellular functions.

"Pathways": A hope-enhancing intervention for patients undergoing treatment for advanced lung cancer.

OBJECTIVE: Observational data suggest hope is associated with the quality of life and survival of people with cancer. This trial examined the feasibility, acceptability, and preliminary outcomes of "Pathways," a hope intervention for people in treatment for advanced lung cancer. METHODS: Between 2020 and 2022, we conducted a single-arm trial of Pathways among participants who were 3-12 weeks into systemic treatment. Pathways consisted of two individual sessions delivered during infusions and three phone calls in which participants discussed their values, goals, and goal strategies with a nurse or occupational therapist. Participants completed standardized measures of hope and goal interference pre- and post-intervention. Feasibility was defined as ≥60% of eligible patients enrolling, ≥70% of participants completing three or more sessions, ≥70% of participants completing post-assessments, and mean acceptability ratings ≥7 out of 10 on intervention relevance, helpfulness, and convenience. Linear regression fixed effects models with covariates modeled pre-post changes in complete case analysis and multiple imputation models. RESULTS: Fifty two participants enrolled: female (59.6%), non-Hispanic White (84.6%), rural (75.0%), and with low educational attainment (51.9% high school degree or less). Except for enrollment (54%), feasibility and acceptability markers were surpassed (77% adherence, 77% retention, acceptability ratings ≥8/10). There was moderate improvement in hope and goal interference from pre-to post-intervention (d = 0.51, p < 0.05 for hope; d = -0.70, p < 0.005 for goal interference). CONCLUSIONS: Strong feasibility, acceptability, and patient-reported outcome data suggest Pathways is a promising intervention to increase hope and reduce cancer-related goal interference during advanced lung cancer treatment.

[Research Progress in the Relationship Between Neurofilament Light Chain Protein and Cognitive Impairment in Type 2 Diabetes Mellitus].

Metabolic abnormality in type 2 diabetes mellitus(T2DM)can cause damage to the central nervous system,leading to cognitive decline.Neurofilament light chain protein(NFL),as a blood marker of neuroaxonal injuries,is significantly associated with the onset of cognitive impairment and affected by the renal function.It can participate in the development of cognitive impairment in T2DM through inflammation,blood-brain barrier breakdown,interaction between microglia and neurons,and Tau protein phosphorylation.We reviewed the mechanism of the occurrence and development of NFL-involved cognitive impairment and the correlation between NFL and renal function in T2DM,hoping to provide a basis for early diagnosis and treatment of cognitive impairment in T2DM patients.

[Explainable artificial intelligence in pathology]. / Erklärbare Künstliche Intelligenz in der Pathologie.

With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of histomorphological and molecular pathological data. Great hopes are placed in artificial intelligence (AI) methods, which have demonstrated the ability to analyze complex clinical, histological, and molecular data for disease classification, biomarker quantification, and prognosis estimation. This paper provides an overview of the latest developments in pathology AI, discusses the limitations, particularly concerning the black box character of AI, and describes solutions to make decision processes more transparent using methods of so-called explainable AI (XAI).

Hope and dementia.

Dementia is a terminal and progressive condition which often brings with it a loss of hope, and feelings of hopelessness in those living with the condition and their family carers. Community nurses are in a unique position of being able to interact with people with dementia and their family carers in their own homes, or the care settings in which they reside, and in some case, will be the only professionals with regular contact with the family. Therefore, they have the opportunity to increase feelings of hope in those they work with. This article will discuss the concept of hope as it relates to dementia. It goes on to give an overview of Snyder's model of hope, which presents hope as a cognitive state, and therefore presents the opportunity for professionals to increase feelings of hope. An overview of the research evidence around hope-based interventions is then given, with the ideas applied to community nursing practice using a case study. This article aims to add some hope-based interventions to the toolkit of community nurses as they work with people and families affected by dementia.

Family Environment, Loneliness, Hope, and Subjective Well-Being of Asian Older Adults.

The current study examined the interactions between family environment, hope, and loneliness, and their subsequent influence on the subjective well-being (SWB) of 345 noninstitutionalized older adults (aged 60 years and above) in Singapore. Door-to-door surveys information was collected on family environment (cohesiveness, relationship closeness, and support), hope, loneliness, and SWB (life satisfaction, happiness, and absence of negative affect). Structural equation modelling was conducted to test competing hypotheses derived from life stress and integrated resource theories. The results revealed that family environment influenced SWB both directly and indirectly. Family environment decreased loneliness and increased SWB. Additionally, family environment influenced SWB by offering increased hope. Family environment sets the context for the SWB of older adults in Singapore. Families should therefore be targeted for interventions to reduce loneliness, increase psychological resources, and raise SWB during old age.

The unique effects of hope and gratitude on psychological distress and well-being in trauma-exposed Hispanic/Latino adults.

OBJECTIVE: Gratitude and hope are well-established predictors of well-being and buffers against posttraumatic stress disorder (PTSD) and anxiety symptoms. However, scarce literature exists that investigates these relationships in a Hispanic/Latino sample. The current study investigates gratitude's and hope's relationship to PTSD and anxiety symptoms and different domains of well-being in trauma-exposed Hispanic/Latino young adults at a large southern university. METHOD: The sample was composed of 732 undergraduate students who were mostly female (80.7%) and young adults, (Mage = 21.8, SD = 4.3), who endorsed experiencing one or more traumatic events via the Life Events Checklist. Students completed an online survey for course credit. RESULTS: Structural equation models were used to analyze the data. Gratitude had a stronger inverse relationship with PTSD symptoms (ß = -.43, 95% CI [-0.50, -0.35]) and anxiety symptoms (ß = -.28, 95% CI [-0.36, -0.20]) compared to hope (ß = .06, 95% CI [-0.01, 0.14]) (ß = -.06, 95% CI [-0.14, 0.02]). Both gratitude and hope were robust predictors of the three domains of well-being. CONCLUSIONS: The current study found that hope and gratitude predicted resilience in trauma-exposed Hispanic/Latino young adults. Decreased levels of gratitude were a stronger predictor of psychological distress and subjective well-being than decreased levels of hope, but hope was a robust predictor of the three well-being domains. The findings of this study may lend support for the development of hope and gratitude interventions in a Hispanic/Latino population for the prevention of PTSD symptoms and anxiety symptoms via engendering higher levels of resilience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using metaphors to build hope and hopefulness from depression.

Helplessness and hopelessness are common key dynamics of depression that often inhibit therapeutic progress and client recovery. Based on a case example, this article examines the processes for effectively communicating therapeutic interventions aimed toward building hope when other approaches have failed. It explores the use of therapeutic metaphors including assessing for positive outcomes, building the PRO Approach for creating therapeutic metaphors and using Hope Theory as an example of an evidence-based process for facilitating both hope and enhanced treatment outcomes. It concludes with an illustrative metaphor within a hypnotic model and a step-by-step process for building your own hope-enhancing metaphors.

Hope and illness expectations: A cross-sectional study in patients with advanced cancer.

BACKGROUND: The fear of taking away hope hinders clinicians' willingness to share serious news with patients with advanced disease. Unrealistic illness expectations, on the other hand, can complicate decision making and end-of-life care outcomes. Exploration of the association between hope and illness expectations can support clinicians in better communication with their patients. AIM: The aim of this study was to explore whether realistic illness expectations are associated with reduced hope in people with advanced cancer. DESIGN: This is a cross-sectional secondary analysis of baseline data from a primary palliative care cluster-randomized trial CONNECT (data collected from July 2016 to October 2020). Hope was measured by Herth Hope Index. Illness expectations were measured by assessing patients' understanding of their treatment goals, life expectancy, and terminal illness acknowledgement. Multivariable regression was performed, adjusting for demographical and clinical confounders. SETTING/PARTICIPANTS: Adult patients with advanced solid cancers recruited across 17 oncology clinics. RESULTS: Data from 672 patients were included in the study, with mean age of 69.3 years (±10.2), 53.6% were female. Proportion of patients indicating realistic expectations varied based on which question was asked from 10% to 46%. Median level of hope was 39 (IQR = 36-43). Multivariate non-inferiority regression did not find any significant differences in hope between patients with more and less realistic illness expectations. CONCLUSIONS: Our results suggest that hope can be sustained while holding both realistic and unrealistic illness expectations. Communication about serious news should focus on clarifying the expectations as well as supporting people's hopes.

A review focusing on the role of pyroptosis in prostate cancer.

As one of the types of programmed cell death, pyroptosis has become a focus of research in recent years. Numerous studies have shown that pyroptosis plays a regulatory role in tumor cell invasiveness, differentiation, proliferation, and metastasis. It has been demonstrated that pyroptosis is involved in the regulation of signaling pathways implicated in the pathogenesis of prostate cancer (PCa). Furthermore, the loss of expression of pyroptosis-related genes in PCa has been reported, and pyroptosis-related genes have demonstrated a considerable ability in predicting the prognosis of PCa. Therefore, the potential role of pyroptosis in regulating the development of PCa warrants further investigation and attention. In this review, we summarize the basics of the role of pyroptosis and also discuss research into the mechanisms of action associated with pyroptosis in PCa. It is hoped that by exploring the potential of the pyroptosis pathway in intervening in PCa, it will provide a viable direction for the diversification of PCa treatment.

[Application and Development of a Chinese Medicine Meridian and Acupoint Intervention in Nursing Practice].

Chinese medicine advocates a holistic and comprehensive approach that emphasizes differential diagnosis, treatment, and nursing as well as a diverse range of healthcare options. Within Chinese medicine, acupuncture techniques targeting meridians and acupoints are recognized as a suitable healthcare modality for promoting health, preventing diseases, and managing existing conditions. This article was designed to explore the practical application and advancement of acupuncture related to meridians and acupoints in the field of nursing. After introducing the development and current landscape of Chinese medicine healthcare, the application of acupoint stimulation within the context of Chinese medicinal nursing is discussed, taking into account clinical expertise, patient preferences, and safety concerns. Next, empirical findings on the impact of acupoint stimulation interventions are presented in hopes of translating clinical knowledge into evidence-based practice. Lastly, future prospects and investments in Chinese medicinal nursing are outlined. Within the realm of professional nursing practice, attaining proficiency in meridian and acupoint interventions requires comprehensive expertise and skills. Healthcare professionals in the nursing field should contemplate enhancing their knowledge and competencies in Chinese medicinal nursing. By providing the best evidence-based care, possessing specialized expertise, and taking patient preferences into account, the quality and completeness of evidence-based healthcare may be improved.

Hope as a Moderator of Intimate Partner Violence and Suicide Risk Behaviors Among Latinas.

The current study investigated the role of hope in the relationship between intimate partner violence (IPV) and suicide risk behaviors among a community sample of Latinas (N = 180). Moderation analyses revealed significant interaction effects demonstrating that both aspects of hope-agency and pathways-were associated with suicide risk behaviors at high levels of IPV. Results suggest hope may be helpful when IPV is at low levels, but it may exacerbate suicide risk when high levels of IPV are experienced among Latinas. Future directions and implications are discussed, including the importance of understanding the unique cultural context in which Latina survivors exist.

What Are the Ethical Obligations Related to a Request for Nonbeneficial Treatment?

It is common for a headline to proclaim promising results of a new cancer drug and for medical oncology offices to be flooded with calls from patients hoping that this new "miracle" drug offers them a chance of cure. Conf.