A1, an innovative fluorinated CXCR4 inhibitor, redefines the therapeutic landscape in colorectal cancer.

Background: Colorectal cancer (CRC) is a globally prevalent malignancy, primarily affecting the colon and rectum, characterized by uncontrolled cellular changes in the intestinal wall lining. Recent evidence underlines the significant role of the CXCL12/CXCR4 axis in the development of CRC, suggesting that inhibiting this pathway could be a promising therapeutic approach. This study focuses on investigating the potential of N, N''-thiocarbonylbis (N'-(3,4-dimethyl phenyl)-2,2,2-trifluoroacetimidamide) (A1), a novel fluorinated CXCR4 inhibitor, through a comprehensive analysis encompassing in silico, in vitro, and in vivo studies.

Beta hydroxybutyrate induces lung cancer cell death, mitochondrial impairment and oxidative stress in a long term glucose-restricted condition.

Background: Metabolic plasticity gives cancer cells the ability to shift between signaling pathways to facilitate their growth and survival. This study investigates the role of glucose deprivation in the presence and absence of beta-hydroxybutyrate (BHB) in growth, death, oxidative stress and the stemness features of lung cancer cells.

Methods And Results: A549 cells were exposed to various glucose conditions, both with and without beta-hydroxybutyrate (BHB), to evaluate their effects on apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) levels using flow cytometry, and the expression of CD133, CD44, SOX-9, and β-Catenin through Quantitative PCR.

Interleukin-1 receptor accessory protein (IL-1RAP): A magic bullet candidate for immunotherapy of human malignancies.

IL-1, plays a role in some pathological inflammatory conditions. This pro-inflammatory cytokine also has a crucial role in tumorigenesis and immune responses in the tumor microenvironment (TME). IL-1 receptor accessory protein (IL-1RAP), combined with IL-1 receptor-1, provides a functional complex for binding and signaling.

Catalase-gold nanoaggregates manipulate the tumor microenvironment and enhance the effect of low-dose radiation therapy by reducing hypoxia.

Radiotherapy as a standard method for cancer treatment faces tumor recurrence and antitumoral unresponsiveness. Suppressive tumor microenvironment (TME) and hypoxia are significant challenges affecting efficacy of radiotherapy. Herein, a versatile method is introduced for the preparation of pH-sensitive catalase-gold cross-linked nanoaggregate (Au@CAT) having acceptable stability and selective activity in tumor microenvironment.

Antitumor activities of a novel fluorinated small molecule (A1) in CT26 colorectal cancer cells: molecular docking and in vitro studies.

Chemotherapeutic treatment of colorectal cancer (CRC) has not been satisfactory until now; therefore, the discovery of more efficient medications is of great significance. Based on available knowledge, the CXCL12/CXCR4 axis plays a significant role in tumorigenesis, and inhibition of CXCR4 chemokine receptor with AMD3100 is one of the most known therapeutic modalities in cancer therapy. Herein, N, N''-thiocarbonylbis(N'-(3,4-dimethylphenyl)-2,2,2-trifluoroacetimidamide) () was synthesized as a potent CXCR4 inhibitor.

Age-dependent immune responses in COVID-19-mediated liver injury: focus on cytokines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury.

Differential expression levels of β-catenin are associated with invasive behavior of both functional and non-functional pituitary neuroendocrine tumor (PitNET).

Background: Although research continues to elucidate the molecular mechanism underlying pituitary tumor pathogenesis, limited information is available on the potential role and expression profile of β-catenin in functional and non-functional pituitary neuroendocrine tumors (PitNETs).

Methods And Results: In the current study, 104 pituitary samples (tumors and cadaveric healthy pituitary tissues) were included and the gene and protein expression levels of β-catenin were assessed by Real-Time PCR and immunohistochemistry, respectively. The correlation between expression level of β-catenin and tumor invasive feature and size as well as patient age, gender, and hormonal level was measured.

Hypothetical versus experienced health state valuation: a qualitative study of adult general public views and preferences.

Objectives: Responses from hypothetical and experienced valuation tasks of health-related quality of life differ, yet there is limited understanding of why these differences exist, what members of the public think about them, and acceptable resolutions. This study explores public understanding of, opinions on, and potential solutions to differences between hypothetical versus experienced responses, in the context of allocating health resources.

Methods: Six focus groups with 30 members of the UK adult public were conducted, transcribed verbatim, and analysed using framework analysis.

Understanding what matters to metastatic castration-resistant prostate cancer (mCRPC) patients when considering treatment options: A US patient preference survey.

Background: Understanding how patients perceive the efficacy, safety, and administrative burden of treatments for metastatic castration-resistant prostate cancer (mCRPC) can facilitate shared-decision making for optimal management. This study sought to elicit patient preferences for mCRPC treatments in the US.

Methods: We conducted a cross-sectional survey using the discrete-choice experiment method.

Catalase application in cancer therapy: Simultaneous focusing on hypoxia attenuation and macrophage reprogramming.

The tumor microenvironment (TME), as an immunosuppressive milieu, has a critical role in tumor progression and increases resistance to the conventional treatments. Among the abundant immunosuppressive cells in the TME, tumor-associated macrophages (TAMs) could be a promising target for reprogramming and potentiating the local anti-tumor response. On the other hand, hypoxia is a major barrier in treating solid tumors, which aggravates the situation and alleviates the anti-tumor immune responses.

Patient Preferences for Benefits, Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes.

Introduction/background: Therapy with infused or injected hypomethylating agents (HMAs) may lead to higher treatment administration burden (ie, local reaction, visit frequency and duration) vs. oral HMAs.   OBJECTIVES: To reveal preferences of US and Canadian patients with myelodysplastic syndromes (MDS) for HMAs' benefits, risks, and administration burden through an online discrete-choice experiment (DCE).

Heterogeneity in preferences for outcomes of integrated care for persons with multiple chronic diseases: a latent class analysis of a discrete choice experiment.

Purpose: For an integrated care programme to be successful, preferences of the stakeholders involved should be aligned. The aim of this study is to investigate to which extent outcomes beyond health are valued and to study the heterogeneity of preferences of those involved in integrated care.

Methods: A discrete choice experiment (DCE) was conducted to elicit preferences for eight Triple Aim outcomes, i.

Value-based person-centred integrated care for frail elderly living at home: a quasi-experimental evaluation using multicriteria decision analysis.

Objective: To evaluate the value of the person-centred, integrated care programme Care Chain Frail Elderly (CCFE) compared with usual care, using multicriteria decision analysis (MCDA).

Design: In a 12-month quasi-experimental study, triple-aim outcomes were measured at 0, 6 and 12 months by trained interviewers during home-visits.

Setting: Primary care, community-based elderly care.

Why Do Adults Value EQ-5D-Y-3L Health States Differently for Themselves Than for Children and Adolescents: A Think-Aloud Study.

Objectives: Following protocol, adults value EQ-5D-Y-3L health states from the perspective of a 10-year-old child. It remains unclear why adults value health states differently for themselves than for a 10-year-old child and whether the latter perspective is representative of adults' preferences for the 8 to 15 years age range of the EQ-5D-Y-3L. This study examines the reasons underlying (potential) differences in adults' health-state preferences for themselves, a 10-year-old child, and 15-year-old adolescent.

[Patients, Partners, Professionals, Payers and Policy Makers Preferences for Integrated Care for Multimorbidity in Germany: A Discrete Choice Experiment].

Aim Of The Work: The aim of this study was to measure and compare the relative importance that patients with multimorbidity, partners and other informal caregivers, professionals, payers and policy makers attribute to different outcome measures of integrated care (IC) programmes in Germany.

Methods: A DCE was conducted, asking respondents to choose between two IC programmes for persons with multimorbidity. Each IC programme was presented by means of attributes or outcomes reflecting the Triple Aim.

Evaluating Complex Health and Social Care Program Using Multi-Criteria Decision Analysis: A Case Study of "Better Together in Amsterdam North".

Objectives: Multi-criteria decision analysis (MCDA) has been recommended to support policy making in healthcare. However, practical applications of MCDA are sparse. One potential use for MCDA is for the evaluation of programs for complex and vulnerable patients.

Bundled payments for chronic diseases increased health care expenditure in the Netherlands, especially for multimorbid patients.

Bundled payments aim to stimulate the integration of healthcare services and ultimately reduce healthcare expenditure growth through improved quality of care. The Netherlands introduced bundled payments for chronic diseases in 2010 by reimbursing providers annually for a bundle of primary care services related to COPD, Diabetes, or Vascular Risk Management. We aimed to assess the long-term effects of these bundled payments on healthcare expenditure.

The disease burden of multimorbidity and its interaction with educational level.

Introduction: Policies to adequately respond to the rise in multimorbidity have top-priority. To understand the actual burden of multimorbidity, this study aimed to: 1) estimate the trend in prevalence of multimorbidity in the Netherlands, 2) study the association between multimorbidity and physical and mental health outcomes and healthcare cost, and 3) investigate how the association between multimorbidity and health outcomes interacts with socio-economic status (SES).

Methods: Prevalence estimates were obtained from a nationally representative pharmacy database over 2007-2016.

Comparing patients' and other stakeholders' preferences for outcomes of integrated care for multimorbidity: a discrete choice experiment in eight European countries.

Objectives: To measure relative preferences for outcomes of integrated care of patients with multimorbidity from eight European countries and compare them to the preferences of other stakeholders within these countries.

Design: A discrete choice experiment (DCE) was conducted in each country, asking respondents to choose between two integrated care programmes for persons with multimorbidity.

Setting: Preference data collected in Austria (AT), Croatia (HR), Germany (DE), Hungary (HU), the Netherlands (NL), Norway (NO), Spain (ES), and UK.

Lead-free transparent shields for diagnostic X-rays: Monte Carlo simulation and measurements.

In recent years, the preference for using lead-free radiation protection shields has increased because of concerns regarding lead poisoning and leakage. In medical and research laboratories, glass shields are preferred because of their transparency. In this study, various glass shields were examined and compared based on the international standards.

Effect of Reflection and Deliberation on Health State Values: A Mixed-Methods Study.

Background: Health economists ask members of the general public to value health states, but it is recognized that individuals construct their preferences during the valuation tasks. Conventional methods rely on one-off interviews that do not give participants time to reflect and deliberate on their preferences.

Objective: This study investigates the effect of reflection and deliberation on health state preferences using the EQ-5D questionnaire and time trade-off valuation method.

Future Directions in Valuing Benefits for Estimating QALYs: Is Time Up for the EQ-5D?

The widespread adoption of the EuroQol 5-dimensional questionnaire (EQ-5D) has been important for the comparability, transparency, and consistency of economic evaluations for informing resource allocation in healthcare. The objectives of this article were to (1) critically assess whether the widespread adoption of the EQ-5D and its time trade-off-based value sets to inform economic evaluation is likely to continue and (2) speculate about how benefits may be measured and valued to inform economic evaluation in the future. Evidence supports the use of the EQ-5D in many areas of health, but there are notable gaps.

Strengthening the evidence-base of integrated care for people with multi-morbidity in Europe using Multi-Criteria Decision Analysis (MCDA).

Background: Evaluation of integrated care programmes for individuals with multi-morbidity requires a broader evaluation framework and a broader definition of added value than is common in cost-utility analysis. This is possible through the use of Multi-Criteria Decision Analysis (MCDA).

Methods And Results: This paper presents the seven steps of an MCDA to evaluate 17 different integrated care programmes for individuals with multi-morbidity in 8 European countries participating in the 4-year, EU-funded SELFIE project.

An exploration of the non-iterative time trade-off method to value health states.

Time Trade-Off (TTO) usually relies on "iteration," which is susceptible to bias. Discrete Choice Experiment with duration (or DCE ) is free of such bias, but respondents find this cognitively more challenging. This paper explores non-iterative TTO with or without lead time: NI(LT)TTO.

Experience-based utility and own health state valuation for a health state classification system: why and how to do it.

In the estimation of population value sets for health state classification systems such as the EuroQOL five dimensions questionnaire (EQ-5D), there is increasing interest in asking respondents to value their own health state, sometimes referred to as "experience-based utility values" or, more correctly, own rather than hypothetical health states. Own health state values differ to hypothetical health state values, and this may be attributable to many reasons. This paper critically examines whose values matter; why there is a difference between own and hypothetical values; how to measure own health state values; and why to use own health state values.