The past, present, and future of tumour deposits in colorectal cancer: Advancing staging for improved prognosis and treatment decision‐making
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ABSTRACT:
SUBMITTER: Chang Z
PROVIDER: S-EPMC11348060 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:ImportanceEngaging in shared decision-making (SDM) can help patients understand and choose treatments according to their values and has been shown to improve patient satisfaction and adherence with treatment. It is well suited for conditions like eczema for which several medically appropriate treatment options exist. However, little is known about the use and experience of SDM in eczema.ObjectiveTo understand experiences, preferences, and expectations for SDM in eczema care settings from the patient and caregiver perspective.Design, setting, and participantsThe National Eczema Association conducted an online survey in January 2021 among self-selected patients and caregivers. Inclusion criteria (US resident, patient with eczema or caregiver of a patient with eczema aged ≤17 years, respondent age ≥18 years) were met by 1313 of 1387 respondents (94.7%). Data analysis was performed from May 2021 to November 2021.Main outcomes and measuresOutcomes were past SDM (using a 9-item SDM questionnaire [SDMQ9]; score ranges transformed to 0-100), present SDM (Control Preferences Scale), and future SDM (self-reported confidence and motivation to engage in SDM) behavior.ResultsAmong the 1313 respondents included in the study, most were female (1046 of 1313 [79.7%]) adult (1086 of 1313 [82.7%]) patients with a mean (SD) patient Recap of Atopic Eczema score of 11.7 (7.2), mean (SD) patient age of 39.5 (22.2) years, and mean (SD) SDMQ9 score of 65.1 (27.4). For present SDM, 479 of 966 (49.6%) reported "I prefer to make the final decision after seriously considering my doctor's opinion," and 655 of 955 (69.4%) reported being very or extremely confident to engage in SDM in the future. Those who reported feeling "very well informed" about the causes of eczema had a 14.7-point higher (95% CI, 9.2-20.2; P < .001, multiple linear regression) SDMQ9 score than those "not adequately informed" and were 3.4 times more likely (95% CI, 2.1-5.7; P < .001, multiple logistic regression) to be confident to engage in future SDM. Respondents reported that they would be motivated to engage in SDM if the clinician initiated SDM, valued input from the patient, and acknowledged that patients are experts on their own bodies or if a treatment is no longer working.Conclusions and relevanceResults of this survey study suggest that a majority of patients with eczema and caregivers prefer a large role in decision-making for their care and that clinicians can initiate and facilitate SDM to improve patient satisfaction with care.
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Project description:Idiopathic pulmonary fibrosis (IPF) is traditionally staged with terms such as "mild", "severe", "early" and "advanced" based on pulmonary function tests. This approach allows physicians to monitor disease progression and advise patients and their families. However, it is not known if the stages of this model reflect distinct biological or clinical phenotypes and the therapeutic and prognostic value of this system is limited. Novel methods of IPF staging have recently been developed. The GAP model includes four baseline variables that were found to be predictive of outcome, as identified by logistic regression. These factors are: gender (G), age (A) and two lung physiology variables (P) (forced vital capacity and diffusing capacity of the lung for carbon monoxide). The clinical utility and accuracy of staging models may be further improved in the future by the integration of dynamic parameters that can be measured over time, as well as biological data from biomarkers which may be able to directly measure disease activity. The development of an evidence-based, multidimensional IPF staging model that builds on the current staging approaches to IPF is an important objective for improving the management of IPF.
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Project description:Infertile couples including cancer survivors stand to benefit from gametes differentiated from embryonic or induced pluripotent stem (ES/iPS) cells. It remains challenging to convert human ES/iPS cells into primordial germ-like cells (PGCLCs) en route to obtaining gametes. Considerable success was achieved in 2016 to obtain fertile offspring starting with mouse ES/iPS cells, however the specification of human ES/iPS cells into PGCLCs in vitro is still not achieved. Human ES cells will not yield patient-specific gametes unless and until hES cells are derived by somatic cell nuclear transfer (therapeutic cloning) whereas iPS cells retain the residual epigenetic memory of the somatic cells from which they are derived and also harbor genomic and mitochondrial DNA mutations. Thus, they may not be ideal starting material to produce autologus gametes, especially for aged couples. Pluripotent, very small embryonic-like stem cells (VSELs) have been reported in adult tissues including gonads, are relatively quiescent in nature, survive oncotherapy and can be detected in aged, non-functional gonads. Being developmentally equivalent to PGCs (natural precursors to gametes), VSELs spontaneously differentiate into gametes in vitro. It is also being understood that gonadal stem cells niche is compromised by oncotherapy and with age. Improving the gonadal somatic niche could regenerate non-functional gonads from endogenous VSELs to restore fertility. Niche cells (Sertoli/mesenchymal cells) can be directly transplanted and restore gonadal function by providing paracrine support to endogenous VSELs. This strategy has been successful in several mice studies already and resulted in live birth in a woman with pre-mature ovarian failure.
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Project description:The evolution of biocrystallography from the pioneers' time to the present era of global biology is presented in relation to the development of methodological and instrumental advances for molecular sample preparation and structure elucidation over the last 6 decades. The interdisciplinarity of the field that generated cross-fertilization between physics- and biology-focused themes is emphasized. In particular, strategies to circumvent the main bottlenecks of biocrystallography are discussed. They concern (i) the way macromolecular targets are selected, designed, and characterized, (ii) crystallogenesis and how to deal with physical and biological parameters that impact crystallization for growing and optimizing crystals, and (iii) the methods for crystal analysis and 3D structure determination. Milestones that have marked the history of biocrystallography illustrate the discussion. Finally, the future of the field is envisaged. Wide gaps of the structural space need to be filed and membrane proteins as well as intrinsically unstructured proteins still constitute challenging targets. Solving supramolecular assemblies of increasing complexity, developing a "4D biology" for decrypting the kinematic changes in macromolecular structures in action, integrating these structural data in the whole cell organization, and deciphering biomedical implications will represent the new frontiers.
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Project description:The uses of antiviral agents are increasing in the new era along with the development of vaccines for the effective control of viral diseases. The main aims of antiviral agents are to minimize harm to the host system and eradicate deadly viral diseases. However, the replications of viruses in host system represent a massive therapeutic challenge than bacteria and fungi. Antiviral drugs not just penetrate to disrupt the virus’ cellular divisions but also have a negative impact on normal physiological pathways in the host. Due to these issues, antiviral agents have a narrow therapeutic index than antibacterial drugs. Nephrotoxicity is the main adverse reaction of antiviral drugs in human and animals. In this chapter, we summarize the antiviral agents’ past, present and future perspectives with the main focus on the brief history of antiviral in animals, miscellaneous drugs, natural products, herbal and repurposing drugs.
| S-EPMC7120554 | biostudies-literature
Project description:The terminal differentiation of the epidermis is a complex physiological process. During the past few decades, medical genetics has shown that defects in the stratum corneum (SC) permeability barrier cause a myriad of pathological conditions, ranging from common dry skin to lethal ichthyoses. Contrarily, molecular phylogenetics has revealed that amniotes have acquired a specialized form of cytoprotection cornification that provides mechanical resilience to the SC. This superior biochemical property, along with desiccation tolerance, is attributable to the proper formation of the macromolecular protein-lipid complex termed cornified cell envelopes (CE). Cornification largely depends on the peculiar biochemical and biophysical properties of loricrin, which is a major CE component. Despite its quantitative significance, loricrin knockout (LKO) mice have revealed it to be dispensable for the SC permeability barrier. Nevertheless, LKO mice have brought us valuable lessons. It is also becoming evident that absent loricrin affects skin homeostasis more profoundly in many more aspects than previously expected. Through an extensive review of aggregate evidence, we discuss herein the functional significance of the thiol-rich protein loricrin from a biochemical, genetic, pathological, metabolic, or immunological aspect with some theoretical and speculative perspectives.
| S-EPMC7177664 | biostudies-literature
Project description:In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the ?-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most ?-lactamases, in some cases act as "slow substrates" or inhibitors of ?-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting ?-lactamases serves as a major rationale for expansion of this class of ?-lactams. We describe the initial discovery and development of the carbapenem family of ?-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.
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Project description:In recent years, Bruton tyrosine kinase (BTK) inhibitors have provided significant advances in the treatment of patients with B-cell malignancies. Ibrutinib was the first BTK inhibitor to be approved, and it changed the standard-of-care treatment for diseases such as chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia, improving efficacy outcomes and safety compared to chemotherapy. In this article, we review the development of zanubrutinib, a next-generation BTK inhibitor, from molecular design to patient-related outcomes. We start this journey by providing insights into the discovery of BTK and the physiologic, genetic, and molecular characterization of patients lacking this kinase, together with the brief treatment landscape in the era of chemo-immunotherapies. Zanubrutinib was originally developed by applying a structure-activity strategy to enhance the specificity as well as enzymatic and pharmacokinetic properties. Preclinical studies confirmed greater specificity and better bioavailability of zanubrutinib compared with that of ibrutinib, which supported the initiation of clinical trials in humans. Preliminary clinical results indicated activity in B-cell malignancies together with an improved safety profile, in line with less off-target effects described in the preclinical studies. The clinical program of zanubrutinib has since expanded significantly, with ongoing studies in a wide range of hemato-oncological diseases and in combination with many other therapies. Zanubrutinib currently is approved for various B-cell malignancies in multiple countries. This story highlights the importance of multidisciplinary collaborative research, from bench to bedside, and provides an example of how the commitment to finding improved treatment options should always run parallel to patient care.
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Project description:mRNA vaccines have emerged as promising alternative platforms to conventional vaccines. Their ease of production, low cost, safety profile and high potency render them ideal candidates for prevention and treatment of infectious diseases, especially in the midst of pandemics. The challenges that face in vitro transcribed RNA were partially amended by addition of tethered adjuvants or co-delivery of naked mRNA with an adjuvant-tethered RNA. However, it wasn't until recently that the progress made in nanotechnology helped enhance mRNA stability and delivery by entrapment in novel delivery systems of which, lipid nanoparticles. The continuous advancement in the fields of nanotechnology and tissue engineering provided novel carriers for mRNA vaccines such as polymeric nanoparticles and scaffolds. Various studies have shown the advantages of adopting mRNA vaccines for viral diseases and cancer in animal and human studies. Self-amplifying mRNA is considered today the next generation of mRNA vaccines and current studies reveal promising outcomes. This review provides a comprehensive overview of mRNA vaccines used in past and present studies, and discusses future directions and challenges in advancing this vaccine platform to widespread clinical use.
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