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Individualizing patient treatment is a core objective of the medical field. Reaching this objective has been elusive owing to the complex set of factors contributing to both disease and health; many factors, from genes to proteins, remain unknown in their role in human physiology. Accurately diagnosing, monitoring, and treating disorders requires advances in biomarker discovery, the subsequent development of accurate signatures that correspond with dynamic disease states, as well as therapeutic interventions that can be continuously optimized and modulated for dose and drug selection. This work highlights key breakthroughs in the development of enabling technologies that further the goal of personalized and precision medicine, and remaining challenges that, when addressed, may forge unprecedented capabilities in realizing truly individualized patient care.

Introduction: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients. Methods: This is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time. Trial registration: This trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397. [ABSTRACT FROM AUTHOR]

Introduction: Nurses, assuming a wide range of clinical and patient care responsibilities in a healthcare team, are highly susceptible to direct and indirect exposure to traumatic experiences. However, literature has shown that nurses with certain traits developed a new sense of personal strength in the face of adversity, known as post‐traumatic growth (PTG). This review aimed to synthesize the best available evidence to evaluate personal and work‐related factors associated with PTG among nurses. Design: Mixed studies systematic review. Methods: Studies examining factors influencing PTG on certified nurses from all healthcare facilities were included. Published and unpublished studies were identified by searching 12 databases from their inception until 4th February 2023. Two reviewers independently screened, appraised, piloted a data collection form, and extracted relevant data. Meta‐summary, meta‐synthesis, meta‐analysis, as well as subgroup and sensitivity analyses were performed. Integration of results followed result‐based convergent design. Results: A total of 98 studies with 29,706 nurses from 18 countries were included. These included 49 quantitative, 42 qualitative, and seven mixed‐methods studies. Forty‐six influencing factors were meta‐analyzed, whereas nine facilitating factors were meta‐summarized. A PTG conceptual map was created. Four constructs emerged from the integration synthesis: (a) personal system, (b) work‐related system, (c) event‐related factors, and (d) cognitive transformation. Conclusion: The review findings highlighted areas healthcare organizations could do to facilitate PTG in nurses. Practical implications include developing intervention programs based on PTG facilitators. Further research should examine the trend of PTG and its dynamic response to different nursing factors. Clinical Relevance: Research on trauma‐focused therapies targeting nurses' mental health is lacking. Therefore, findings from this review could inform healthcare organizations on the PTG phenomenon and developing support measures for nurses through healthcare policies and clinical practice. [ABSTRACT FROM AUTHOR]

Multiple myeloma is an incurable hematological malignancy that relies on drug combinations for first and secondary lines of treatment. The inclusion of proteasome inhibitors, such as bortezomib, into these combination regimens has improved median survival. Resistance to bortezomib, however, is a common occurrence that ultimately contributes to treatment failure, and there remains a need to identify improved drug combinations. We developed the quadratic phenotypic optimization platform (QPOP) to optimize treatment combinations selected from a candidate pool of 114 approved drugs. QPOP uses quadratic surfaces to model the biological effects of drug combinations to identify effective drug combinations without reference to molecular mechanisms or predetermined drug synergy data. Applying QPOP to bortezomib-resistant multiple myeloma cell lines determined the drug combinations that collectively optimized treatment efficacy. We found that these combinations acted by reversing the DNA methylation and tumor suppressor silencing that often occur after acquired bortezomib resistance in multiple myeloma. Successive application of QPOP on a xenograft mouse model further optimized the dosages of each drug within a given combination while minimizing overall toxicity in vivo, and application of QPOP to ex vivo multiple myeloma patient samples optimized drug combinations in patient-specific contexts.

Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications.