Geospatial Imprecision With Constraints for Precision Public Health: Algorithm Development and Validation.

BACKGROUND: Location and environmental social determinants of health are increasingly important factors in both an individual's health and the monitoring of community-level public health issues. OBJECTIVE: We aimed to measure the extent to which location obfuscation techniques, designed to protect an individual's privacy, can unintentionally shift geographical coordinates into neighborhoods with significantly different socioeconomic demographics, which limits the precision of findings for public health stakeholders. METHODS: Point obfuscation techniques intentionally blur geographic coordinates to conceal the original location. The pinwheel obfuscation method is an existing technique in which a point is moved along a pinwheel-like path given a randomly chosen angle and a maximum radius; we evaluate the impact of this technique using 2 data sets by comparing the demographics of the original point and the resulting shifted point by cross-referencing data from the United States Census Bureau. RESULTS: Using poverty measures showed that points from regions of low poverty may be shifted to regions of high poverty; similarly, points in regions with high poverty may be shifted into regions of low poverty. We varied the maximum allowable obfuscation radius; the mean difference in poverty rate before and after obfuscation ranged from 6.5% to 11.7%. Additionally, obfuscation inadvertently caused false hot spots for deaths by suicide in Cook County, Illinois. CONCLUSIONS: Privacy concerns require patient locations to be imprecise to protect against risk of identification; precision public health requires accuracy. We propose a modified obfuscation technique that is constrained to generate a new point within a specified census-designated region to preserve both privacy and analytical accuracy by avoiding demographic shifts.

Action-plan and as-needed therapy in allergic rhinitis.

Action-plan is a written set of instructions that helps patient manage their symptoms and respond to worsening of their condition. The action-plan usually includes information on how to recognize, treat, and prevent worsening of symptoms. The plan also helps patient understand when to use their medications, how much to use, and how often to use them as-needed. An action-plan should be developed through a discussion between the patient and the physician, reflecting the patient's severity, preferences, and values and should be regularly updated to reflect changes in the person's condition. In asthma, action-plans and as-needed therapy are already well utilized. Unlike asthma, the importance of an action-plan has been overlooked in allergic rhinitis (AR), but its importance has recently been recognized. AR is a chronic condition that affects people differently, and can cause a range of symptoms, including nasal congestion, runny nose, sneezing, itching, and watery eyes. Therefore, an action-plan and as-needed therapy can help patients manage these symptoms more effectively, reducing the impact on their daily activities and quality of life. Furthermore, it can be tailored to meet the personal needs of each patient, based on the severity of their symptoms, their triggers, and their overall health. Because action-plan can help patients adhere to their treatment regimen by providing clear instructions on when and how to take medication, it can help patients stay on track with their treatment, reducing the likelihood of missed doses and treatment failures. Overall, an action-plan and as-needed therapy are important components of a comprehensive treatment plan for patients with AR. They can help to improve symptom control, prevent complications, and promote adherence to treatment, leading to better outcomes and a higher quality of life.

Animal-free production of hen egg ovalbumin in engineered Saccharomyces cerevisiae via precision fermentation.

To enable the sustainable production of ovalbumin (OVA) without relying on animal sources, the generally recognized as safe (GRAS) host Saccharomyces cerevisiae was used for the precision fermentation-based production of recombinant OVA. For this purpose, a signal peptide derived from EPX1, the most abundant extracellular protein produced by Pichia pastoris, was identified as a novel signal peptide for the efficient secretion of OVA in S. cerevisiae. To improve OVA secretion and cell growth, three helper proteins (PDI1, KAR2, and HAC1) present in the endoplasmic reticulum were expressed individually or in combination. Notably, the +P1/K2 strain coexpressing PDI1 and KAR2 with OVA produced 2 mg/L of OVA in the medium fraction; this value was 2.6-fold higher than the corresponding value for the control strain without helper proteins. Finally, a glucose-limited fed-batch fermentation process using the +P1/K2 strain yielded 132 mg/L of total OVA with 8 mg/L of extracellular OVA.

NTRK3-Rearranged Prostatic Acinar Adenocarcinoma: Report of a Patient and Review of the Literature.

Molecular investigations have led to increased therapeutic options for prostatic adenocarcinoma. A single case report of a PRPSAP1::NTRK3 gene fusion occurring in prostate cancer was previously reported. A review of the literature revealed that NTRK gene rearrangements are exceedingly rare molecular events in prostate cancer. NTRK gene fusions can be oncogenic drivers or develop as resistance mechanisms. The tumor-agnostic approvals of TRK inhibitors by the FDA provide additional rationale for molecular investigations of aggressive prostatic adenocarcinomas. This may prove to be an additional therapeutic option for patients with aggressive prostatic carcinomas refractory to initial therapy. We report a case of an aggressive castrate-resistant prostatic adenocarcinoma with a BMP6::NTRK3 gene fusion.

Analytical and Clinical Validation of a Target-Enhanced Whole Genome Sequencing-Based Comprehensive Genomic Profiling Test.

Evaluation of the test performance of the Target enhanced whole-genome sequencing (TE-WGS) assay for comprehensive oncology genomic profiling. The analytical validation of the assay included sensitivity and specificity for single nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs), revealing a revealed a sensitivity of 99.8% for SNVs and 99.2% for indels. The positive predictive value (PPV) was 99.3% SNVs and 98.7% indels. Clinical validation was benchmarked against established orthogonal methods and demonstrated high concordance with reference methods. TE-WGS provides insights beyond targeted panels by comprehensive analysis of key biomarkers and the entire genome encompassing both germline and somatic findings.

Evolving or immutable - phase I solid tumor trials in the era of precision oncology.

In the era of precision oncology (PO), systemic therapies for patients (pts) with solid tumors have shifted from chemotherapy (CT) to targeted therapy (TT) and immunotherapy (IO). This systematic survey describes features of trials enrolling between 2010 and 2020, focusing on inclusion criteria, type of dose escalation scheme (DES) utilized, and use of expansion cohorts (ECs). A literature search identified phase I studies in adults with solid tumors published January 1, 2000- December 31, 2020 from 12 journals. We included only studies enrolling between 2010 and 2020 to better capture the PO era. Two reviewers abstracted data; a third established concordance. Of 10,744 studies, 10,195 were non-topical or enrolled prior to 2010; 437 studies were included. The most common drug classes were TT (47.6%), IO (22%), and CT (6.9%). In studies which reported race, patients were predominantly white (61.7%) or Asian (25.7%), followed by black (6.5%) or other (6.1%). Heterogeneity was observed in the reporting and specification of study inclusion criteria. Only 40.1% of studies utilized ECs, and among the studies which used ECS, 46.6% were defined by genomic selection. Rule-based DES were used in 89% of trials; a 3+3 design was used in 80.5%. Of all drugs tested, 37.5% advanced to phase II, while 10.3% garnered regulatory licensure (for an indication tested in phase I). In the era of PO, TT and IO have emerged as the most studied agents in phase I trials. Rule-based DES, which are more relevant for escalating CT, are still chiefly utilized.

It provides families with other avenues for treatment when there are no other options Surgeons' perspectives of being part of a precision medicine trial for poor prognosis paediatric cancer patients: A short report.

OBJECTIVE: Precision medicine is transforming cancer treatment, yet the perspectives of surgeons who often play a critical role in the delivery of precision medicine remain understudied. METHODS: We conducted semi-structured interviews with 13 surgeons involved in a precision medicine trial for children with poor prognosis cancer. We explored knowledge of genetics, confidence with somatic and germline results, ratings of benefit to stakeholders and willingness to undertake surgical procedures. RESULTS: Surgeons generally had positive attitudes towards precision medicine but expressed concerns about families' unrealistic expectations, mixed opinions on the benefits and the use of research-only biopsies. Most surgeons rated their genetics knowledge as 'good' (69%) and felt 'very confident' in identifying genetic specialists (66%), but 'not confident' (66.6%) in making treatment recommendations. Surgeons' willingness to undertake a procedure was influenced by potential patient benefit. CONCLUSIONS: Our findings support the need for more workforce and training support for surgeons to fully engage with precision medicine.

The realization of medical devices for precision surgery - development and implementation of 'stop-and-go' imaging technologies.

INTRODUCTION: Surgery and biomedical imaging encompass a big share of the medical-device market. The ever-mounting demand for precision surgery has driven the integration of these two into the field of image-guided surgery. A key-question herein is how imaging modalities can guide the surgical decision-making process. Through performance-based design, chemists, engineers, and doctors need to build a bridge between imaging technologies and surgical challenges. AREAS-COVERED: This perspective article highlights the complementary nature between the technological design of an image-guidance modality and the type of procedure performed. The specific roles of the involved professionals, imaging technologies, and surgical indications are addressed. EXPERT-OPINION: Molecular-image-guided surgery has the potential to advance pre-, intra- and post-operative tissue characterization. To achieve this, surgeons need the access to well-designed indication-specific chemical-agents and detection modalities. Hereby, some technologies stimulate exploration ('go'), while others stimulate caution ('stop'). However, failing to adequately address the indication-specific needs rises the risk of incorrect tool employment and sub-optimal surgical performance. Therefore, besides the availability of new technologies, market growth is highly dependent on the practical nature and impact on real-life clinical care. While urology currently takes the lead in the widespread implementation of image-guidance technologies, the topic is generic and its popularity spreads rapidly within surgical oncology.

Digital applications for diet monitoring, planning, and precision nutrition for citizens and professionals: a state of the art.

The objective of this review was to critically examine existing digital applications, tailored for use by citizens and professionals, to provide diet monitoring, diet planning, and precision nutrition. We sought to identify the strengths and weaknesses of such digital applications, while exploring their potential contributions to enhancing public health, and discussed potential developmental pathways. Nutrition is a critical aspect of maintaining good health, with an unhealthy diet being one of the primary risk factors for chronic diseases, such as obesity, diabetes, and cardiovascular disease. Tracking and monitoring one's diet has been shown to help improve health and weight management. However, this task can be complex and time-consuming, often leading to frustration and a lack of adherence to dietary recommendations. Digital applications for diet monitoring, diet generation, and precision nutrition offer the promise of better health outcomes. Data on current nutrition-based digital tools was collected from pertinent literature and software providers. These digital tools have been designed for particular user groups: citizens, nutritionists, and physicians and researchers employing genetics and epigenetics tools. The applications were evaluated in terms of their key functionalities, strengths, and limitations. The analysis primarily concentrated on artificial intelligence algorithms and devices intended to streamline the collection and organization of nutrition data. Furthermore, an exploration was conducted of potential future advancements in this field. Digital applications designed for the use of citizens allow diet self-monitoring, and they can be an effective tool for weight and diabetes management, while digital precision nutrition solutions for professionals can provide scalability, personalized recommendations for patients, and a means of providing ongoing diet support. The limitations in using these digital applications include data accuracy, accessibility, and affordability, and further research and development are required. The integration of artificial intelligence, machine learning, and blockchain technology holds promise for improving the performance, security, and privacy of digital precision nutrition interventions. Multidisciplinarity is crucial for evidence-based and accessible solutions. Digital applications for diet monitoring and precision nutrition have the potential to revolutionize nutrition and health. These tools can make it easier for individuals to control their diets, help nutritionists provide better care, and enable physicians to offer personalized treatment.

Textbook outcome of laparoscopic hepatectomy in the context of precision surgery: A single center experience.

OBJECTIVE: Laparoscopic hepatectomy (LH) has become a common surgery for the treatment of liver tumor. To evaluate the surgical quality of laparoscopic hepatectomy under the context of precision surgery with Textbook outcome (TO), a comprehensive and holistic assessment approach. METHODS: A total of 1056 patients who underwent laparoscopic hepatectomy from May 2016 and December 2022 were enrolled in the study. All the patients were performed hepatectomy. The rate of TO and factors associated with achieving TO were examined. RESULTS: Among the 1056 patients, 75 % patients achieved TO. The main reason limited patients achieving textbook outcomes was prolonged length of hospital stay (LOS). The univariate analysis indicated that age>65, ASA classification ≥3, liver cirrhosis, tumor size > 3 cm, tumor number ≥2, type of primary cancer, and IWATE DSS were significantly associated with non-achievement of TO. The multivariate analysis indicated that the ASA classification ≥3 and advanced difficulty level in IWATE DSS independent factors associated with achieving TO. Reaching TO can significantly prolong the postoperative recurrence time and overall survival time of hepatocellular carcinoma patients. CONCLUSION: In the context of precision surgery, 75 % patients undergoing laparoscopic hepatectomy achieved a TO. Patients who achieved TO had significantly improved survival.

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design.

Purpose: Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. Materials and Methods: We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Results: Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Conclusion: Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

Letter to editor: Bridging the gap: robotic applications in cerebral aneurysms neurointerventions - a systematic review.

The letter critically evaluates the role of robotic applications in cerebral aneurysm neurointerventions, synthesizing a diverse array of studies to elucidate both the potential benefits and inherent limitations of this emerging technology. The review highlights the advancements in precision, efficiency, and patient outcomes facilitated by robotic platforms, while also acknowledging challenges such as the steep learning curve and the need for further research to establish long-term efficacy and cost-effectiveness. By navigating through the complexities of robotic-assisted neurosurgery, the review provides valuable insights into the transformative potential of robotics in optimizing treatment paradigms and improving patient care.

Genomic medicine advances for brain tumors.

Cancer genome profiling has revealed important genetic alterations that serve as prognostic indicators and guides for treatment decisions, enabling precision medicine. The shift to molecular diagnosis of brain tumors, as reflected in the 2021 World Health Organization Classification of Tumors of the Central Nervous System, is a crucial role for treatment decision-making. This review discusses the significance and role of cancer genome profiling in precision medicine for malignant brain tumors, particularly gliomas. Furthermore, we explore the progress in cancer genome analysis, focusing on cancer gene panel testing, integration of genomic information in brain tumor classification, and hereditary tumors. Additionally, we discuss the transformative effect of genomic medicine on early detection, risk assessment, and precision medicine strategies. The tumor mutational burden in brain tumors is considered low, but the application of molecular targeted drugs, such as isocitrate dehydrogenase inhibitors, v-raf murine sarcoma viral oncogene homolog B1 inhibitors, fibroblast growth factor receptor inhibitors, neurotrophic tyrosine receptor kinase, mechanistic target of rapamycin inhibitors, and anti-programmed death receptor-1 antibody drugs are promising for glioma treatment. We also discuss the future prospects of molecular targeted drugs.

Spectrum of NMDA Receptor Variants in Neurodevelopmental Disorders and Epilepsy.

N-methyl-D-aspartate receptors (NMDAR) are ligand-gated ion channels mediating excitatory neurotransmission and are important for normal brain development, cognitive abilities, and motor functions. Pathogenic variants in the Glutamate receptor Ionotropic N-methyl-D-aspartate (GRIN) genes (GRIN1, GRIN2A-D) encoding NMDAR subunits have been associated with a wide spectrum of neurodevelopmental disorders and epilepsies ranging from treatable focal epilepsies to devastating early-onset developmental and epileptic encephalopathies. Genetic variants in NMDA receptor genes can cause a range of complex alterations to receptor properties resulting in various degrees of loss-of-function, gain-of-function, or mixtures thereof. Understanding how genetic variants affect the function of the receptors, therefore, represents an important first step in the ongoing development towards targeted therapies. Currently, targeted treatment options for GRIN-related diseases are limited. However, treatment with memantine has been reported to significantly reduce seizure frequency in a few individuals with developmental and epileptic encephalopathies harboring de novo gain-of-function GRIN2A missense variants, and supplementary treatment with L-serine has been associated with improved motor and cognitive performance as well as reduced seizure frequency in patients with GRIN2B loss-of-function missense variants as well as GRIN2A and GRIN2B null variants.

Personalized medicine in old age psychiatry and Alzheimer's disease.

Elderly patients show us unfolded lives with unique individual characteristics. An increasing life span is associated with increasing physical and mental disease burden. Alzheimer's disease (AD) is an increasing challenge in old age. AD cannot be cured but it can be treated. The complexity of old age and AD offer targets for personalized medicine (PM). Targets for stratification of patients, detection of patients at risk for AD or for future targeted therapy are plentiful and can be found in several omic-levels.

BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug.

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

The Progression of Microbiome Therapeutics for the Management of Gastrointestinal Diseases and Beyond.

There has been an increased ability to investigate human microbiota through next generation sequencing and functional assessment. This advancement has rapidly expanded our ability to study and manipulate the gastrointestinal microbiome to mitigate disease. Fecal microbiota transplantation (FMT), a therapy which broadly transfers the entire intestinal ecosystem, has been explored as a potential therapeutic in a variety of gastrointestinal, hepatic and extraintestinal conditions. The field however continues to evolve with a movement towards precision microbiome therapeutics individualizing care for various disorders. This review will describe the use of FMT, microbiota restoration and precision microbiome therapeutics focusing in gastrointestinal and hepatic diseases.