Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Quantitative Blood Serum IVDr NMR Spectroscopy in Clinical Metabolomics of Cancer, Neurodegeneration, and Internal Medicine.

Despite more than two decades of metabolomics having joined the "omics" scenery, to date only a few novel blood metabolite biomarkers have found their way into the clinic. This is changing now by massive large-scale population metabolic phenotyping for both healthy and disease cohorts. Here, nuclear magnetic resonance (NMR) spectroscopy is a method of choice, as typical blood serum markers can be easily quantified and by knowledge of precise reference concentrations, more and more NMR-amenable biomarkers are established, moving NMR from research to clinical application. Besides customized approaches, to date two major commercial platforms have evolved based on either 600 MHz (14.1 Tesla) or 500 MHz (11.7 Tesla) high-field NMR systems. This chapter provides an introduction into the field of quantitative in vitro diagnostics research (IVDr) NMR at 600 MHz and its application within clinical research of cancer, neurodegeneration, and internal medicine.

Development of a bionic hexapod robot with adaptive gait and clearance for enhanced agricultural field scouting.

High agility, maneuverability, and payload capacity, combined with small footprints, make legged robots well-suited for precision agriculture applications. In this study, we introduce a novel bionic hexapod robot designed for agricultural applications to address the limitations of traditional wheeled and aerial robots. The robot features a terrain-adaptive gait and adjustable clearance to ensure stability and robustness over various terrains and obstacles. Equipped with a high-precision Inertial Measurement Unit (IMU), the robot is able to monitor its attitude in real time to maintain balance. To enhance obstacle detection and self-navigation capabilities, we have designed an advanced version of the robot equipped with an optional advanced sensing system. This advanced version includes LiDAR, stereo cameras, and distance sensors to enable obstacle detection and self-navigation capabilities. We have tested the standard version of the robot under different ground conditions, including hard concrete floors, rugged grass, slopes, and uneven field with obstacles. The robot maintains good stability with pitch angle fluctuations ranging from -11.5° to 8.6° in all conditions and can walk on slopes with gradients up to 17°. These trials demonstrated the robot's adaptability to complex field environments and validated its ability to maintain stability and efficiency. In addition, the terrain-adaptive algorithm is more energy efficient than traditional obstacle avoidance algorithms, reducing energy consumption by 14.4% for each obstacle crossed. Combined with its flexible and lightweight design, our robot shows significant potential in improving agricultural practices by increasing efficiency, lowering labor costs, and enhancing sustainability. In our future work, we will further develop the robot's energy efficiency, durability in various environmental conditions, and compatibility with different crops and farming methods.

A machine learning-based online web calculator to aid in the diagnosis of sarcopenia in the US community.

Background: Sarcopenia places a heavy healthcare burden on individuals and society. Recognizing sarcopenia and intervening at an early stage is critical. However, there is no simple and easy-to-use prediction tool for diagnosing sarcopenia. The aim of this study was to construct a well-performing online web calculator based on a machine learning approach to predict the risk of low lean body mass (LBM) to assist in the diagnosis of sarcopenia. Methods: Data from the National Health and Nutritional Examination Surveys 1999-2004 were selected for model construction, and the included data were randomly divided into training and validation sets in the ratio of 75:25. Six machine learning methods- Classification and Regression Trees, Logistic Regression, Neural Network, Random Forest, Support Vector Machine, and Extreme Gradient Boosting (XGBoost)-were used to develop the model. They are screened for features and evaluated for performance. The best-performing models were further developed as an online web calculator for clinical applications. Results: There were 3046 participants enrolled in the study and 815 (26.8%) participants with LBM. Through feature screening, height, waist circumference, race, and age were used as machine learning features to construct the model. After performance evaluation and sensitivity analysis, the XGBoost-based model was determined to be the best model with better discriminative performance, clinical utility, and robustness. Conclusion: The XGBoost-based model in this study has excellent performance, and the online web calculator based on it can easily and quickly predict the risk of LBM to aid in the diagnosis of sarcopenia in adults over the age of 60.

Precision prevention in occupational health: a conceptual analysis and development of a unified understanding and an integrative framework.

Introduction: Precision prevention implements highly precise, tailored health interventions for individuals by directly addressing personal and environmental determinants of health. However, precision prevention does not yet appear to be fully established in occupational health. There are numerous understandings and conceptual approaches, but these have not yet been systematically presented or synthesized. Therefore, this conceptual analysis aims to propose a unified understanding and develop an integrative conceptual framework for precision prevention in occupational health. Methods: Firstly, to systematically present definitions and frameworks of precision prevention in occupational health, six international databases were searched for studies published between January 2010 and January 2024 that used the term precision prevention or its synonyms in the context of occupational health. Secondly, a qualitative content analysis was conducted to analyze the existing definitions and propose a unified understanding. Thirdly, based on the identified frameworks, a multi-stage exploratory development process was applied to develop and propose an integrative conceptual framework for precision prevention in occupational health. Results: After screening 3,681 articles, 154 publications were reviewed, wherein 29 definitions of precision prevention and 64 different frameworks were found, which can be summarized in eight higher-order categories. The qualitative content analysis revealed seven themes and illustrated many different wordings. The proposed unified understanding of precision prevention in occupational health takes up the identified themes. It includes, among other things, a contrast to a "one-size-fits-all approach" with a risk- and resource-oriented data collection and innovative data analytics with profiling to provide and improve tailored interventions. The developed and proposed integrative conceptual framework comprises three overarching stages: (1) data generation, (2) data management lifecycle and (3) interventions (development, implementation and adaptation). Discussion: Although there are already numerous studies on precision prevention in occupational health, this conceptual analysis offers, for the first time, a proposal for a unified understanding and an integrative conceptual framework. However, the proposed unified understanding and the developed integrative conceptual framework should only be seen as an initial proposal that should be critically discussed and further developed to expand and strengthen both research on precision prevention in occupational health and its practical application in the workplace.

Integrating deep phenotyping with genetic analysis: a comprehensive workflow for diagnosis and management of rare bone diseases.

Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

BACKGROUND: Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. METHODS: From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. RESULTS: Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. CONCLUSIONS: In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. REGISTRATION: ClinicalTrials.gov Identifier: NCT01000701.

[Application of Artificial Intelligence Models in Nursing Research].

In recent years, the rapid development of artificial intelligence has enhanced the efficiency of medical services, accuracy of disease prediction, and innovation in the healthcare industry. Among the many advances, machine learning has become a focal point of development in various fields. Although its use in nursing research and clinical care has been limited, technological progress promises broader applications of machine learning in these areas in the future. In this paper, the authors discuss the application of machine learning in nursing research and care. First, the types and classifications of machine learning are introduced. Next, common neural machine learning models, including recurrent neural networks, transformers, and natural language processing, are described and analyzed. Subsequently, the principles and steps of machine learning are explored and compared to traditional statistical methods, highlighting the quality-monitoring strategies used by machine learning models and the potential limitations and challenges of using machine learning. Finally, interdisciplinary collaboration is encouraged to share knowledge between information technology and nursing disciplines, analyze the advantages and disadvantages of various analytical models, continuously review the research process, and reflect on methodological limitations. Following this course, can help maximize the potential of artificial-intelligence-based technologies to drive innovation and progress in nursing research.

Leveraging non-coding regions to guarantee the accuracy of small-sized panel-based tumor mutational burden estimates.

Accurate estimation of tumor mutational burden (TMB) as a predictor of responsiveness to immune checkpoint inhibitors in gene panel assays requires an adequate panel size. The current calculations of TMB only consider coding regions, while most of gene panel assays interrogate non-coding regions. Leveraging the non-coding regions is a potential solution to address this panel size limitation. However, the impact of including non-coding regions on the accuracy of TMB estimates remains unclear. This study investigated the validity of leveraging non-coding regions to supplement panel size using the OncoGuide NCC Oncopanel System (NOP). The aim of this study was to evaluate test performance against orthogonal assays and the association with responsiveness to immune checkpoint inhibitors was not included in the evaluation. We compared TMB status and values between TMB calculated only from coding regions (NOP-coding) and from both coding and non-coding regions (NOP-overall) using whole exome sequencing (WES) and FoundationOne®CDx (F1CDx) assay. Our findings revealed that NOP-overall significantly improved the overall percent agreement (OPA) with TMB status compared with NOP-coding for both WES (OPA: 96.7% vs. 73.3%, n = 30) and F1CDx (OPA: 90.0% vs. 73.3%). Additionally, the mean difference in TMB values compared with WES was lower for NOP-overall (3.55 [95% CI: 0.98-6.13]) than for NOP-coding (6.22 [95% CI: 3.73-8.70]). These results exemplify the utility of incorporating non-coding regions to maintain accurate TMB estimates in small-sized panels.

Genomic and clinical landscape of metastatic hormone receptors-positive breast cancers carrying ESR1 alterations.

BACKGROUND: Somatic genetic alterations of the estrogen receptor 1 gene (ESR1) are enriched in endocrine therapy-resistant, estrogen receptor-positive (ER+) metastatic breast cancer (mBC). Herein, we investigated and compared the clinical and genomic landscape of ESR1-mutant (ESR1MUT) and ESR1 wild type (ESR1WT) ER+/ human epidermal growth factor receptor 2 (HER2)- mBCs. METHODS: Clinical and genomic data were retrieved from cBioPortal using the publicly-available MSK MetTropism dataset. Metastatic, ER+/HER2- mBC samples were included in the analysis. Only oncogenic and likely oncogenic alterations according to OncoKB were included. Statistical analyses were carried out using alpha level of 0.05, with a false discovery rate threshold of 10% for multiple comparisons using the Benjamini-Hochberg method. RESULTS: Among 679 samples, 136 ESR1MUT among 131 tumors were found (19.2%). The frequency of ESR1MUT was higher in ductal versus lobular mBC (21.2% versus 13.8%, P = 0.052) and enriched in liver metastasis compared with other sites (22.5% versus 12.7%; q = 0.02). Compared with ESR1WT mBC, ESR1MUT tumors showed higher fraction of genome altered (FGA) {[0.28 interquartile range (IQR), 0.15-0.43] versus 0.22 (0.11-0.38); P = 0.04} and tumor mutational burden (TMB) [4.89 (IQR 3.46-6.85) versus 3.92 (2.59-6.05) mut/Mb; P = 0.001]. Tumors harboring p.E380X alterations showed higher TMB compared with those with H11-12 alterations [8.24 (IQR 5.06-15.3) versus 4.89 (IQR 3.46-6.75) mut/Mb; P = 0.01]. Genetic alterations of TP53 were enriched in ESR1WT tumors (36% versus 14%) [odds ratio (OR) 3.17, 95% confidence interval (CI) 1.88-5.64, q = 0.001]. Considering signaling pathways, ESR1MUT tumors showed a lower occurrence of TP53 (OR 0.48, 95% CI 0.30-0.74; q = 0.003) and MAPK (OR 0.29, 95% CI 0.11-0.65; q = 0.009) alterations. TP53 (q < 0.001), CDH1 (q < 0.001), and ERBB2 (q < 0.001) demonstrated mutual exclusivity with ESR1MUT. CONCLUSIONS: ER+/HER2- mBCs carrying ESR1MUT exhibit a divergent genomic background, characterized by a lower prevalence of TP53 and MAPK pathway alterations. Less common ESR1 alterations falling outside the H11-H12 region seem to occur in tumors with higher TMB, deserving further investigation to understand their potential actionability.

Drug development and evidence for lung cancer targeted therapy in Eastern Asia.

The development of targeted drugs in the Eastern Asia region is going through a flourishing stage. With the continuous advancement of technology and medical research, biotechnology companies and research institutions in the region have made significant progress in cancer field. The Eastern Asian region not only actively participates in clinical trials, but is also committed to developing personalized medical plans to meet the diverse genotypes and phenotypes of patients. The governments and enterprises are increasingly valuing innovation, strengthening international cooperation, and promoting drug development. This paper summarizes the development of genetic testing technology, targeted drugs approval, ongoing promising clinical trials in the field of lung cancer and the important progress made by governments in the Eastern Asian region, and proposed key factors that will contribute to the promising future prospects in the region. The targeted drug market in the Eastern Asian region is expected to drive the medical field forward.

Advancing Precision Rhinoplasty: Preoperative Digital 3D Surgical Planning.

The aim of the study is to assess the efficacy and advantages of utilizing state-of-the-art three-dimensional (3D) reconstruction technology in preoperative planning for rhinoplasty surgery. It is a study of a single rhinoplasty case that was operated at a tertiary hospital. The patient was assessed through a detailed history, blood investigations, radiological investigations and preoperative 3D (three-dimensional) reconstruction of the face and nose. The study utilized high-resolution CT scans and 3D reconstruction software like 3D (three-dimensional) Slicer and Blender 3D (three-dimensional) to analyze nasal anatomy for preoperative planning in rhinoplasty. External and internal nasal measurements were taken, and axial cross-section analysis was conducted to assess nasal structure deviation. The benefits of 3D (three-dimensional) visualization in surgical planning were evaluated, and surgical management was based on preoperative reconstructions. Comprehensive preoperative evaluations were performed, adhering to ethical guidelines. Preoperative 3D (three-dimensional) reconstruction planning methods facilitated precise surgical planning and execution in rhinoplasty with satisfactory outcomes for both the patient and the surgeon. Incorporating 3D (three-dimensional) reconstruction technology in rhinoplasty preoperative planning enhances surgical precision and patient satisfaction, ensuring optimized surgical outcomes while adhering to ethical standards.

Development of a Topological-Insulator-Based Quantum Resistance Standard.

This paper describes the characterization of the quantum anomalous Hall (QAH) effect resistor with Chromium-doped Bismuth Antimony Telluride with the efforts in coupling directly to a programmable Josephson voltage standard (PJVS) at zero magnetic field. The precision measurement of the QAH resistance was performed under the presence of microwave signal biased to the PJVS. Understanding such effect will help to improve the experimental set-up for integrating multiple quantum electrical standards in a single system.

Strongly quenched activatable theranostic nanogel for precision imaging-guided photodynamic therapy and enhanced immunotherapy.

Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings. In this study, we developed a near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and combined immunotherapy for rapidly growing tumors. Although NIR fluorescence and phototoxicity of NATNgel are strongly quenched, these can be selectively activated inside target tumor cells. A high tumor-to-background ratio (7.31 ±â€¯1.40) in NIR fluorescence imaging could be achieved in NATNgel-treated mice, enabling real-time image-guided PDT. The combination of PDT and anti-PD-1 antibody therapy resulted in complete tumor regression. Histopathological evaluation of major organs and blood chemistry analysis revealed no side effects of the combined treatment regimen. In addition, the combination treatment completely suppressed the growth of rechallenged tumors. Overall, NATNgel is a safe and promising theranostic material for precision imaging-guided PDT and enhanced immunotherapy.

Effect of a Multifactorial Weight Loss Intervention on HDL Cholesterol Efflux Capacity and Immunosenescence: A Randomized Controlled Trial.

OBJECTIVE: Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. METHOD: CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. RESULTS: Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (-3.32% ± 12.54% and -6.74% ± 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. CONCLUSIONS: A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.

[Precision medicine in oncology: A reality without equity]. / La médecine de précision en cancérologie : une réalité sans équité.

The prognostic of certain cancers improved significantly in recent years thanks not only to the launch of innovative treatments but also to progress made in the diagnostic field. Thus, next-generation sequencing (NGS) became paramount to help characterizing tumors and selecting the most pertinent treatments. The survey conducted by a multi stakeholder committee, at the end of 2022, with 103 actors of the management of cancer patients (public and private centers, labs, prescribers, biologists, pathologists, direction) confirmed the heterogeneity of use of NGS tests across France due to, mainly, the lack of systematic reimbursement of related costs. Référentiel des actes innovants hors nomenclature de biologie (RIHN) covers, in a delayed and partial way, only half of costs engaged by centers. Only those with a critical mass of patients or with a sufficient funding capacity can guarantee an access to large panels. Postponing the initiation of a required treatment represents a risk of loss of opportunity for patients who cannot benefit of this technology. NGS large panels tests, an efficiency lever for cancer treatment, must be part of the care toolbox. Those with a demonstration of value created should nowadays be fully reimbursed by collectivity after HAS' evaluation, for a fair access throughout the territory. Precision diagnostic can open the way to a more personalized and efficient medicine.

Efficacy of inflammation-based stratification for add-on celecoxib or minocycline in major depressive disorder: Protocol of the INSTA-MD double-blind placebo-controlled randomised clinical trial.

Introduction: Different lines of evidence confirm the involvement of the immune system in the pathophysiology of major depressive disorder. Up to 30% of depressed patients present with an immune-mediated subtype, characterized by peripheral inflammation (high-sensitive C-reactive protein (hsCRP) ≥ 3 mg/l) and an atypical symptom profile with fatigue, anhedonia, increased appetite, and hypersomnia. This immune-mediated subtype of MDD is associated with poorer response to first-line antidepressant treatment. Consequently, strategies for immune-targeted augmentation should be prioritised towards patients with this subtype. Meta-analyses have shown modest but heterogeneous treatment effects with immune-targeted augmentation in unstratified MDD cohorts, with celecoxib and minocycline as most promising first-line treatment options. However, no study has prospectively evaluated the effectiveness of a priori stratification by baseline inflammation levels for add-on celecoxib or minocycline in MDD. Methods: The INSTA-MD trial is a multicentre, 12-week, randomised, double-blind, placebo-controlled, parallel-group stratified clinical trial of adjunctive minocycline or celecoxib to treatment-as-usual for patients with MDD. Two hundred forty adult patients with Major Depressive Disorder who failed to remit with one or two trials of antidepressant treatment will be enrolled and allocated to high-hsCRP (hsCRP ≥3 mg/L) or low-hsCRP (hsCRP <3 mg/L) strata, where disproportional stratified sampling will ensure equally sized strata. Participants in each hsCRP stratum will be randomised to augment their ongoing antidepressant treatment with either adjunctive minocycline, celecoxib or placebo for a duration of 12 weeks, resulting in six treatment arms of each 40 participants. The primary objective is to evaluate the efficacy of immune-targeted augmentation with minocycline or celecoxib versus placebo, and the use of baseline hsCRP stratification to predict treatment response. Additionally, we will perform a head-to-head analysis between the two active compounds. The primary outcome measure is change in the Hamilton Depression Rating Scale (HDRS-17) total score. Secondary outcome measures will be response and remission rates, and change in inflammation-specific symptoms, adverse events and therapy acceptability (adherence). Further exploratory analyses will be performed with an array of peripheral inflammatory biomarkers, metabolic outcomes and physiological data. Expected impact: The aim of INSTA-MD is to advance the use of immune-targeted precision psychiatry, by supporting the implementation of targeted hsCRP screening and treatment of immune-mediated MDD as a cost-effective intervention in primary care settings. Based on previous studies, we expect immune-targeted augmentation with minocycline or celecoxib to yield a superior remission rate of 15-30% compared to treatment as usual for immune-mediated cases of MDD. By treating immune-related depression early in the treatment algorithm with repurposed first-line anti-inflammatory treatments, we can significantly improve the outcomes of these patients, and reduce the global societal and economic burden of depression. Ethics and dissemination: This protocol has been approved by the Medical Ethics Review Board (CTR - 04/08/2023). Registration details: Trial registration number NCT05644301 (Clinical trial.gov), EU-CT 2022-501692-35-00.

Matching traditional Chinese medicine and western medicine-based research: Advanced nutraceutical development for proactive gastric cancer prevention.

Gastric cancer (GC), the third leading cause of cancer-related death globally, is complex and heterogeneous. This review explores multidisciplinary investigations of traditional Chinese medicine (TCM) combined with Western medical practices, emphasizing the development of nutraceuticals for cancer prevention. Using advanced analytical chemistry and food chemistry techniques, this study investigated how TCM components may be optimized for nutraceutical development. Focusing on molecular interactions with GC pathways, particularly the NF-κB, PI3K/Akt, and Wnt/ß-catenin pathways, we examined the effects of TCM polyherbal formulas, extracts, and isolated compounds. These agents modulate apoptosis and cellular proliferation, underscoring their potential in preventive strategies. The convergence of nutraceutical and medicine food homology studies highlights a significant shift towards integrating TCM-derived compounds in a preventive health framework. This approach aims not only to enhance efficacy and reduce side effects but also to champion a preventive paradigm using personalized medicine to advance proactive health maintenance and disease prevention. The combination of TCM and western medical practices offers promising avenues for future research and practical applications in GC prevention.

Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.

Hematopoietic and leukemic stem cells homeostasis: the role of bone marrow niche.

The bone marrow microenvironment (BMM) has highly specialized anatomical characteristics that provide a sanctuary place for hematopoietic stem cells (HSCs) that allow appropriate proliferation, maintenance, and self-renewal capacity. Several cell types contribute to the constitution and function of the bone marrow niche. Interestingly, uncovering the secrets of BMM and its interaction with HSCs in health paved the road for research aiming at better understanding the concept of leukemic stem cells (LSCs) and their altered niche. In fact, they share many signals that are responsible for interactions between LSCs and the bone marrow niche, due to several biological similarities between LSCs and HSCs. On the other hand, LSCs differ from HSCs in their abnormal activation of important signaling pathways that regulate survival, proliferation, drug resistance, invasion, and spread. Targeting these altered niches can help in better treatment choices for hematological malignancies and bone marrow disorders in general and acute myeloid leukemia (AML) in particular. Moreover, targeting those niches may help in decreasing the emergence of drug resistance and lower the relapse rate. In this article, the authors reviewed the most recent literature on bone marrow niches and their relations with either normal HSCs and AML cells/LSC, by focusing on pathogenetic and therapeutic implications.