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Abstract Aims Racial disparities exist in clinical outcomes for valvular heart disease (VHD). It is unknown whether clinician segregation contributes to these disparities. Among an adequately insured population, we evaluated the relationship between clinician segregation in a hospital and receipt of care by a cardiologist according to patient race. We also evaluated the association between clinician segregation, race and care by a cardiologist on 30‐day readmission and 1‐year survival. Methods and results Using Optum's Clinformatics® Data Mart Database (CDM, US commercial and Medicare beneficiaries) from 2010 to 2018, we identified patients with a primary diagnosis of VHD. Hospitals were categorized into low, medium and high segregation groups (SG), according to clinician segregation index (SI). SI can range from 0–1 (0: the ratio of Black to White patients is the same for all clinicians; 1: each clinician treats only Black or only White patients). Outcomes were analysed using generalized linear mixed effect models. Among 8649 patients [median age 75 (67–82), 45.4% female, 16.1% Black, 83.9% White], odds of care from a cardiologist did not vary across race for all SGs [Low SG adjusted odds ratio (aOR): 0.79 (95% CI: 0.58–1.08), P = 0.14; Medium SG aOR: 0.86 (95% CI: 0.60–1.25), P = 0.43; High SG aOR: 1.07 (95% CI: 0.68–1.69), P = 0.76]. Among those that received care from a cardiologist, there was no difference in the 30‐day readmission between Black and White patients across SGs [Low SG aOR: 1.05 (95% CI: 0.83–1.31), P = 0.70; Medium SG aOR: 1.22 (95% CI: 0.92–1.61), P = 0.17; High SG aOR: 0.81 (95% CI: 0.57–1.17), P = 0.27]. Among patients that did not receive care from a cardiologist, Black patients in low SG had higher odds of 30‐day readmission compared to White patients [aOR: 2.74 (95%CI:1.38–5.43), P

Abstract Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty patients were randomized, 36 received treatment, and 25 were evaluable for the primary endpoint. After cycle 1, there was peripheral expansion of higher proportion of tumor-associated TCR clones in Arm A than in Arm B (p = 0.0025) that remained higher at day 21, meeting the pre-specified endpoint on two-sample T-test (p = 0.052), but not on sensitivity analysis by Wilcoxon test (p = 0.13). At the median follow up of 25.8 months, 2-year DFS was 76% in Arm A and 56% in Arm B (p = 0.28). There were no new safety signals. In conclusion, neoadjuvant ICB prior to CRT was safe and was associated with immunologically and clinically favorable outcomes, warranting larger confirmatory studies.

Developmental dyscalculia (DD) affects 2-6% of the population. Yet, a readily accessible list of potential interventions for DD is not available or can be easily found by educators. With a large percentage of the population afflicted with DD, educators should be made aware of what supportive approaches are available. The purpose of this study was to construct a literature review to locate and identify strategies tailored for this particular learning disability that can be used in the classroom. Results indicated that a total of seven evidence-based interventions are available for DD. Of the seven available options, all reported evidence of effectiveness in terms of helping to improve mathematical learning abilities for individuals. The need for future research into interventions for DD will assist students in improving their understanding of how they can handle mathematical tasks.

Objective: Machine learning (ML) may allow for improved discernment of hemodynamics and oxygen delivery compared to standard invasive monitoring. We hypothesized that an ML algorithm could predict impaired delivery of oxygen (IDO2) with comparable discrimination to invasive mixed venous oxygen saturation (SvO2) measurement. Methods: A total of 230 patients not on mechanical circulatory support (MCS) managed with a pulmonary artery catheter (PAC) were identified from 1012 patients admitted to a single cardiovascular intensive care unit (CVICU) between April 2021 and January 2022. Physiologic data were collected prospectively by the data analytics engine. Inadequate delivery of oxygen (IDO2) was defined as SvO2 ≤50%. Fifty-four patients were used to train the model, which was then validated in 176 patients. Three simulated monitoring situations were constructed by downsampling the physiologic data set to exclude all SvO2 sources (scenario A); all PAC data but allowing for SvO2 values (scenario B); and all PAC data, including SvO2 and cardiac index (CI) (scenario C). The ML platform then calculated the likelihood of IDO2 for rolling 30-minute intervals and compared these values against the gold standard SvO2 values using receiver operating characteristic (ROC) curve analysis to establish discriminatory power. Results: A total of 1047 laboratory-validated SvO2 values were collected for the validation group. The area under the ROC curve for the IDO2 index was 0.89 (95% confidence interval, 0.87-0.91) with the full data set. When blinded to all PAC and SvO2 sources, the AUC was 0.78 (95% confidence interval, 0.75-0.81). Conclusions: The IDO2 index is capable of detecting SvO2 ≤50% with good discriminatory function in non-MCS CVICU patients in a variety of monitoring situations. Further investigation of IDO2 detection and clinical endpoints is needed.

BackgroundElicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites vs combined, fractional delivery at multiple sites affected T-cell breadth compared to standard, single site vaccination.MethodsWe randomized 90 participants to receive recombinant adenovirus 5 (rAd5) vector with HIV inserts gag, pol and env via three different strategies. The Standard group received vaccine at a single anatomic site (n = 30) compared to two polytopic (multisite) vaccination groups: Separated (n = 30), where antigens were separately administered to four anatomical sites, and Fractioned (n = 30), where fractions of each vaccine component were combined and administered at four sites. All groups received the same total dose of vaccine.FindingsCD8 T-cell response rates and magnitudes were significantly higher in the Fractioned group than Standard for several antigen pools tested. CD4 T-cell response magnitudes to Pol were higher in the Separated than Standard group. T-cell epitope mapping demonstrated greatest breadth in the Fractioned group (median 8.0 vs 2.5 for Standard, Wilcoxon p = 0.03; not significant after multiplicity adjustment for co-primary endpoints). IgG binding antibody response rates to Env were higher in the Standard and Fractioned groups vs Separated group.InterpretationThis study shows that the number of anatomic sites for which a vaccine is delivered and distribution of its antigenic components influences immune responses in humans.FundingNational Institute of Allergy and Infectious Diseases, NIH.

The vast majority of membrane phospholipids (PLs) include two asymmetrically positioned fatty acyls: oxidizable polyunsaturated fatty acids (PUFA) attached predominantly at the sn2 position, and non-oxidizable saturated/monounsaturated acids (SFA/MUFA) localized at the sn1 position. The peroxidation of PUFA-PLs, particularly sn2-arachidonoyl(AA)- and sn2-adrenoyl(AdA)-containing phosphatidylethanolamines (PE), has been associated with the execution of ferroptosis, a program of regulated cell death. There is a minor subpopulation (≈1-2 mol %) of doubly PUFA-acylated phospholipids (di-PUFA-PLs) whose role in ferroptosis remains enigmatic. Here we report that 15-lipoxygenase (15LOX) exhibits unexpectedly high pro-ferroptotic peroxidation activity towards di-PUFA-PEs. We revealed that peroxidation of several molecular species of di-PUFA-PEs occurred early in ferroptosis. Ferrostatin-1, a typical ferroptosis inhibitor, effectively prevented peroxidation of di-PUFA-PEs. Furthermore, co-incubation of cells with di-AA-PE and 15LOX produced PUFA-PE peroxidation and induced ferroptotic death. The decreased contents of di-PUFA-PEs in ACSL4 KO A375 cells was associated with lower levels of di-PUFA-PE peroxidation and enhanced resistance to ferroptosis. Thus, di-PUFA-PE species are newly identified phospholipid peroxidation substrates and regulators of ferroptosis, representing a promising therapeutic target for many diseases related to ferroptotic death.

Abstract Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant‐producing cells and lower surfactant‐protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12 mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term = 150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45 min before tissue collection. Lung function and structure were similar in control lambs (n = 16, 11 ewes) and lambs from asthma ewes (n = 14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n = 12, 8 ewes) compared to those from controls (P = 0.003) or asthma ewes (P = 0.008). Lung expression of surfactant protein genes SFTPA (P = 0.048) and SFTPB (P

Life in academia can be difficult. Studies of faculty show high levels of stress leading to impaired productivity, exhaustion, pessimism, and disillusionment. Methods for addressing workplace stress including mentoring, professional/social interaction, and work-family enrichment have been well documented. This co/autoethnographic study examined a Community of Practice (CoP) composed of seven university faculty members over a 20-year period. A CoP can mitigate the stressors of academic careers, while improving quality of life. This study examined the role of our CoP in our personal and professional lives. Emergent themes included: professional development, shared play, and commitment, ultimately forming a community of care. This study and its findings may be useful for both faculty and those involved in faculty development.

Holistic and ecological approaches to mental health support have been identified by many as best-practice approaches for creating and sustaining well-being. Those who experience mental health challenges including, for example, Borderline Personality Disorder (BPD), often struggle to find adequate, sustainable and ongoing care from clinical settings, and recent research shows that additional strategies such as peer support programs, arts approaches, and holistic school-based collaboration work effectively. More generally, the mainstream population continues to suffer from outdated, overly medicalised and frequently inaccurate notions of the experience of poor mental health and the effective support of those who suffer, and peer- and school-integrated approaches go some way toward better education about mental ill-health. This article uses a creative ecologies model (Harris, 2016) to help schools implement student- and family-led support programs for students experiencing mental health challenges in school settings.

Building from a panel at the 2022 National Communication Association (NCA) annual convention, the present article seeks to ground communication studies/sciences as central to interdisciplinary conversations surrounding sexuality education and communication. Communication is integral to sexuality education, and topics of communication, sex, and sexuality education are researched across disciplines. Still, research on sexuality education within communication studies remains under-attended, and interdisciplinary sexuality education research remains siloed by academic discipline. Presenting a forum featuring both emerging and leading scholars in the field of communication researching sex(uality) education, the present article seeks to establish the academic discipline of communication as integral to research on sexuality education. To do so, we first discuss communication as an academic discipline and its advancements in sexuality education research. Next, communication scholars offer their expertise in sex(uality education) communication topics including family conversations, cultural influence, health inequities in education, and medicine. Collectively, these perspectives offer an understanding of current sexual health research in the field of communication, as well as next steps through direct application to conversations about sex, improvement to our medical and education systems, and community-based education and intervention. It is our hope that this article fosters a larger conversation about the importance of communication (studies/sciences) in sexuality education.

BACKGROUND: Stroke is a sudden-onset, uncontrollable event; stroke-related stress may impede rehabilitation and recovery. Lifetime stress may sensitize patients to experiencing greater stroke-related stress and indirectly affect outcomes. We examine lifetime stress as predictor of poststroke acute stress and examine lifetime and acute stress as predictors of 3- and 12-month functional status. We also compare acute stress and baseline National Institutes of Health Stroke Scale as predictors of poststroke functional status. METHODS: Between 2016 and 2020 the STRONG Study (Stroke, Stress, Rehabilitation, and Genetics) enrolled adults with new radiologically confirmed stroke 2 to 10 days poststroke onset at 28 acute care US hospitals. Participants were interviewed 3 times: acute admission (acute stress; Acute Stress Disorder Interview), 3 months (Fugl-Meyer Upper Extremity motor impairment [Fugl-Meyer Upper Arm Assessment; N=431], modified Rankin Scale [3 months; N=542], Stroke Impact Scale-Activities of Daily Living [3 months; N=511], Lifetime Stress Exposure Inventory), and 12 months (modified Rankin Scale, N=533; Stroke Impact Scale 3.0 Activities of Daily Living; N=485; Telephone Montreal Cognitive Assessment; N=484) poststroke. Structural equation models examined whether acute stress predicted 3- and 12-month functional outcomes, and mediated an association between lifetime stress and outcomes controlling for demographics and initial National Institutes of Health Stroke Scale. Standardized betas are reported. RESULTS: Sample (N=763) was 19 to 95 years old (mean=63; SD=14.9); 448 (58.7%) were male. Acute stress scores ranged from 0 to 14 (mean, 3.52 [95% CI, 3.31-3.73]). Controlling for age, gender, baseline National Institutes of Health Stroke Scale, and race and ethnicity, higher lifetime stress predicted higher acute stress (β=0.18, P0.18), but Fugl-Meyer scores (χ2[1]=7.01, P=0.008) less strongly than baseline National Institutes of Health Stroke Scale. CONCLUSIONS: Lifetime stress/trauma is associated with more poststroke acute stress, which is associated with greater motor and cognitive impairment and disability 3 and 12 months poststroke. Poststroke interventions for acute stress may help mitigate stroke-related disability.

Despite numerous efforts to generate mature human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), cells often remain immature, electrically isolated, and may not reflect adult biology. Conductive polymers are attractive candidates to facilitate electrical communication between hPSC-CMs, especially at sub-confluent cell densities or diseased cells lacking cell-cell junctions. Here we electrospun conductive polymers to create a conductive fiber mesh and assess if electrical signal propagation is improved in hPSC-CMs seeded on the mesh network. Matrix characterization indicated fiber structure remained stable over weeks in buffer, scaffold stiffness remained near in vivo cardiac stiffness, and electrical conductivity scaled with conductive polymer concentration. Cells remained adherent and viable on the scaffolds for at least 5 days. Transcriptomic profiling of hPSC-CMs cultured on conductive substrates for 3 days showed upregulation of cardiac and muscle-related genes versus non-conductive fibers. Structural proteins were more organized and calcium handling was improved on conductive substrates, even at sub-confluent cell densities; prolonged culture on conductive scaffolds improved membrane depolarization compared to non-conductive substrates. Taken together, these data suggest that blended, conductive scaffolds are stable, supportive of electrical coupling in hPSC-CMs, and promote maturation, which may improve our ability to model cardiac diseases and develop targeted therapies.

Human 12-lipoxygenase (12-LOX) is a key enzyme involved in platelet activation, and the regulation of its activity has been targeted for the treatment of heparin-induced thrombocytopenia. Despite the clinical importance of 12-LOX, the exact mechanisms by which it affects platelet activation are not fully understood, and the lack of structural information has limited drug discovery efforts. In this study, we used single-particle cryo-electron microscopy to determine high-resolution structures (1.7-2.8 Å) of human 12-LOX. Our results showed that 12-LOX can exist in multiple oligomeric states, from monomer to hexamer, which may affect its catalytic activity and membrane association. We also identified different conformations within the 12-LOX dimer, which likely represent different time points in its catalytic cycle. Furthermore, we identified small molecules bound to 12-LOX. The active site of the 12-LOX tetramer was occupied by an endogenous 12-LOX inhibitor, a long-chain acyl coenzyme A. In addition, we found that the 12-LOX hexamer can simultaneously bind to arachidonic acid and ML355, a selective 12-LOX inhibitor that has passed a phase 1 clinical trial for the treatment of heparin-induced thrombocytopenia and received a fast-track designation by the Food and Drug Administration. Overall, our findings provide novel insights into the assembly of 12-LOX oligomers, their catalytic mechanism, and small molecule binding, paving the way for further drug development targeting the 12-LOX enzyme.

Polyunsaturated fatty acids (PUFAs) have been extensively studied for their health benefits because they can be oxidized by lipoxygenases to form bioactive oxylipins. In this study, we investigated the impact of double bond placement on the kinetic properties and product profiles of human platelet 12-lipoxygenase (h12-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), and human endothelial 15-lipoxygenase-2 (h15-LOX-2) by using 22-carbon (C22) fatty acid substrates with differing double bond content. With respect to kcat/KM values, the loss of Δ4 and Δ19 led to an 18-fold loss of kinetic activity for h12-LOX, no change in kinetic capability for h15-LOX-1, but a 24-fold loss for h15-LOX-2 for both C22-FAs. With respect to the product profiles, h12-LOX produced mainly 14-oxylipins. For h15-LOX-1, the 14-oxylipin production increased with the loss of either Δ4 and Δ19, however, the 17-oxylipin became the major species upon loss of both Δ4 and Δ19. h15-LOX-2 produced mostly the 17-oxylipin products throughout the fatty acid series. This study also investigated the effects of various 17-oxylipins on platelet activation. The results revealed that both 17(S)-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-DHA (17-HDHA) and 17-hydroxy-4Z,7Z,10Z,13Z,15E-DPAn6 (17-HDPAn6) demonstrated anti-aggregation properties with thrombin or collagen stimulation. 17-hydroxy-7Z,10Z,13Z,15E,19Z-DPAn3 (17-HDPAn3) exhibited agonistic properties, and 17-hydroxy-7Z,10Z,13Z,15E-DTA (17-HDTA) showed biphasic effects, inhibiting collagen-induced aggregation at lower concentrationsbut promoting aggregation at higher concentrations. Both 17-hydroxy-13Z,15E,19Z-DTrA (17-HDTrA), and 17-hydroxy-13Z,15E-DDiA (17-HDDiA) induced platelet aggregation. In summary, the number and placement of the double bonds affect platelet activation, with the general trend being that more double bonds generally inhibit aggregation, while less double bonds promote aggregation. These findings provide insights into the potential role of specific fatty acids and their metabolizing LOX isozymes with respect to cardiovascular health.

Autonomous experimentation is an emerging area of research, primarily related to autonomous vehicles, scientific combinatorial discovery approaches in materials science and drug discovery, and iterative research loops of planning, experimentation, and analysis. However, autonomous approaches developed in these contexts are difficult to apply to high-dimensional mapping technologies, such as scanning hyperspectral imaging of biological systems, due to sample complexity and heterogeneity. We briefly cover the history of adaptive sampling algorithms and surrogate modeling in order to define autonomous adaptive data acquisition as an objective-based, flexible building block for future biological imaging experimentation driven by intelligent infrastructure. We subsequently summarize the recent implementations of autonomous adaptive data acquisition (AADA) for scanning hyperspectral imaging, assess how these address the difficulties of autonomous approaches in hyperspectral imaging, and highlight the AADA design variation from a goal-oriented perspective. Finally, we present a modular AADA architecture that embeds AADA-driven flexible building blocks to address the challenge of time resolution for high-dimensional scanning hyperspectral imaging of nonequilibrium dynamical systems. In our example research-driven experimental design case, we propose an AADA infrastructure for time-resolved, noninvasive, and label-free scanning hyperspectral imaging of living biological systems. This AADA infrastructure can accurately target the correct state of the system for experimental workflows that utilize subsequent expensive, high-information-content analytical techniques.

Background. Baseline lung allograft dysfunction (BLAD) after lung transplant is associated with an increased risk of dying, but the association with health-related quality of life (HRQL) and exercise capacity is not known. We hypothesized that BLAD would be associated with reduced HRQL and 6-min walk distance (6MWD) at 1 y post–lung transplant. Methods. We analyzed patients who underwent lung transplants in our program from 2004 to 2018 who completed 1-y 36-item Short Form (SF-36) questionnaire and 6MWD testing. We secondarily analyzed the Beck Depression Inventory and Borg dyspnea scores in patients using the available data. We defined BLAD as a failure of both forced expiratory volume in 1 s and forced vital capacity to reach ≥80% predicted of a healthy reference population’s lung function on 2 consecutive tests ≥3 wk apart at any time point posttransplant. We tested the relationship between BLAD status and SF-36 physical component summaries and 6MWD using least squares regression, adjusting for age at transplant, sex at birth, and primary lung disease. Results. Two hundred sixty-four patients were included, 96 (36%) of whom met the criteria for BLAD. Patients with interstitial lung disease as an indication for transplant and those who received older, female, and heavy smoking donors were at increased risk of BLAD. SF-36 physical component summary scores were lower in patients with BLAD (75 versus 85; P = 0.0076), as were 6MWD values (528 versus 572 m; P = 0.0053). BLAD was associated with lower SF-36 scores (P = 0.0025) and 6MWD (P = 0.0008) in adjusted regression models at 1 y posttransplant. We did not observe differences in Beck Depression Inventory or Borg scores. Conclusions. BLAD was associated with reduced HRQL and 6MWD scores at 1 y posttransplant in adjusted models. This suggests that poor posttransplant lung function could contribute to lower HRQL and exercise capacity in lung recipients and is worthy of further exploration in terms of causes, prevention, and treatment.

IMPORTANCE:. The current definition of central line-associated bloodstream infection (CLABSI) may overestimate the true incidence of CLABSI as it is often unclear whether the bloodstream infection (BSI) is secondary to the central line or due to another infectious source. OBJECTIVES:. We aimed to assess the prevalence and outcomes of central CLABSI at our institution, to identify opportunities for improvement, appropriately direct efforts for infection reduction, and identify gaps in the CLABSI definition and its application as a quality measure. DESIGN, SETTING, AND PARTICIPANTS:. Retrospective cross-sectional study of patients identified to have a CLABSI in the period 2018–2022 cared for at the value-based purchasing (VBP) units of a 1200-bed tertiary care hospital located in Cleveland, OH. Each CLABSI episode was assessed for relationship with central venous catheter (CVC), suspected secondary source of BSI, mortality associated with the CLABSI hospital encounter, and availability of infectious disease physician or primary physician documentation of infectious source. MAIN OUTCOMES AND MEASURES:. CLABSI episodes were classified as CVC related, CVC unrelated, and CVC relationship unclear. Mortality during the same encounter as the CLABSI event was assessed as an outcome measure. Descriptive statistics were performed. RESULTS:. A total of 340 CLABSI episodes occurred in adult patients in VBP units. Majority of the CLABSI, 77.5% (266), occurred in the ICU. Of the CLABSI analyzed, 31.5% (107) were classified as unrelated to the CVC; 25.0% (85) had an unclear source; 43% (148) were classified as CVC related. For CVC-related cases, Staphylococcus and Candida were the predominant organisms. For the CVC unrelated and unclear groups Enterococcus was most prevalent. The mortality rate was lowest among patients classified with a CVC-related BSI. The positive predictive value (PPV) of the Centers for Disease Control and Prevention CLABSI definition to predict a true CVC-related infection was found to be 58.0%. CONCLUSIONS AND RELEVANCE:. The definition of CLABSI as a surrogate for catheter-related BSI is inadequate, with a PPV of 58.0% (43.1–67.6%). Efforts should be redirected toward revising the CLABSI definition and possibly reevaluating its criteria. Resources should be assigned to further investigate and systematically prevent BSIs from secondary sources while adhering to existing CLABSI prevention bundles.

The antimicrobial properties of Schiff bases and their corresponding amines were assessed by exploring the impact of substituent variations on these activities. The present study involved the synthesis of Schiff base compounds and their corresponding sec-amines, characterization, antibacterial testing, and molecular docking studies. These compounds featured diverse structural components, including alkyl chains, phenyl and methoxy groups. Three of the synthesized compounds are new, viz. N-[(2,3-dimethoxyphenyl) methylene]-1-propanamine (1), N-[(2,3-dimethoxyphenyl)methyl]-1-propanamine (2) and N-[(2,3-dimethoxyphenyl)methylene]-1-butanamine (3). The assessment of antibacterial properties targeted two strains recognized as opportunistic pathogens. Notably, all Schiff base compounds possessing the −C=N moiety exhibited good antibacterial activity against P. aeruginosa and P. agglomerans. Specifically, 1 and 3 demonstrated exceptional effectiveness against the tested bacterial strains, showcasing promising antibacterial capabilities. Furthermore, binding energy calculations revealed that compounds 1 and 3 exhibited binding energies of −3.9, −4.1, and −3.8, −3.9 kcal/mol with respect to P. agglomerans and P. aeruginosa candidate proteins, respectively. This underscores the strong interaction between the synthesized compounds and the bacterial strains, further supporting their potential as potent antimicrobial agents. P. aeruginosa and P. agglomerans were found to be sensitive to both compounds 1 and 3, as well as the standard control ampicillin. The MIC values for P. aeruginosa were 10 mM for 1, and 6 mM for 3. While for P. agglomerans, the MIC values were 6 mM for both 1 and 3.

Colorectal cancer encompasses a heterogeneous group of malignancies that differ in pathophysiological mechanisms, immune response and infiltration, therapeutic response, and clinical prognosis. Numerous studies have highlighted the clinical relevance of tumor-infiltrating immune cells among different types of colorectal tumors yet vary in cell type definitions and cell identification strategies. The distinction of immune signatures is particularly challenging when several immune subtypes are involved but crucial to identify novel intercellular mechanisms within the tumor microenvironment. In this review, we compile human and non-human studies on tumor-infiltrating immune cells and provide an overview of immune subtypes, their pathophysiological functions, and their prognostic role in colorectal cancer. We discuss how differentiating immune signatures can guide the development of immunotherapeutic targets and personalized treatment regimens. We analyzed comprehensive human protein biomarker profiles across the entire immune spectrum to improve interpretability and application of tumor studies and to ultimately enhance immunotherapy and advance precision medicine for colorectal cancer patients.