Mentoring as a complex adaptive system - a systematic scoping review of prevailing mentoring theories in medical education.

BACKGROUND: Effective mentorship is an important component of medical education with benefits to all stakeholders. In recent years, conceptualization of mentorship has gone beyond the traditional dyadic experienced mentor-novice mentee relationship to include group and peer mentoring. Existing theories of mentorship do not recognize mentoring's personalized, evolving, goal-driven, and context-specific nature. Evidencing the limitations of traditional cause-and-effect concepts, the purpose of this review was to systematically search the literature to determine if mentoring can be viewed as a complex adaptive system (CAS). METHODS: A systematic scoping review using Krishna's Systematic Evidence-Based Approach was employed to study medical student and resident accounts of mentoring and CAS in general internal medicine and related subspecialties in articles published between 1 January 2000 and 31 December 2023 in PubMed, Embase, PsycINFO, ERIC, Google Scholar, and Scopus databases. The included articles underwent thematic and content analysis, with the themes identified and combined to create domains, which framed the discussion. RESULTS: Of 5,704 abstracts reviewed, 134 full-text articles were evaluated, and 216 articles were included. The domains described how mentoring relationships and mentoring approaches embody characteristics of CAS and that mentorship often behaves as a community of practice (CoP). Mentoring's CAS-like features are displayed through CoPs, with distinct boundaries, a spiral mentoring trajectory, and longitudinal mentoring support and assessment processes. CONCLUSION: Recognizing mentorship as a CAS demands the rethinking of the design, support, assessment, and oversight of mentorship and the role of mentors. Further study is required to better assess the mentoring process and to provide optimal training and support to mentors.

Nitrophenols in the environment: An update on pretreatment and analysis techniques since 2017.

Nitrophenols, a versatile intermediate, have been widely used in leather, medicine, chemical synthesis, and other fields. Because these components are widely applied, they can enter the environment through various routes, leading to many hazards and toxicities. There has been a recent surge in the development of simple, rapid, environmentally friendly, and effective techniques for determining these environmental pollutants. This review provides a comprehensive overview of the latest research progress on the pretreatment and analysis methods of nitrophenols since 2017, with a focus on environmental samples. Pretreatment methods include liquid-liquid extraction, solid-phase extraction, dispersive extraction, and microextraction methods. Analysis methods mainly include liquid chromatography-based methods, gas chromatography-based methods, supercritical fluid chromatography. In addition, this review also discusses and compares the advantages/disadvantages and development prospects of different pretreatment and analysis methods to provide a reference for further research.

Characterizing Neighborhood Vulnerabilities in Mild Cognitive Impairment using the Environmental Justice Index.

Background: There is a need for integration and comprehensive characterization of environmental determinants of Alzheimer's disease. The Environmental Justice Index (EJI) is a new measure that consolidates multiple environmental health hazards. Objective: This analysis aims to explore how environmental vulnerabilities vary by race/ethnicity and whether they predict cognitive outcomes in a clinical trial of mild cognitive impairment (MCI). Methods: We used data from a clinical trial of 107 MCI participants (28% minorities). Using the EJI, we extracted 40 measures of neighborhood environmental and social vulnerability including air and water pollution, access to recreational spaces, exposure to coal and lead mines, and area poverty. We also examined the relationship of the EJI to the Area Deprivation Index (ADI). Data was analyzed using regressions, correlations, and t-tests. Results: Environmental Burden Rank (EBR) across the sample (0.53±0.32) was near the 50th percentile nationally. When divided by race/ethnicity, environmental (p = 0.025) and social (p < 0.0001) vulnerabilities were significantly elevated for minorities, specifically for exposure to ozone, diesel particulate matter, carcinogenic air toxins, and proximity to treatment storage and disposal sites. ADI state decile was not correlated with the EBR. Neither EBR nor ADI were a significant predictor of cognitive decline. Conclusions: To our knowledge, this is the first study to link the EJI to an MCI trial. Despite limitations of a relatively small sample size, the study illustrates the potential of the EJI to provide deeper phenotyping of the exposome and diversity in clinical trial subjects.

Neurological features of Hansen disease: a retrospective, multicenter cohort study.

To elucidate the neurological features of Hansen disease. The medical records of patients with confirmed Hansen disease transferred from the neurology department were reviewed, and all medical and neurological manifestations of Hansen disease were assessed. Eleven patients with confirmed Hansen disease, 10 with newly detected Hansen disease and 1 with relapsed Hansen disease, who visited neurology departments were enrolled. The newly detected patients with Hansen disease were classified as having lepromatous leprosy (LL, n = 1), borderline lepromatous leprosy (BL, n = 2), borderline leprosy (BB, n = 2), borderline tuberculoid leprosy (BT, n = 1), tuberculoid leprosy (TT, n = 2), or pure neural leprosy (PNL, n = 2). All of the patients with confirmed Hansen were diagnosed with peripheral neuropathy (100.00%, 11/11). The symptoms and signs presented were mainly limb numbness (100.00%, 11/11), sensory and motor dysfunction (100.00%, 11/11), decreased muscle strength (90.90%, 10/11), and skin lesions (81.81%, 9/11). Nerve morphological features in nerve ultrasonography (US) included peripheral nerve asymmetry and segmental thickening (100.00%, 9/9). For neuro-electrophysiology feature, the frequency of no response of sensory nerves was significantly higher than those of motor nerves [(51.21% 42/82) vs (24.70%, 21/85)(P = 0.0183*)] by electrodiagnostic (EDX) studies. Nerve histological features in nerve biopsy analysis included demyelination (100.00%, 5/5) and axonal damage (60.00%, 3/5). In addition to confirmed diagnoses by acid-fast bacteria (AFB) staining (54.54%, 6/11) and skin pathology analysis (100.00%, 8/8), serology and molecular technology were positive in 36.36% (4/11) and 100.00% (11/11) of confirmed patients of Hansen disease, respectively. It is not uncommon for patients of Hansen disease to visit neurology departments due to peripheral neuropathy. The main pathological features of affected nerves are demyelination and axonal damage. The combination of nerve US, EDX studies, nerve biopsy, and serological and molecular tests can improve the diagnosis of Hansen disease.

Use of the Chinese version of the MATRICS Consensus Cognitive Battery to assess cognitive functioning in individuals with high risk for psychosis, first-episode schizophrenia and chronic schizophrenia: a systematic review and meta-analysis.

More than one hundred studies have used the mainland Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) to assess cognition in schizophrenia, but the results of these studies, the quality of the reports, and the strength of the evidence provided in the reports have not been systematically assessed. We identified 114 studies from English-language and Chinese-language databases that used the Chinese MCCB to assess cognition in combined samples of 7394 healthy controls (HC), 392 individuals with clinical high risk for psychosis (CHR-P), 4922 with first-episode schizophrenia (FES), 1549 with chronic schizophrenia (CS), and 2925 with schizophrenia of unspecified duration. The mean difference (MD) of the composite MCCB T-score (-13.72) and T-scores of each of the seven cognitive domains assessed by MCCB (-14.27 to -7.92) were significantly lower in individuals with schizophrenia than in controls. Meta-analysis identified significantly greater cognitive impairment in FES and CS than in CHR-P in six of the seven domains and significantly greater impairment in CS than FES in the reasoning and problem-solving domain (i.e., executive functioning). The only significant covariate of overall cognitive functioning in individuals with schizophrenia was a negative association with the severity of psychotic symptoms. These results confirm the construct validity of the mainland Chinese version of MCCB. However, there were significant limitations in the strength of the evidence provided about CHR-P (small pooled sample sizes) and the social cognition domain (inconsistency of results across studies), and the quality of many reports (particularly those published in Chinese) was rated 'poor' due to failure to report sample size calculations, matching procedures or methods of handling missing data. Moreover, almost all studies were cross-sectional studies limited to persons under 60 with at least nine years of education, so longitudinal studies of under-educated, older individuals with schizophrenia are needed.

Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment.

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.

Analysis of clinical risk factors for metabolic bone disease of prematurity.

Objective: To analyze clinical data related to preterm infants and identify risk factors for metabolic bone disease of prematurity (MBDP). Methods: This study involved 856 newborns with a gestational age of less than 37 weeks or a weight of less than 1,500g at the Second Hospital of Jilin University. Multifactorial analysis was performed using logistic regression models to explore the risk factors for MBDP. Linear regression was used to investigate the factors affecting the time of alkaline phosphatase (ALP) exceedance and the peak value of ALP in the MBDP group. Results: In the MBDP group, ALP excesses occurred in preterm infants at an average of 39.33 days after birth, and the mean value of peak ALP was 691.41 IU/L. Parenteral nutrition and the application of assisted ventilation were independent risk factors for MBDP, with ORs of 1.02 and 1.03 respectively. Gestational age was found to be a protective factor for earlier time of onset of ALP exceedance (ß = 2.24,) and the increase in the peak value of ALP (ß = -16.30). Conclusion: Parenteral nutrition and the application of assisted ventilation are independent risk factors for MBDP. Gestational age is a major factor influencing the time of onset of ALP exceedance and the peak value of ALP in infants with MBDP.

Despite mandated primary series, health care personnel still hesitant about COVID-19 vaccine and immunizing children.

IMPORTANCE: Healthcare personnel (HCP) are important messengers for promoting vaccines, for both adults and children. Our investigation describes perceptions of fully vaccinated HCP about COVID-19 vaccine for themselves and primary series for their children. OBJECTIVE: To determine associations between sociodemographic, employment characteristics and perceptions of COVID-19 vaccines among HCP overall and the subset of HCP with children, who were all mandated to receive a COVID-19 vaccine, in a large US metropolitan region. DESIGN: Cross-sectional survey of fully vaccinated HCP from a large integrated health system. SETTING: Participants were electronically enrolled within a multi-site NYS healthcare system from December 21, 2021, to January 21, 2022. PARTICIPANTS: Of 78,000 employees, approximately one-third accessed promotional emails; 6,537 employees started surveys and 4165 completed them. Immunocompromised HCP (self-reported) were excluded. EXPOSURE(S) (FOR OBSERVATIONAL STUDIES): We conducted a survey with measures including demographic variables, employment history, booster status, child vaccination status; vaccine recommendation, confidence, and knowledge. MAIN OUTCOME(S) AND MEASURES: The primary outcome was COVID-19 vaccine hesitancy for all dose types - primary series or booster doses - among HCP. RESULTS: Findings from 4,165 completed surveys indicated that almost 17.2 % of all HCP, including administrative and clinical staff, were hesitant or unsure about receiving a COVID-19 vaccine booster, despite the NYS recommendation to do so. Depending on age group, between 20 % and 40 % of HCP were hesitant about having their children vaccinated for COVID-19, regardless of clinical versus non-clinical duties. In multivariable regression analyses, lack of booster dose, unvaccinated children, females, income less than $50,000, and residence in Manhattan remained significantly associated with vaccine hesitancy. CONCLUSIONS AND RELEVANCE: Despite mandated COVID-19 vaccination, a substantial proportion of HCP remained vaccine hesitant towards adult booster doses and pediatric COVID-19 vaccination. While provider recommendation has been the mainstay of combatting COVID-19 vaccine hesitancy, a gap exists between HCP-despite clinical or administrative status-and the ability to communicate the need for vaccination in a healthcare setting. While previous studies describe the HCP vaccine mandate as a positive force to overcome vaccine hesitancy, we have found that despite a mandate, there is still substantial COVID-19 vaccine hesitancy, misinformation, and reluctance to vaccinate children.

Identification and validation of anoikis-related genes to clarify the prognosis and immune mechanisms of patients with low-grade glioma.

BACKGROUND: Low-grade glioma (LGG) has an extremely poor prognosis, and the mechanism leading to malignant development has not been determined. The aim of our study was to clarify the function and mechanism of anoikis and TIMP1 in the malignant progression of LGG. METHODS: We screened 7 anoikis-related genes from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a prognostic-predicting model. The study assessed the clinical prognosis, pathological characteristics, and immune cell infiltration in both high- and low-risk groups. Additionally, the potential modulatory effects of TIMP1 on proliferation, migration, and anoikis in LGG were investigated both in vivo and in vitro. RESULTS: In this study, we identified seven critical genes, namely, PTGS2, CCND1, TIMP1, PDK4, LGALS3, CDKN1A, and CDKN2A. Kaplan‒Meier (K‒M) curves demonstrated a significant correlation between clinical features and overall survival (OS), and single-cell analysis and mutation examination emphasized the heterogeneity and pivotal role of hub gene expression imbalances in LGG development. Immune cell infiltration and microenvironment analysis further elucidated the relationships between key genes and immune cells. In addition, TIMP1 promoted the malignant progression of LGG in both in vitro and in vivo models. CONCLUSIONS: This study confirmed that TIMP1 promoted the malignant progression of LGG by inhibiting anoikis, providing insights into LGG pathogenesis and potential therapeutic targets.

A retrospective cohort study of neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitors in locally advanced rectal cancer.

INTRODUCTION: This study aimed to investigate the safety and efficacy of neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitors (ICIs) in patients with locally advanced rectal cancer (LARC). Patients diagnosed with LARC and treated with programmed cell death protein-1 (PD-1) inhibitors were recruited. METHODS: Four different treatment strategies were employed in this study: plan A [long-course radiotherapy + PD-1 inhibitor/capecitabine + PD-1 inhibitor/XELOX+ total mesorectal excision (TME)], plan B (long-course radiotherapy + capecitabine + PD-1 inhibitor/XELOX + TME), plan C (short-course radiotherapy + PD-1 inhibitor/XELOX + TME), and plan D (PD-1 inhibitor/XELOX + short-course radiotherapy + TME). The basic information about patients, pathological indicators, adverse events, and efficacy indexes of treatment plans were analyzed. RESULTS: 96.8 % of patients were mismatch repair proficient (pMMR) and only 2 patients belonged to mismatch repair deficient (dMMR). The 2 patients with dMMR showed a pathological complete response (pCR) rate of 100 %, while the pCR rate of pMMR patients was 43.3 %. The overall tumor descending rate reached 79 %, and the anus-retained rate was 88.7 % in all LARC patients. Plan A exhibited the highest pCR rate of 60 %, and plan C had the highest tumor descending rate and anal preservation rate. Radiation enteritis was the most common adverse event in LARC patients after neoadjuvant therapy, and its incidence was the highest in Plan A. CONCLUSION: Neoadjuvant chemoradiotherapy combined with ICIs demonstrated favorable efficacy and safety in treating LARC patients.

A Biodegradable Nanosuspension Locally Used for Inhibiting Postoperative Recurrence and Brain Metastasis of Breast Cancer.

Addressing the urgent need to prevent breast cancer postoperative recurrence and brain metastasis, Fe-metal organic framework (MOF)-coated hollow mesoporous organosilica nanoparticles (HMON) with tumor microenvironment dual-responsive degradability were prepared to encapsulate doxorubicin (DOX), formulating a tissue-adhesive nanosuspension for perioperative topical medication. This nanosuspension can not only retain the sustainably released drug in the postoperative residual tumor sites but also enhance the intracellular oxidative stress of tumors for remarkable tumor ferroptosis. Interestingly, the nanosuspension can act as an immune amplifier, which could not only stimulate DC cells to secrete chemokines for T cell recruitment but also elevate antigen exposure to facilitate the antigen presentation in lymph nodes. Thus, this nanosuspension could significantly activate antitumor immune responses in both in situ tumors and metastatic encephaloma for enhanced immunotherapy. In conjunction with the clinical PD-1 antibody, the locally administered nanosuspension could achieve an advanced therapeutic outcome for inhibiting postoperative recurrence and metastasis.

Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

Diabetes mellitus in patients with heart failure and reduced ejection fraction: a post hoc analysis from the WARCEF trial.

Patients with heart failure with reduced ejection fraction (HFrEF) and diabetes mellitus (DM) have an increased risk of adverse events, including thromboembolism. In this analysis, we aimed to explore the association between DM and HFrEF using data from the "Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction" (WARCEF) trial. We analyzed factors associated with DM using multiple logistic regression models and evaluated the effect of DM on long-term prognosis, through adjusted Cox regressions. The primary outcome was the composite of all-cause death, ischemic stroke, or intracerebral hemorrhage; we explored individual components as the secondary outcomes and the interaction between treatment (warfarin or aspirin) and DM on the risk of the primary outcome, stratified by relevant characteristics. Of 2294 patients (mean age 60.8 (SD 11.3) years, 19.9% females) included in this analysis, 722 (31.5%) had DM. On logistic regression, cardiovascular comorbidities, symptoms and ethnicity were associated with DM at baseline, while age and body mass index showed a nonlinear association. Patients with DM had a higher risk of the primary composite outcome (Hazard Ratio [HR] and 95% Confidence Intervals [CI]: 1.48 [1.24-1.77]), as well as all-cause death (HR [95%CI]: 1.52 [1.25-1.84]). As in prior analyses, no statistically significant interaction was observed between DM and effect of Warfarin on the risk of the primary outcome, in any of the subgroups explored. In conclusion, we found that DM is common in HFrEF patients, and is associated with other cardiovascular comorbidities and risk factors, and with a worse prognosis.

FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion.

BACKGROUND: Emerging evidences suggest that aberrant metabolites contributes to the immunosuppressive microenvironment that leads to cancer immune evasion. Among tumor immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are pathologically activated and extremely immunosuppressive, which are closely associated with poor clinical outcomes of cancer patients. However, the correlation between MDSCs mediated immunosuppression and particular cancer metabolism remained elusive. METHODS: Spontaneous lung adenocarcinoma and subcutaneous mouse tumor models, gas chromatography-mass spectrometry (GC-MS) and immunofluorescence assay of patient-derived lung adenocarcinoma tissues, and flow cytometry, RNA sequencing and Western blotting of immune cells, were utilized. RESULTS: Metabolite profiling revealed a significant accumulation of acetic acids in tumor tissues from both patients and mouse model, which contribute to immune suppression and cancer progression significantly through free fatty acid receptor 2 (FFAR2). Furthermore, FFAR2 is highly expressed in the myeloid-derived suppressor cells (MDSCs) from the tumor of lung adenocarcinoma (LUAD) patients which is greatly associated with poor prognosis. Surprisingly, whole or myeloid Ffar2 gene deletion markedly inhibited urethane-induced lung carcinogenesis and syngeneic tumor growth with reduced MDSCs and increased CD8+ T cell infiltration. Mechanistically, FFAR2 deficiency in MDSCs significantly reduced the expression of Arg1 through Gαq/Calcium/PPAR-γ axis, which eliminated T cell dysfunction through relieving L-Arginine consumption in tumor microenvironment. Therefore, replenishment of L-Arginine or inhibition to PPAR-γ restored acetic acids/FFAR2 mediated suppression to T cells significantly. Finally, FFAR2 inhibition overcame resistance to immune checkpoint blockade through enhancing the recruitment and cytotoxicity of tumor-infiltrating T cells. CONCLUSION: Altogether, our results demonstrate that the acetic acids/FFAR2 axis enhances MDSCs mediated immunosuppression through Gαq/calcium/PPAR-γ/Arg1 signaling pathway, thus contributing to cancer progression. Therefore, FFAR2 may serve as a potential new target to eliminate pathologically activated MDSCs and reverse immunosuppressive tumor microenvironment, which has great potential in improving clinical outcomes of cancer immunotherapy.

Ocular microvascular alteration in patients with myocardial infarction-a new OCTA study.

Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.

Case Report: Temporary pacing using active fixation lead and invasive electrophysiology studies for immune checkpoint inhibitor associated reversible advanced atrioventricular block.

A case of immune checkpoint inhibitors (ICIs)-associated myocarditis with reversible advanced atrioventricular block (AVB) was reported. We innovatively used active fixation lead connected to an external device for prolonged temporary pacing until atrioventricular conduction recovered. Invasive electrophysiology studies were performed to evaluate atrioventricular conduction in detail. Long-term follow-up for nearly 120-days and repeated long-term electrocardiography was conducted to ensure the conduction system was truly recovered.

Educational status affects prognosis of patients with heart failure with reduced ejection fraction: A post-hoc analysis from the WARCEF trial.

AIMS: The influence of social determinants of health (SDOH) on the prognosis of Heart Failure and reduced Ejection Fraction (HFrEF) is increasingly reported. We aim to evaluate the contribution of educational status on outcomes in patients with HFrEF. METHODS: We used data from the WARCEF trial, which randomized HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational status of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended. We analysed the impact of the educational status on the risk of the primary composite outcome of all-cause death, ischemic stroke (IS) and intracerebral haemorrhage (ICH); components of the primary outcome were also analysed as secondary outcomes. RESULTS: 2295 patients were included in this analysis; of these, 992 (43.2%) had a low educational level, 947 (41.3%) had a medium education level and the remaining 356 (15.5%) showed a high educational level. Compared to patients with high educational level, those with low educational status showed a high risk of the primary composite outcome (adjusted hazard ratio [aHR]: 1.31, 95% confidence intervals [CI] 1.02-1.69); a non-statistically significant association was observed in those with medium educational level (aHR: 1.20, 95%CI: .93-1.55). Similar results were observed for all-cause death, while no statistically significant differences were observed for IS or ICH. CONCLUSION: Compared to patients with high educational levels, those with low educational status had worse prognosis. SDOH should be considered in patients with HFrEF. CLINICAL TRIAL REGISTRATION: NCT00041938.

MK-BMC: a Multi-Kernel framework with Boosted distance metrics for Microbiome data for Classification.

MOTIVATION: Research on human microbiome has suggested associations with human health, opening opportunities to predict health outcomes using microbiome. Studies have also suggested that diverse forms of taxa such as rare taxa that are evolutionally related and abundant taxa that are evolutionally unrelated could be associated with or predictive of a health outcome. Although prediction models were developed for microbiome data, no prediction models currently exist that use multiple forms of microbiome-outcome associations. RESULTS: We developed MK-BMC, a Multi-Kernel framework with Boosted distance Metrics for Classification using microbiome data. We propose to first boost widely used distance metrics for microbiome data using taxon-level association signal strengths to up-weight taxa that are potentially associated with an outcome of interest. We then propose a multi-kernel prediction model with one kernel capturing one form of association between taxa and the outcome, where a kernel measures similarities of microbiome compositions between pairs of samples being transformed from a proposed boosted distance metric. We demonstrated superior prediction performance of (i) boosted distance metrics for microbiome data over original ones and (ii) MK-BMC over competing methods through extensive simulations. We applied MK-BMC to predict thyroid, obesity, and inflammatory bowel disease status using gut microbiome data from the American Gut Project and observed much-improved prediction performance over that of competing methods. The learned kernel weights help us understand contributions of individual microbiome signal forms nicely. AVAILABILITY AND IMPLEMENTATION: Source code together with a sample input dataset is available at https://github.com/HXu06/MK-BMC.

Assessing social cognition in patients with schizophrenia and healthy controls using the reading the mind in the eyes test (RMET): a systematic review and meta-regression.

The reading the mind in the eyes test (RMET) - which assesses the theory of mind component of social cognition - is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91-20.60) in patients and 25.53 (95% CI 25.19-25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score - RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning.