Research on the cascading mechanism of "urban built environment-air pollution-respiratory diseases": a case of Wuhan city.

Background: Most existing studies have only investigated the direct effects of the built environment on respiratory diseases. However, there is mounting evidence that the built environment of cities has an indirect influence on public health via influencing air pollution. Exploring the "urban built environment-air pollution-respiratory diseases" cascade mechanism is important for creating a healthy respiratory environment, which is the aim of this study. Methods: The study gathered clinical data from 2015 to 2017 on patients with respiratory diseases from Tongji Hospital in Wuhan. Additionally, daily air pollution levels (sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter (PM2.5, PM10), and ozone (O3)), meteorological data (average temperature and relative humidity), and data on urban built environment were gathered. We used Spearman correlation to investigate the connection between air pollution and meteorological variables; distributed lag non-linear model (DLNM) was used to investigate the short-term relationships between respiratory diseases, air pollutants, and meteorological factors; the impacts of spatial heterogeneity in the built environment on air pollution were examined using the multiscale geographically weighted regression model (MGWR). Results: During the study period, the mean level of respiratory diseases (average age 54) was 15.97 persons per day, of which 9.519 for males (average age 57) and 6.451 for females (average age 48); the 24 h mean levels of PM10, PM2.5, NO2, SO2 and O3 were 78.056 µg/m3, 71.962 µg/m3, 54.468 µg/m3, 12.898 µg/m3, and 46.904 µg/m3, respectively; highest association was investigated between PM10 and SO2 (r = 0.762, p < 0.01), followed by NO2 and PM2.5 (r = 0.73, p < 0.01), and PM10 and PM2.5 (r = 0.704, p < 0.01). We observed a significant lag effect of NO2 on respiratory diseases, for lag 0 day and lag 1 day, a 10 µg/m3 increase in NO2 concentration corresponded to 1.009% (95% CI: 1.001, 1.017%) and 1.005% (95% CI: 1.001, 1.011%) increase of respiratory diseases. The spatial distribution of NO2 was significantly influenced by high-density urban development (population density, building density, number of shopping service facilities, and construction land, the bandwidth of these four factors are 43), while green space and parks can effectively reduce air pollution (R2 = 0.649). Conclusion: Previous studies have focused on the effects of air pollution on respiratory diseases and the effects of built environment on air pollution, while this study combines these three aspects and explores the relationship between them. Furthermore, the theory of the "built environment-air pollution-respiratory diseases" cascading mechanism is practically investigated and broken down into specific experimental steps, which has not been found in previous studies. Additionally, we observed a lag effect of NO2 on respiratory diseases and spatial heterogeneity of built environment in the distribution of NO2.

Predicting left ventricular remodeling post-MI through coronary physiological measurements based on computational fluid dynamics.

Early detection of left ventricular remodeling (LVR) is crucial. While cardiac magnetic resonance (CMR) provides valuable information, it has limitations. Coronary angiography-derived fractional flow reserve (caFFR) and index of microcirculatory resistance (caIMR) offer viable alternatives. 157 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention were prospectively included. 23.6% of patients showed LVR. Machine learning algorithms constructed three LVR prediction models: Model 1 incorporated clinical and procedural parameters, Model 2 added CMR parameters, and Model 3 included echocardiographic and functional parameters (caFFR and caIMR) with Model 1. The random forest algorithm showed robust performance, achieving AUC of 0.77, 0.84, and 0.85 for Models 1, 2, and 3. SHAP analysis identified top features in Model 2 (infarct size, microvascular obstruction, admission hemoglobin) and Model 3 (current smoking, caFFR, admission hemoglobin). Findings indicate coronary physiology and echocardiographic parameters effectively predict LVR in patients with STEMI, suggesting their potential to replace CMR.

Fusion-driven cutaneous and superficial mesenchymal and adnexal tumors-A clinicopathologic and molecular study of 15 cases, including a novel case of ACTB::ZMIZ2-rearranged adnexal carcinoma.

BACKGROUND: While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology. AIMS: Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms. MATERIALS & METHODS: Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained. RESULTS: Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1-83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1). DISCUSSION AND CONCLUSION: Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.

Cutaneous Malignant Mixed Tumor With Pulmonary Metastasis: A Case Report and Literature Review.

BACKGROUND: Cutaneous malignant mixed tumor (MMT) is a rare sweat gland-derived tumor characterized by admixed malignant epithelial cells and chondromyxoid stroma. Approximately 50 cases have been described in the literature. Metastasis, which may occur in more than one-third of cases, is most common in the lung. METHODS: We summarized the clinicopathologic features of a patient with cutaneous MMT metastatic to the lungs. A literature review of similar cases was completed using Web of Science, Scopus, and PubMed databases. RESULTS: A woman in her 70s presented with an enlarging mass on her left eyebrow; histopathologic examination showed large islands of atypical cells with increased mitotic activity, admixed with necrosis on a background of fibrotic and chondromyxoid stroma. Multiple lung nodules were identified during follow-up. Examination of a pulmonary core needle biopsy specimen was consistent with metastatic cutaneous MMT. Literature review identified 10 cases published between 1980 and 2017. Most primary tumors were large (≥4 cm). Local recurrence was uncommon, and the lung was the only metastatic site in 5 cases. Histopathologically, metastatic tumors were described as more cellular, with diminished stromal tissue compared with the primary lesion. CONCLUSION: This is 1 of the 11 reports of cutaneous MMT with metastasis to the lungs found in the English-language literature published after 1980. Of note, most reports were published before 1990, making this case study one of the few contemporary descriptions of cutaneous MMT with pulmonary metastases. We think that the present case report will increase the awareness of this rare tumor.

Primary melanoma of the nipple: Report of 10 cases including coexistence with Paget's disease.

Primary melanoma of the nipple (PMN) is exceedingly rare, with only single cases reported to date. We identified 10 patients with PMN: 5 females, 5 males, median age 55.5 years (range 29-66) at diagnosis of melanoma in situ (4 cases) or invasive melanoma (6 cases, Breslow depth 0.2 mm to 3.5 mm). Follow-up was available for all 10 patients (median 19 months, range 1-183). Nine patients had no evidence of disease; one patient died of disease (13.5 months) after presenting with a nodal metastasis. One case was exceptional, because the patient presented with a pigmented lesion that histopathologically exhibited co-existence of melanoma in situ and Paget disease, a challenging differential diagnosis due to immunohistochemical pitfalls in distinction between melanoma in situ and the pigmented variant of mammary Paget disease. Here we report the second largest series of PMN including a case of PMN colliding with mammary Paget disease, to raise awareness of these rare malignancies.

Glycemic Status and Myocardial Strain by Cardiac MRI in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: It is uncertain how various degree of glycemic status affect left ventricular (LV) myocardial strain in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). PURPOSE: To investigate the relationship of glycemic status and myocardial strain in STEMI patients. STUDY TYPE: Prospective cohort study. POPULATION: 282 STEMI patients with cardiac magnetic resonance imaging 5 ± 2 days post-PPCI. Patients were divided into three groups based on the level of glycated hemoglobin A1c (HbA1c) (group 1: HbA1c < 5.7%; group 2: 5.7% ≤ HbA1c < 6.5%; group 3: HbA1c ≥ 6.5%). FIELD STRENGTH/SEQUENCE: 3.0-T; late gadolinium enhancement, balanced steady-state free precession cine sequence, black blood fat-suppressed T2-weighted. ASSESSMENT: LV function, myocardial strain, and infarct characteristics (infarct size, microvascular obstruction, and intramyocardial hemorrhage) were compared among the three groups by one-way analysis of variance (ANOVA) or Wilcoxon rank sum test. Intraobserver and interobserver reproducibility of LV myocardial strain was evaluated. STATISTICAL TESTS: ANOVA or Wilcoxon rank sum test, Pearson chi-square or Fisher's exact test, Spearman's correlation analyses and multivariable linear regression analysis. A two-tailed P value <0.05 was considered statistically significant. RESULTS: Infarct characteristics were similar among the three groups (P = 0.934, P = 0.097, P = 0.533, respectively). Patients with HbA1c ≥ 6.5% had decreased LV myocardial strain compared with HbA1c 5.7%-6.4%, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strain. However, no significant differences in myocardial strain were observed between patients with HbA1c 5.7%-6.4% and HbA1c < 5.7% (P = 0.716; P = 0.294; P = 0.883, respectively). After adjustment for confounders, HbA1c as a continuous variable (beta coefficient [ß] = -0.676; ß = 0.172; ß = 0.205, respectively) and HbA1c ≥ 6.5% (ß = -3.682; ß = 0.552; ß = 0.681, respectively) were both independently associated with decreased GRS, GCS, and GLS. DATA CONCLUSION: Patients with uncontrolled blood glucose (categorized in group HbA1c ≥ 6.5%) had worse myocardial strain. The level of HbA1c appeared to be independently associated with decreased myocardial strain in STEMI patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Ductal Carcinoma Arising in a Squamous Epithelial Inclusion Cyst within an Axillary Lymph Node: A Challenging Nodal Metastasis.

Introduction. Assessment of axillary lymph nodes in breast carcinoma is an important part of staging to guide appropriate clinical management. Lymph node inclusions of different types, including nevoid, squamous, and glandular, are rare but have been reported in multiple different anatomic locations including the axilla. These can result in diagnostic challenges and pose risks of misdiagnoses. Rarely, malignancies may arise intrinsic to otherwise incidental benign nodal inclusions. Case Presentation. We report a case of ductal carcinoma diagnosed within a squamous epithelial inclusion cyst within an axillary lymph node in a patient with pure ductal carcinoma in situ (DCIS) of the ipsilateral right breast. To our knowledge, this is the fifth report in the literature of breast carcinoma confirmed within an axillary inclusion in a patient with pure DCIS. Evaluation of the primary DCIS and lymph node inclusions, by routine and immunohistochemical stains, was performed for assessment. Discussion. The presence of lymph node inclusions can pose a challenge in assessment of benignity and malignancy, on frozen and permanent histologic sections. Pathologists should carefully evaluate lymph node inclusions to ensure that intrinsic malignancies are not missed within rare otherwise benign appearing incidental epithelial rests.

Assessment of PD-L1, TROP2, and nectin-4 expression in penile squamous cell carcinoma.

OBJECTIVES: There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers include programmed death-ligand 1 (PD-L1), trophoblast cell-surface antigen 2 (TROP2), and nectin-4; however, there is a paucity of data pertaining to these biomarkers. Herein, we investigated the expression of PD-L1, TROP2, and nectin-4 in a well-annotated cohort of pSCCs. METHODS: A single-institution pathology archive was queried for patients who had a partial or total penectomy for pSCC between January 2000 and December 2022. Whole-slide sections were stained with antibodies against PD-L1 (22C3), TROP2, and nectin-4. Expression in tumor cells was quantified using H-scores (0-300). Associations between IHC expression, human papilloma virus (HPV) status, clinicopathologic findings, and outcome parameters were evaluated. RESULTS: This study included 121 patients. For PD-L1, the median combined positive and H-scores were 1 and 0, respectively; 32.7 % of the cases had an H-score>0. Compared to PD-L1-negative tumors, PD-L1-positive tumors had higher pT stage and grade. The median TROP2 and nectin-4 H-scores were 230 and 140, respectively, with high TROP2 and nectin-4, defined by an H-score>200, noted in 80.7 % and 10.9 % of cases, respectively. High-risk HPV-positive cases had higher TROP2 and nectin-4 scores compared to HPV-negative cases. Patients with high TROP2 expression had significantly more disease progression, and patients with high nectin-4 expression had significantly fewer deaths due to disease. CONCLUSIONS: High expression of TROP2 and nectin-4 in pSCC support evaluation of these markers as therapeutic targets pending validation of our findings.

Association Between Obstructive Sleep Apnea and Cardiovascular Events in Acute Coronary Syndrome Patients With or Without Revascularization　- A Prospective Cohort Study.

BACKGROUND: The effects of obstructive sleep apnea (OSA) on the prognosis of acute coronary syndrome (ACS) without revascularization remain unclear, so the aim of the present study was to elucidate the association of OSA with subsequent cardiovascular events in ACS patients with and without revascularization.Methods and Results: We prospectively recruited hospitalized ACS patients undergoing sleep monitoring between June 2015 and January 2020. OSA was defined as an apnea-hypopnea index ≥15 events/h. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Among 1,927 patients, 52.6% had OSA and 69.4% underwent revascularization. During a 2.9-year follow-up (1.5-3.6 years), the risk of MACCE was similar in patients with or without revascularization. OSA was an independent predictor of MACCE in the non-revascularization group (22.6% vs. 14.6%; hazard ratio (HR) 1.861; 95% confidence interval (CI) 1.239-2.796; P=0.003) but not in revascularization group (22.3% vs. 19.3%; HR 1.135; 95% CI 0.882-1.460; P=0.324). The incremental risk in the non-revascularization group was attributable to more hospitalizations for unstable angina (14.2% vs. 8.6%; HR 1.896; 95% CI 1.124-3.199; P=0.016). CONCLUSIONS: For patients with ACS, OSA was independently associated with higher risk of recurrent cardiovascular events among patients without revascularization but not among patients undergoing revascularization. The benefits of suitable OSA treatment for patients without revascularization need further investigation.

An Unexpected Diagnosis Uncovered by Quantitative Molecular Findings: A Case Report.

A 74-year-old male presented with rectal pain; workup uncovered an anal mass, and a diagnosis of melanoma was rendered via histologic examination and immunohistochemical (IHC) studies. Droplet digital PCR (ddPCR)-based BRAF testing was performed and revealed the presence of BRAF V600E, which is a common targetable genetic alteration in melanoma. Interestingly, the ratio of mutant to wild-type copy number was low (0.3%), whereas tumor cell percentage on tissue slides was 90%. With additional workup, BRAF V600E IHC confirmed a very small subset of BRAF V600E-positive cells, and a next-generation sequencing (NGS) panel revealed a pathogenic KIT variant, p.L576P, with an allele frequency of 63%. It was initially hypothesized that the main driver of the melanoma was the KIT alteration, whereas a small subclone (not detected by NGS, which has a 5% limit of detection) was driven by the BRAF V600E detected by ddPCR. To determine whether there were morphologic differences between the 2 clones, a careful review of the histology was performed and revealed distinct morphology of the BRAF V600E-positive cells, including pale cytoplasm, nuclear grooves, and infiltrating eosinophils. Additional IHC workup of the BRAF V600E-positive cells showed coexpression of CD1a, Langerin, and S100, diagnostic of Langerhans cell histiocytosis (LCH). This diagnosis was unexpected and would have been missed without highly sensitive molecular testing; yet it is of clinical importance for the patient. This case raises interesting biology questions regarding the relationship between melanoma and LCH; moreover, it highlights the importance of integrating quantitative information in molecular data interpretation.

Eosinophils in metastatic melanoma.

The potential significance of tissue eosinophils melanomas is unknown. We strove to determine a potential association between the presence of tissue eosinophils and prognosis of patients with metastatic melanoma (MM). A retrospective electronic data base was queried to identify patients (age ≥18 years) evaluated January 1, 2011-October 1, 2022 (inclusive) at our multi-site medical center, who had metastatic melanoma and at least 1 biopsy of melanoma or a melanocytic nevus that was reported to show eosinophils. Patient demographics, histopathological tumor features, AJCC classification parameters, and peripheral blood eosinophilia (PBE) obtained during the patients' routine care were recorded. Seven patients met inclusion criteria had checkpoint inhibitor therapy for MM; 4/7 had prominent eosinophil infiltrates among their melanocytic nevi or/and melanomas, and all had absent or less than predicted tumor progression. In our small cohort of patients undergoing immunotherapy for metastatic melanoma, the presence of tissue eosinophils among nevi or melanomas was associated with a favorable response. While lymphocytes have been considered key in the host response to melanoma, the role of eosinophils may be underappreciated.

A graph-based genome and pan-genome variation of the model plant Setaria.

Setaria italica (foxtail millet), a founder crop of East Asian agriculture, is a model plant for C4 photosynthesis and developing approaches to adaptive breeding across multiple climates. Here we established the Setaria pan-genome by assembling 110 representative genomes from a worldwide collection. The pan-genome is composed of 73,528 gene families, of which 23.8%, 42.9%, 29.4% and 3.9% are core, soft core, dispensable and private genes, respectively; 202,884 nonredundant structural variants were also detected. The characterization of pan-genomic variants suggests their importance during foxtail millet domestication and improvement, as exemplified by the identification of the yield gene SiGW3, where a 366-bp presence/absence promoter variant accompanies gene expression variation. We developed a graph-based genome and performed large-scale genetic studies for 68 traits across 13 environments, identifying potential genes for millet improvement at different geographic sites. These can be used in marker-assisted breeding, genomic selection and genome editing to accelerate crop improvement under different climatic conditions.

Coronary angiography-derived index of microcirculatory resistance and evolution of infarct pathology after ST-segment-elevation myocardial infarction.

AIMS: This study sought to evaluate the association of coronary angiography-derived index of microcirculatory resistance (angio-IMR) measured after primary percutaneous coronary intervention (PPCI) with the evolution of infarct pathology during 3-month follow-up after ST-segment-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Patients with STEMI undergoing PPCI were prospectively enrolled between October 2019 and August 2021. Angio-IMR was calculated using computational flow and pressure simulation immediately after PPCI. Cardiac magnetic resonance (CMR) imaging was performed at a median of 3.6 days and 3 months. A total of 286 STEMI patients (mean age 57.8 years, 84.3% men) with both angio-IMR and CMR at baseline were included. High angio-IMR (>40 U) occurred in 84 patients (29.4%) patients. Patients with angio-IMR >40 U had a higher prevalence and extent of MVO. An angio-IMR >40 U was a multivariable predictor of infarct size with a three-fold higher risk of final infarct size >25% (adjusted OR 3.00, 95% CI 1.23-7.32, P = 0.016). Post-procedure angio-IMR >40 U significantly predicted presence (adjusted OR 5.52, 95% CI 1.65-18.51, P = 0.006) and extent (beta coefficient 0.27, 95% CI 0.01-0.53, P = 0.041) of myocardial iron at follow-up. Compared with patients with angio-IMR ≤40 U, those with angio-IMR >40 U had less regression of infarct size and less resolution of myocardial iron at follow-up. CONCLUSIONS: Angio-IMR immediately post-PPCI showed a significant association with the extent and evolution of infarct pathology. An angio-IMR >40 U indicated extensive microvascular damage with less regression of infarct size and more persistent iron at follow-up.

Surfactants Improving the Wetting Behavior and Adhesion Mechanism of Pesticide Dilution Droplets on Jujube Leaf Surfaces.

Fruit tree leaves have different chemical compositions and diverse wax layer structures that result in different patterns of wetting and pesticide solution spreading on their surface. Fruit development is a time when pests and diseases occur, during which a large number of pesticides are needed. The wetting and diffusion properties of pesticide droplets on fruit tree leaves were relatively poor. To solve this problem, the wetting characteristics of leaf surfaces with different surfactants were studied. The contact angle, surface tension, adhesive tension, adhesion work, and solid-liquid interfacial tension of five surfactant solution droplets on jujube leaf surfaces during fruit growth were studied by the sessile drop method. C12E5 and Triton X-100 have the best wetting effects. Two surfactants were added to a 3% beta-cyfluthrin emulsion in water, and field efficacy tests were carried out on peach fruit moths in a jujube orchard at different dilutions. The control effect is as high as 90%. During the initial stage when the concentration is low, due to the surface roughness of the leaves, the surfactant molecules adsorbed at the gas-liquid and solid-liquid interfaces reach an equilibrium, and the contact angle on the leaf surface changes slightly. With increasing surfactant concentration, the pinning effect in the spatial structure on the leaf surface is overcome by liquid droplets, thereby significantly decreasing the contact angle. When the concentration is further increased, the surfactant molecules form a saturated adsorption layer on the leaf surface. Due to the existence of a precursor water film in the droplets, surfactant molecules on the interface continuously move to the water film on the surface of jujube tree leaves, thus causing interactions between the droplets and the leaves. The conclusion of this study provides theoretical guidance for the wettability and adhesion of pesticides on jujube leaves, so as to achieve the purpose of reducing pesticide use and improving pesticide efficacy.

Proteomic and Clinicopathologic Assessment of Penile Amyloidosis: A Single Institutional Review of 12 Cases.

OBJECTIVES: There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings. METHODS: Since 2008, our reference laboratory has performed liquid chromatography/tandem mass spectrometry (LC-MS/MS) for amyloid typing. The institutional pathology archive and reference laboratory database were queried to retrospectively identify all penile surgical pathology specimens with LC-MS/MS results between January 1, 2008, and November 23, 2022. Archived H&E-stained and Congo red-stained sections were re-reviewed. RESULTS: Twelve cases of penile amyloidosis were identified, which represented 0.35% (n = 3,456) of penile surgical specimens. AL-type amyloid was most frequent (n = 7), followed by keratin-type amyloid (n = 3) and ATTR (transthyretin)-type amyloid (n = 2). AL-type amyloid cases often showed diffuse dermal/lamina propria deposition, whereas all keratin-type amyloid cases were localized to the superficial dermis. Two cases with keratin-type amyloid had concomitant cutaneous findings (penile intraepithelial neoplasia and condyloma). CONCLUSIONS: This series, the largest to date, demonstrates that penile amyloidosis has a heterogeneous proteomic landscape. To the best of our knowledge, this is the first study describing ATTR (transthyretin)-type penile amyloid.

Multiplex Immunofluorescence Image Quality Checking Using DAPI Channel-referenced Evaluation.

Multiplex immunofluorescence (MxIF) images provide detailed information of cell composition and spatial context for biomedical research. However, compromised data quality could lead to research biases. Comprehensive image quality checking (QC) is essential for reliable downstream analysis. As a reliable and specific staining of cell nuclei, 4',6-diamidino-2-phenylindole (DAPI) signals were used as references for tissue localization and auto-focusing across MxIF staining-scanning-bleaching iterations and could potentially be reused for QC. To confirm the feasibility of using DAPI as QC reference, pixel-level DAPI values were extracted to calculate signal fluctuations and tissue content similarities in staining-scanning-bleaching iterations for identifying quality issues. Concordance between automatic quantification and human experts' annotations were evaluated on a data set consisting of 348 fields of view (FOVs) with 45 immune and tumor cell markers. Cell distribution differences between subsets of QC-pass vs QC-failed FOVs were compared to investigate the downstream effects. Results showed that 87.3% FOVs with tissue damage and 73.4% of artifacts were identified. QC-failed FOVs showed elevated regional gathering in cellular feature space compared with the QC-pass FOVs. Our results supported that DAPI signals could be used as references for MxIF image QC, and low-quality FOVs identified by our method must be cautiously considered for downstream analyses.

Prognostic Implications of OSA in Acute Coronary Syndrome by Obesity Status.

BACKGROUND: A close relationship exists between OSA and obesity. The impact of obesity on the prognostic significance of OSA in patients with acute coronary syndrome (ACS) remains unclear. RESEARCH QUESTION: Do the effects of OSA on subsequent cardiovascular events in patients with ACS vary with obesity status? STUDY DESIGN AND METHODS: This is a prospective cohort study. Patients 18 to 85 years of age who were hospitalized for ACS were consecutively enrolled and underwent portable sleep monitoring after clinical stabilization. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary end point was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, hospitalization for ACS, stroke, ischemia-driven revascularization, or hospitalization for heart failure. RESULTS: Among 1,920 patients enrolled (84.5% male; mean age ± SD, 56.4 ± 10.5 years), 1,013 (52.8%) had OSA, and 718 (37.4%) were obese (BMI ≥ 28 kg/m2). During 2.9 years (1.5, 3.6 years) follow-up, the incidence of MACCE was significantly higher in patients with obesity than in patients without obesity (hazard ratio [HR], 1.29; 95% CI, 1.06-1.58; P = .013). Although the prevalence of OSA was lower in patients without obesity than in those with obesity (43.9% vs 67.5%; P < .001), OSA independently predicted the incidence of MACCE only in patients without obesity (adjusted HR, 1.34; 95% CI, 1.03-1.75; P = .03), but not in patients with obesity (adjusted HR, 1.10; 95% CI, 0.78-1.55; P = .58). No significant interaction between obesity and OSA was noted (P for interaction = .35). The incremental risk associated with OSA in patients without obesity might be explained by more hospitalization for ACS and ischemia-driven revascularization. INTERPRETATION: For patients with ACS, OSA was independently associated with an increased risk of subsequent events, particularly among patients without obesity. These findings highlight the importance of identifying OSA in nonobese patients with ACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03362385; URL: www. CLINICALTRIALS: gov.