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Every day, we learn about others’ decisions from various sources. We perceive some of these decisions as choices and others as rejections. Does the mere perception of another’s decision as a choice versus as a rejection influence our own behavior? Are we more likely to conform to another’s decision if we view it in one way or the other? The current research investigates the social influence of decision frames. Eight studies, including a field study conducted during a livestreaming event hosted by an influencer with over 1.5 million followers, find that people are more likely to conform to another’s decision if it is perceived as a rejection than if it is perceived as a choice. This effect happens because consumers are more likely to attribute another’s decision to product quality as opposed to personal preference, when consumers perceive another’s decision as a rejection than as a choice. The inference about quality versus personal preference in turn increases conformity. This research bridges the existing literatures on decision framing, social influence, and perceptions of quality and personal preference, and it offers important implications for marketers and influencers.

A tokamak relies on the axisymmetric magnetic fields to confine fusion plasmas and aims to deliver sustainable and clean energy. However, misalignments arise inevitably in the tokamak construction, leading to small asymmetries in the magnetic field known as error fields (EFs). The EFs have been a major concern in the tokamak approaches because a small level EFs, even less than 0.1 %, can drive a plasma disruption. Contrary to conventional wisdom, we report that the EFs in a tokamak can be favorably used for controlling plasma instabilities, such as edge-localized modes (ELMs), while maintaining a hot fusion plasma at a temperature of 100 million kelvin. A novel optimization tailors the EFs to maintain an edge 3D response for ELM control with a minimized core 3D response to avoid plasma disruption and unnecessary degradation. We design and demonstrate such an edge-localized 3D response at the Korean Superconducting Tokamak Advanced Research facility, benefiting from its unique flexibility to change many degrees of freedom in the 3D coil space for the various fusion plasma regimes. This favorable control of the tokamak EF represents a notable advance for designing intrinsically 3D tokamaks to optimize stability and confinement for the next-step fusion reactors.

Migraine is a neurovascular disorder that affects approximately 12% of the global population. While its exact causes are still being studied, researchers believe that nociceptors in the trigeminal ganglia play a key role in the pain signals of migraine. These nociceptors innervate the intracranial meninges and convey pain signals from the meninges to the thalamus. Targeting these nociceptors is considered promising due to their accessibility and distinct molecular profile, which includes the expression of several transient receptor potential (TRP) channels. These channels have been linked to various pain conditions, including migraine. This review discusses the role and mechanisms of nociceptors in migraine, the challenges of current antimigraine drugs, and the evidence for well-studied and emerging TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.

Transforming growth factor-β-activated kinase 1 (TAK1), which is highly expressed and aberrantly activated in triple-negative breast cancer (TNBC), plays a pivotal role in metastasis and progression. This makes it a potential therapeutic target for TNBC. Previously, we reported lectin galactoside-binding soluble 3 binding protein (LGALS3BP) as a negative regulator of TAK1 signaling in the inflammatory response and inflammation-associated cancer progression. However, the role of LGALS3BP and its molecular interaction with TAK1 in TNBC remain unclear. This study aimed to investigate the function and underlying mechanism of action of LGALS3BP in TNBC progression and determine the therapeutic potential of nanoparticle-mediated delivery of LGALS3BP in TNBC. We found that LGALS3BP overexpression suppressed the overall aggressive phenotype of TNBC cells in vitro and in vivo. LGALS3BP inhibited TNF-α-mediated gene expression of matrix metalloproteinase 9 (MMP9), which encodes a protein crucial for lung metastasis in TNBC patients. Mechanistically, LGALS3BP suppressed TNF-α-mediated activation of TAK1, a key kinase linking TNF-α stimulation and MMP9 expression in TNBC. Nanoparticle-mediated delivery enabled tumor-specific targeting and inhibited TAK1 phosphorylation and MMP9 expression in tumor tissues, suppressing primary tumor growth and lung metastasis in vivo. Our findings reveal a novel role of LGALS3BP in TNBC progression and demonstrate the therapeutic potential of nanoparticle-mediated delivery of LGALS3BP in TNBC.

Supplementary Figure S1. Transcriptomic analyses for molecular subtypes Supplementary Figure S2. Identification of the subtypes in LUSC TCGA cohort (n=431) Supplementary Figure S3. The genomic difference across subtypes in LUSC. Supplementary Figure S4. Estimation of Stromal and immune score and distribution of infiltrating immune cells for tumor and noncancer control sample in LUSC Supplementary Figure S5. The immune landscape and micro-environmental signature in LUSC TCGA cohort (n=431) Supplementary Figure S6. The dual roles of stroma are described by distinct gene expression patterns in tumor(subtype A and B) and noncancer control samples. Supplementary Figure S7. Distribution of infiltrating immune cells for tumor and noncancer control sample in LUSC Supplementary Figure S8. Distinct expression pattern of M1 and M2 signature genes in LUSC subtypes Supplementary Figure S9. Comparison of immune contents between subtypes in our LUSC cohort (n=101) and TCGA LUSC cohort (n=431) Supplementary Figure S10. Immune related pathways enriched for genes which have copy number variants. Supplementary Figure S11. Comparison of the LUSC expression subtypes with the previously defined subtypes Supplementary Figure S12. Clinical association analysis across subtypes Supplementary Figure S13. Survival analysis across subtypes

The clinical features of 101 LUSC patients enrolled in this study.

The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples. We used the information to predict subtype-specific interactions within the LUSC microenvironment and to connect genomic alterations with immune signatures. Hierarchical clustering based on gene expression and mutational profiling revealed subtypes that were either immune defective or immune competent. We analyzed infiltrating stromal and immune cells to further characterize the tumor microenvironment. Elevated expression of macrophage 2 signature genes in the immune competent subtype confirmed that tumor-associated macrophages (TAM) linked inflammation and mutation-driven cancer. A negative correlation was evident between the immune score and the amount of somatic copy-number variation (SCNV) of immune genes (r = −0.58). The SCNVs showed a potential detrimental effect on immunity in the immune-deficient subtype. Knowledge of the genomic alterations in the tumor microenvironment could be used to guide design of immunotherapy options that are appropriate for patients with certain cancer subtypes. Cancer Immunol Res; 6(7); 848–59. ©2018 AACR.

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Purpose:The plasticity of innate lymphoid cells (ILCs) has been reported in vitro and in the microenvironment of the intestine. However, whether ILC plasticity contributes to regulation of the tumor microenvironment remains unknown. In this study, we explored plasticity of ILCs in human lung cancer.Experimental Design:We analyzed immune subsets and cytokine expression in lung cancers freshly obtained from 80 patients and explored conversion of ILC1 into ILC3 in coculture with lung cancer cells. Prognostic effects of converted ILC3 and related pathway were evaluated by retrospective cohort composed of 875 patients with lung cancer.Results:Low percentages of ILC1, and high percentages of ILC3 were found in pulmonary squamous cell carcinomas (SqCC) but not adenocarcinomas (ADC). In non–small-cell lung cancers, the percentage of ILC3 was associated with IL23 expression in tumor cells but not immune cells. In cocultures, tumor cells of SqCCs converted ILC1 into ILC3 by producing IL23, thus promoting IL17-mediated tumor cell proliferation. Consistently, among IL17+ immune cells, the percentages of ILCs were higher in SqCCs than ADCs. Furthermore, the numbers of CD3−RORγt+ ILC3, IL17 expression level, and IL23- or IL17RA-expressing tumor cells were associated with short survival of patients with SqCC but not ADC.Conclusions:Conversion from ILC1 into ILC3 by IL23-producing SqCCs promotes IL17-mediated tumor progression, resulting in a poor prognosis.

ROC curves of each center in the prospective comparison cohort

Supplementary file

Supplementary Materials and Methods

Purpose:Nodule evaluation is challenging and critical to diagnose multiple pulmonary nodules (MPNs). We aimed to develop and validate a machine learning–based model to estimate the malignant probability of MPNs to guide decision-making.Experimental Design:A boosted ensemble algorithm (XGBoost) was used to predict malignancy using the clinicoradiologic variables of 1,739 nodules from 520 patients with MPNs at a Chinese center. The model (PKU-M model) was trained using 10-fold cross-validation in which hyperparameters were selected and fine-tuned. The model was validated and compared with solitary pulmonary nodule (SPN) models, clinicians, and a computer-aided diagnosis (CADx) system in an independent transnational cohort and a prospective multicentric cohort.Results:The PKU-M model showed excellent discrimination [area under the curve; AUC (95% confidence interval (95% CI)), 0.909 (0.854–0.946)] and calibration (Brier score, 0.122) in the development cohort. External validation (583 nodules) revealed that the AUC of the PKU-M model was 0.890 (0.859–0.916), higher than those of the Brock model [0.806 (0.771–0.838)], PKU model [0.780 (0.743–0.817)], Mayo model [0.739 (0.697–0.776)], and VA model [0.682 (0.640–0.722)]. Prospective comparison (200 nodules) showed that the AUC of the PKU-M model [0.871 (0.815–0.915)] was higher than that of surgeons [0.790 (0.711–0.852), 0.741 (0.662–0.804), and 0.727 (0.650–0.788)], radiologist [0.748 (0.671–0.814)], and the CADx system [0.757 (0.682–0.818)]. Furthermore, the model outperformed the clinicians with an increase of 14.3% in sensitivity and 7.8% in specificity.Conclusions:After its development using machine learning algorithms, validation using transnational multicentric cohorts, and prospective comparison with clinicians and the CADx system, this novel prediction model for MPNs presented solid performance as a convenient reference to help decision-making.

Supplementary Figures and Table

Background: Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head shaking. Approximately 2.1% of chickens died or were culled due to severe symptoms. Five carcasses were submitted to the Avian Disease Division of the Animal and Plant Quarantine Agency (APQA) for disease diagnosis. Results: Broilers displayed severe pericarditis and perihepatitis associated with gross lesions. Broilers also displayed microscopic lesions in the cerebrum and in the granular layer of the cerebellum, which were associated with multifocal perivascular cuffing and purulent necrosis in the cerebrum, and severe meningitis with heterophil and lymphocyte infiltration. Staphylococcus spp. were identified in the liver and heart using bacteriological culture. PCR/RT-PCR assays revealed that broilers were negative for avian Clostridium botulinum, Newcastle disease virus, and avian encephalomyelitis virus. Bacterial and viral metagenomic analysis of brain samples revealed the presence of Pseudomonas spp. and Marek’s disease virus, which are known etiological agents of chicken meningoencephalitis. Conclusions: This study reports a diagnostic analysis of gross and histopathological lesions from 32-day-old broilers displaying unique neurological symptoms that revealed the presence of the several neurological diseases including meningoencephalitis.

Background Chronic kidney disease (CKD) has a significant impact on global health. Studies have shown that subclinical thyroid dysfunction may be related to CKD, but the association between subclinical thyroid dysfunction and CKD in the general population is unclear. We aimed to evaluate the risk of CKD according to thyroid function status in a large cohort. Methods We analyzed data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 3,257 participants aged ≥ 19 years who underwent thyroid and kidney function assessments were included in this study. CKD was defined as an estimated glomerular filtration rate 2 and/or urine albumin-creatinine ratio ≥ 30 mg/g. The risk of CKD according to thyroid function status was assessed using logistic regression, adjusted for potential confounders. Results Overall, 6.7% of the participants had CKD. There were no significant differences in thyroid-stimulating hormone and free thyroxine levels between the groups with and without CKD. The proportion of participants with CKD was significantly different among the thyroid function status groups (p = 0.012) and tended to increase significantly in the following order: subclinical hyperthyroidism (1.5%), euthyroidism (6.6%), and subclinical hypothyroidism (12.6%) (p for trend Conclusion Subclinical hypothyroidism is an independent predictor of CKD in the general population.

Background Recently, diastolic stress testing and invasive hemodynamic measurements have been emphasized for diagnosis of heart failure with preserved ejection fraction (HFpEF) because when determined using noninvasive parameters it can fall into a nondiagnostic intermediate range. The current study evaluated the discriminative and prognostic roles of invasive measured left ventricular end‐diastolic pressure in the population with suspected HFpEF, particularly for patients with intermediate Heart Failure Association Pre‐test Assessment, Echocardiography & Natriuretic Peptide, Functional Testing, Final Etiology (HFA‐PEFF) score. Methods and Results A total of 404 patients with symptoms or signs of HF and preserved left ventricular systolic function were enrolled. All subjects underwent left heart catheterization with left ventricular end‐diastolic pressure measurement for confirmation of HFpEF (≥16 mm Hg). The primary outcome was all‐cause death or readmission due to HF within 10 years. Among the study population, 324 patients (80.2%) were diagnosed as invasively confirmed HFpEF, and 80 patients (19.8%) were as noncardiac dyspnea. The patients with HFpEF showed a significantly higher HFA‐PEFF score than the patients with noncardiac dyspnea (3.8±1.8 versus 2.6±1.5, P P P P =0.030). Conclusions The HFA‐PEFF score is a moderately useful tool for predicting future adverse events in suspected HFpEF, and invasively measured left ventricular end‐diastolic pressure can provide additional information to discriminate patient prognosis, particularly in those with intermediate HFA‐PEFF scores. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04505449.

Cooperativity is used by living systems to circumvent energetic and entropic barriers to yield highly efficient molecular processes. Cooperative structural transitions involve the concerted displacement of molecules in a crystalline material, as opposed to typical molecule-by-molecule nucleation and growth mechanisms which often break single crystallinity. Cooperative transitions have acquired much attention for low transition barriers, ultrafast kinetics, and structural reversibility. However, cooperative transitions are rare in molecular crystals and their origin is poorly understood. Crystals of 2-dimensional quinoidal terthiophene (2DQTT-o-B), a high-performance n-type organic semiconductor, demonstrate two distinct thermally activated phase transitions following these mechanisms. Here we show reorientation of the alkyl side chains triggers cooperative behavior, tilting the molecules like dominos. Whereas, nucleation and growth transition is coincident with increasing alkyl chain disorder and driven by forming a biradical state. We establish alkyl chain engineering as integral to rationally controlling these polymorphic behaviors for novel electronic applications.

BackgroundLimited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations.MethodsThis is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity.Results1,383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32 – 1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70 – 6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83 – 12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63 – 3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20 – 2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66 – 3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89 – 22.6]). Hispanic ethnicity, timing and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status.ConclusionsUsing one of the largest registries on cancer and COVID-19, we identified patient and BC related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to Non-Hispanic White patients.FundingThis study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L. Warner; P30-CA046592 to Christopher R. Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K. Shah and Dimpy P. Shah; and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P. Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication.Clinical Trial NumberCCC19 registry is registered on ClinicalTrials.gov,NCT04354701.

Introduction: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness on postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (>70 years) who underwent bipolar hemiarthroplasty (BHA). Methods: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: patient-controlled analgesia (PCA) group (n=132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n=99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin (Hb), length of hospital stay, and total morphine usage after surgery. Results: Postoperative resting VAS at 6 hours and 48 hours was significantly lower in the PNB+PCA group compared with the PCA group (p=0.075, p=0.0318, respectively). However, there was no significant difference in either resting VAS at 24 hours or active VAS. Complications of pneumonia and delirium until one month postoperative were significantly lower in the PNB + PCA group than the PCA group (p=0.0022, p=0.0055, respectively). Conclusion: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium.

Background This study aimed to identify the healthcare providers’ experience and perspectives toward end-of-life care decisions focusing on end-of-life discussion and physician’s order of life-sustaining treatment documentation in Korea which are major parts of the Life-Sustaining Treatment Act. Methods A cross-sectional survey was conducted using a questionnaire developed by the authors. A total of 474 subjects—94 attending physicians, 87 resident physicians, and 293 nurses—participated in the survey, and the data analysis was performed in terms of frequency, percentage, mean and standard deviation using the SPSS 24.0 program. Results Study results showed that respondents were aware of terminal illness and physician’s order of life-sustaining treatment in Korea well enough except for some details. Physicians reported uncertainty in terminal state diagnosis and disease trajectory as the most challenging. Study participants regarded factors (related to relationships and communications) on the healthcare providers’ side as the major impediment to end-of-life discussion. Study respondents suggested that simplification of the process and more staff are required to facilitate end-of-life discussion and documentation. Conclusion Based on the study results, adequate education and training for better end-of-life discussion are required for future practice. Also, a simple and clear procedure for completing a physician’s order of life-sustaining treatment in Korea should be prepared and legal and ethical advice would be required. Since the enactment of the Life-Sustaining Treatment Act, several revisions already have been made including disease categories, thus continuous education to update and support clinicians is also called for.

This study aimed to add real-world evidence to the literature regarding the effectiveness and safety of durvalumab consolidation (DC) after concurrent chemoradiotherapy (CCRT) in the treatment of unresectable stage III non-small cell lung cancer (NSCLC). Using a hospital-based NSCLC patient registry and propensity score matching in a 2:1 ratio, we conducted a retrospective cohort study of patients with unresectable stage III NSCLC who completed CCRT with and without DC. The co-primary endpoints were 2-year progression-free survival and overall survival. For the safety evaluation, we evaluated the risk of any adverse events requiring systemic antibiotics or steroids. Of 386 eligible patients, 222 patients—including 74 in the DC group—were included in the analysis after propensity score matching. Compared with CCRT alone, CCRT with DC was associated with increased progression-free survival (median: 13.3 vs. 7.6 months, hazard ratio[HR]: 0.63, 95% confidence interval[CI]: 0.42–0.96) and overall survival (HR: 0.47, 95% CI: 0.27–0.82) without an increased risk of adverse events requiring systemic antibiotics or steroids. While there were differences in patient characteristics between the present real-world study and the pivotal randomized controlled trial, we demonstrated significant survival benefits and tolerable safety with DC after the completion of CCRT.

Purpose The aim of this study was to compare the anatomical structures of the acetabular rim around the anterior inferior iliac spine (AIIS) ridge that indicate anterior focal coverage of acetabulum between the sexes using a three-dimensional (3D) model. Methods 3D models of 71 adults (38 men and 33 women) with normal hip joints were used. Based on the location of the inflection point (IP) of the acetabular rim around the AIIS ridge, the patients were classified into anterior and posterior types, and the ratios thereof for each sex were compared. Coordinates for the IP, the most anterior point (MAP), and the most lateral point (MLP) were obtained and compared between the sexes and between anterior and posterior types. Results Coordinates for IPs in men were located anterior and inferior to those in women. MAP coordinates for men were located inferior to those for women, and MLP coordinates for men were located lateral and inferior to those for women. Comparing AIIS ridge types, we noted that coordinates for IPs of the anterior type were located medial, anterior, and inferior to those of the posterior type. Meanwhile, MAP coordinates of the anterior type were located inferior to those of the posterior type, and MLP coordinates of the anterior type were located lateral and inferior to those of the posterior type. Conclusion Anterior focal coverage of the acetabulum appears to differ between the sexes, and this difference may affect the development of pincer-type femoroacetabular impingement (FAI). Additionally, we found that anterior focal coverage differs according to anterior or posterior positioning of the bony prominence around the AIIS ridge, which may affect development of FAI.

IntroductionThe spread of COVID-19 pandemic in early 2020 has significantly affected the tourism industry. Most current tourism research on emergencies focuses on issues such as the revitalization of the tourism economy. However, research on aspects such as visitor perception has not received sufficient attention, This study contributes to the literature by analyzing the effects of social interactions, multidimensional perceived value, fear of COVID-19, and age on travelers’ travel intentions during the COVID-19 pandemic.MethodThis study constructs a structural equation model, formulates the corresponding hypotheses, investigates Chinese travelers, and verifies the moderating effect of COVID-19 fear.ResultsAll of the proposed hypotheses were verified. The three dimensions of perceived value and satisfaction had a significant mediating effect in the relationship between perceived quality and travel intention, and that fear of COVID-19 had a significant moderating effect in the relationship between satisfaction and travel intention. With the moderation of fear of COVID-19, age had a significantly negative effect on travel intention.DiscussionGiven extant research demonstrating that both math activities and math talk predict children’s math skills, our results stress the need for multimethod studies that differentiate among these HME opportunitiesThe findings confirmed a significant mediating effect of the three dimensions of perceived value and satisfaction on perceived quality and travel intention. fear of COVID-19 had a significant moderating effect on satisfaction and travel intention. In addition, age had a significant negative effect on travel intention under the moderation of fear of COVID-19; thus, travel intention decreases with age.

BACKGROUND: Coronary microvascular dysfunction is a clinically significant component of ischemic heart disease. There can be heterogenous patterns of coronary microvascular dysfunction defined by invasive physiologic indexes such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR). We sought to compare the prognosis of coronary microvascular dysfunction according to different patterns of CFR and IMR. METHODS: The current study included 375 consecutive patients undergoing invasive physiologic assessment for suspected stable ischemic heart disease and intermediate but functionally nonsignificant epicardial stenosis (fractional flow reserve, >0.80). According to cutoff values of invasive physiologic indexes reflecting microcirculatory function (CFR, RESULTS: Cumulative incidence of the primary outcome was significantly different among the 4 groups (group 1, 20.1%; group 2, 18.8%; group 3, 33.9%; and group 4, 45.0%; overall P P =0.019) and elevated IMR subgroups (HR, 3.307 [95% CI, 1.519–7.202]; P =0.003). Conversely, the risk of primary outcome was not significantly different between elevated and low IMR in preserved CFR subgroups (HR, 0.926 [95% CI, 0.428–2.005]; P =0.846). Furthermore, as continuous variables, IMR-adjusted CFR (adjusted HR, 0.644 [95% CI, 0.537–0.772]; P P =0.515) was not. CONCLUSIONS: Among patients with suspected stable ischemic heart disease who were found to have an intermediate but functionally nonsignificant epicardial stenosis, depressed CFR was associated with an increased risk of cardiovascular death and admission for heart failure. However, elevated IMR alone with preserved CFR showed limited prognostic value in this population.

We recruited 50 patients with unresectable stage III NSCLC who received CCRT between March 2020 and March 2021. Durvalumab consolidation (DC) was administered to patients (n = 23) without progression after CCRT and programmed death-ligand 1 (PD-L1) ≥ 1%. Blood samples were collected before (C0) and after CCRT (C1) to calculate PBC counts and analyze CTCs. CTCs, isolated by the CD-PRIMETM system, exhibited EpCAM/CK+/CD45− phenotype in BioViewCCBSTM. At median follow-up of 27.4 months, patients with residual CTC clusters at C1 had worse median PFS than those without a detectable CTC cluster (11.0 vs. 27.8 months, p = 0.032), and this trend was noted only in the DC group (p = 0.034). Patients with high platelets at C1 (PLThi, >252 × 103/µL) had worse median PFS than those with low platelets (PLTlo) (5.9 vs. 17.1 months, p < 0.001). In multivariable analysis, PLThi and residual CTC clusters at C1 were independent risk factors for PFS, and DC group with PLThi and residual CTC clusters at C1 showed the worst median PFS (2.6 months, HR 45.16, p = 0.001), even worse than that of the CCRT alone group with PLThi (5.9 months, HR 15.39, p = 0.001). The comprehensive analysis of CTCs and PBCs before and after CCRT revealed that the clearance of CTC clusters and platelet counts at C1 might be potential biomarkers for predicting survival.

Background Coronary microvascular dysfunction (CMD) has been considered as a possible cause of cardiac diastolic dysfunction. The current study evaluated the association between cardiac diastolic dysfunction and CMD, and their prognostic implications in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Methods and Results A total of 330 patients without left ventricular systolic dysfunction (ejection fraction ≥50%) and significant epicardial coronary stenosis (fractional flow reserve >0.80) were analyzed. Cardiac diastolic dysfunction was defined by echocardiographic parameters (early diastolic transmitral flow velocity/early diastolic mitral annular velocity, e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Overt CMD was defined as coronary flow reserve P =0.002). Patients with cardiac diastolic dysfunction showed significantly higher risk of the primary outcome than those without (adjusted hazard ratio [HR], 2.996 [95% CI, 1.888–4.755]; P P P =0.006) but not in patients without cardiac diastolic dysfunction (interaction P P for comparison=0.034). Conclusions There was significant association between the presence of cardiac diastolic dysfunction and overt CMD. Both cardiac diastolic dysfunction and overt CMD were associated with increased risk of cardiovascular death or admission for heart failure. Integration of overt CMD into cardiac diastolic dysfunction showed improvement of the risk stratification in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Registration DIAST‐CMD (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function) registry; Unique identifier: NCT05058833.