Measuring functional connectivity in frequency-domain helps to better characterize brain function.

Resting-state functional connectivity (FC) is widely used in multivariate pattern analysis of functional magnetic resonance imaging (fMRI), including identifying the locations of putative brain functional borders, predicting individual phenotypes, and diagnosing clinical mental diseases. However, limited attention has been paid to the analysis of functional interactions from a frequency perspective. In this study, by contrasting coherence-based and correlation-based FC with two machine learning tasks, we observed that measuring FC in the frequency domain helped to identify finer functional subregions and achieve better pattern discrimination capability relative to the temporal correlation. This study has proven the feasibility of coherence in the analysis of fMRI, and the results indicate that modeling functional interactions in the frequency domain may provide richer information than that in the time domain, which may provide a new perspective on the analysis of functional neuroimaging.

Changes in expression of breast cancer tumor biomarkers between primary tumors and corresponding metastatic sites: common patterns and relationships with survival.

PURPOSE: In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS. METHODS: Patients diagnosed at our center with metastatic breast cancer (2011-2020) were included. ER/PR were stratified as < 1%/1-10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2-, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed. RESULTS: Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1-10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2- to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2- (5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05). CONCLUSION: Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.

Latent Class Proportional Hazards Regression with Heterogeneous Survival Data.

Heterogeneous survival data are commonly present in chronic disease studies. Delineating meaningful disease subtypes directly linked to a survival outcome can generate useful scientific implications. In this work, we develop a latent class proportional hazards (PH) regression framework to address such an interest. We propose mixture proportional hazards modeling, which flexibly accommodates class-specific covariate effects while allowing for the baseline hazard function to vary across latent classes. Adapting the strategy of nonparametric maximum likelihood estimation, we derive an Expectation-Maximization (E-M) algorithm to estimate the proposed model. We establish the theoretical properties of the resulting estimators. Extensive simulation studies are conducted, demonstrating satisfactory finite-sample performance of the proposed method as well as the predictive benefit from accounting for the heterogeneity across latent classes. We further illustrate the practical utility of the proposed method through an application to a mild cognitive impairment (MCI) cohort in the Uniform Data Set.

Effects of vaginal progesterone and placebo on preterm birth and antenatal outcomes in women with singleton pregnancies and short cervix on ultrasound: a meta-analysis.

Background: Vaginal progesterone in preterm birth and adverse outcomes caused by cervical insufficiency remains controversial. To address it, the effect of vaginal progesterone on preterm delivery and perinatal outcome of single pregnancy women with short cervix (less than 25 mm) was systematically evaluated by meta-analysis. Methods: "Vaginal progesterone," "placebo," "ultrasound," "cervix," "singleton pregnancy," "preterm birth," and "antenatal outcomes" were entered to screen clinical studies PubMed, Embase, and the Chinese Biomedical Literature Database (CBM). The study population consisted of women with singleton pregnancies and a short cervix on ultrasound, and were assigned into the progesterone group (n = 1,368) and the placebo group (n = 1,373). Treatment began after the patient was diagnosed with short cervix until delivery. Neonatal survival rate, Neonatal Intensive Care Unit (NICU) admission rate, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), neonatal mortality, and birth weight <1,500 g were analyzed. Results: A total of 8 articles, totaling 2,741 study subjects, were enrolled. The progesterone group exhibited an obvious reduced rate of preterm birth at <34 weeks (OR = 0.67, 95% CI: 0.53∼0.84; Z = 3.53, P = 0.004), preterm birth at <32 weeks (OR = 0.46, 95% CI: 0.28∼0.77; Z = 2.99, P = 0.003), NICU admission rate (OR = 0.45, 95% CI: 0.30∼0.66; Z = 0.15, P < 0.0001), RDS rate (OR = 0.42, 95% CI: 0.28∼0.63; Z = 4.25, P < 0.0001), IVH incidence rate (OR = 0.40, 95% CI: 0.17∼0.95; Z = 2.08, P = 0.04), neonatal mortality (OR = 0.25, 95% CI: 0.13∼0.46; Z = 4.39, P < 0.0001), and proportion of neonates with birth weight < 1,500 g (OR = 0.45, 95% CI: 0.32∼0.64; Z = 4.50, P < 0.0001). Conclusion: Vaginal progesterone lowered the incidences of preterm birth and adverse pregnancy outcomes in women with singleton pregnancies and a short cervix.

Frequency-specific segregation and integration of human cerebral cortex: An intrinsic functional atlas.

The cognitive and behavioral functions of the human brain are supported by its frequency multiplexing mechanism. However, there is limited understanding of the dynamics of the functional network topology. This study aims to investigate the frequency-specific topology of the functional human brain using 7T rs-fMRI data. Frequency-specific parcellations were first performed, revealing frequency-dependent dynamics within the frontoparietal control, parietal memory, and visual networks. An intrinsic functional atlas containing 456 parcels was proposed and validated using stereo-EEG. Graph theory analysis suggested that, in addition to the task-positive vs. task-negative organization observed in static networks, there was a cognitive control system additionally from a frequency perspective. The reproducibility and plausibility of the identified hub sets were confirmed through 3T fMRI analysis, and their artificial removal had distinct effects on network topology. These results indicate a more intricate and subtle dynamics of the functional human brain and emphasize the significance of accurate topography.

Continuous Glucose Monitoring Metrics and Hemoglobin A1c Relationship in Patients with Type 2 Diabetes Treated by Hemodialysis.

Background:There is a need for accurate glycemic control metrics in patients with diabetes and end-stage kidney disease (ESKD). Hence, we assessed the relationship of continuous glucose monitoring (CGM) metrics and laboratory-measured hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2D) treated by hemodialysis. Methods: This prospective observational study included adults (age 18-80 years) with T2D (HbA1c 5%-12%), treated by hemodialysis (for at least 90 days). Participants used a Dexcom G6 Pro CGM for 10 days. Correlation analyses between CGM metrics [mean glucose, glucose management indicator (GMI), and time-in-range (TIR 70-180 mg/dL)] and HbA1c were performed. Results: Among 59 participants (mean age was 57.7 ± 9.3 years, 58% were female, 86% were non-Hispanic blacks), the CGM mean glucose level was 188.9 ± 45 mg/dL (95% CI: 177.2, 200.7), the mean HbA1c and GMI were 7.1% ± 1.3% and 7.8% ± 1.1%, respectively (difference 0.74% ± 0.95). GMI had a strong negative correlation with TIR 70-180 mg/dL (r = -0.96). The correlation between GMI and HbA1c (r = 0.68) was moderate. Up to 29% of participants had a discordance between HbA1c and GMI of <0.5%, with 22% having a discordance between 0.5% and 1%, and 49% having a discordance of >1%. Conclusions: In patients with diabetes and ESKD treated by hemodialysis, the GMI has a strong correlation with TIR, while HbA1c underestimated the average glucose and GMI. Given the limitations of HbA1c in this population, GMI or mean glucose and TIR may be considered as more appropriate glucose control markers.

Effects of long-term closed and socially isolating spaceflight analog environment on default mode network connectivity as indicated by fMRI.

Long-term manned spaceflight and extraterrestrial planet settlement become the focus of space powers. However, the potential influence of closed and socially isolating spaceflight on the brain function remains unclear. A 180-day controlled ecological life support system integrated experiment was conducted, establishing a spaceflight analog environment to explore the effect of long-term socially isolating living. Three crewmembers were enrolled and underwent resting-state fMRI scanning before and after the experiment. We performed both seed-based and network-based analyses to investigate the functional connectivity (FC) changes of the default mode network (DMN), considering its key role in multiple higher-order cognitive functions. Compared with normal controls, the leader of crewmembers exhibited significantly reduced within-DMN and between-DMN FC after the experiment, while two others exhibited opposite trends. Moreover, individual differences of FC changes were further supported by evidence from behavioral analyses. The findings may shed new light on the development of psychological protection for space exploration.

Continuous Glucose Monitoring-Guided Insulin Administration in Long-Term Care Facilities: A Randomized Clinical Trial.

OBJECTIVES: To evaluate the efficacy of real-time continuous glucose monitoring (rt-CGM) in adjusting insulin therapy in long-term care facilities (LTCF). DESIGN: Prospective randomized clinical trial. SETTINGS AND PARTICIPANTS: Insulin-treated patients with type 2 diabetes (T2D) admitted to LTCF. METHODS: Participants in the standard of care wore a blinded CGM with treatment adjusted based on point-of-care capillary glucose results before meals and bedtime (POC group). Participants in the intervention (CGM group) wore a Dexcom G6 CGM with treatment adjusted based on daily CGM profile. Treatment adjustment was performed by the LTCF medical team, with a duration of intervention up to 60 days. The primary endpoint was difference in time in range (TIR 70-180 mg/dL) between treatment groups. RESULTS: Among 100 participants (age 74.73 ± 11 years, 80% admitted for subacute rehabilitation and 20% for nursing home care), there were no significant differences in baseline clinical characteristics between groups, and CGM data were compared for a median of 17 days. There were no differences in TIR (53.38% ± 30.16% vs 48.81% ± 28.03%, P = .40), mean daily mean CGM glucose (184.10 ± 43.4 mg/dL vs 190.0 ± 45.82 mg/dL, P = .71), or the percentage of time below range (TBR) <70 mg/dL (0.83% ± 2.59% vs 1.18% ± 3.54%, P = .51), or TBR <54 mg/dL (0.23% ± 0.85% vs 0.56% ± 2.24%, P = .88) between rt-CGM and POC groups. CONCLUSIONS AND IMPLICATIONS: The use of rtCGM is safe and effective in guiding insulin therapy in patients with T2D in LTCF resulting in a similar improvement in glycemic control compared to POC-guided insulin adjustment.

Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF.

INTRODUCTION: Inflammation appears early in cystic fibrosis (CF) pathogenesis, with specific elevated inflammatory markers in bronchoalveolar lavage fluid (BALF) correlating with structural lung disease. Our aim was to identify markers of airway inflammation able to predict bronchiectasis progression over two years with high sensitivity and specificity. METHODS: Children with CF with two chest computed tomography (CT) scans and bronchoscopies at a two-year interval were included (n= 10 at 1 and 3 years and n= 27 at 3 and 5 years). Chest CTs were scored for increase in bronchiectasis (Δ%Bx), using the PRAGMA-CF score. BALF collected with the first CT scan were analyzed for neutrophil% (n= 36), myeloperoxidase (MPO) (n= 25), neutrophil elastase (NE) (n= 26), and with a protein array for inflammatory and fibrotic markers (n= 26). RESULTS: MPO, neutrophil%, and inducible T-cell costimulator ligand (ICOSLG), but not clinical characteristics, correlated significantly with Δ%Bx. Evaluation of neutrophil%, NE, MPO, interleukin-8 (IL-8), ICOSLG, and hepatocyte growth factor (HGF), for predicting an increase of > 0.5% of Δ%Bx in two years, showed that IL-8 had the best sensitivity (82%) and specificity (73%). Neutrophil%, ICOSLG and HGF had sensitivities of 85, 82, and 82% and specificities of 59, 67 and 60%, respectively. The odds ratio for risk of >0.5% Δ%Bx was higher for IL-8 (12.4) than for neutrophil%, ICOSLG, and HGF (5.9, 5.3, and 6.7, respectively). Sensitivity and specificity were lower for NE and MPO). CONCLUSIONS: High levels of IL-8, neutrophil%, ICOSGL and HGF in BALF may be good predictors for progression of bronchiectasis in young children with CF.

Validation Study of the Newly Proposed Refined Diagnostic Criteria for Malignant Phyllodes Tumor With 136 Borderline and Malignant Phyllodes Tumor Cases.

The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria. This validation study included 136 borderline (borderline phyllodes tumor [BoPT]) and MPT cases that were not included in the initial study. We evaluated tumor classifications based on both the Refined Criteria and the WHO criteria. The Refined Criteria defines MPT when these criteria are met (1) stromal overgrowth with ≥ 1 feature(s) of marked stromal cellularity, marked stromal cytologic atypia, or ≥10 mitoses per 10 high-power fields (10 mitoses/10 HPFs) or (2) marked stromal cellularity with ≥1 feature(s) of marked stromal cytologic atypia, ≥10 mitoses/10 HPFs or permeative border. The WHO criteria require all 5 morphologic features (stromal overgrowth, permeative border, marked stromal cellularity, marked stromal cytologic atypia, and ≥10 mitoses/10 HPFs) for an MPT diagnosis. Using the Refined Criteria, none of the 61 BoPTs developed metastasis and 40.0% of the 75 MPTs developed metastases; local recurrence was seen in 11.5% BoPTs and 25.3% MPTs. Using the WHO criteria, 9.6% of the 94 BoPTs developed metastases and 50.0% of the 42 MPTs developed metastases; 14.9% of the BoPTs had local recurrence and 28.6% of the MPTs had local recurrence. Nine (30.0%) of the 30 tumors that developed distant metastases were diagnosed as BoPTs by the WHO criteria. When we combined the 75 MPTs from this validation cohort with the 65 MPT cases from the published data using the Refined Criteria, 50 (35.7%) of the 140 MPTs developed metastases, whereas 8 cases with metastases were <5 cm. In the univariate analysis with log-rank test, stromal overgrowth, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses/10 HPFs, presence of heterologous components other than liposarcomatous component, and presence of stromal necrosis were significantly associated with the risk of metastasis (all with P < 0.05). In multivariate analysis with Cox proportional hazard regression, stromal overgrowth and marked stromal cellularity were significantly associated with metastasis (both with P < 0.001). The Refined Criteria are superior to the WHO criteria in predicting the clinical outcomes of BoPTs and MPTs. Using the Refined Criteria, 35.7% of 140 patients with MPT developed metastases, whereas none (0%) of the patients with BoPT developed metastases. Patients with MPT have a high metastatic rate; these patients may benefit from systemic chemotherapy or targeted therapies. In contrast, patients with BoPT may be managed with complete local excision alone without chemotherapy.