Citations

Objective: Perimenopause is an under-recognized life stage that is often accompanied by complex and fluctuating symptoms. We aimed to quantify the prevalence of perimenopause uncertainty and explore the underlying drivers. Methods: We conducted a mixed-methods study using a cross-sectional survey of US women aged 35 years and above (N=7,640). We estimated the prevalence of perimenopause uncertainty and examined subgroup differences by age and symptom severity. Content analysis of free-text responses (n=409) identified key uncertainty drivers. Results: Overall, 34% (95% CI: 33%-35%) of participants reported being unsure of their reproductive stage. Uncertainty varied by age and symptom severity ( P < 0.001), peaking at 42% (95% CI: 41%-43%) among those aged 40-44 and 37% (95% CI: 36%-38%) among those with severe symptom burden. Content analysis revealed three main uncertainty drivers. Symptom confusion and attribution were the most common (56%), reflecting difficulties interpreting bodily changes and distinguishing perimenopause from other causes. Knowledge gaps and information seeking accounted for 28% of responses, highlighting limited health literacy, age-based assumptions, and active searches for evidence. Barriers to confirmation and care (16%) described dismissive health care encounters and reluctance to acknowledge perimenopause. Younger women (35-39 y) were more likely to cite knowledge gaps, while health care barriers peaked in the 40-44 age group ( P = 0.05). Conclusion: Perimenopause uncertainty is a prevalent and clinically meaningful phenomenon. Conceptually distinct from illness-focused uncertainty, this universal transition frequently involves ambiguity and limited validation. Clarifying symptom patterns, addressing knowledge gaps, and reducing barriers to confirmation may support women during perimenopause.

Objective: Perimenopause is the time leading up to a woman’s last menstrual cycle and includes the 12 months afterward. Studies that systematically compare perimenopause symptoms across diverse cultural and geographic settings are lacking. This study, utilizing data from Flo, an international mobile health application, aimed to assess global knowledge and symptom experiences related to perimenopause. Methods: This cross-sectional survey was conducted via the Flo application, offered to users aged 18 years and above. The primary endpoints were knowledge of perimenopause symptoms from all survey participants, and self-reported perimenopause symptoms for survey participants aged 35 years and above. Secondary analyses compared knowledge scores and symptoms across geographic regions. Results: A total of 17,494 women from 158 countries were included. Commonly recognized perimenopause symptoms included hot flashes (71%), sleep problems (68%), and weight gain (65%). Of the participants, 12,681 were aged 35 years or above, with the most common self-reported symptoms being fatigue (83%), physical and mental exhaustion (83%), irritability (80%), depressive mood (77%), sleep problems (76%), digestive issues (76%), and anxiety (75%). This pattern of symptoms was similar among those who self-reported being in perimenopause, though higher than in those not in perimenopause. International variation in perimenopause symptom knowledge and symptoms experienced was noted ( P <0.001). Conclusions: This survey highlights a discordance between perimenopause knowledge and actual symptoms experienced across diverse global populations. While hot flashes were the most widely recognized symptom, respondents aged 35 years or above most commonly reported experiencing fatigue, physical and mental exhaustion, and irritability.

Abstract Objective Perimenopause is an under-recognized life stage that may be accompanied by complex and fluctuating symptoms. We aimed to quantify the prevalence of perimenopause uncertainty and explore the underlying drivers. Methods We conducted a mixed-methods study based on a cross-sectional survey of U.S. women aged 35 years and above (N=7,640). Closed-ended responses were analyzed to estimate the prevalence of perimenopause uncertainty with subgroup differences investigated by age and symptom severity. Content analysis of free-text responses (n=409) was conducted to identify the main uncertainty drivers. Results Overall, 34% of participants reported being unsure of their reproductive stage. Uncertainty peaked among those aged 40-44 (42%) and was highest among those with severe symptom burden (37%). The content analysis revealed three main uncertainty drivers. Symptom confusion and attribution was the most common (56%), reflecting difficulties interpreting bodily changes and distinguishing perimenopause from other causes. Knowledge gaps and information seeking accounted for 28% of responses, highlighting limited health literacy, assumptions about age, and active searches for evidence. Barriers to confirmation and care (16%) described dismissive healthcare encounters and reluctance to acknowledge perimenopause. Younger women (35-39 years) were more likely to cite knowledge gaps, while healthcare barriers peaked in the 40-44 age group. Conclusion Perimenopause uncertainty is a prevalent and clinically meaningful challenge. This uncertainty is conceptually distinct from illness-focused models: it is a universal transition with ambiguity and often lack of validation. Better symptom recognition and targeted communication is a crucial first step toward improving women’s awareness and support during perimenopause.

ABSTRACT Objective The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales. Methods Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post‐contrast gadolinium enhancement resolution at 6 months post‐treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow‐up. Results Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39–55); male: female 1.3:1). Median nadir mRS and EDSS were 2 (IQR 2–3) and 4 (IQR 2.5–6). At initial treatment, 129 (63.9%) received prolonged corticosteroids ≥ 4 weeks (group A 1 ), 36 (17.8%) received corticosteroids < 4 weeks (B 1 ), 21 (10.4%) received corticosteroids plus sarcoidosis‐directed immunosuppressant (E), and 16 (7.9%) received corticosteroids plus non‐sarcoidosis‐directed agents (F). In 167 cases with sufficient imaging, there were no significant differences in contrast enhancement resolution at 6 months (A 1 27/106 (25.5%), B 1 9/28 (32.1%), E 5/19 (26.3%), F 5/14 (35.7%); Fisher's exact p = 0.76). There were no significant differences in changes in mRS or EDSS among treatment groups (Kruskal–Wallis p = 0.69 and 0.63, respectively) after median follow‐up of 46.5 months (IQR 18–91.3). Interpretation Different initial immunosuppression strategies did not correlate with MRI contrast enhancement resolution at 6 months or clinical scales (mRS, EDSS). However, conclusions are limited by retrospective design, imbalanced cohorts, and insensitivity of binary MRI outcomes and available clinical scales for treatment response in neurosarcoidosis.

Abstract Objective Perimenopause is an under-recognized transition poorly measured by existing tools, which often overlook symptoms characteristic of this phase. To address this, we developed and validated the Perimenopause Symptom Scale (Peri-SS): a concise, phase-specific, psychometrically robust instrument for digital self-assessment and research use among U.S. women aged 35-59 who self-reported in perimenopause. Methods We conducted a longitudinal validation study with 1,255 U.S. women aged 35-59 (633 identified as perimenopausal) recruited via Prolific. Participants completed the Peri-SS, Menopause Rating Scale (MRS), and EuroQol 5-Dimension, 5-Level (EQ-5D-5L) at baseline and 7-14 days later. Following COSMIN guidelines, we assessed structural validity, internal consistency, test-retest reliability, criterion and construct validity, and responsiveness to change. Results The Peri-SS demonstrated strong psychometric performance. Confirmatory factor analysis confirmed a four-domain structure (vasomotor, psychological, sexual, physical), with excellent model fit (CFI = 0.932, RMSEA = 0.069). Internal consistency was excellent (α = 0.90 overall; domain range 0.73-0.86), and test-retest reliability was high (ICC = 0.82). Criterion validity was strong, with Peri-SS scores highly correlated with MRS (r = 0.88). Construct validity was supported through moderate correlations with EQ-5D-5L utilities (ρ = -0.50) and effective discrimination between groups by age, menopausal status, and hormone therapy use. The scale was also responsive to symptom changes over time (η² = 0.277). Conclusions The Peri-SS is a reliable, valid, responsive tool for assessing perimenopausal symptom burden. Its concise format and strong psychometric performance make it well-suited for research, clinical care, and digital health applications. Two sentence summary The Perimenopause Symptom Scale (Peri-SS) is a novel 16-item instrument developed to measure symptom burden during perimenopause across four domains. In a validation study among U.S. women aged 35-59 years, the Peri-SS demonstrated strong reliability, validity, and responsiveness, supporting its use in research, clinical care, and digital health settings.

Abstract Purpose To investigate the feasibility of rapid CEST MRI acquisition for evaluating oxidative phosphorylation (OXPHOS) in human skeletal muscle at 3T, utilizing ultrafast Z‐spectroscopy (UFZ) combined with MRI and the Polynomial and Lorentzian line‐shape Fitting (PLOF) technique. Methods UFZ MRI on muscle was evaluated with turbo spin echo (TSE) and 3D EPI readouts. Five healthy subjects performed in‐magnet plantar flexion exercise (PFE) and subsequent changes of amide, PCr, and partial PCr mixed Cr (Cr + ) CEST dynamic signals post‐exercise were enabled by PLOF fitting. PCr/Cr CEST signal was further refined through pH correction by using the ratios between PCr/Cr and amide signals, named PCAR/CAR, respectively. Results UFZ MRI with TSE readout significantly reduces acquisition time, achieving a temporal resolution of <50 s for collecting high‐resolution Z‐spectra. Following PFE, the recovery/decay times (τ) for both PCr and Cr in the gastrocnemius muscle of the calf were notably longer when determined using PCr/Cr CEST compared to those after pH correction with amideCEST, namely = 87.1 ± 15.8 s and = 98.1 ± 20.4 s versus = 32.9 ± 19.7 s and = 43.0 ± 13.0 s, respectively. obtained via 31 P MRS ( = 50.3 ± 6.2 s) closely resemble those obtained from pH‐corrected PCr/Cr CEST signals. Conclusion The outcomes suggest potential of UFZ MRI as a robust tool for non‐invasive assessment of mitochondrial function in skeletal muscles. pH correction is critical for the reliable OXPHOS measurement by CEST.

Abstract Histological and lineage immunofluorescence examination revealed that healthy conducting airways of humans and animals harbor sporadic poorly differentiated epithelial patches mostly in the dorsal noncartilage regions that remarkably manifest squamous differentiation. In vitro analysis demonstrated that this squamous phenotype is not due to intrinsic functional change in underlying airway basal cells. Rather, it is a reversible physiological response to persistent Wnt signaling stimulation during de novo differentiation. Squamous epithelial cells have elevated gene signatures of glucose uptake and cellular glycolysis. Inhibition of glycolysis or a decrease in glucose availability suppresses Wnt-induced squamous epithelial differentiation. Compared with pseudostratified airway epithelial cells, a cascade of mucosal protective functions is impaired in squamous epithelial cells, featuring increased epithelial permeability, spontaneous epithelial unjamming, and enhanced inflammatory responses. Our study raises the possibility that the squamous differentiation naturally occurring in healthy airways identified herein may represent “vulnerable spots” within the airway mucosa that are sensitive to damage and inflammation when confronted by infection or injury. Squamous metaplasia and hyperplasia are hallmarks of many airway diseases, thereby expanding these areas of vulnerability with potential pathological consequences. Thus, investigation of physiological and reversible squamous differentiation from healthy airway basal cells may provide critical knowledge to understand pathogenic squamous remodeling, which is often nonreversible, progressive, and hyperinflammatory.

Abstract Background The AMP‐activated protein kinase (AMPK) is a central regulator of energy homeostasis, with deregulation leading to cancer and other diseases. However, how this pathway is dysregulated in cancer has not been well clarified. Methods Using a tandem affinity purification/mass‐spec technique and biochemical analyses, we identified tumor protein D52 (TPD52) as an AMPKα‐interacting molecule. To explore the biological effects of TPD52 in cancers, we conducted biochemical and metabolic assays in vitro and in vivo with cancer cells and TPD52 transgenic mice. Finally, we assessed the clinical significance of TPD52 expression in breast cancer patients using bioinformatics techniques. Results TPD52, initially identified to be overexpressed in many human cancers, was found to form a stable complex with AMPK in cancer cells. TPD52 directly interacts with AMPKα and inhibits AMPKα kinase activity in vitro and in vivo. In TPD52 transgenic mice, overexpression of TPD52 leads to AMPK inhibition and multiple metabolic defects. Clinically, high TPD52 expression predicts poor survival of breast cancer patients. Conclusion The findings revealed that TPD52 is a novel regulator of energy stress‐induced AMPK activation and cell metabolism. These results shed new light on AMPK regulation and understanding of the etiology of cancers with TPD52 overexpression.