Journals
2025 EN
West Valerie C. · Owen Kaelyn E. · Inguito Kameron L.
+10 more
ABSTRACT The actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G‐) actin‐binding transcription factor, myocardin‐related transcription factor‐a (MRTF). We determined that decreasing the proportion of G‐actin in tenocytes by treatment with TGFβ1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G‐actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis‐like phenotype. To parse out the effects of F‐actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Exposure of cells to cytochalasin D increases the proportion of G‐actin in tenocytes. However, as compared to latrunculin A, cytochalasin D has a differential effect on MRTF localization by increasing nuclear MRTF. This led to an opposing effect on the regulation of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α‐smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.
Journals
2025 EN
Grosu IoanaGeorgeta · Iuga Dinu · Tatman Ben P.
+3 more
Abstract A 17 O solid‐state NMR method for salt/co‐crystal discrimination in binary compounds of carboxylic acids is presented. The method incorporates a quick and relatively inexpensive labelling protocol for mechanochemical 17 O enrichment of the carboxyl oxygen positions, as previously described by Metro et al. Angew. Chem. 2017, 56, 6803, followed by a visual interpretation of the recorded 17 O solid‐state magic‐angle spinning (MAS) NMR spectra in terms of the nature of the enriched oxygen sites in the prepared binary compound. Care must be taken where variable‐temperature changes in the 17 O MAS spectra are observed. Nevertheless, we observe that, at low temperatures, the averaging effect of chemical exchange of the carboxyl/carboxylate moieties can be avoided and two well separated 17 O lines are obtained for a carboxylic acid, whereas the almost equivalent carboxylate oxygen sites give rise to a single NMR signal. The method is illustrated in two cases, one in which salts can be identified also from their 1 H solid‐state NMR spectra by the absence of high ppm resonances due to hydrogen bonding, and another one, the more general case of organic crystals with multiple hydrogen bonding, where only 17 O solid‐state NMR spectra can be employed for salt/co‐crystal discrimination. A quantitative analysis of 17 O solid‐state NMR spectral parameters can provide useful information in structural studies by NMR crystallography approaches.
Journals
2025 EN
Zheng Kaifeng · Patra Nirmalendu · Marcella Nicholas
+9 more
Molten salts are crucial materials with exceptional properties that make them suitable for applications such as heat transfer media, coolants, and liquid fuels in molten salt nuclear reactors and the concentrated solar power industry. Understanding their properties requires unraveling the intricate mysteries of their structure. To achieve this, advanced characterization tools are essential. Among various techniques, X‐ray absorption fine structure (XAFS) stands out as a versatile method capable of studying the structure of molten salts under in situ conditions. This review highlights recent advancements in the application of XAFS for investigating the local structure of molten salts, discusses its limitations and potential improvements, and explores complementary approaches such as simulations, machine learning, and correlative experimental methods.
Journals
2025 EN
Zheng Kaifeng · Patra Nirmalendu · Marcella Nicholas
+9 more
The Front Cover symbolizes, amid crystalline salt formations and glowing pools of molten salt, the atomic complexity of molten salt systems and the advanced tools used to study them. X‐ray absorption fine structure (XAFS) spectroscopy under in‐situ conditions is the focus of this Review by A. I. Frenkel and co‐workers (DOI: 10.1002/cmtd.202400097 ), which highlights recent advances and emerging synergies with machine learning—depicted as two giant pyramid‐shaped networks—alongside simulations and complementary experimental techniques that illuminate these dynamic materials.
Journals
2025 EN
Lynch Brigid M. · Bassett Julie K. · Milne Roger L.
+5 more
Abstract Background Previous estimates of the number of cancers attributable to physical inactivity in the United States have typically focused on only three malignancies (colon, endometrial, and postmenopausal breast cancer). Contemporary epidemiologic evidence suggests that physical inactivity could contribute to up to 15 types of cancer, and a dose–response effect has been demonstrated for 13 of these. This study estimated the number of cancers diagnosed in the United States in 2015 due to physical inactivity for these 13 sites. Methods Data from the 2005 National Health Interview Survey were used to estimate physical activity prevalence and, with the assumption of a 10‐year latency period, 2015 cancer incidence data from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Incidence US Cancer Statistics Public Use Database. Results The potential impact fraction was estimated to be 4.1%, which meant that 30,951 of 761,625 incident cancers at the 13 sites could have been prevented in the United States in 2015 if adults had increased physical activity by one category in 2005 (approximately 7.5 additional metabolic equivalent task hours per week [MET‐h/week]). Theoretically, 85,415 of 761,625 incident cancers at the 13 sites (population attributable fraction, 11.2%) could have been prevented if all adults had achieved the highest level of physical activity (>30 MET‐h/week). Conclusions When estimates are based on updated epidemiologic evidence regarding physical inactivity and cancer risk, substantially more cancers are attributable to physical inactivity than previously reported. A greater focus on physical activity promotion is warranted for cancer control in the United States.
Journals
2025 EN
DuBois Steven G. · Ogawa Chitose · Moreno Lucas
+19 more
Abstract Background This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma. Methods Patients aged 2–21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m 2 ) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28‐day cycles. Results Twenty‐five patients were treated. No dose‐limiting toxicity occurred in monotherapy; one patient had dose‐limiting toxicities in the combination therapy cohort (grade 3 mucositis and grade 4 neutropenia). The recommended phase 2 dose for both monotherapy and combination therapy was 15 mg/m 2 . Twenty‐two patients (88%) had one or more treatment‐related adverse event(s) (TRAEs), and 18 (72%) experienced grade ≥3 TRAEs. Myelosuppression was the most common high‐grade TRAE observed in the combination therapy cohort. At both dose levels, steady‐state plasma concentrations exceeded xenograft 90% inhibitory concentration levels. In the monotherapy cohort, one patient had a minor response, and one patient had stable disease, both continuing for >12 months. In the combination therapy cohort, two patients had a partial response, two had a minor response, and six had stable disease. Overall, the response rate, according to New Approaches to Neuroblastoma Therapy version 2.0 criteria, was 8%, and the disease control rate was 52%. Conclusions LY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof‐of‐concept clinical responses were observed, future studies with biomarker‐selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition.
Journals
2025 EN
Hoffman Richard M. · Wolf Andrew M. D. · Raoof Sana
+8 more
Abstract Multicancer early detection (MCED) tests are an emerging technology for cancer screening. MCED tests can detect cancer signals from multiple cancers concurrently in biological samples such as blood, urine, saliva, or other bodily fluids. Some tests can suggest the most likely cancer origin, whereas others report cancer detected somewhere in the body. Although some MCED tests are currently commercially available, none are approved by the Food and Drug Administration or endorsed by any clinical practice guideline or recommendation. Most insurance companies do not currently cover MCED testing. MCED tests have not yet been evaluated for safety and effectiveness in randomized controlled trials. Because patients already are asking for MCED test prescriptions or for interpretation of results from tests acquired elsewhere, clinicians should be prepared to discuss what is known about the benefits, risks, and uncertainties of MCED testing, including performance characteristics in screening populations and preferred follow‐up strategies for positive test results. At this time, clinicians should not feel obligated to initiate discussions about MCED testing with their patients. However, clinicians should engage patients who inquire about getting tested or previous MCED test results in shared decision‐making, and take the opportunity to offer and help patients complete age‐ and sex‐appropriate guideline‐recommended cancer screenings. In this article, the current evidence and issues around MCED testing are summarized, and a framework for shared decision‐making discussions is provided.
Journals
2025 EN
Khorsandi Nikka · Vohra Poonam · Samghabadi Peyman
+4 more
Abstract Introduction Racial differences have been identified in the distribution of cervical high‐risk human papillomavirus (hrHPV) subtypes; however, there is limited understanding of hrHPV subtypes in anal specimens based on patient race/ethnicity. This knowledge gap limits possible vaccination and/or treatment efforts and may not provide optimal coverage in diverse populations. Materials and Methods This preliminary study evaluates anal hrHPV subtype distribution and cytological outcomes in a diverse population accessing care at a large, urban, publicly funded hospital over a 2‐year period. The primary objectives were to analyze anal hrHPV subtypes and associated cytologic diagnoses, focusing on disparities among demographic groups, including racial and ethnic diversity, and among individuals living with human immunodeficiency virus (HIV). Results Ninety‐two patients were identified with a predominance of male (87%) and gay‐identifying (50%) individuals and a significant representation from Hispanic/Latinx (36%) and White (36%) backgrounds. A majority (88%) were living with HIV, and only a small fraction (7%) had received HPV vaccination. The most common hrHPV subtypes identified were non‐16 and 18 hrHPV subtypes (46%). No significant differences were identified in distribution of HPV subtypes among different races/ethnicities or between sexual and gender minorities and heterosexual, cisgender‐identifying individuals. However, individuals with HIV were more likely to have atypical cytologic diagnoses and non‐16/18 HPV subtypes. Conclusions The findings underscore the prevalence of non‐16/18 hrHPV subtypes in a racially and ethnically diverse urban population, particularly among individuals living with HIV. The study highlights the need for expanded HPV subtype surveillance and vaccine development to ensure equitable prevention strategies across diverse populations.
Journals
2025 EN
Karimkhan Afreen · Xia Rong · Diaz DeAnna
+7 more
Abstract Background Mutations in DICER1 are uncommon, poorly understood, and infrequently found in thyroid nodules. Methods The objective of this study was to investigate category III/IV thyroid nodules according to The Bethesda System for Reporting Thyroid Cytopathology with DICER1 gene mutations detected in fine‐needle aspiration cytology samples using ThyroSeq v3 molecular testing, with a focus on an exploration of the clinical and histopathologic outcomes of these nodules. In this multicenter study spanning more than 6 years, nodules were retrospectively analyzed for patient demographics, clinical course, cytologic features, and histopathology, where available. Results In total, 88 patients with somatic DICER1 mutations were included, with a mean age of 39.6 years and a female predominance. All mutations were in the somatic hotspot region, most commonly at the codon 5437 site. Most excised nodules showed benign histologic features (65.9%). Interestingly, the rate of malignancy was higher in this cohort compared with that in the national average. Conclusions DICER1 mutations appear to confer a higher risk of malignancy, but are not associated with any specific cytological or histopathological distinguishing features.
Journals
2025 EN
Yu Austin · Poulson Trevor · Butler Zachary
+3 more
ABSTRACT Background Chondrosarcoma accounts for 20% of all bone sarcomas and may present with soft tissue extension. The presence of an extraosseous component, along with positive surgical margins, independently have been associated with increased risk of local recurrence and decreased survival. The purpose of this investigation is to describe the treatment and outcomes of six chondrosarcoma patients who presented with chondrosarcoma with soft tissue extension along with positive surgical margins post negative en bloc resection. Case This was a retrospective review over a consecutive 13‐year period. Data including treatment details and outcomes were included. All patients underwent attempted negative margin en bloc resection and encountered unplanned positive margins on intraoperative determination or postoperative pathology (R1). A total of six cases were identified. Average age (SD) was 61.8 years (6.11) with median (IQR) follow‐up of 17.0 months (10.3–39.5). Three (50.0%) cases arose in the extremities, and 3 (50.0%) cases in the pelvis. All patients underwent attempted negative margin en bloc resection. Three (50.0%) cases recurred with median (IQR) time to recurrence of 10.0 months (9.0–31.0). At study conclusion, 5 (83.3%) were alive with median (IQR) survival of 20.5 months (11.3–41.0). Conclusion Despite limited sample size, our data reflected a significantly higher recurrence rate compared to either chondrosarcomas with positive margins or extraosseous extension. Our cohort represents a high‐risk subgroup of chondrosarcoma patients, which may dictate increased monitoring and guide future treatment recommendations for these patients.