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1.
Laryngoscope ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39360516

RESUMO

OBJECTIVES/HYPOTHESIS: To evaluate costs associated with perioperative gastrostomy tube (G-tube) placement for neonates with Robin sequence (PRS) that undergo mandibular distraction osteogenesis (MDO). METHODS: Retrospective chart review was performed to examine the medical records of neonates with RS who received treatment at our institution between 2012 and 2021. Patients under 6 months of age that underwent MDO for RS were included. Billing records of hospital costs over a 2-year period were analyzed. RESULTS: The study included 26 total patients with 11 in the MDO-only group, 9 in G-tube after MDO group, and 6 in G-tube before MDO group. There was a significant difference (p < 0.001) in total hospital costs between groups with MDO-only group averaging $119,532 (SD ± $$ \pm $$ 33,503), the G-tube after MDO group averaging $245,315 (SD ± $$ \pm $$ 102,327), and G-tube before MDO group averaging $252,300 (SD ± $$ \pm $$ 84,990). Multiple linear regression was performed controlling for genetic syndrome and birth weight, which still showed a statistically significant difference in total cost between the MDO-only group and G-tube after MDO (p = 0.006), and between the MDO-only group and G-tube prior to MDO (p = 0.01). There was a significant difference in costs between all three groups for total inpatient/outpatient costs with MDO-only group averaging $78,502 (SD ± $$ \pm $$ 30,953), the G-tube after MDO group averaging $176,125 (SD ± $$ \pm $$ 84,315), and the G-tube prior to MDO group averaging $156,309 (SD ± $$ \pm $$ 95,746). CONCLUSIONS: MDO performed without perioperative G-tube placement may reduce charges by >$100,000. The associated improvement of dysphagia after MDO surgery and potential for avoiding a G-tube has tremendous downstream cost and social benefits for families. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

2.
Br J Pharmacol ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39354889

RESUMO

This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT2A receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.

3.
Target Oncol ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271577

RESUMO

Diffuse-type gastric cancer (DGC) accounts for approximately one-third of gastric cancer diagnoses but is a more clinically aggressive disease with peritoneal metastases and inferior survival compared with intestinal-type gastric cancer (IGC). The understanding of the pathogenesis of DGC has been relatively limited until recently. Multiomic studies, particularly by The Cancer Genome Atlas, have better characterized gastric adenocarcinoma into molecular subtypes. DGC has unique molecular features, including alterations in CDH1, RHOA, and CLDN18-ARHGAP26 fusions. Preclinical models of DGC characterized by these molecular alterations have generated insight into mechanisms of pathogenesis and signaling pathway abnormalities. The currently approved therapies for treatment of gastric cancer generally provide less clinical benefit in patients with DGC. Based on recent phase II/III clinical trials, there is excitement surrounding Claudin 18.2-based and FGFR2b-directed therapies, which capitalize on unique biomarkers that are enriched in the DGC populations. There are numerous therapies targeting Claudin 18.2 and FGFR2b in various stages of preclinical and clinical development. Additionally, there have been preclinical advancements in exploiting unique therapeutic vulnerabilities in several models of DGC through targeting of the focal adhesion kinase (FAK) and Hippo pathways. These preclinical and clinical advancements represent a promising future for the treatment of DGC.

4.
Nat Commun ; 15(1): 7780, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237510

RESUMO

The potential weakening of the Atlantic Meridional Overturning Circulation (AMOC) in response to anthropogenic forcing, suggested by climate models, is at the forefront of scientific debate. A key AMOC component, the Florida Current (FC), has been measured using submarine cables between Florida and the Bahamas at 27°N nearly continuously since 1982. A decrease in the FC strength could be indicative of the AMOC weakening. Here, we reassess motion-induced voltages measured on a submarine cable and reevaluate the overall trend in the inferred FC transport. We find that the cable record beginning in 2000 requires a correction for the secular change in the geomagnetic field. This correction removes a spurious trend in the record, revealing that the FC has remained remarkably stable. The recomputed AMOC estimates at ~26.5°N result in a significantly weaker negative trend than that which is apparent in the AMOC time series obtained with the uncorrected FC transports.

5.
Int J Pediatr Otorhinolaryngol ; 185: 112077, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39217865

RESUMO

OBJECTIVES: Although parotid gland malignancies are uncommon, they nevertheless represent a cause of morbidity and mortality in the pediatric population. Few studies have sought to identify disparities related to their presentation, treatment, and survival. There is a need to understand these variations to improve care for historically underrepresented groups. STUDY DESIGN: Retrospective Cohort Study. SETTING: Surveillance, Epidemiology, and End Results (SEER) Program Database. METHODS: Analysis of pediatric patients with parotid gland malignancies between 2000 and 2019. Race and ethnicity were classified as Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic for multivariable analysis. Outcomes included tumor size and stage at diagnosis, survival, and need for facial nerve sacrifice. Kaplan-Meier analysis was used to analyze survival. Multivariable logistic regression was conducted to identify predictors of outcomes. RESULTS: 149 patients met the criteria for inclusion. Stratified by race/ethnicity, Non-Hispanic Black (Median 23 mm, IQR 15-33), Asian (30 mm, 14-32), and Hispanic (23 mm, 20-28) patients had larger tumors at presentation than Non-Hispanic White patients (18 mm, 12-25, p = 0.017). Disease-specific survival differed by time-to-treatment (log-rank, p = 0.01) and overall survival differed by income (p < 0.001). On multivariable analysis, Hispanic patients were more likely to experience facial nerve sacrifice (OR 3.71, 95%CI 1.25-11.6, p = 0.020), and Non-Hispanic Black (OR 3.37, 0.95-11.6, = 0.053) and Asian (OR 5.67, 1.46-22.2, p = 0.011) patients presented with larger tumors compared to Non-Hispanic White patients. CONCLUSIONS: Variations in presentation and treatment exist across race and ethnicity in pediatric parotid cancer. Identifying these disparities may help improve access and outcomes for underserved patient populations. LEVEL OF EVIDENCE: III.


Assuntos
Disparidades em Assistência à Saúde , Neoplasias Parotídeas , Programa de SEER , Humanos , Masculino , Feminino , Criança , Estudos Retrospectivos , Neoplasias Parotídeas/terapia , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Pré-Escolar , Estados Unidos , Adolescente , Estadiamento de Neoplasias , Lactente
6.
Artigo em Inglês | MEDLINE | ID: mdl-39240222

RESUMO

Mitomycin C is an alkylating agent with the ability to suppress fibroblast proliferation and activity, making it a powerful antifibrotic. It has therefore become popular in glaucoma filtering surgeries, used both intraoperatively during bleb formation and postoperatively as an adjunct to bleb needling. This report presents a rare but serious risk of bleb needling with Mitomycin C at the slit lamp, where inadvertent movement of the patient resulted in an orbital injection. The patient quickly developed focal tissue inflammation and necrosis, presenting one day after the procedure with complete ptosis, ophthalmoplegia, and a palpable orbital mass. After appropriate imaging and an excisional biopsy to exclude infectious, infiltrative, and neoplastic causes, this was managed with close observation and continued improvement, and resolution of most orbital sequelae.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39158474

RESUMO

A 68-year-old woman was seen in oculoplastic consultation with a medial canthal lesion initially diagnosed as an atypical fibroxanthoma. On excisional biopsy, she was found to have a spindle cell carcinoma, which is a rare and reportedly more aggressive form of squamous cell carcinoma. We highlight the surgical technique of biopsy and reconstruction, the detailed histologic and immunohistochemical analysis required for accurate diagnosis, considerations for adjuvant treatment, and suggestions for systemic workup and surveillance. This case adds to the small body of available literature on primary spindle cell carcinoma of the ocular surface and ocular adnexa, which we have summarized. We hope that as more data becomes available, there will be clearer diagnostic and treatment algorithms for this uncommon presentation.

8.
J Eat Disord ; 12(1): 121, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169420

RESUMO

BACKGROUND: The oculomotor circuit spans many cortical and subcortical areas that have been implicated in psychiatric disease. This, combined with previous findings, suggests that eye tracking may be a useful method to investigate eating disorders. Therefore, this study aimed to assess oculomotor behaviors in youth with and without an eating disorder. METHODS: Female youth with and without an eating disorder completed a structured task involving randomly interleaved pro-saccade (toward at a stimulus) and anti-saccade (away from stimulus) trials with video-based eye tracking. Differences in saccades (rapid eye movements between two points), eye blinks and pupil were examined. RESULTS: Youth with an eating disorder (n = 65, Mage = 17.16 ± 3.5 years) were compared to healthy controls (HC; n = 65, Mage = 17.88 ± 4.3 years). The eating disorder group was composed of individuals with anorexia nervosa (n = 49), bulimia nervosa (n = 7) and other specified feeding or eating disorder (n = 9). The eating disorder group was further divided into two subgroups: individuals with a restrictive spectrum eating disorder (ED-R; n = 43) or a bulimic spectrum eating disorder (ED-BP; n = 22). In pro-saccade trials, the eating disorder group made significantly more fixation breaks than HCs (F(1,128) = 5.33, p = 0.023). The ED-BP group made the most anticipatory pro-saccades, followed by ED-R, then HCs (F(2,127) = 3.38, p = 0.037). Groups did not differ on rate of correct express or regular latency pro-saccades. In anti-saccade trials, groups only significantly differed on percentage of direction errors corrected (F(2, 127) = 4.554, p = 0.012). The eating disorder group had a significantly smaller baseline pupil size (F(2,127) = 3.60, p = 0.030) and slower pro-saccade dilation velocity (F(2,127) = 3.30, p = 0.040) compared to HCs. The ED-R group had the lowest blink probability during the intertrial interval (ITI), followed by ED-BP, with HCs having the highest ITI blink probability (F(2,125) = 3.63, p = 0.029). CONCLUSIONS: These results suggest that youth with an eating disorder may have different oculomotor behaviors during a structured eye tracking task. The oculomotor behavioral differences observed in this study presents an important step towards identifying neurobiological and cognitive contributions towards eating disorders.


Video based eye tracking is a promising method for studying differences between individuals with and without a psychiatric disease of interest. While some studies have explored oculomotor behaviors in individuals with an eating disorder, much remains unknown. The present study investigated saccades (fast eye movements between two points), eye blinks and pupil responses between female youth (aged 10­25 years) with and without an eating disorder during a pro-saccade (looking at a point) and anti-saccade (looking away from a point) eye tracking task. Individuals with an eating disorder made more pro-saccade guesses, had a smaller pupil size and blinked less before a trial started. In individuals with a restrictive type eating disorder (e.g., anorexia nervosa restrictive type), pupil responses may have a relationship with emotional dysregulation (poorly regulated emotional responses). Overall, this study represents an important step towards identifying oculomotor behavior differences in individuals with an eating disorder compared to controls.

9.
Viruses ; 16(8)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39205192

RESUMO

The SARS-CoV-2 main protease (Mpro) is initially synthesized as part of polyprotein precursors that undergo autoproteolysis to release the free mature Mpro. To investigate the autoprocessing mechanism in transfected mammalian cells, we examined several fusion precursors, with the mature SARS-CoV-2 Mpro along with the flanking amino acids (to keep the native substrate sequences) sandwiched between different tags. Our analyses revealed differential proteolysis kinetics at the N- and C-terminal cleavage sites. Particularly, N-terminal processing is differentially influenced by various upstream fusion tags (GST, sGST, CD63, and Nsp4) and amino acid variations at the N-terminal P1 position, suggesting that precursor catalysis is flexible and subject to complex regulation. Mutating Q to E at the N-terminal P1 position altered both precursor catalysis and the properties of the released Mpro. Interestingly, the wild-type precursors exhibited different enzymatic activities compared to those of the released Mpro, displaying much lower susceptibility to known inhibitors targeting the mature form. These findings suggest the precursors as alternative targets for antiviral development. Accordingly, we developed and validated a high-throughput screening (HTS)-compatible platform for functional screening of compounds targeting either the N-terminal processing of the SARS-CoV-2 Mpro precursor autoprocessing or the released mature Mpro through different mechanisms of action.


Assuntos
Antivirais , Proteases 3C de Coronavírus , SARS-CoV-2 , SARS-CoV-2/enzimologia , SARS-CoV-2/genética , SARS-CoV-2/efeitos dos fármacos , Humanos , Antivirais/farmacologia , Antivirais/metabolismo , Antivirais/química , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/genética , Proteases 3C de Coronavírus/química , Proteólise , Células HEK293 , Tratamento Farmacológico da COVID-19 , COVID-19/virologia
11.
J Neurosurg ; : 1-9, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39178472

RESUMO

OBJECTIVE: Chordomas are rare tumors that originate from undifferentiated remnants of the notochord. Currently, there are no established guidelines regarding the choice of adjuvant radiation modality for patients surgically treated for chordomas. Using a nationwide, multicenter database, the authors aimed to compare long-term survival outcomes associated with the use of proton or photon adjuvant therapy for the management of chordomas of skull base and spine. METHODS: The National Cancer Database (NCDB) was queried for chordoma cases from 2004 to 2017. Patient, tumor, and treatment characteristics were extracted from the database. The primary outcome was overall survival (OS). Kaplan-Meier survival analyses were conducted to investigate differences in outcome on propensity score-matched cohorts of patients treated with proton or photon adjuvant radiotherapy. RESULTS: Of the 3490 patients available, 424 met the inclusion criteria for this study. In the prematching analysis, patients receiving adjuvant photon therapy were significantly older (median age 57.0 vs 45.0 years, p < 0.001) and were more commonly male (61% vs 43%, p < 0.001) compared with those receiving proton therapy. Races were equally distributed among radiotherapy modalities (p = 0.64). Patients with chordomas of the mobile spine or sacrum were less likely to receive proton compared with photon therapy (37% vs 58%). Patients receiving proton therapy were more often represented among private insurance holders (69% vs 52%, p < 0.001) as well as in the highest income quartile (52% vs 40%, p = 0.008). Patients traveled farther to receive proton, as opposed to photon, therapy (median 59.0 vs 34.9 miles, p < 0.001). On postmatching Kaplan-Meier analysis encompassing all chordoma cases, no difference in OS between photon and proton therapy was revealed (HR 0.75, 95% CI 0.39-1.44; p = 0.39). A Kaplan-Meier analysis only including patients with skull base chordomas reached similar results (HR 0.83, 95% CI 0.31-2.22; p = 0.71). In patients with spine chordomas, however, a significant difference was found, as proton therapy exhibited a superior OS over photon therapy (HR 0.28, 95% CI 0.09-0.81; p = 0.012). CONCLUSIONS: Based on this nationwide analysis, patients with private insurance and higher income were more likely to receive proton adjuvant radiotherapy, while those with spinal or sacral chordomas were less likely to receive this modality. Despite this disparity, an OS benefit was observed in patients with chordomas of the spine and sacrum who received adjuvant proton therapy, in comparison with a matched cohort of patients treated with photon therapy. Conversely, this advantageous outcome was not evident in cases of chordomas located at the skull base.

12.
bioRxiv ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39091739

RESUMO

Cellular responses to environmental stimuli are typically thought to be governed by genetically encoded programs. We demonstrate that melanoma cells can form and maintain cellular memories during the acquisition of therapy resistance that exhibit characteristics of cellular learning and are dependent on the transcription factor AP-1. We show that cells exposed to a low dose of therapy adapt to become resistant to a high dose, demonstrating that resistance was not purely selective. The application of therapy itself results in the encoding of transient gene expression into cellular memory and that this encoding occurs for both transiently induced and probabilistically arising expression. Chromatin accessibility showed concomitant persistence. A two-color AP-1 reporter system showed that these memories are encoded in cis, constituting an example of activating cis epigenetics. Our findings establish the formation and maintenance of cellular memories as a critical aspect of gene regulation during the development of therapy resistance.

13.
BMC Cancer ; 24(1): 959, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107707

RESUMO

BACKGROUND: Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation. RESULTS: A total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03-3.19). CONCLUSIONS: Increased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival.


Assuntos
Metilação de DNA , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Características da Vizinhança , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Estados Unidos/epidemiologia , Fatores Socioeconômicos , Características de Residência
14.
Cancer Res Commun ; 4(8): 2282-2294, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39113608

RESUMO

As many as 30% of the patients with non-small cell lung cancer harbor oncogenic KRAS mutations, which leads to extensive remodeling of the tumor immune microenvironment. Although co-mutations in several genes have prognostic relevance in KRAS-mutated patients, their effect on tumor immunogenicity are poorly understood. In the present study, a total of 189 patients with non-small cell lung cancer underwent a standardized analysis including IHC, whole-exome DNA sequencing, and whole-transcriptome RNA sequencing. Patients with activating KRAS mutations demonstrated a significant increase in PDL1 expression and CD8+ T-cell infiltration. Both were increased in the presence of a co-occurring TP53 mutation and lost with STK11 co-mutation. Subsequent genomic analysis demonstrated that KRAS/TP53 co-mutated tumors had a significant decrease in the expression of glycolysis-associated genes and an increase in several genes involved in lipid metabolism, notably lipoprotein lipase, low-density lipoprotein receptor, and LDLRAD4. Conversely, in the immune-excluded KRAS/STK11 co-mutated group, we observed diminished lipid metabolism and no change in anaerobic glycolysis. Interestingly, in patients with low expression of lipoprotein lipase, low-density lipoprotein receptor, or LDLRAD4, KRAS mutations had no effect on tumor immunogenicity. However, in patients with robust expression of these genes, KRAS mutations were associated with increased immunogenicity and associated with improved overall survival. Our data further suggest that the loss of STK11 may function as a metabolic switch, suppressing lipid metabolism in favor of glycolysis, thereby negating KRAS-induced immunogenicity. Hence, this concept warrants continued exploration, both as a predictive biomarker and potential target for therapy in patients receiving ICI-based immunotherapy. SIGNIFICANCE: In patients with lung cancer, we demonstrate that KRAS mutations increase tumor immunogenicity; however, KRAS/STK11 co-mutated patients display an immune-excluded phenotype. KRAS/STK11 co-mutated patients also demonstrated significant downregulation of several key lipid metabolism genes, many of which were associated with increased immunogenicity and improved overall survival in KRAS-mutated patients. Hence, alteration to lipid metabolism warrants further study as a potential biomarker and target for therapy in patients with KRAS-mutated lung cancer.


Assuntos
Quinases Proteína-Quinases Ativadas por AMP , Carcinoma Pulmonar de Células não Pequenas , Metabolismo dos Lipídeos , Neoplasias Pulmonares , Mutação , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas Serina-Treonina Quinases/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Metabolismo dos Lipídeos/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Masculino , Feminino , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Idoso , Pessoa de Meia-Idade , Antígeno B7-H1/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
Pediatr Clin North Am ; 71(4): 693-706, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39003011

RESUMO

With recent gains in telehealth access across health sectors, this editorial explores adolescent-specific health issues where innovative use of virtual care is improving outcomes and access for adolescents. These include contraception, obesity, gender-affirming care, mental health, and eating disorder care. Clinicians caring for adolescents should be aware of advances in this field to maximize opportunities for their patients to receive evidence-based care in a manner that supports health equity and confidentiality concerns while understanding the evolving regulatory landscape of telehealth.


Assuntos
Saúde do Adolescente , Atenção Primária à Saúde , Telemedicina , Adolescente , Humanos , Serviços de Saúde do Adolescente , Acessibilidade aos Serviços de Saúde
17.
Mater Horiz ; 11(16): 3805-3818, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39005193

RESUMO

Recent advances in active materials and fabrication techniques have enabled the production of cyclically self-deployable metamaterials with an expanded functionality space. However, designing metamaterials that possess continuously tunable mechanical properties after self-deployment remains a challenge, notwithstanding its importance. Inspired by push puppets, we introduce an efficient design strategy to create reversibly self-deployable metamaterials with continuously tunable post-deployment stiffness and damping. Our metamaterial comprises contracting actuators threaded through beads with matching conical concavo-convex interfaces in networked chains. The slack network conforms to arbitrary shapes, but when actuated, it self-assembles into a preprogrammed configuration with beads gathered together. Further contraction of the actuators can dynamically tune the assembly's mechanical properties through the beads' particle jamming, while maintaining the overall structure with minimal change. We show that, after deployment, such metamaterials exhibit pronounced tunability in bending-dominated configurations: they can become more than 35 times stiffer and change their damping capability by over 50%. Through systematic analysis, we find that the beads' conical angle can introduce geometric nonlinearity, which has a major effect on the self-deployability and tunability of the metamaterial. Our work provides routes towards reversibly self-deployable, lightweight, and tunable metamaterials, with potential applications in soft robotics, reconfigurable architectures, and space engineering.

18.
bioRxiv ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39005406

RESUMO

Resistance to cancer therapy is driven by both cell-intrinsic and microenvironmental factors. Previous work has revealed that multiple resistant cell fates emerge in melanoma following treatment with targeted therapy and that, in vitro, these resistant fates are determined by the transcriptional state of individual cells prior to exposure to treatment. What remains unclear is whether these resistant fates are shared across different genetic backgrounds and how, if at all, these resistant fates interact with the tumor microenvironment. Through spatial transcriptomics and single-cell RNA sequencing, we uncovered distinct resistance programs in melanoma cells shaped by both intrinsic cellular states and the tumor microenvironment. Consensus non-negative matrix factorization revealed shared intrinsic resistance programs across different cell lines, highlighting the presence of universal and unique resistance pathways. In patient samples, we demonstrated that these resistance programs coexist within individual tumors and associate with diverse immune signatures, suggesting that the tumor microenvironment and distribution of resistant fates are closely connected. Single-cell resolution spatial transcriptomics in xenograft models revealed both intrinsically determined and extrinsically influenced resistant fates. Overall, this work demonstrates that each therapy resistant fate coexists with a distinct immune microenvironment in tumors and that, in vivo, tissue features, such as regions of necrosis, can influence which resistant fate is adopted.

19.
World J Gastrointest Endosc ; 16(6): 335-342, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38946853

RESUMO

BACKGROUND: Improved adenoma detection rate (ADR) has been demonstrated with artificial intelligence (AI)-assisted colonoscopy. However, data on the real-world application of AI and its effect on colorectal cancer (CRC) screening outcomes is limited. AIM: To analyze the long-term impact of AI on a diverse at-risk patient population undergoing diagnostic colonoscopy for positive CRC screening tests or symptoms. METHODS: AI software (GI Genius, Medtronic) was implemented into the standard procedure protocol in November 2022. Data was collected on patient demographics, procedure indication, polyp size, location, and pathology. CRC screening outcomes were evaluated before and at different intervals after AI introduction with one year of follow-up. RESULTS: We evaluated 1008 colonoscopies (278 pre-AI, 255 early post-AI, 285 established post-AI, and 190 late post-AI). The ADR was 38.1% pre-AI, 42.0% early post-AI (P = 0.77), 40.0% established post-AI (P = 0.44), and 39.5% late post-AI (P = 0.77). There were no significant differences in polyp detection rate (PDR, baseline 59.7%), advanced ADR (baseline 16.2%), and non-neoplastic PDR (baseline 30.0%) before and after AI introduction. CONCLUSION: In patients with an increased pre-test probability of having an abnormal colonoscopy, the current generation of AI did not yield enhanced CRC screening metrics over high-quality colonoscopy. Although the potential of AI in colonoscopy is undisputed, current AI technology may not universally elevate screening metrics across all situations and patient populations. Future studies that analyze different AI systems across various patient populations are needed to determine the most effective role of AI in optimizing CRC screening in clinical practice.

20.
Anticancer Res ; 44(8): 3375-3380, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39060061

RESUMO

BACKGROUND/AIM: Allostatic load (AL) is a measure of chronic stress that is associated with worse cancer outcomes. The purpose of this retrospective cohort study was to investigate the relationship between AL and uveal melanoma (UM) clinical features. PATIENTS AND METHODS: AL score was calculated as a composite of ten biomarkers in 111 patients with UM from the University of Illinois Hospital. One point was assigned to an AL score for each biomarker based on predetermined cutoff values. Linear and logistic regression analyses evaluated the relationship between AL score and several tumor clinical characteristics. RESULTS: High AL score had a significant relationship with extraocular extension (p=0.015). There was also a significant difference in mean blood glucose levels between the different tumor size groups (p=0.029). Higher AL scores also had a trend of being associated with a smaller tumor size (p=0.069). CONCLUSION: AL score was significantly associated with the presence of extraocular extension for uveal melanoma, while the smallest tumor size group was associated with the highest blood glucose level. No other significant correlations were found between AL and other clinical features of UM. The relationship between AL score and extraocular extension warrants further investigation. Additional research is needed to evaluate socioeconomic factors and their effect on the relationship between chronic stress and the clinical features of UM.


Assuntos
Alostase , Melanoma , Neoplasias Uveais , Humanos , Neoplasias Uveais/patologia , Melanoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Alostase/fisiologia , Adulto , Glicemia/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/sangue , Idoso de 80 Anos ou mais
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