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1.
Chem Biodivers ; : e202400719, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958461

RESUMEN

A versatile and efficient chemo selective synthesis of 4-aryl-3-formyl-2H-chromenes (AFC) was undertaken using Pd-catalyzed cross-coupling conditions. The key oxidative transmetalation was successfully applied to a significant range of substitutions on the chromene moiety and aryl ring in Ar(BOH)3, accommodating both electron-rich and electron-deficient groups. These π-extended scaffolds exhibited green-yellow fluorescence with a large Stokes shift and high quantum yield. Measurement of photophysical properties revealed that the compound with methoxy substitution in the chromene ring, 3t, caused a significant bathochromic shift. The AFCs obtained from this method can be transformed into biologically active 4-aryl-3-iminoantipyrine-2H-chromenes (AAC) through functionalization of the formyl chromenes. The AFCs and AACs with methoxy substitutions (3t and 4e) were docked against AChE inhibition, and compound 4e had the lowest binding energy of -11.20 kcal/mol. DFT calculations performed on representative compounds revealed that compound 4e is more reactive than 3t, which is in accordance with the docking studies.

2.
Inorg Chem ; 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38946199

RESUMEN

The functionalization of polyoxovanadate clusters is promising but of great challenge due to the versatile coordination geometry and oxidation state of vanadium. Here, two unprecedented silsesquioxane ligand-protected "fully reduced" polyoxovanadate clusters were fabricated via a facial solvothermal methodology. The initial mixture of the two polyoxovanadate clusters with different colors and morphologies (green plate V14 and blue block V6) was successfully separated as pure phases by meticulously controlling the assembly conditions. Therein, the V14 cluster is the highest-nuclearity V-silsesquioxane cluster to date. Moreover, the transformation from a dimeric silsesquioxane ligand-protected V14 cluster to a cyclic hexameric silsesquioxane ligand-protected V6 cluster was also achieved, and the possible mechanism termed "ligand-condensation-involved dissociation reassembly" was proposed to explain this intricate conversion process. In addition, the robust V6 cluster was served as a heterogeneous catalyst for the synthesis of important heterocyclic compounds, quinazolinones, starting from 2-aminobenzamide and aldehydes. The V6 cluster exhibits high activity and selectivity to access pure quinazolinones under mild conditions, where the high selectivity was attributed to the confinement effect of the macrocyclic silsesquioxane ligand constraining the molecular freedom of the reaction species. The stability and recyclability as well as the tolerance of a wide scope of aldehyde substrates endow the V6 cluster with a superior performance and appreciable potential in catalytic applications.

3.
Cancer Lett ; : 217100, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38969158

RESUMEN

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7%) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio=2.14, 95% CI=1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR=2.5, 95%CI=1.3-4.7) and PD-1 inhibitors (multivariate HR=2.0, 95%CI=1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value=0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.

4.
Eur Radiol ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834786

RESUMEN

OBJECTIVES: We aimed to develop and validate a radiomics nomogram based on dual-energy computed tomography (DECT) images and clinical features to classify the time since stroke (TSS), which could facilitate stroke decision-making. MATERIALS AND METHODS: This retrospective three-center study consecutively included 488 stroke patients who underwent DECT between August 2016 and August 2022. The eligible patients were divided into training, test, and validation cohorts according to the center. The patients were classified into two groups based on an estimated TSS threshold of ≤ 4.5 h. Virtual images optimized the visibility of early ischemic lesions with more CT attenuation. A total of 535 radiomics features were extracted from polyenergetic, iodine concentration, virtual monoenergetic, and non-contrast images reconstructed using DECT. Demographic factors were assessed to build a clinical model. A radiomics nomogram was a tool that the Rad score and clinical factors to classify the TSS using multivariate logistic regression analysis. Predictive performance was evaluated using receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA) was used to compare the clinical utility and benefits of different models. RESULTS: Twelve features were used to build the radiomics model. The nomogram incorporating both clinical and radiomics features showed favorable predictive value for TSS. In the validation cohort, the nomogram showed a higher AUC than the radiomics-only and clinical-only models (AUC: 0.936 vs 0.905 vs 0.824). DCA demonstrated the clinical utility of the radiomics nomogram model. CONCLUSIONS: The DECT-based radiomics nomogram provides a promising approach to predicting the TSS of patients. CLINICAL RELEVANCE STATEMENT: The findings support the potential clinical use of DECT-based radiomics nomograms for predicting the TSS. KEY POINTS: Accurately determining the TSS onset is crucial in deciding a treatment approach. The radiomics-clinical nomogram showed the best performance for predicting the TSS. Using the developed model to identify patients at different times since stroke can facilitate individualized management.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38851486

RESUMEN

BACKGROUND: The relationship between keratoconus and various allergic diseases has been a subject of controversy. OBJECTIVE: In the present study, a systematic review and meta-analysis was conducted to investigate the association between allergic rhinitis (AR) and keratoconus. METHODS: Relevant and eligible studies from PubMed, Web of Science, and Cochrane Library were systematically reviewed to evaluate the association between AR and keratoconus. Observational studies containing the number of patients with and without keratoconus and the number of patients with keratoconus diagnosed with or without AR were included. Two reviewers independently screened for eligible studies and extracted data from the included studies. A bivariate meta-analysis was conducted to compare the odds of keratoconus occurrence in patients with and without AR. The main outcome was the odds ratio of keratoconus occurrence in patients with AR. A sensitivity test was performed using the adjusted odds ratio reported in the included studies to validate the findings. RESULTS: Seven studies involving 775,574 participants were included in this meta-analysis. Among them, 29,082 patients had keratoconus. The pooled odds ratio of keratoconus occurrence in patients with AR was 1.71 (95% confidence interval [CI]: 1.36-2.15; P < 0.001; I2 = 96%), and the pooled adjusted odds ratio was 1.72 (95% CI: 1.23-2.40; P = 0.001; I2 = 97%). CONCLUSION: Patients with AR showed significantly higher odds of keratoconus occurrence than those without AR. Future studies are warranted to investigate the causal relationship and evaluate the cost-effectiveness of early screening using methods such as corneal topography and referral for keratoconus in patients with AR.

7.
Viruses ; 16(6)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38932232

RESUMEN

Background: The effects of antihistamines on cancer risk and prognosis have been inconsistent across cancers. The aim of this multi-center cohort study was to investigate the association between antihistamine use and the risk of liver cancer in individuals with viral hepatitis. Methods: This multi-center cohort study included individuals diagnosed with hepatitis B or hepatitis C between January 2008 and March 2022. For antihistamine-treated patients, the index date was the date of antihistamine prescription, and for non-users, it was the date of hepatitis diagnosis. Participants were followed for five years, with the primary outcome of interest being new-onset liver cancer. The incidence rate and the adjusted hazard ratio (aHR) along with its 95% confidence interval (CI) of the outcome were calculated. Subgroup analyses were conducted, stratified by types of viral hepatitis including hepatitis C and hepatitis B. An additional validation study was performed. Results: The study included a total of 7748 patients with viral hepatitis. The incidence rate was 12.58 per 1000 person-years in patients with viral hepatitis on antihistamines, compared to 3.88 per 1000 person-years in those without antihistamine use. After adjusting for factors including age, sex, body mass index (BMI), comorbidities, laboratory data of liver function tests, comedications, and the use of antiviral therapies, the risk of new-onset liver cancer was significantly higher in patients on antihistamines (aHR = 1.83, 95% CI, 1.28-2.60). In patients with hepatitis C, the incidence rate in the antihistamine group was 15.73 per 1000 person-years, while non-users had a rate of 4.79 per 1000 person-years. Patients with hepatitis C on antihistamines had a significantly higher risk of developing liver cancer (aHR = 3.24, 95% CI, 2.16-4.86). Conclusions: This multi-center cohort study reported an increased risk of liver cancer in patients with hepatitis B or hepatitis C treated with antihistamines. Long-term follow-up studies are warranted to validate the findings.


Asunto(s)
Antagonistas de los Receptores Histamínicos , Neoplasias Hepáticas , Humanos , Femenino , Masculino , Antagonistas de los Receptores Histamínicos/uso terapéutico , Antagonistas de los Receptores Histamínicos/efectos adversos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Persona de Mediana Edad , Incidencia , Estudios de Cohortes , Factores de Riesgo , Adulto , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Anciano
8.
Cell Commun Signal ; 22(1): 259, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715050

RESUMEN

Ubiquitination and deubiquitination are important forms of posttranslational modification that govern protein homeostasis. Deubiquitinating enzymes (DUBs), a protein superfamily consisting of more than 100 members, deconjugate ubiquitin chains from client proteins to regulate cellular homeostasis. However, the dysregulation of DUBs is reportedly associated with several diseases, including cancer. The tumor microenvironment (TME) is a highly complex entity comprising diverse noncancerous cells (e.g., immune cells and stromal cells) and the extracellular matrix (ECM). Since TME heterogeneity is closely related to tumorigenesis and immune evasion, targeting TME components has recently been considered an attractive therapeutic strategy for restoring antitumor immunity. Emerging studies have revealed the involvement of DUBs in immune modulation within the TME, including the regulation of immune checkpoints and immunocyte infiltration and function, which renders DUBs promising for potent cancer immunotherapy. Nevertheless, the roles of DUBs in the crosstalk between tumors and their surrounding components have not been comprehensively reviewed. In this review, we discuss the involvement of DUBs in the dynamic interplay between tumors, immune cells, and stromal cells and illustrate how dysregulated DUBs facilitate immune evasion and promote tumor progression. We also summarize potential small molecules that target DUBs to alleviate immunosuppression and suppress tumorigenesis. Finally, we discuss the prospects and challenges regarding the targeting of DUBs in cancer immunotherapeutics and several urgent problems that warrant further investigation.


Asunto(s)
Enzimas Desubicuitinizantes , Microambiente Tumoral , Humanos , Enzimas Desubicuitinizantes/metabolismo , Evasión Inmune , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/enzimología , Neoplasias/metabolismo , Escape del Tumor , Microambiente Tumoral/inmunología , Ubiquitinación
10.
Genome Biol ; 25(1): 141, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807159

RESUMEN

BACKGROUND: Reproductive isolation can result from adaptive processes (e.g., ecological speciation and mutation-order speciation) or stochastic processes such as "system drift" model. Ecological speciation predicts barriers to gene flow between populations from different environments, but not among replicate populations from the same environment. In contrast, reproductive isolation among populations independently adapted to the same/similar environment can arise from both mutation-order speciation or system drift. RESULTS: In experimentally evolved populations adapting to a hot environment for over 100 generations, we find evidence for pre- and postmating reproductive isolation. On one hand, an altered lipid metabolism and cuticular hydrocarbon composition pointed to possible premating barriers between the ancestral and replicate evolved populations. On the other hand, the pronounced gene expression differences in male reproductive genes may underlie the postmating isolation among replicate evolved populations adapting to the same environment with the same standing genetic variation. CONCLUSION: Our study confirms that replicated evolution experiments provide valuable insights into the mechanisms of speciation. The rapid emergence of the premating reproductive isolation during temperature adaptation showcases incipient ecological speciation. The potential evidence of postmating reproductive isolation among replicates gave rise to two hypotheses: (1) mutation-order speciation through a common selection on early fecundity leading to an inherent inter-locus sexual conflict; (2) system drift with genetic drift along the neutral ridges.


Asunto(s)
Calor , Aislamiento Reproductivo , Masculino , Adaptación Fisiológica/genética , Animales , Femenino , Especiación Genética , Metabolismo de los Lípidos
11.
Clin Cosmet Investig Dermatol ; 17: 953-959, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699407

RESUMEN

Squamous cell carcinoma (SCC) in situ can occur on any skin or mucus surface and is more commonly found in elderly patients on areas of skin that have been sunburnt. Most previous case reports are from dermatologists, with few published reports from pathologists. In this study, three patients underwent pathological routine and auxiliary immunohistochemical (IHC) examination and were ultimately diagnosed with pagetoid SCC in situ - a different diagnosis from the initial clinical assessment. All three patients received a complete resection of the skin mass. After follow-up, as of June 2023, the patients had no tumour recurrence or metastasis. Pagetoid SCC in situ is a particular type of SCC in situ that has no specific features in clinical manifestations, gross diagnosis or histopathological sections. The final diagnosis depends on IHC staining. Pagetoid SCC in situ expresses EMA, CK5/6 and p63 but not CEA, CK8 or S-100, which are expressed in extramammary Paget's disease. Pagetoid SCC in situ is usually only locally invasive, and the main treatment is complete surgical resection. The prognosis is related to human papillomavirus infection, surgical margin closure, disease location, tumour thickness and other factors.

12.
BMC Public Health ; 24(1): 1405, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802740

RESUMEN

BACKGROUND: In an effort to identify factors associated with frailty transitions that trigger a significant difference in preventing and postponing the progression of frailty, questions regarding the role of cognitive leisure activities on various aspects of older adults' health were raised. However, the relationship between cognitive leisure activities and frailty transitions has rarely been studied. METHODS: A total of 5367 older Chinese adults aged over 60 years from the China Health and Retirement Longitudinal Study (CHARLS) were selected as participants. The 2nd wave of the CHARLS in 2013 was selected as the baseline, and sociodemographic and health-related status baseline data were collected. The FRAIL Scale was used to measure frailty, while cognitive leisure activities were measured by the Cognitive Leisure Activity Index (CLAI) scores, which consisted of playing mahjong or cards, stock investment, and using the internet. After two years of follow-up, frailty transition from baseline was assessed at the 3rd wave of the CHARLS in 2015. Ordinal logistic regression analysis was used to examine the relationship between cognitive leisure activities and frailty transitions. RESULTS: During the two-year follow-up of 5367 participants, the prevalence of frailty that improved, remained the same and worsened was 17.8% (957/5367), 57.5% (3084/5367) and 24.7% (1326/5367), respectively. Among all participants, 79.7% (4276/5367), 19.6% (1054/5367), and 0.7% (37/5367) had CLAI scores of 0, 1, and 2 to 3, respectively. In the univariate analysis, there was a statistically significant association between a score of 2 to 3 on the Cognitive Leisure Activity Index and frailty transitions (odds ratio [OR] = 1.93, 95% CI 0.03 to 1.29, p = .04), while all other covariates were not significantly different across the three groups. After adjusting for covariates, participants with more cognitive leisure activities had a higher risk of frailty improvement than those without cognitive leisure activities (odds ratio [OR] = 1.99, 95% CI 1.05 to 3.76, p = .04). CONCLUSIONS: Cognitive leisure activities were positively associated with the risk of frailty improvement in older adults, mainly when participating in multiple such activities. Older adults may be encouraged to participate in a wide variety of cognitive leisure activities to promote healthy aging.


Asunto(s)
Cognición , Fragilidad , Actividades Recreativas , Humanos , Actividades Recreativas/psicología , China/epidemiología , Anciano , Estudios Longitudinales , Masculino , Femenino , Persona de Mediana Edad , Fragilidad/psicología , Fragilidad/epidemiología , Anciano de 80 o más Años , Anciano Frágil/psicología , Anciano Frágil/estadística & datos numéricos
14.
bioRxiv ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38765969

RESUMEN

Investigating the intricate and rapid folding kinetics of large RNA-protein complexes (RNPs), like the bacterial ribosome, remains a formidable challenge in structural biology. Previous genetic approaches to probe assembly have focused on modulating the expression of either r-proteins or assembly factors. Here, anti-sense oligonucleotides (ASOs) were used to disrupt native RNA/RNA and RNA/protein interactions, in order to generate novel folding intermediates. In an in vitro co-transcriptional assembly assay, 8 assembly inhibitor ASOs were identified. Using cryo-electron microscopy, 38 new intermediate structures were determined resulting from the specific inhibitions. In particular a novel intermediate class provided compelling evidence of independent rRNA domain folding before proper interdomain docking. Three PNAs targeting domain-I of 23S-rRNA further subdivided the previously identified assembly core into smaller blocks representing the earliest steps in assembly. The resulting assembly graph reveals template-directed RNA foldon docking and domain consolidation, which provides a hierarchical view of the RNP assembly process.

15.
Crit Rev Oncol Hematol ; : 104386, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38735505

RESUMEN

INTRODUCTION: The use of nanoliposomal irinotecan (nal-IRI) is a novel regimen for pancreatic cancer, featuring a longer half-life and increased area under the concentration-time curve. However, comprehensive systematic reviews or meta-analyses evaluating its efficacy as a second-line treatment have been scarce. Therefore, this study aims to review the current body of evidence on nal-IRI, assessing its overall clinical performances regarding the disease. METHODS: A systemic literature search was conducted based on articles published before September 26, 2023 in PubMed, Cochrane Library, EMBASE, and Web of Science databases. The fixed effect model was performed to calculate pooled mean difference and odds ratio for essential outcomes, such as overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and adverse events. RESULTS: A total of 21 studies, including 3017 patients with locally advanced unresectable or metastatic pancreatic cancers, were considered eligible. The use of nal-IRI, together with 5-fluorouracil and leucovorin, resulted in significantly improved PFS and OS, with a pooled mean difference of 1.01 months (95% confidence interval (95%CI)=0.97-1.05, p<0.01) and 0.29 months (95% CI=0.18-0.39, p<0.01) respectively; a pooled risk ratio of 2.06 (95%CI=1.30-3.27, p=0.002) for ORR compared to other second-line regimens. Nonetheless, an increased risk of grade 3 or greater neutropenia, anemia, hypokalemia, diarrhea, and vomiting was also noted. CONCLUSION: Nal-IRI-based second-line treatments exhibited significantly improved PFS, OS and ORR compared to other available treatments in advanced pancreatic cancer. Further research is necessary to corroborate these findings and define the role of nal-IRI in both first and later lines of therapy.

16.
Ann Clin Lab Sci ; 54(2): 254-257, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38802163

RESUMEN

OBJECTIVE: The present study aims to explore the clinicopathological characteristics of Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (IFDCS; EBV+ IFDCS). CASE REPORT: The case involved a 32-year-old woman who underwent surgical resection of a splenic nodule. Histological examination and immunohistochemistry were performed using cluster of differentiation (CD) markers, and in-situ hybridization was conducted to detect EBV-encoded RNA (EBER). RESULTS: A microscopic analysis revealed neoplastic cells with various morphologies, including round, ovoid, or spindled shapes, dispersed within a prominent lymphoplasmacytic infiltrate. The tumor cells exhibited nuclear atypia, with some resembling Reed-Sternberg cells. The immunohistochemistry demonstrated focal positivity for follicular dendritic cell markers, such as CD21, CD23 and CD35, and focal negativity for other markers, including CD3, CD34, CD20, CD79a, myeloperoxidase and HMB45. Additionally, the EBER staining showed strongly positive results. The patient showed no local recurrence or metastasis during the 13-month follow-up. CONCLUSION: A comprehensive understanding of EBV+IFDCS, including its clinicopathological features and immunohistochemical characteristics, is crucial for accurate diagnosis and differential diagnosis of this rare tumor.


Asunto(s)
Sarcoma de Células Dendríticas Foliculares , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Femenino , Sarcoma de Células Dendríticas Foliculares/patología , Sarcoma de Células Dendríticas Foliculares/virología , Sarcoma de Células Dendríticas Foliculares/diagnóstico , Adulto , Herpesvirus Humano 4/aislamiento & purificación , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/diagnóstico , Neoplasias del Bazo/patología , Neoplasias del Bazo/virología , Neoplasias del Bazo/diagnóstico , Inmunohistoquímica , Inflamación/patología , Inflamación/virología
17.
J Med Virol ; 96(4): e29549, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38563352

RESUMEN

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.


Asunto(s)
Infecciones por Papillomavirus , Embarazo , Femenino , Humanos , Recién Nacido , Adulto , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Investigación , Taiwán/epidemiología , Factores de Riesgo
18.
Opt Express ; 32(7): 12601-12608, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571078

RESUMEN

Silicon avalanche photodiode (APD) single-photon detectors in space are continuously affected by radiation, which gradually degrades their dark count performance. From August 2016 to June 2023, we conducted approximately seven years (2507 days) of in-orbit monitoring of the dark count performance of APD single-photon detectors on the Micius Quantum Science Experimental Satellite. The results showed that due to radiation effects, the dark count growth rate was approximately 6.79 cps/day @ -24 °C and 0.37 cps/day @ -55 °C, with a significant suppression effect on radiation-induced dark counts at lower operating temperature. Based on the proposed radiation damage induced dark count annealing model, simulations were conducted for the in-orbit dark counts of the detector, the simulation results are consistent with in-orbit test data. In May 2022, four of these detectors underwent a cumulative 5.7 hours high-temperature annealing test at 76 °C, dark count rate shows no measurable changes, consistent with annealing model. As of now, these ten APD single-photon detectors on the Micius Quantum Science Experimental Satellite have been in operation for approximately 2507 days and are still functioning properly, providing valuable experience for the future long-term space applications of silicon APD single-photon detectors.

19.
Opt Express ; 32(7): 12645-12655, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571082

RESUMEN

The space time frequency transfer plays a crucial role in applications such as space optical clock networks, navigation, satellite ranging, and space quantum communication. Here, we propose a high-precision space time frequency transfer and time synchronization scheme based on a simple intensity modulation/direct detection (IM/DD) laser communication system, which occupies a communication bandwidth of approximately 0.2%. Furthermore, utilizing an optical-frequency comb time frequency transfer system as an out-of-loop reference, experimental verification was conducted on a 113 km horizontal atmospheric link, with a long-term stability approximately 8.3 × 10-16 over a duration of 7800 seconds. Over an 11-hour period, the peak-to-peak wander is approximately 100 ps. Our work establishes the foundation of the time frequency transfer, based on the space laser communication channel, for future ground-to-space and inter-satellite links.

20.
Front Immunol ; 15: 1331994, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562939

RESUMEN

Introduction: No prior meta-analysis has investigated the impact of programmed cell death protein 1 (PD-1) inhibitor therapy on survival outcomes in patients with advanced or recurrent uterine cancers (including both corpus and cervical cancers). Methods: A comprehensive search of PubMed and Embase databases was conducted, covering the past 10 years (up to August 2023) and encompassing all clinical research related to uterine cancer. Five randomized controlled trials and one cohort study met the inclusion criteria and were included in the meta-analysis. Data on patient demographics, clinical characteristics, treatment regimens, and survival outcomes were extracted. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as the relative risk of grade 3 or higher adverse events, were pooled using random-effects models. Results: Patients receiving PD-1 inhibitors had better OS (HR, 0.65, 95% CI, 0.59-0.72; P<.001) and PFS (HR, 0.59, 95% CI, 0.49-0.70; P<.001) than those receiving variable non-PD-1 inhibitor therapies among 3452 uterine cancer patients. The leave-one-out meta-analysis of the HR of OS showed no individual study impact on the estimation of the overall effect size. Subgroup analysis revealed better OS in the PD-1 inhibitors use than the controls in cervical cancer (HR, 0.68, 95% CI, 0.59-0.79), endometrial cancer (HR, 0.62, 95% CI, 0.54-0.72), and pembrolizumab use (HR, 0.66, 95% CI, 0.57-0.75) subgroups. Patients with advanced cervical cancer, who had CPS > 1, receiving PD-1 inhibitors have statistically significant benefits in OS compared to controls (HR, 0.65, 95% CI, 0.53-0.80). The pooled HR for overall survival was 0.71 (95% CI, 0.60-0.82; P<.001) in patients who received PD-1 inhibitors as compared to those who did not receive PD-1 inhibitors in proficient mismatch repair (MMR) endometrial cancer patients. However, in deficient MMR patients, the HR was 0.30 (95% CI, 0.13-0.70). The relative risk of grade 3 or higher adverse events was not higher in the PD-1 inhibitor group (relative risk, 1.12, 95% CI, 0.98-1.27). Conclusion: Survival was significantly better using PD-1 inhibitor therapy than variable non-PD-1 inhibitor chemotherapies among patients with advanced or recurrent uterine cancers.


Asunto(s)
Neoplasias Endometriales , Neoplasias del Cuello Uterino , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico , Estudios de Cohortes , Recurrencia Local de Neoplasia
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