HOTAIR Promotes the Hyperactivation of PI3K/Akt and Wnt/ß-Catenin Signaling Pathways via PTEN Hypermethylation in Cervical Cancer.

The mechanisms underlying the sustained activation of the PI3K/AKT and Wnt/ß-catenin pathways mediated by HOTAIR in cervical cancer (CC) have not been extensively described. To address this knowledge gap in the literature, we explored the interactions between these pathways by driving HOTAIR expression levels in HeLa cells. Our findings reveal that HOTAIR is a key regulator in sustaining the activation of both signaling pathways. Specifically, altering HOTAIR expression-either by knockdown or overexpression-significantly influenced the transcriptional activity of the PI3K/AKT and Wnt/ß-catenin pathways. Additionally, we discovered that HIF1α directly induces HOTAIR transcription, which in turn leads to the epigenetic silencing of the PTEN promoter via DNMT1. This process leads to the sustained activation of both pathways, highlighting a novel regulatory axis involving HOTAIR and HIF1α in cervical cancer. Our results suggest a new model in which HOTAIR sustains reciprocal activation of the PI3K/AKT and Wnt/ß-catenin pathways through the HOTAIR/HIF1α axis, thereby contributing to the oncogenic phenotype of cervical cancer.

Genomic landscape of early-stage prostate adenocarcinoma in Mexican patients: an exploratory study.

BACKGROUND: Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients. METHODS: Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants. RESULTS: Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA's. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified. CONCLUSIONS: This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.

A microRNA Profile Regulates Inflammation-Related Signaling Pathways in Young Women with Locally Advanced Cervical Cancer.

Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.

Predictors of Endocrine Resistance in a Cohort of Mexican Breast Cancer Patients.

Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.

The every woman study™ low- and middle-income countries edition protocol: A multi-country observational study to assess opportunities and challenges to improving survival and quality of life for women with ovarian cancer.

BACKGROUND: Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap. METHODS: This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team. CONCLUSION: This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.

A retrospective analysis of perioperative medications for opioid-use disorder and tapering additional postsurgical opioids via a transitional pain service.

AIMS: To investigate perioperative opioid requirements in patients on methadone or buprenorphine as medication for opioid-use disorder (MOUD) who attended a transitional pain clinic (Personalized Pain Program, PPP). METHODS: This retrospective cohort study assessed adults on MOUD with surgery and attendance at the Johns Hopkins PPP between 2017 and 2022. Daily non-MOUD opioid use over 6 time-points was evaluated with regression models controlling for days since surgery. The time to complete non-MOUD opioid taper was analysed by accelerated failure time and Kaplan-Meier models. RESULTS: Fifty patients (28 on methadone, 22 on buprenorphine) were included with a median age of 44.3 years, 54% male, 62% Caucasian and 54% unemployed. MOUD inpatient administration occurred in 92.8% of patients on preoperative methadone but only in 36.3% of patients on preoperative buprenorphine. Non-MOUD opioid use decreased over time postoperatively (ß = -0.54, P < .001) with a median decrease of 90 mg morphine equivalents (MME) between the first and last PPP visit, resulting in 46% tapered off by PPP completion. Older age and duration in PPP were associated with lower MME, while mental health conditions, longer hospital stays and higher discharge opioid prescriptions were associated with higher MME. The average time to non-MOUD opioid taper was 1.79× longer in patients on buprenorphine (P = .026), 2.75× in males (P = .023), 4.66× with mental health conditions (P < .001), 2.37× with chronic pain (P = .031) and 3.51× if on preoperative non-MOUD opioids; however, higher initial MOUD level decreased time to taper (P = .001). CONCLUSIONS: Postoperative opioid tapering utilizing a transitional pain service is possible in patients on MOUD.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

Factors Associated with Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy.

INTRODUCTION: Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. METHODS: Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. RESULTS: We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread (P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread (P = 0.002). CONCLUSION: Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence.

CT-guided core needle biopsies of head and neck tumors: a comprehensive monocenter analysis of safety and outcomes.

BACKGROUND: Although core needle biopsy is an important tool in minimally invasive tissue sampling and diagnostics for head and neck masses, comprehensive data about safety and outcomes is lacking. PURPOSE: To retrospectively evaluate the diagnostic performance and safety of computed tomography (CT)-guided percutaneous core needle biopsy of head and neck masses. MATERIAL AND METHODS: This retrospective single-center study included patients from 04/2007 to 12/2021, and a total of 156 core needle biopsies were evaluated. The initial histopathological results were compared with the long-term final diagnosis to evaluate the diagnostic yield of CT-guided core needle biopsies. The patients' age, sex, and history of malignancy, as well as procedural complications and radiation exposure were collected. RESULTS: A total of 156 biopsies of 150 patients (mean age 56 years ± 17; 89 men) were evaluated. 57.3% (86/150) of patients had a history of malignancy. 55.1% (86/156) of the lesions were accessed by an infrahyoid needle approach. 92.9% (145/156) of biopsies yielded conclusive results. There were no false positives and 4 false negatives, resulting in a total false negative rate of 2.7% (4/145) and a total diagnostic yield of 90.4% (141/156). There were nine puncture-related complications (9/156-5.7%). None of the complications required further reintervention. The average dose length product was 311.3 mGy × cm. CONCLUSION: CT-guided core needle biopsies of head and neck masses showed excellent results with high diagnostic yield and clinical safety. CLINICAL RELEVANCE STATEMENT: General anesthesia for open biopsy carries a higher risk for elderly patients, and fine needle aspiration has a poor reputation in terms of its diagnostic yield. This study focuses on safety and diagnostic yield of CT-guided core needle biopsies. KEY POINTS: • CT-guided core needle biopsy in head and neck tumors was a reliable and safe procedure. • The most common cause for an inconclusive biopsy result was a shortage of tissue collected during the biopsy. • During our study period of nearly 15 years, the radiation exposure of head and neck biopsies decreased.

A Novel Microsnare and Microwire Coil Retrieval Technique.

Coil migration during endovascular embolization is a complication that can result in thromboembolic occlusion leading to potentially large infarcts if not removed. Microsnares are commonly used to remove migrated coils. Current techniques, however, struggle in cases where the microsnare is unable to loop over and secure a free end of the coil. We present a case in which a microsnare combined with a microwire successfully removed a migrated coil in a patient with a bleeding hepatic pseudoaneurysm post-embolization. This technique proved beneficial when traditional methods were insufficient, especially in small vessels or coil packs that cannot be snared. The synergy of the microsnare and microwire technique presents a promising solution for challenging migrated coil retrievals.

Air Pollution and Lung Cancer: Contributions of Extracellular Vesicles as Pathogenic Mechanisms and Clinical Utility.

PURPOSE OF REVIEW: This review addresses the pressing issue of air pollution's threat to human health, focusing on its connection to non-small cell lung cancer (NSCLC) development. The aim is to explore the role of extracellular vesicles (EVs) as potential pathogenic mechanisms in lung cancer, including NSCLC, induced by air pollutants. RECENT FINDINGS: Recent research highlights EVs as vital mediators of intercellular communication and key contributors to cancer progression. Notably, this review emphasizes the cargo of EVs released by both cancerous and non-cancerous lung cells, shedding light on their potential role in promoting various aspects of tumor development. The review underscores the importance of comprehending the intricate interplay between air pollution, biological damage mechanisms, and EV-mediated communication during NSCLC development. Major takeaways emphasize the significance of this understanding in addressing air pollution-related lung cancer. Future research avenues are also highlighted, aiming to enhance the applicability of EVs for diagnosis and targeted therapies, ultimately mitigating the inevitable impact of air pollution on NSCLC development and treatment.

Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet).

Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< -1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA-miRNA-mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.

Percepciones sobre la importancia de las ciencias básicas en estudiantes de odontología y medicina / Perceptions of the importance of basic sciences in odontology and medical students

Introducción: El aprovechamiento de los cursos de ciencias básicas puede depender de las percepciones estudiantiles sobre la importancia de estos en su vida profesional, por lo que se hace necesario determinar el grado de importancia que los estudiantes le confieren a este tipo de cursos. Materiales y métodos: Se presentó un cuestionario con 9 declaraciones a 54 estudiantes de odontología y medicina. Las respuestas se pasaron a una escala numérica para su análisis. Se usó una prueba de U de Mann-Whitney con el fin de evaluar diferencias entre estudiantes de ambas facultades. Resultados: Los estudiantes en conjunto mostraron tener una buena opinión de la importancia de las ciencias básicas en la práctica clínica. Se observó también que es mayor la proporción de estudiantes de odontología que consideran que la investigación básica no es útil para su práctica clínica. Conclusión: Los estudiantes consideran las ciencias básicas necesarias para un buen desempeño profesional.

Introduction: The benefit of basic science courses may depend on students' perceptions of the importance of these courses in their professional life, therefore, it's necessary to determine the degree of importance that students give to this type of courses. Materials and methods: A questionnaire with 9 statements was presented to 54 dental and medical students. The responses were converted to a numerical scale for analysis. Using a Mann-Whitney U test, differences between students from both faculties were evaluated. Results: The students showed a good opinion of the importance of basic sciences in clinical practice. It was also observed that the proportion of dental students who consider that basic research is not useful for their clinical practice is higher. Conclusion: Students consider the basic sciences necessary for good professional performance.

Factors associated with emergency room readmission after elective surgery for ovarian carcinoma.

BACKGROUND: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors. METHODS: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors. RESULTS: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45). CONCLUSION: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems. TRIAL REGISTRATION: researchregistry7882.

Pathogenic variant profile in DNA damage response genes correlates with metastatic breast cancer progression-free survival in a Mexican-mestizo population.

Introduction: Metastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies. Methods: We sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing. Results: Overall, we found 22 variants -9 of them reported for the first time- and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort. Discussion: Our results reflected the unique characteristics of the Mexican-mestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population.

Methyltransferase-like (METTL) homologues participate in Nicotiana benthamiana antiviral responses.

Methyltransferase (MTase) enzymes catalyze the addition of a methyl group to a variety of biological substrates. MTase-like (METTL) proteins are Class I MTases whose enzymatic activities contribute to the epigenetic and epitranscriptomic regulation of multiple cellular processes. N6-adenosine methylation (m6A) is a common chemical modification of eukaryotic and viral RNA whose abundance is jointly regulated by MTases and METTLs, demethylases, and m6A binding proteins. m6A affects various cellular processes including RNA degradation, post-transcriptional processing, and antiviral immunity. Here, we used Nicotiana benthamiana and plum pox virus (PPV), an RNA virus of the Potyviridae family, to investigated the roles of MTases in plant-virus interaction. RNA sequencing analysis identified MTase transcripts that are differentially expressed during PPV infection; among these, accumulation of a METTL gene was significantly downregulated. Two N. benthamiana METTL transcripts (NbMETTL1 and NbMETTL2) were cloned and further characterized. Sequence and structural analyses of the two encoded proteins identified a conserved S-adenosyl methionine (SAM) binding domain, showing they are SAM-dependent MTases phylogenetically related to human METTL16 and Arabidopsis thaliana FIONA1. Overexpression of NbMETTL1 and NbMETTL2 caused a decrease of PPV accumulation. In sum, our results indicate that METTL homologues participate in plant antiviral responses.

MR angiography facilitates the differentiation of aneurysmal from unicameral bone cysts.

OBJECTIVES: The objective of this work was to evaluate the incremental value of MR angiography over plain radiographs and MRI for the differentiation of aneurysmal bone cysts (ABCs) from unicameral bone cysts (UBCs). METHODS: Thirty-six juvenile patients with histologically secured primary ABCs or UBCs were included in this retrospective study. Two radiologists assessed all obtained images in a blinded fashion using a catalog of previously suggested imaging findings. A second readout with supplementary MR angiography images was performed after 8 weeks to prevent observer recall bias. Diagnostic accuracy parameters were calculated for individual imaging findings, and overall diagnostic accuracy and diagnostic confidence were assessed for all readouts. Receiver operating characteristic (ROC) curve comparison was used to determine the incremental value of MR angiography. RESULTS: Of 16 imaging features, only abnormal vascularization in MR angiography provided sufficient diagnostic accuracy for the identification of ABCs. Other imaging features such as fluid-fluid levels and internal septations were insufficient for the differentiation of UBCs from ABCs. Availability of MR angiography images significantly increased diagnostic accuracy (94.4 vs 75.0% and 83.3 vs 69.4%, respectively, p < 0.05) and diagnostic confidence (4.5 vs 3.7, p < 0.05) of reading radiologists. CONCLUSION: The presence of arterial feeders in MR angiography can accurately discriminate primary ABCs from UBCs and increases the diagnostic accuracy and diagnostic confidence of reporting radiologists. ADVANCES IN KNOWLEDGE: Radiographic differentiation of cystic bone lesions such as ABCs and UBCs remains challenging. We demonstrate that MR angiography provides incremental value and suggest inclusion in standard examination protocols.

Associations between serum high-density lipoprotein cholesterol levels and cause-specific mortality in a general population of 345 000 men and women aged 20-79 years.

BACKGROUND: Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied. METHODS: A total of 344 556 individuals (20-79 years, 52 % women) recruited from population-based health screening during 1985-2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of <30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99 and >99 mg/dl (< 0.78, 0.78-1.01, 1.04-1.27, 1.30-1.53, 1.55-1.79, 1.81-2.04, 2.07-2.31, 2.33-2.56, >2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health. RESULTS: During a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50-59 mg/dl (1.30-1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels >99 mg/dl (>2.56 mmol/L) were 1.32 (1.21-1.43), 1.05 (0.89-1.24), 1.26 (1.09-1.46) and 1.68 (1.48-1.90) for all-cause, CVD, cancer and non-CVD/non-cancer mortality, respectively. For HDL-C levels <30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24-1.36), 1.55 (1.44-1.67), 1.14 (1.05-1.23) and 1.19 (1.10-1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes. CONCLUSIONS: Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.

Diagnostic Value of DECT-Based Collagen Mapping for Assessing the Distal Tibiofibular Syndesmosis in Patients with Acute Trauma.

Background: Injury to the distal tibiofibular syndesmosis (DTFS) is common in patients with trauma to the ankle, but diagnostic accuracy of conventional X-ray and CT is insufficient. A novel dual energy CT (DECT) post-processing algorithm enables color-coded mapping of collagenous structures, which can be utilized to assess the integrity of the DTFS. Methods: Patients were included in this retrospective study if they underwent third-generation dual-source DECT followed by 3T-MRI or ankle joint surgery within 14 days between January 2016 and December 2021. Three radiologists blinded to all patient data independently evaluated grayscale images and, after 8 weeks, grayscale and collagen mapping images for the presence of ligamentous injury or avulsion fractures of the DTFS. MRI and surgery provided the reference standard. Diagnostic accuracy parameters were calculated for all ratings, and a comparison of ROC curve analysis was performed to evaluate the incremental diagnostic value of color-coded images over grayscale images. Results: A total of 49 patients (median age 49 years; 32 males) were evaluated. Application of collagen mapping significantly increased sensitivity (25/30 [83%] vs. 20/30 [67%]), specificity (110/118 [93%] vs. 70/118 [60%]), positive predictive value (25/33 [76%] vs. 20/67 [30%]), negative predictive value (110/115 [96%] vs. 70/80 [88%]), and accuracy (134/147 [91%] vs. 90/147 [61%]) for the detection of injury to the DTFS (all parameters, p < 0.001). Collagen mapping achieved higher diagnostic confidence, image quality, and noise scores compared to grayscale CT (all parameters, p < 0.001). Conclusions: Collagen mapping yields substantially higher diagnostic accuracy and confidence for assessing the integrity of the distal tibiofibular syndesmosis compared to grayscale CT in patients with acute trauma. The application of this algorithm can accelerate the adequate diagnosis and treatment of DTFS injury in clinical routine.