Search Results (148)

The 26th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Saskatoon, Saskatchewan, on 17–18 October 2024. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with hepatocellular and biliary tract cancers. Specialists from the fields of medical and radiation oncology, interventional radiology, pathology and laboratory medicine, and general and hepatobiliary surgery participated in presentations and discussions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular and biliary tract cancers. Full article

The DNA mismatch repair (MMR) system plays a crucial role in repairing DNA damage and regulating cell cycle arrest induced by cadmium (Cd) stress. To elucidate the mechanism by which miRNAs target AtMSH2 in regulating Arabidopsis’ response to Cd stress, the wild-type Arabidopsis, Atmsh2 mutant, and three miRNA-overexpressing transgenic lines were grown hydroponically in half-strength MS solution containing cadmium (Cd) at concentrations of 0, 0.5, 1, 2, and 3 mg/L for 5 days. miRNA-seq analysis, bioinformatics prediction, dual-luciferase reporter assays, and qRT-PCR results demonstrated that miR5651, miR170-3p, and miR171a-3p specifically targeted AtMSH2 and their expression levels showed a significant negative correlation. Compared to wild-type (WT) Arabidopsis, Cd stress tolerance was significantly enhanced in miRNA-overexpressing transgenic lines. Moreover, exogenous application of these three miRNAs in half-strength MS liquid medium also markedly improved Cd stress tolerance in wild-type Arabidopsis. Furthermore, the expression of these three miRNAs expression was further upregulated by Cd stress in a dose-dependent manner. Additionally, DNA damage response in miRNA-overexpressing transgenic lines was promoted based on the expression of DNA repair, DNA damage signaling, and cell cycle genes, which differed from both wild-type and Atmsh2 plants. Taken together, miR5651, miR170-3p, and miR171a-3p participated in Cd stress response and improved plant Cd tolerance by mediating the expression of AtMSH2. Our study provides novel insights into the epigenetic mechanisms of Cd tolerance in plants, which sheds light on breeding for stress resilience in phytoremediation. Full article

Background: Sexual assault affects millions globally each year, yet research on survivors’ resilience remains limited and methodologically inconsistent. Resilience after sexual assault is a multidimensional and deeply personal process shaped by psychological, social, and systemic influences. Understanding this complexity requires research methodologies that can capture both measurable patterns and lived experiences. Objectives: This integrative review explores how mixed-methods research (MMR) has been used to study resilience and healing following sexual assault. Methods: Using the framework by Whittemore and Knafl, four databases (PubMed, CINAHL, PsychInfo, and EMBASE) were searched for peer-reviewed primary research articles published between 2014 and 2024. Studies were screened and appraised independently by two reviewers using predefined inclusion and exclusion criteria and a modified Johns Hopkins Nursing Evidence-Based Practice (JHNEBP) tool. Results: Six studies met the inclusion criteria, revealing substantial variation in how mixed-methods approaches were applied. Half of the studies cited a “completeness” rationale for integrating qualitative and quantitative strands, while others emphasized enhancement, triangulation, or discovery of new insights. Integration strategies included connecting datasets sequentially, merging findings at the interpretation stage, or building new frameworks from combined results. However, only one study used a joint display to visually represent integration, highlighting an ongoing underutilization of visual synthesis tools in trauma research. Measures of resilience and associated outcomes also varied widely across studies, underscoring the complex and multidimensional nature of resilience following sexual assault. Conclusions: This review suggests that MMR can offer a deeper, more nuanced understanding of resilience among sexual assault survivors and calls attention to the need for intentional integration strategies to maximize insight. Full article

We revisit 77 relaxed (extra)solar multibody (sub)systems containing 2–9 bodies orbiting about gravitationally dominant central bodies. The listings are complete down to (sub)systems with 5 orbiting bodies and additionally contain 33 smaller systems with 2–4 orbiting bodies. Most of the multiplanet systems (68) have been observed outside of our solar system, and very few of them (5) exhibit classical Laplace resonances (LRs). The remaining 9 subsystems have been found in our solar system; they include 7 well-known satellite groups in addition to the four gaseous giant planets and the four terrestrial planets, and they exhibit only one classical Laplace resonant chain, the famous Galilean LR. The orbiting bodies (planets, dwarfs, or satellites) appear to be locked in/near global mean-motion resonances (MMRs), as these are determined in reference to the orbital period of the most massive (most inert) body in each (sub)system. We present a library of these 77 multibody subsystems for future use and reference. The library listings of dynamical properties also include regular spacings of the orbital semimajor axes. Regularities in the spatial configurations of the bodies were determined from patterns that had existed in the mean tidal field that drove multibody migrations toward MMRs, well before the tidal field was erased by the process of `gravitational Landau damping’ which concluded its work when all major bodies had finally settled in/near the global MMRs presently observed. Finally, detailed comparisons of results help us discern the longest commonly-occurring MMR chains, distinguish the most important groups of triple MMRs, and identify a new criterion for the absence of librations in triple MMRs. Full article

We propose a method to reconstruct a 3D coordinate system and a vascular map for the operation of magnetic medical robots (MMRs) controlled by a magnetic navigation system (MNS) using two 2D X-ray images and four corners of an MNS. Utilizing the proposed method, we calculated the relative rotation angle of a C-arm considering its rotational precision error. We derived the position information and 3D coordinate system of an MNS workspace in which the magnetic fields are generated and controlled by an MNS. The proposed method can also be utilized to reconstruct vascular maps. Reconstructed vascular maps are in the 3D coordinate system of the C-arm and can be transformed into the 3D coordinate system of an MNS workspace to generate the magnetic flux density with the desired direction and magnitude at the position of the MMR. The proposed method allows us to remotely and precisely control the MMR inserted into the vessel by controlling the external magnetic field. The proposed method was validated through in vitro experiments with an MNS mock-up and a vascular jig. Finally, the proposed method was applied to in vivo experiments where the MMR was inserted into the superficial femoral artery of a mini pig to remotely control the motion of the MMR. This research will enable precise and effective control of MMRs in various medical procedures utilizing an MNS. Full article

Colorectal cancer (CRC) is the third most common cancer in the world, with increasing incidence and mortality rates. Standard conventional treatments for CRC are surgery, chemotherapy, and radiotherapy. Recently, immunotherapy has been introduced as a promising alternative to CRC treatment that utilizes patients’ immune system to combat cancer cells. The beneficial effect of immune checkpoint inhibitors, specifically anti-PD-1/ PD-L1, has been ascribed to the abundance of DNA replication errors that result in the formation of neoantigens. Such neoantigens serve as distinct flags that amplify the immune response when checkpoint inhibitors (ICIs) are administered. DNA replication errors in CRC patients are expressed as two statuses: the first is the deficient mismatch repair (MSI-H/dMMR) with a higher overall immune response and survival rate than the second status of patients with proficient mismatch repair (MSS/pMMR). There is a limitation to using anti-PD-1/PD-L1 as it is only confined to MSI-H/dMMR, where there is an abundance of T-cell inhibitory ligands (PD-L1). This calls for investigating new therapeutic interventions to widen the scope of ICIs’ role in the treatment of CRC. Autophagy modulation provides a good example. Autophagy is a cellular process that plays a crucial role in maintaining cellular homeostasis and has been studied for its impact on tumor development, progression, and response to treatment. In this review, we aim to highlight autophagy as a potential determinant in tumor immune response and to study the impact of autophagy on the tumor immune microenvironment. Moreover, we aim to investigate the value of a combination of anti-PD-1/PD-L1 agents with autophagy modulators as an adjuvant therapeutic approach for CRC treatment. Full article

Background: The COVID-19 pandemic had significant impacts on healthcare systems, including the disruption of essential services such as childhood immunization. Containment measures, such as social distancing, contributed to reduced adherence to vaccination programs, increasing the risk of re-emerging vaccine-preventable diseases. We aim to assess the evolution of childhood vaccination coverage in Brazil from 2010 to 2024, identifying trends before, during, and after the COVID-19 pandemic. Methods: An interrupted time series (ITS) study was conducted using publicly available aggregated data on vaccination coverage for children under one year of age. Prais–Winsten regression models were applied to estimate trend changes and evaluate the impact of the pandemic on immunization levels. Results: The findings indicate a progressive decline in vaccination coverage between 2010 and 2019, which was intensified in 2020 by the pandemic. The BCG vaccine showed the greatest decline (−24.88%, p < 0.001), while pentavalent and hepatitis B vaccines decreased annually by −3.72% and −2.21%, respectively. From 2021 onwards, a gradual recovery in coverage was observed, with significant increases for BCG (+7.48% per year, p < 0.001), hepatitis B (+7.45%, p = 0.014), and MMR (+6.73%, p = 0.017) vaccines. Discussion: The results highlight a concerning decline in childhood immunization, exacerbated by the pandemic but showing recent signs of recovery. This scenario underscores structural challenges within the National Immunization Program, requiring coordinated efforts to reverse vaccination losses and ensure system resilience in the face of future crises. Full article

The integrity of the genome is maintained by mismatch repair (MMR) proteins that recognize and repair base mismatches and insertion/deletion errors generated during DNA replication and recombination. A defective MMR system results in genome-wide instability and the progressive accumulation of mutations. Tumors exhibiting deficient MMR (dMMR) and/or high levels of microsatellite instability (termed “microsatellite instability high”, or MSI-H) have been shown to possess fundamental differences in clinical, pathological, and molecular characteristics, distinguishing them from their “microsatellite stable” (MSS) counterparts. Molecularly, they are defined by a high mutational burden, genetic instability, and a distinctive immune profile. Their distinct genetic and immunological profiles have made dMMR/MSI-H tumors particularly amenable to treatment with immune checkpoint inhibitors (ICIs). The ongoing development of biomarker-driven therapies and the evaluation of novel combinations of immune-based therapies, with or without the use of conventional cytotoxic treatment regimens, continue to refine treatment strategies with the goals of maximizing therapeutic efficacy and survival outcomes in this distinct patient population. Moreover, the resultant knowledge of the mechanisms by which these features are suspected to render these tumors more responsive, overall, to immunotherapy may provide information regarding the potential optimization of this therapeutic approach in tumors with proficient MMR (pMMR)/MSS tumors. Full article

Background: In non-metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC), traditional prognostic factors, such as pN staging, often fail to distinguish patient outcomes effectively. Methods: This retrospective study included a cohort of 792 dMMR CRC patients who underwent surgical treatment without neoadjuvant chemoradiotherapy or immunotherapy. Traditional prognostic factors were compared with lymph node-based models (NLN, LNR, LOODS) for their ability to predict overall survival (OS) and disease-free survival (DFS). Results: The study demonstrated that traditional factors, such as histologic type, differentiation, and vascular invasion, had limited predictive value in dMMR CRC. Furthermore, the pN stage failed to effectively distinguish between pN1 and pN2 for both OS (p = 0.219) and DFS (p = 0.095). Conversely, LOODS demonstrated superior performance over traditional pN staging in predicting both OS and DFS (p < 0.001). A prognostic model combining LOODS with age exhibited superior predictive performance compared with the traditional TN staging system. Conclusions: LOODS was identified as a more effective independent prognostic factor compared with traditional pN staging, enabling more precise stratification of pN+ patients in non-metastatic dMMR CRC, highlighting its potential utility in guiding postoperative treatment and optimizing therapeutic strategies. Full article

Recent clinical trials have suggested that solid cancers with mismatch repair (MMR) deficiency are highly responsive to immunotherapy, regardless of cancer types. Previous MMR-related studies on breast cancer have predominantly focused on germline variants. However, the somatic MMR alterations have not been comprehensively characterized in breast cancer. In this study, we integrated genomic, transcriptomic, and clinical data from over 3000 breast cancer cases across six public cohorts. Our findings revealed that 1.2% of breast cancers harbored oncogenic somatic MMR alterations, with triple-negative breast cancer (TNBC) demonstrating the highest mutation rate at 3.1%. Additionally, somatic MMR alterations were significantly associated with microsatellite instability-high (MSI-H) and MMR-related mutational signatures, indicating that somatic MMR alterations led to impaired function of the MMR system. Biallelic inactivation of MMR genes resulted in a more pronounced loss of MMR function compared to monoallelic inactivation. Importantly, these MMR alterations significantly increased the tumor mutational burden (TMB) and neoantigen load in breast cancer, regardless of MSI-H status. These findings indicate that the frequency of MMR alterations is highest in TNBC and that MMR alterations in breast cancer can lead to MMR functional deficiencies, suggesting that some patients harboring such alterations may benefit from immunotherapy. Full article

Background and Objectives: Despite the well-established role of the BRCA and mismatch repair (MMR) genes in DNA damage repair pathways, a substantial proportion of familial cancer cases still lack pathogenic variants in those genes. Next Generation Sequencing (NGS) panels have emerged as a powerful tool to identify hereditary cancer at-risk individuals and subsequently provide them with accurate management. Materials and Methods: Families harbouring PVs in RAD50, RAD51C, RAD51D, and BRIP1 were identified by analysing a cancer-predisposing genes panel using Ion S5 system technology. A retrospective cohort of 155 families tested only for the BRCAs of MMR genes were reanalysed, prompted by an increase in familial cases or new cancer diagnoses among index cases. Results: We identified 40 families through molecular reanalysis (33 with Hereditary Breast and Ovarian Cancer (HBOC) and 7 with Lynch Syndrome (LS)), with positive test results among 155 families lacking BRCA or MMR mutations. The most frequently mutated genes after ATM and CHEK2 were BRIP1, RAD51D, and RAD51C with 16, 13, and 9 positive families, respectively. The phenotype–genotype correlations not only revealed ovarian and HER-negative breast cancer predispositions but also other cancer types, particularly lung and gastric, and individuals with a second or third distinct cancer episode. Conclusions: Broader ranges of malignancies, including gastric, lung, and bladder, have been identified among BRIP1, RAD51D, and RAD51C positive families. The results generated using NGS provide a comprehensive genetic landscape in each patient that could explain the diversity of phenotypes shown in PV families that, combined with non-genetic factors, might enable accurate surveillance and personalized treatments. NGS reanalysis doubled our diagnostic yield and was a good strategy to identify hereditary cancer families that would otherwise be overlooked. Full article

Objectives: Our objectives were to evaluate the safety of the simultaneous vaccination of Japanese encephalitis attenuated live vaccine (JEV-L) and measles, mumps, and rubella combined attenuated live vaccine (MMR) in children and to provide a reference for the implementation of the strategy of simultaneous vaccination with the two vaccines. Methods: The data of adverse events following immunization (AEFI) and vaccination for JEV-L and MMR from 2020 to 2023 were extracted through the Guangdong Province Vaccine Distribution and Vaccination Management Information System and the Chinese National AEFI Information System (CNAEFIS). The inclusion criteria were that children were born after 1 October 2019, and received the first dose of JEV-L or MMR after 1 June 2020, in accordance with the starting age for vaccination (8 months). The study used the number of vaccine doses as the denominator to calculate and compare the reporting rates of cases and calculated the relative risk (RR) of adverse reactions and the 95% confidence interval (CI). Results: In Guangzhou, a total of 214,238 doses of JEV-L were administered to children. JEV-L and MMR were co-administered in 464,009 doses, and MMR was administered separately in 241,150 doses. The overall reporting incidence rates of AEFI (per 100,000 doses) for JEV-L, the simultaneous vaccination group, and MMR were 11.20, 53.02, and 60.96, respectively. Among children aged 8 months in Guangzhou, 57.98% (463,512/799,423) received the simultaneous administration of JEV-L and MMR. In the reported AEFI events, general reactions accounted for 87.50% in the JEV-L group, 88.21% in the simultaneous vaccination group, and 89.80% in the MMR separate group. The incidence rates of common adverse reactions were 9.80, 46.7, and 54.74, respectively. The incidence rates of rare adverse reactions were 0.93, 3.88, and 2.90, respectively. The reporting incidence rates of fever ≥38.6 °C after vaccination were 4.20, 16.16, and 17.83 for the JEV-L separate group, simultaneous vaccination group, and MMR separate group, respectively. There was a significant difference between the simultaneous vaccination group and the JEV-L separate group (RR = 3.848, 95% CI = 1.927, 7.683), while no significant difference was found compared with the MMR separate group (RR = 0.906, 95% CI = 0.623, 1.318). The simultaneous vaccination group showed no significant differences in the reporting incidence rates of local redness and induration compared with the two separate vaccination groups (RR = 1.385, 95% CI = 0.144, 13.315; RR = 0.390, 95% CI = 0.087, 1.743; RR = 0.520, 95% CI = 0.033, 8.314). No significant differences were found in the incidence rates of rare adverse reactions such as maculopapular rash, urticaria, and thrombocytopenic purpura. Conclusions: The AEFI reporting incidence rate for the first dose of the simultaneous vaccination of JEV-L and MMR in 8-month-old children in Guangzhou is between the rates of the two separate groups. Compared with the MMR separate group, the simultaneous vaccination group does not increase the risk of adverse reactions. Full article

We describe a method of determining three-body and four-body Laplace-like phase angles with the potential to librate about a mean value in multiplanet extrasolar systems. Unlike in past searches of N-body results, this method relies on global mean-motion resonances (MMRs) and takes into consideration the location of the most massive planet that defines the 1:1 global MMR in each (sub)system. We compiled lists of potentially librating phase angles and prevalent MMRs in 35 real multibody systems, and we discuss their properties in conjunction with recent investigations of librations discovered in sophisticated N-body simulations. We hope that our results will facilitate systematic libration searches in dynamical models of compact systems with three or more orbiting bodies. Full article

Objectives: This study aims to develop performance indicators for service robotics in senior community-based environments and analyze their impact on independent living and quality of life for older adults. Methods: To achieve this, a sequential exploratory design within the Mixed Methods Research (MMR) framework was employed, integrating qualitative research (Focus Group Interview, FGI) and quantitative research (Analytic Hierarchy Process, AHP). The FGIs were conducted with a panel of six experts over three rounds, leading to the identification of six key performance indicators (KPIs) for service robotics in senior communities: Technical Performance, User-Centered Performance, Social and Psychological Impact, Ethical and Safety Performance, Economic and Operational Performance, and Service Efficiency. Following this, the AHP analysis was conducted with a final sample of 29 participants from an initial 32 respondents. Results: The AHP analysis results revealed that Technical Performance (rank 1, 0.256) was the most critical factor, followed by User-Centered Performance (rank 2, 0.205) and Social and Psychological Impact (rank 3, 0.167). These findings suggest that enhancing a user-friendly, intuitive UI/UX is essential for ensuring ease of use by older adults. Additionally, while Ethical and Safety Performance (rank 3, 0.139), Economic and Operational Performance (rank 4, 0.126), and Service Efficiency (rank 5, 0.105) had relatively lower importance scores, the study highlights the necessity of establishing optimized systems through ethical and safety standards and emphasizes that real-time monitoring systems play a crucial role in enhancing operational efficiency. Conclusions: Enhancing service robotics performance requires prioritizing technical capabilities and user-centered design, along with ethical standards and real-time monitoring. This study proposes a structured evaluation framework to support more effective robotic solutions in senior care environments. Full article

Specific prevention of measles, mumps, and rubella (MMR) is the main prerequisite for a radical reduction in the incidence of these infections in the Kyrgyz Republic (KR). An increase in the number of seronegative individuals observed in recent years has led to an increase in measles incidence. This is directly related to a decrease in collective immunity, which provides protection for the population only in conditions of a high density of immunized individuals and their uniform distribution in the population. The only way to estimate the number of immunized individuals is by conducting serological surveys of collective immunity. Aim of the study: The aim was to study the level of collective immunity to the MMR viruses in the KR. Materials and methods: This study involved a cohort of 6617 residents (volunteers) aged 1 to 70⁺ years, formed in accordance with the Rospotrebnadzor program “Assessment of collective immunity to vaccine-preventable and other relevant infections” and stratified by age and region of residence. During the study, participants filled out a questionnaire and gave venous blood samples to determine IgG antibodies to MMR viruses (ELISA using certified Russian test systems). Results: In December 2023, collective immunity ensured epidemiological well-being only with respect to rubella. The volunteer seropositivity was 94.2% (95% CI: 93.7–94.8). The average measles seropositivity was 78.9% (95% CI: 77.9–79.9). It was significantly lower in children aged 1–17 years and significantly higher than the cohort average in individuals aged ≥18 years. The average mumps seropositivity was 76.4% (95% CI: 75.3–77.4), with the minimum level noted among individuals aged 12–29 years (63.8%; 95% CI: 61.4–66.2). The maximum levels of mumps seropositivity were noted among children aged 6–11 years and older adults who had likely experienced mumps (50–70⁺ years). Seroprevalence distributions by activity correlated with age distributions (all infections). Conclusions: The system of targeted prophylaxis of vaccine-preventable infections adopted in the KR has contributed to the formation of a high level of rubella collective immunity and, to a lesser extent, measles and mumps immunity. The recent trend towards increases in measles and mumps incidence in the KR requires additional efforts to increase collective immunity to these infections. Full article