Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers.

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

Comparison of the success rate of tracheal intubation between stylet and bougie with a hyperangulated videolaryngoscope: a randomised controlled trial.

Hyperangulated videolaryngoscopes are known to increase the success rate of tracheal intubation in the setting of difficult airway management when used with a stylet or bougie. However, there is controversy over which adjunct is more useful. This randomised study aimed to compare first attempt tracheal intubation success rate between a stylet and bougie when using a hyperangulated videolaryngoscope. We recruited patients aged > 20 years who were scheduled for elective surgery under general anaesthesia and required tracheal intubation. We only included patients with factors predicting difficult tracheal intubation based on pre-anaesthesia airway evaluation. Tracheal intubation was attempted using a Glidescope® with either a stylet or bougie as an adjunct according to group assignment. Primary outcome was the success rate of the first tracheal intubation attempt, and secondary outcomes were success of second and third attempts; tracheal intubation time; and occurrence of sore throat, dysphagia or hoarseness. A total of 166 patients were included. The success rate of the first tracheal intubation attempt was significantly higher in patients allocated to the bougie group compared with those allocated to the stylet group (81/83 (98%) vs. 73/83 (88%), respectively; p = 0.032). The number of patients who needed two attempts was significantly lower in those allocated to the bougie group compared with those allocated to the stylet group (1/83 (1%) vs. 9/83 (11%), respectively; p = 0.018). Each group had one patient (1%) where tracheal intubation was achieved after a third attempt. There was no significant difference in the occurrence of sore throat, dysphagia and hoarseness between the two groups. When difficult tracheal intubation is anticipated and a hyperangulated videolaryngoscope is used, the success rate of the first attempt is higher when a bougie is used compared with a stylet.

Optimized collection optic design for divertor Thomson scattering diagnostics in KSTAR.

Last year, the KSTAR divertor material was changed from carbon to tungsten tiles. An optimized collection optic design for divertor Thomson scattering diagnostics in KSTAR was conducted for electron temperature (1-100 eV) and electron density (1 × 1018-1 × 1019 m-3) profile diagnostics. This diagnostic system will utilize a 1064 nm Nd:YAG laser directly from the K-top port toward the beam dump located at K-bottom, while collecting scattered light from five spatial points in the divertor area via collection optics situated in the j-middle port. Given spatial limitations, the solid angle of measurement points is limited, and the collection optic design facing the tungsten divertor is susceptible to stray light. So, the design of the collection optic is important for divertor Thomson scattering diagnostics. For optimal performance, we performed two types of collection optic designs: Cooke-triplet and double-Gaussian. We present performance ray tracing analysis results for both designs and derive the optimal design.

Association of Balance Impairment with Risk of Incident Dementia among Older Adults.

BACKGROUND: A growing body of data suggests that balance impairment may be linked to the onset of dementia. OBJECTIVES: However, a large-scale epidemiologic investigation is needed to clarify its association in older adults. DESIGN: A retrospective-prospective hybrid database. SETTING: Cox proportional hazards regression model was used to assess the relationship between balance impairment and the risk of incident dementia, and the results were provided as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). All participants were tracked until the date of incident dementia, death, or 31 December 2019 whichever came first. PARTICIPANTS: We analyzed 143,788 older adults who had at least one health screening between 2009 and 2019 from the Korea National Health Insurance Service-Senior Cohort. MEASUREMENTS: A total of 3,774 cases of dementia were discovered throughout 850,425 person-years of follow-up investigation. Balance impairment was associated with a risk of dementia compared to those without balance impairment (adjusted hazard ratio [aHR] 1.83; 95% CI, 1.69-2.00; P value <0.001). RESULTS: Risks of the Alzheimer's disease (aHR, 1.80; 95% CI, 1.65-1.96; P for trend <0.001) and the vascular dementia (aHR, 2.94; 95% CI, 1.89-4.58; P for trend <0.001) showed comparable trends and findings. CONCLUSIONS: Balance impairment was found to be independently associated with an increased risk of dementia in older adults.

CRISPR-Cas9 and beyond: identifying target genes for developing disease-resistant plants.

Throughout the history of crop domestication, desirable traits have been selected in agricultural products. However, such selection often leads to crops and vegetables with weaker vitality and viability than their wild ancestors when exposed to adverse environmental conditions. Considering the increasing human population and climate change challenges, it is crucial to enhance crop quality and quantity. Accordingly, the identification and utilization of diverse genetic resources are imperative for developing disease-resistant plants that can withstand unexpected epidemics of plant diseases. In this review, we provide a brief overview of recent progress in genome-editing technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) technologies. In particular, we classify disease-resistant mutants of Arabidopsis thaliana and several crop plants based on the roles or functions of the mutated genes in plant immunity and suggest potential target genes for molecular breeding of genome-edited disease-resistant plants. Genome-editing technologies are resilient tools for sustainable development and promising solutions for coping with climate change and population increases.

Prognostic factors and impact of bone invasion in T1/2 size (<4 cm) gingival squamous cell carcinoma.

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered.

Assisted reproductive techniques and subsequent risk of asthma and allergic rhinitis in offspring: a nationwide birth cohort study in South Korea.

OBJECTIVE: The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. PATIENTS AND METHODS: This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. RESULTS: We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. CONCLUSIONS: Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.

Sex differences in the global burden of multidrug- resistant tuberculosis without extensive drug resistance in the general population and people living with HIV/AIDS, 1990-2019.

OBJECTIVE: Currently, human immunodeficiency virus (HIV) and multi-drug resistant tuberculosis (MDR-TB) without extensive drug resistance (XDR) are significant challenges in terms of the global burden of disease. This study aimed to evaluate the trends of the global burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR, focusing on differences in socioeconomic status and sex for 204 countries and territories across periods from 1990 to 2019. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) 2019 study were obtained to construct a separate index measuring the burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated for each case and group. A population-attributable fraction approach was used to assess mortality and incidence of HIV/AIDS and MDR-TB coinfection. 95% uncertainty intervals (UIs) were presented for all measures. RESULTS: Our global estimates suggest that there were approximately 450,000 (95% UI 247,000-785,000) incident cases of MDR-TB without XDR and 109,000 (43,000-210,000) deaths caused by MDR-TB without XDR among individuals who were HIV-negative in 2019. For HIV-positive individuals, the corresponding figures were approximately 47,000 (33,000-67,000) incident cases of MDR-TB and 19,000 (8,000-36,000) deaths due to MDR-TB in the same year. In 2019, higher numbers of incident cases and deaths were observed in males compared to females among individuals who were HIV-negative. Conversely, for HIV-positive individuals, females had higher numbers of incident cases and deaths compared to males. Specifically, the estimated numbers for incident cases were 23,000 (15,000-33,000) for females and 24,000 (17,000-35,000) for males, while the estimated numbers for deaths were 9,600 (4,000-17,900) for females and 9,800 (4,100-18,500) for males. Male-to-female ratios have remained above 1.0 from 1990 to 2019 in both incident cases and number of deaths for HIV-negative individuals. However, for HIV and MDR-TB coinfection, both ratios were below 1.0 in most of the time series. CONCLUSIONS: Males had more cases and deaths due to MDR-TB without XDR than females in HIV-negative patients, while females faced a higher incidence and mortality in HIV/AIDS-MDR-TB without XDR. Interventions are needed to deal with such factors, which increase the burden of coinfection among females across the world.

National trends in the prevalence of hepatitis B and C in South Korea, before and during the COVID-19 pandemic (2007-2021) - a nationwide representative study.

OBJECTIVE: Due to the various changes caused by the COVID-19 pandemic, some infectious diseases showed different epidemiology and prevalence during the pandemic. However, there is a lack of comprehensive studies on trends in the prevalence of hepatitis B and C related to the pandemic. Thus, we compared the prevalence of hepatitis B and C before and during the COVID-19 pandemic in South Korea. SUBJECTS AND METHODS: We conducted a comprehensive trend analysis with a nationwide serial cross-sectional survey from 2007 to 2021 (n=86,931) using the Korea National Health and Nutrition Examination Survey (KNHANES). The changes in the prevalence of hepatitis B and C were evaluated using a weighted regression model to assess the impact of the COVID-19 pandemic. RESULTS: From 2007 to 2021, 86,931 Korean adults aged 19 or older were included in the KNHANES data. The prevalence of hepatitis B showed a declining trend until the onset of the pandemic (1.80% in 2007-2009; 1.08% in 2016-2019; and 1.01% in 2020), at which point this trend reversed (1.39% in 2021). The prevalence of hepatitis C remained stable (0.14% in 2007-2009 and 0.18% in 2016-2019), with no particular surge related to the COVID-19 pandemic (ßdiff, -0.002; 95% CI, -0.761 to 0.756). For hepatitis B, old age was identified as a pandemic-related vulnerable factor (ratio of odds ratio, 1.68; 95% CI, 1.05-2.70). CONCLUSIONS: In this study, unlike other infectious diseases, hepatitis B and C did not show a decreasing trend during the pandemic. In particular, hepatitis B showed a rebound trend during the pandemic, which was noticeable in those aged 60 or older. Further studies are needed to support these findings.

Manipulation of a quasi-natural cell block for high-efficiency transplantation of adherent somatic cells

Recent advances have raised hope that transplantation of adherent somatic cells could provide dramatic new therapies for various diseases. However, current methods for transplanting adherent somatic cells are not efficient enough for therapeutic applications. Here, we report the development of a novel method to generate quasi-natural cell blocks for high-efficiency transplantation of adherent somatic cells. The blocks were created by providing a unique environment in which cultured cells generated their own extracellular matrix. Initially, stromal cells isolated from mice were expanded in vitro in liquid cell culture medium followed by transferring the cells into a hydrogel shell. After incubation for 1 day with mechanical agitation, the encapsulated cell mass was perforated with a thin needle and then incubated for an additional 6 days to form a quasi-natural cell block. Allograft transplantation of the cell block into C57BL/6 mice resulted in perfect adaptation of the allograft and complete integration into the tissue of the recipient. This method could be widely applied for repairing damaged cells or tissues, stem cell transplantation, ex vivo gene therapy, or plastic surgery.

Comparative fine structure of the epididymal spermatozoa from three Korean shrews with considerations on their phylogenetic relationships

This study examined the fine structures of epididymal spermatozoa on the lesser white-toothed shrew (Crocidura suaveolens), the Japanese white-toothed shrew (C. dsinezumi) and the big white-toothed shrew (C. lasiura) belonging to the subfamily Crocidurinae living in Korea. In the spermatozoa of C. suaveolens, the head has a large acrosome, a smooth inner acrosomal membrane and a wavy, finger-like, electron-dense apical body. The neck has a solid proximal centriole that is filled with electron-dense material. These results showed the spermatozoa of C. suaveolens possess the characteristics of both Crocidurinae and Soricinae. In C. dsinezumi and C. lasiura, the head has a large acrosome, a serrated inner acrosomal membrane and a common apical body. The neck has a fistulous proximal centriole with slightly dense elec tron granules. These results showed the typical characteristics of Crocidurinae. Although C. suaveolens belongs to the subfamily Crocidurinae, the spermatozoan morphology is different from C. dsinezumi and C. lasiurai because it has conserved characteristicsof the subfamily Soricinae.