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Introduction Fertility‐sparing treatments using oral progestins have demonstrated promising oncologic outcomes for endometrial intraepithelial neoplasia and early‐stage endometrial cancer. However, the high recurrence rate remains a major concern, and the literature on long‐term follow‐up outcomes is limited. This study aimed to identify recurrence risk factors by analyzing clinicopathological and molecular profiles in a cohort with a median follow‐up of 9 years. Material and Methods This retrospective study included patients under 45 years of age who were diagnosed with endometrial intraepithelial neoplasia or endometrial cancer and received fertility‐sparing treatments at our center between 2010 and 2021. Patients who achieved complete responses were categorized according to recurrence status. Demographic, clinical, and molecular data were compared between groups. The primary endpoint was to identify risk factors for recurrence; secondary endpoints assessed obstetric and oncologic outcomes in patients with relapse. Results Out of 40 patients, 8 underwent hysterectomy within 1.5 years, while 32 responded to treatment and continued follow‐up. The recurrence and non‐recurrence groups contained 20 and 12 patients, respectively, with a median follow‐up of 107.5 months (range, 35–175 months). Multivariate analysis showed that a family history of cancer (HR = 2.597, p = 0.039) and treatment with megestrol acetate as the initial therapy (HR = 3.130, p = 0.021) were independent risk factors for shorter time to recurrence. Although mismatch repair deficiency was positively correlated with recurrence, the association did not reach statistical significance (p = 0.057). Four out of 24 patients were upstaged after hysterectomy, and all were in the recurrence group. Nine patients (22.5%) achieved pregnancy, with three successfully conceiving after achieving complete response following retreatment. Conclusions In patients with long‐term follow‐up after fertility‐sparing treatment, a family history of cancer and initial treatment with megestrol acetate were significantly associated with recurrence. Fertility‐sparing treatment demonstrated a 62.5% recurrence rate at 10 years. Recurrence was more likely in patients initially treated with megestrol acetate or those with a family history of cancer. As most patients lacked high‐risk molecular features, conservative treatment may remain a safe option for selected individuals under close long‐term surveillance.

Anti-EGFR monoclonal antibodies are essential for metastatic colorectal cancer (CRC) treatment, however, resistance remains problematic in KRAS / NRAS / BRAF wild-type patients. RAS protein activator-like 2 (RASAL2) regulates RAS signaling by catalyzing the conversion of RAS. This study investigates the pathogenicity of the germline RASAL2 c.2423 A > G variant, identified in a high-risk family, and its potential role in CRC progression and therapy resistance. Population analysis reveals its rarity in East Asians (0.01%) but an increased prevalence in Taiwanese CRC patients (1.63%). Functional studies demonstrate that RASAL2 c.2423 A > G enhances RAS signaling, causing sustained ERK phosphorylation and increased CRC cell proliferation. Additionally, RASAL2 -mutant cells require higher doses of cetuximab for ERK suppression and growth inhibition, indicating resistance to anti-EGFR therapy via abnormal RAS activation. According to the American College of Medical Genetics and Genomics criteria, the variant is likely pathogenic. Our study highlights RASAL2 c.2423 A > G as a potential biomarker for CRC risk and therapy response.

The COVID-19 pandemic struck the world unguarded, some places outperformed others in COVID-19 containment. This longitudinal study considered a comparative evaluation of COVID-19 containment across 50 distinctly governed regions between March 2020 and November 2021. Our analysis distinguishes between a pre-vaccine phase (March–November 2020) and a vaccinating phase (December 2020–November 2021). In the first phase, we develop an indicator, termed lockdown efficiency (LE), to estimate the efficacy of measures against monthly case numbers. Nine other indicators were considered, including vaccine-related indicators in the second phase. Linear mixed models are used to explore the relationship between each government policy & hygiene education (GP&HE) indicator and each vital health & socioeconomic (VH&SE) measure. Our ranking shows that surveyed countries in Oceania and Asian outperformed countries in other regions for pandemic containment prior to vaccine development. Their success appears to be associated with non-pharmaceutical interventions, acting early, and adjusting policies as needed. After vaccines have been distributed, maintaining non-pharmacological intervention is the best way to achieve protection from variant viral strains, breakthrough infections, waning vaccine efficacy, and vaccine hesitancy limiting of herd immunity. The findings of the study provide insights into the effectiveness of emerging infectious disease containment policies worldwide.

We aimed to evaluate the successful long-term use of dienogest for the management of pelvic pain and bleeding control in perimenopausal women with symptomatic adenomyosis using real-world data. All women aged ≥ 40 years with adenomyosis who complained of dysmenorrhea and/or menorrhagia and received dienogest between September 2018 and December 2021 were retrospectively recruited. The primary outcome was successful long-term use of dienogest for pelvic pain and/or bleeding control. A total of 87 women were analyzed. Overall, forty-nine (56%) patients had excellent pain control, but 17 (20%) eventually underwent hysterectomy, while 21 (24%) received dienogest for over 24 months (mean 33.5 ± 8.5 months). According to subgroup analysis by age (≥ 45 vs. <45), older women easily discontinued dienogest due to side effects (51% vs. 30%, p  = 0.047) but less frequently changed to surgery (11% vs. 30%, p  = 0.012) than younger women. Older age, higher CA-125 value, and larger uterine size before treatment were linked to poorer long-term responses to dienogest. As risk factor, uterine volume > 352.7 cm 3 reflects easier treatment failure (sensitivity = 65.4%, specificity = 66.7%, area = 0.68, p  = 0.032). In perimenopausal women with symptomatic adenomyosis, nearly half of the treated patients benefitted from dienogest. Our informative findings can assist clinicians in pre-treatment counseling and identifying factors correlated with treatment effectiveness.

Construction operation sequencing is vital for effectively managing construction job sites. In this regard, it is important that junior engineers learn construction operation sequencing on construction sites. In Taiwan, senior engineers teach construction operation sequencing to junior engineers by using documents or two‐dimensional (2D) shop drawings. However, many junior engineers find it difficult to understand construction operation sequencing when their instructors use 2D illustrations. With the COVID‐19 public health crisis serving as a catalyst for changes in the nature of training across fields, there is an opportunity to review the traditional approach for training in construction operation sequencing. Therefore, this study develops a construction building information modeling (BIM)‐based learning and training (CBLT) system to train junior engineers employed by general contractors. The proposed approach and system are applied to a building project in Taiwan as a case study to verify their effectiveness in practice. The results demonstrate that a CBLT system is an effective visual learning and training platform for junior engineers to learn construction operation sequencing. The CBLT system not only increases learning and training efficiency but also facilitates the transfer and reuse of senior engineers’ knowledge and experience for effective construction operation sequencing at job sites, which is particularly valuable for junior engineers.

Background Cingulin (CGN) is a pivotal cytoskeletal adaptor protein located at tight junctions. This study investigates the link between CGN mutation and increased cancer susceptibility through genetic and mechanistic analyses and proposes a potential targeted therapeutic approach. Methods In a high-cancer-density family without known pathogenic variants, we performed tumor-targeted and germline whole-genome sequencing to identify novel cancer-associated variants. Subsequently, these variants were validated in a 222 cancer patient cohort, and CGN c.3560C > T was identified as a potential cancer-risk allele. Both wild-type (WT) (c.3560C > C) and variant (c.3560C > T) were transfected into cancer cell lines and incorporated into orthotopic xenograft mice model for evaluating their effects on cancer progression. Western blot, immunofluorescence analysis, migration and invasion assays, two-dimensional gel electrophoresis with mass spectrometry, immunoprecipitation assays, and siRNA applications were used to explore the biological consequence of CGN c.3560C > T. Results In cancer cell lines and orthotopic animal models, CGN c.3560C > T enhanced tumor progression with reduced sensitivity to oxaliplatin compared to the CGN WT. The variant induced downregulation of epithelial marker, upregulation of mesenchymal marker and transcription factor, which converged to initiate epithelial-mesenchymal transition (EMT). Proteomic analysis was conducted to investigate the elements driving EMT in CGN c.3560C > T. This exploration unveiled overexpression of IQGAP1 induced by the variant, contrasting the levels observed in CGN WT. Immunoprecipitation assay confirmed a direct interaction between CGN and IQGAP1. IQGAP1 functions as a regulator of multiple GTPases, particularly the Rho family. This overexpressed IQGAP1 was consistently associated with the activation of Rac1, as evidenced by the analysis of the cancer cell line and clinical sample harboring CGN c.3560C > T. Notably, activated Rac1 was suppressed following the downregulation of IQGAP1 by siRNA. Treatment with NSC23766, a selective inhibitor for Rac1-GEF interaction, resulted in the inactivation of Rac1. This intervention mitigated the EMT program in cancer cells carrying CGN c.3560C > T. Consistently, xenograft tumors with WT CGN showed no sensitivity to NSC23766 treatment, but NSC23766 demonstrated the capacity to attenuate tumor growth harboring c.3560C > T. Conclusions CGN c.3560C > T leads to IQGAP1 overexpression, subsequently triggering Rac1-dependent EMT. Targeting activated Rac1 is a strategy to impede the advancement of cancers carrying this specific variant.

Background Mathematical and statistical models are used to predict trends in epidemic spread and determine the effectiveness of control measures. Automatic regressive integrated moving average (ARIMA) models are used for time-series forecasting, but only few models of the 2019 coronavirus disease (COVID-19) pandemic have incorporated protective behaviors or vaccination, known to be effective for pandemic control. Methods To improve the accuracy of prediction, we applied newly developed ARIMA models with predictors (mask wearing, avoiding going out, and vaccination) to forecast weekly COVID-19 case growth rates in Canada, France, Italy, and Israel between January 2021 and March 2022. The open-source data was sourced from the YouGov survey and Our World in Data. Prediction performance was evaluated using the root mean square error (RMSE) and the corrected Akaike information criterion (AICc). Results A model with mask wearing and vaccination variables performed best for the pandemic period in which the Alpha and Delta viral variants were predominant (before November 2021). A model using only past case growth rates as autoregressive predictors performed best for the Omicron period (after December 2021). The models suggested that protective behaviors and vaccination are associated with the reduction of COVID-19 case growth rates, with booster vaccine coverage playing a particularly vital role during the Omicron period. For example, each unit increase in mask wearing and avoiding going out significantly reduced the case growth rate during the Alpha/Delta period in Canada (–0.81 and –0.54, respectively; both p < 0.05). In the Omicron period, each unit increase in the number of booster doses resulted in a significant reduction of the case growth rate in Canada (–0.03), Israel (–0.12), Italy (–0.02), and France (–0.03); all p < 0.05. Conclusions The key findings of this study are incorporating behavior and vaccination as predictors led to accurate predictions and highlighted their significant role in controlling the pandemic. These models are easily interpretable and can be embedded in a “real-time” schedule with weekly data updates. They can support timely decision making about policies to control dynamically changing epidemics.

In Taiwan, lower nonpolio enterovirus activity during the coronavirus disease pandemic in 2020 compared with 2014-2019 might be attributable to adherence to nonpharmaceutical interventions. The preventable fraction among unexposed persons indicated that 90% of nonpolio enterovirus activity might have been prevented during 2014-2019 by adopting the same measures enforced in 2020.

Taiwan was a coronavirus disease 2019 (COVID-19) outlier, with an extraordinarily long transmission-free record: 253 days without locally transmitted infections while the rest of the world battled wave after wave of infection. The appearance of the alpha variant in May 2021, closely followed by the delta variant, disrupted this transmission-free streak. However, despite low vaccination coverage (<1%), outbreaks were well-controlled. This study analyzed the time to border closure and conducted one-sample t test to compare between Taiwan and Non-Taiwan countries prior to vaccine introduction. The study also collected case data to observe the dynamics of omicron transmission. Time-varying reproduction number,Rt, was calculated and was used to reflect infection impact at specified time points and model trends of future incidence. The study analyzed and compare the time to border closure in Taiwan and non-Taiwan countries. The mean times to any border closure from the first domestic case within each country were -21 and 5.98 days, respectively (P < .0001). The Taiwanese government invested in quick and effective contact tracing with a precise quarantine strategy in lieu of a strict lockdown. Residents followed recommendations based on self-discipline and unity. The self-discipline in action is evidenced in Google mobility reports. The central and local governments worked together to enact non-pharmaceutical interventions (NPIs), including universal masking, social distancing, limited unnecessary gatherings, systematic contact tracing, and enhanced quarantine measures. The people cooperated actively with pandemic-prevention regulations, including vaccination and preventive NPIs. This article describes four key factors underlying Taiwan's success in controlling COVID-19 transmission: quick responses; effective control measures with new technologies and rolling knowledge updates; unity and cooperation among Taiwanese government agencies, private companies and organizations, and individual citizens; and Taiwanese self-discipline.

Left ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p  < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p  = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04–9.97; p  = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.