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CDK4/6 inhibitors combined with endocrine therapy prolonged survival in hormone receptor (HR)-positive and HER2-negative advanced breast cancer. We investigated whether CDK4/6 inhibitors enhance radiosensitivity and their underlying mechanisms of this subtype of breast cancer. In vitro and in vivo experiments were conducted using two HR-positive and HER2-negative breast cancer cell lines (MCF-7 and T-47D), CDK4/6 inhibitors (ribociclib and palbociclib) and radiotherapy (RT) to assess the biological functions and mechanisms. The radiation-enhancing effect was assessed using clonogenic assays; γH2AX and 53BP1 levels were assessed by immunofluorescence to evaluate DNA damage. The levels of phospho (p)-ERK, c-Myc, and DNA-double strand break (DSB)-related molecules, p-DNA-PKcs, Rad51, and p-ATM, were assessed by western blotting. We used an NF-κB p65 transcription factor assay kit to evaluate NF-κB activity. We evaluated the antitumor effect of the combination of RT and ribociclib through the MCF-7 orthotopic xenograft model. The synergistic effects of combining RT with ribociclib and palbociclib pretreatment were demonstrated by clonogenic assay. CDK4/6 inhibitors synergistically increased the numbers of RT-induced γH2AX and 53BP1, downregulated the expression of p-DNA-PKcs, Rad51 and p-ATM activated by RT, and reduced RT-triggering p-ERK expression, NF-κB activation, and its down-streaming gene, c-Myc. Combined ribociclib and RT reduced the growth of MCF-7 cell xenograft tumors, and downregulated the immunohistochemical expression of p-ERK, p-NF-κB p65, and c-Myc compared to that in the control group. Combining CDK4/6 inhibitors enhanced radiosensitivity of HR-positive and HER2-negative breast cancer cells at least by reducing DNA-DSB repair and weakening the activation of ERK and NF-κB signaling by RT.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Objective The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. Methods The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. Results A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). Conclusion The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.

Plain English summary Food addiction is related to eating disorders and may overlap with a variety of disorders, including binge-eating disorder, night-eating syndrome, bulimia nervosa or other conditions. Therefore, it is important for healthcare providers to assess food addiction and one commonly used method is using the Yale Food Addiction Scale (YFAS) developed by Gearhardt and her colleagues. The YFAS has been updated and revised into two versions: the YFAS 2.0 and modified YFAS 2.0 (i.e., mYFAS 2.0). Psychometric testing studies have reported the feasibility and adequate properties for both the YFAS 2.0 and mYFAS 2.0. However, prior studies’ findings were based on classical test theory (CTT) findings. The present study thus used a modern test theory (i.e., Rasch models) to examine if both the YFAS 2.0 and mYFAS 2.0 have similarly satisfactory psychometric properties shown in the CTT findings. The present findings using Rasch models support the use of both the YFAS 2.0 and mYFAS 2.0 to assess food addiction among youth. Therefore, healthcare providers may use either the YFAS 2.0 or mYFAS 2.0 to assess levels of food addiction.

Background/Purpose: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles. Methods: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan–Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression. Results: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p

IntroductionThe most widely used instruments to assess food addiction – the Yale Food Addiction Scale 2.0 (YFAS 2.0) and its modified version (mYFAS 2.0) – have not been validated in a Taiwanese population. The present study compared the psychometric properties between the Taiwan versions of YFAS 2.0 and mYFAS 2.0 among university students.MethodsAn online survey comprising the YFAS 2.0, mYFAS 2.0, Weight Self-Stigma Questionnaire (WSSQ) and International Physical Activity Questionnaire-Short Form (IPAQ-SF) were used to assess food addiction, self-stigma, and physical activity.ResultsAll participants (n = 687; mean age = 24.00 years [SD ± 4.48 years]; 407 females [59.2%]) completed the entire survey at baseline and then completed the YFAS 2.0 and mYFAS 2.0 again three months later. The results of confirmatory factor analysis (CFA) indicated that the YFAS 2.0 and mYFAS 2.0 both shared a similar single-factor solution. In addition, both the YFAS 2.0 and mYFAS 2.0 reported good internal consistency (Cronbach’s α = 0.90 and 0.89), good test-retest reliability (ICC = 0.71 and 0.69), and good concurrent validity with the total scores being strongly associated with the WSSQ (r = 0.54 and 0.57; p < 0.01), and less strongly associated with BMI (r = 0.17 and 0.13; p < 0.01) and IPAQ-SF (r = 0.23 and 0.25; p < 0.01).DiscussionBased on the findings, the Taiwan versions of the YFAS 2.0 and mYFAS 2.0 appear to be valid and reliable instruments assessing food addiction.

Abstract The vagus nerve plays an essential role in homeostasis and inflammation. Clinically, peptic ulcer patients without helicobacter pylori (HP) infection may provide a population for studying the effect of vagal hyperactivity. There were interests in the association of gastrointestinal disease and urogenital disorders. Herein, we try to investigate subsequent risk of benign prostatic hyperplasia (BPH) in non-HP infected peptic ulcer patients. We identified 17,672 peptic ulcer admission male patients newly diagnosed in 1998–2007 from Taiwan Health Insurance Database, and 17,672 male comparison without peptic ulcer, frequency matched by age, and index-year. We assessed subsequent incidence of BPH in each cohort by the end of 2013, and then compared the risk of developing BPH between individuals with and without peptic ulcer. In addition, peptic ulcer patients underwent surgery were also examined. There were 2954 peptic ulcer patients and 2291 comparisons noted with the occurrence of BPH (25.35 and 16.70 per 1000 person-years, respectively). Compared to comparisons, peptic ulcer patients had a 1.45- and 1.26-fold BPH risk in multivariable Cox model and Fine and Gray model (95% CI 1.37–1.54 and 1.19–1.34). In age-stratified analysis, the highest risk of BPH was in 45–59 years (interaction p

Abstract Precision medicine is becoming the standard of care in anti-cancer treatment. The personalized precision management of cancer patients highly relies on the improvement of new technology in next generation sequencing and high-throughput big data processing for biological and radiographic information. Systemic precision cancer therapy has been developed for years. However, the role of precision medicine in radiotherapy has not yet been fully implemented. Emerging evidence has shown that precision radiotherapy for cancer patients is possible with recent advances in new radiotherapy technologies, panomics, radiomics and dosiomics. This review focused on the role of precision radiotherapy in non-small cell lung cancer and demonstrated the current landscape.

Background and purpose: Thoracic re-irradiation may be an alternative treatment for lung cancer patients who develop intrathoracic locoregional recurrence without systemic progression. This study aimed to retrospectively assess locoregional control, clinical outcomes, and toxicities in lung cancer patients who received thoracic re-irradiation. Materials and methods: We retrospectively reviewed 50 lung cancer patients who received thoracic re-irradiation using conventional photon radiotherapy (RT) and stereotactic body radiotherapy (SBRT) between 2009 and 2017. The correlations of clinicopathologic factors, treatment factors, and dosimetric factors of RT with time to local progression (TTLP), progression-free survival (PFS), and overall survival (OS) after starting thoracic re-irradiation were calculated using log-rank tests and Cox regression models. Results: The median re-irradiation dose in equivalent dose in 2-Gy fractions was 51.1 Gy, and the mean re-irradiation planning target volume was 201.58 ml. The median mean lung dose (MLD) was 4.18 Gy, and the total lung volumes receiving a dose of 5 Gy (lung V5) and of 20 Gy (V20) were 19.8% and 5.85%, respectively. The TTLP, PFS, and OS were 18.0, 5.9, and 25.1 months, respectively. Lung V5 (p

Background The incidence of follicular lymphoma (FL) in Taiwan has not been well investigated since its inclusion as a histological subtype in the Taiwan Cancer Registry in 2008. The purpose of this study was to describe the incidence patterns of FL in Taiwan and compare the trends with those in other racial groups in the United States. Materials and methods We conducted an epidemiological study using population-based data from the Taiwan Cancer Registry, Ministry of Health and Welfare, and the 18 Surveillance, Epidemiology, and End Results (SEER) registries to evaluate the FL incidence from 2008 to 2017. We calculated the annual percent change (APC) to describe the trends in the incidence of FL in subpopulations defined by race and sex over time. Results The annual age-adjusted incidence rate of FL in Taiwan increased significantly from 0.59 per 100,000 persons in 2008 to 0.82 per 100,000 persons in 2017, with an APC of 3.2. By contrast, the incidence rate in whites in the United States during the same period decreased from 3.42 to 2.74 per 100,000 persons, with an APC of −2.1. We found no significant change for the blacks (APC, −1.5%), Hispanics (APC, −0.7%), and Asians or Pacific Islanders (APC, +0.7%). The temporal trend was similar between the males and females. The relative frequency of FL among the incident non-Hodgkin lymphoma (NHL) cases also increased significantly in Taiwan from 7.64% in 2008 to 11.11% in 2017 (APC = 3.8). The relative frequency of FL among the incident NHL cases in the whites decreased from 2008 to 2012 (APC, −3.8%) and then stabilized after 2012 (APC, −0.2%). By contrast, little change in relative frequency of FL among the incident NHL cases was observed in the blacks, Hispanics, and APIs between 2008 and 2017. Conclusion We found increases in the incidence of FL and the relative frequency of FL among the incident NHL cases in both males and females in Taiwan from 2008 to 2017. The FL incidence rates were unchanged for all races and sex groups in the United States, except for the decreases in the whites.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by prolonged fever, cytopenia, hepatosplenomegaly, and hemophagocytosis. This occurs as a result of activated macrophages and impaired function of natural killer cells and/or cytotoxic T lymphocytes. The NF-κB pathway plays a crucial role in hyperinflammation. Matrin3 (MATR3) is a nuclear RNA/DNA-binding protein that plays multiple roles in the regulation of gene expression. We enroll 62 patients diagnosed with secondary HLH and hemophagocytosis. Peripheral blood (PB) from 25 patients and 30 healthy volunteers and good quality bone marrow (BM) samples from 47 patients are collected and used for analysis. Clinical parameters, including age, sex, etiology, ferritin, fibrinogen, triglyceride, and viral infection status, had no association with survival prediction. Patients with downregulation of NF-κB and MATR3mRNA expression in the BM had a higher mortality rate. MATR3mRNA expression in PB was lower in patients compared to that in healthy volunteers. We use shRNA-MATR3-KD-THP1 cells to determine the efficacy of phagocytosis. We note that shRNA-MATR3-KD-THP1 cells had a higher phagocytic effect on necrotic Jurkat E6 cells and carboxylate modified polystyrene latex beads. Herein, we provide evidence of a new marker for clinical translation that can serve as a potential treatment target for secondary HLH.

Multiple myeloma is increasingly being recognised as more than one disease, characterised by marked cytogenetic, molecular, and proliferative heterogeneity. The prognosis is widely varied, ranging from low to very high-risk, based on cytogenetic and molecular studies. Although novel agents, such as proteasome inhibitors and immunomodulators, have been developed, which have improved treatment responses and disease prognosis, multiple myeloma remains an incurable disease. Based on highly sensitive detection tools, such as gene expression profiling and next generation sequence analysis, and the understanding of the pathogenesis of multiple myeloma, many potential agents, including monoclonal antibodies, drug-conjugated antibodies, drugs targeted to molecular abnormalities, microRNA inhibitors or mimics, and immune therapies, such as chimeric antigen receptors T cells and anti-PD1 agents, can be considered personalised therapies. In this paper, multiple myeloma pathogenesis and potential molecular and immunotherapies are reviewed.

This study estimates the environmental efficiency of 150 economies during the period of 2010–2017 to understand the environmental efficiency trend worldwide. This research adopts the meta-Malmquist approach to compare and capture the dynamic change in environmental efficiency among different income groups. The empirical results indicate that among the four income groups, only the low-income group suffers from regression in terms of environmental efficiency, while the high-income group achieves the greatest progress. For the high-income group, the source of improvement originates from the frontier shift rather than from efficiency change. By contrast, the improvement of the lower-income groups results from the catching-up effect. With regard to the effect of the Paris Agreement, only the lower middle-income group exhibits a statistical difference between the two periods, and environmental efficiency increases after the adoption of the Paris Agreement. The fight against global warming cannot succeed by relying only on specific countries. The whole world must cooperate and improve together, and thus, additional help must be devoted to the low-income group. The statistical results support that differences exist in terms of environmental efficiency among the four income groups. In particular, the low-income group is deteriorating.

Gene mutation and pathogenesis bacteria are highly associated with colorectal cancer (CRC) development and progression. Autophagy is a self-clearance pathway to degrade abnormal proteins and infected bacteria in cells. Autophagy plays a dual role in cancer development. Among the autophagy-related (ATG) proteins, ATG5 is the key component required for the core machinery of autophagy. However, the role of ATG5 in CRC malignancy remains unclear. Herein, we found that a high ATG5 protein level was correlated with poor overall survival (OS) and disease-free survival (DFS) of 118 patients with CRC. After stratification with demographic and clinicopathologic factors, a high ATG5 protein level was significantly correlated with unfavorable overall survival in female and elder (>60 year) CRC patients and tumor tissues with poor differentiation, late T stages (III + IV), whereas the ATG5 protein level was positively associated with the overall survival in CRC patients without lymph node invasion and radiation therapy. In contrast, a high ATG5 protein level was significantly associated with worse DFS in CRC patients with early stage of AJCC and no radiation therapy. In addition, colorectal cancer cells stably harboring small interfering RNA (siRNA) against ATG5 diminished the tumorsphere formation and sensitized cancer cells to chemotherapeutic agents. Taken together, our results suggest that ATG5 might be a prognostic biomarker for CRC and a potential therapeutic target for CRC patients.

Pancreatic cancer (PC) is a global health problem that features a very high mortality rate. The UL16 binding protein 2 (ULBP2) is a new biomarker for PC detection. This study develops a simple, reliable, and inexpensive immunosensor for the detection of the ULBP2 antigen while also investigating the effects of an array configuration of connected sensors and zinc oxide (ZnO) nanoparticles on the immunosensor’s sensitivity. The ULBP2 antibody was immobilized onto the screen-printed carbon electrode (SPCE) surfaces of three different sensors: a simple SPCE (ULBP2-SPCE); an SPCE array, which is a series of identical SPCE connected to each other at different arrangements of rows and columns (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3); and an SPCE combined with ZnO nanoparticles (ULBP2-ZnO/SPCE). Impedance spectrum measurements for the immunosensors to ULBP2 antigen were conducted and compared. According to the result, the array configurations (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3) show an improvement of sensitivity compared to the ULBP2-SPCE alone, but the improvement is not as significant as that of the ULBP2-ZnO/SPCE configuration (ULBP2-ZnO/SPCE > ULBP2-SPCE: 18 times larger). The ULBP2-ZnO/SPCE immunosensor has a low limit of detection (1 pg/mL) and a high sensitivity (332.2 Ω/Log(pg/mL)), excellent linearity (R2 = 0.98), good repeatability (coefficients of variation = 5.03%), and is stable in long-term storage (retaining 95% activity after 28 days storage). In an array configuration, the immunosensor has an increased signal-to-noise ratio (ULBP2-SPCE-1x3 > ULBP2-SPCE: 1.5-fold) and sensitivity (ULBP2-SPCE-1x3 > ULBP2-SPCE: 2.6-fold). In conclusion, either the modification with ZnO nanoparticles onto the sensor or the use of an array configuration of sensors can enhance the immunosensor’s sensitivity. In this study, the best immunosensor for detecting ULBP2 antigens is the ULBP2-ZnO/SPCE immunosensor.

This review summarizes the state of high-entropy alloys and their combinatorial approaches, mainly considering their magnetic applications. Several earlier studies on high-entropy alloy properties, such as magnetic, wear, and corrosion behavior; different forms, such as thin films, nanowires, thermal spray coatings; specific treatments, such as plasma spraying and inclusion effects; and unique applications, such as welding, are summarized. High-entropy alloy systems that were reported for both their mechanical and magnetic properties are compared through the combination of their Young’s modulus, yield strength, remanent induction, and coercive force. Several potential applications requiring both mechanical and magnetic properties are reported.

Cisplatin-induced acute kidney injury (AKI) is a major concern among clinicians in prescribing cisplatin-based chemotherapy. This study evaluated and compared the ability of urinary biomarkers, including urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and the urinary albumin to creatinine ratio (ACR) to predict cisplatin-induced AKI. Thirty-three cancer patients receiving cisplatin-based chemotherapy were prospectively studied, including 10 (30%) who developed AKI (the study group). Changes of urinary biomarkers were compared at 4 hours, 8 hours, and 12 hours, and 1 day, 2 days, 3 days, and 4 days after cisplatin intravenous infusions (75 mg/m2) versus the baseline. There was a significant increase in urinary NGAL levels from 12 hours to 4 days (p

Super scan pattern on technetium-99m methyldiphosphonate (Tc-99m MDP) bone scintigraphy is a special condition of extremely high bone uptake relative to soft tissue with absent or faint renal radioactivity visualization, which is usually seen in diffuse bone metastases or discrete endocrine entities. Here, two cases with super bone scan are presented. One was a young man diagnosed with gastric cancer. The other was a middle-aged woman with a history of breast cancer with recent recurrence. Both cases had 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) diagnosis simultaneously. Based on imaging of 18F-FDG PET/CT, diffusely incremental 18F-FDG avidity in spine/pelvis on PET and subtle erosion of cortical bone on CT were seen. The cytological results of bone marrow biopsy showed evidence of malignant metastasis. However, there were several focal discrepant findings between the 18F-FDG PET/CT and Tc-99m MDP bone scan. According to integration of both imaging findings and the result of bone marrow biopsy, we believe that the disseminated malignant spread in bone marrow is a primitive alternation in the super bone scan and that it is also as a result of neoplasm-related endocrine factors.

Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant inherited cancer syndrome that expresses nonendocrine and endocrine tumors. Here, we describe a 42-year-old man with an initial presentation of low back pain and hypertension. Clinical assessments revealed pheochromocytoma, medullary thyroid carcinoma with bone metastasis, and parathyroid hyperplasia. MEN 2A was diagnosed, and a family history of pheochromocytoma was traced. Surgical resection of the pheochromocytoma of the adrenal gland resulted in a cure of the patient’s hypertension. He received systemic chemotherapy with the “MAID” regimen (mesna, doxorubicin, ifosfamide, and dacarbazine) over three cycles of 3 weeks each, and showed a partial response.

The Philadelphia (Ph) chromosome and/or Breakpoint cluster region-Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML). However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1%) with the classic Ph chromosome, 6 (7.2%) with a variant Ph chromosome, and 9 (10.7%) with additional chromosome abnormalities. Fifty-four (64.3%) cases harbored b3a2 transcripts, 29 (34.5%) had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first- and second-line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second-line therapy had a significant poor impact (p

Hypertrophic osteoarthropathy (HOA) is characterized by clubbed fingers and periosteal new bone formation. Etiologically, it can be divided into primary and secondary HOA, but its pathogenesis is uncertain. We report a 42-year-old male patient who suffered from painful clubbing fingers and toes. Serial examinations revealed periosteal new bone formation in the four limb long bones and a solid mass lesion in the right upper lung field. Pathologic examination of the resected mass lesion showed squamous cell carcinoma. After surgery and chemotherapy, the severity of clubbed fingers decreased and joint pain improved. Follow-up bone scan also suggested regression of the uptake of radioactivity in the four limb bones. We concluded that the HOA in this case was probably caused by lung cancer.

BACKGROUND: Cellular senescence is a specialized form of growth arrest that is generally irreversible. Upregulated p16, p53, and p21 expression and silencing of E2F target genes have been characterized to promote the establishment of senescence. It can be further aided by the transcriptional repression of proliferation-associated genes by the action of HP1γ, HMGA, and DNMT proteins to produce a repressive chromatin environment. Therefore, senescence has been suggested to functions as a natural brake for tumor development and plays a critical role in tumor suppression and aging. METHODOLOGY/PRINCIPAL FINDINGS: An in vitro senescence model has been established by using K562 cells treated with 50 nM doxorubicin (DOX). Since p53 and p16 are homozygously deleted in the K562 cells, the DOX-induced senescence in K562 cells ought to be independent of p53 and p16-pRb pathways. Indeed, no change in the expression of the typical senescence-associated premalignant cell markers in the DOX-induced senescent K562 cells was found. MicroRNA profiling revealed upregulated miR-375 in DOX-induced senescent K562 cells. Treatment with miR-375 inhibitor was able to reverse the proliferation ability suppressed by DOX (p

Strategy-optimization is a fundamental element of dynamic and complex team sports such as soccer, American football, and basketball. As the amount of data that is collected from matches in these sports has increased, so has the demand for data-driven decisionmaking support. If alternative strategies need to be balanced, a data-driven approach can uncover insights that are not available from qualitative analysis. This could tremendously aid teams in their match preparations. In this work, we propose a novel Markov modelbased framework for soccer that allows reasoning about the specific strategies teams use in order to gain insights into the efficiency of each strategy. The framework consists of two components: (1) a learning component, which entails modeling a team's offensive behavior by learning a Markov decision process (MDP) from event data that is collected from the team's matches, and (2) a reasoning component, which involves a novel application of probabilistic model checking to reason about the efficacy of the learned strategies of each team. In this paper, we provide an overview of this framework and illustrate it on several use cases using real-world event data from three leagues. Our results show that the framework can be used to reason about the shot decision-making of teams and to optimise the defensive strategies used when playing against a particular team. The general ideas presented in this framework can easily be extended to other sports. [ABSTRACT FROM AUTHOR]