A High-Performance Deep Neural Network Model for BI-RADS Classification of Screening Mammography.

Globally, the incidence rate for breast cancer ranks first. Treatment for early-stage breast cancer is highly cost effective. Five-year survival rate for stage 0-2 breast cancer exceeds 90%. Screening mammography has been acknowledged as the most reliable way to diagnose breast cancer at an early stage. Taiwan government has been urging women without any symptoms, aged between 45 and 69, to have a screening mammogram bi-yearly. This brings about a large workload for radiologists. In light of this, this paper presents a deep neural network (DNN)-based model as an efficient and reliable tool to assist radiologists with mammographic interpretation. For the first time in the literature, mammograms are completely classified into BI-RADS categories 0, 1, 2, 3, 4A, 4B, 4C and 5. The proposed model was trained using block-based images segmented from a mammogram dataset of our own. A block-based image was applied to the model as an input, and a BI-RADS category was predicted as an output. At the end of this paper, the outperformance of this work is demonstrated by an overall accuracy of 94.22%, an average sensitivity of 95.31%, an average specificity of 99.15% and an area under curve (AUC) of 0.9723. When applied to breast cancer screening for Asian women who are more likely to have dense breasts, this model is expected to give a higher accuracy than others in the literature, since it was trained using mammograms taken from Taiwanese women.

Caregivers' Technology Acceptance of an In-Home Care Management App: A Mixed-Methods Study.

Taiwan faces challenges in providing long-term family care as its population rapidly ages. This study aimed to construct a health application that could effectively meet family caregivers' needs in providing home care. Mixed methods were adopted to explore their acceptance of the application, as well as to gather their suggestions for improving the application. A nonrandomized controlled group pretest-posttest design was utilized. The participants were family caregivers who were recruited via purposive sampling at a regional hospital in Taipei, Taiwan. The caregivers used the application to monitor and manage the health of those they were caring for. Elderly family caregivers scored 1.57 and 1.16 points higher than their middle-aged counterparts in terms of performance expectancy (0.61-2.53, P = .01) and effort expectancy (0.25-2.06, P = .01), respectively. The caregivers opined that it was convenient to use the application for managing the health data of their patients, and resources and solutions for overcoming problems when using the application were easily within their reach. They also suggested that relevant information for promoting patient mental health could also be included in the application. Thus, the software is acceptable to all the family caregivers regardless of age, indicating that it can assist family caregivers in the future in performing home care management.

Role of the Nod Factor Hydrolase MtNFH1 in Regulating Nod Factor Levels during Rhizobial Infection and in Mature Nodules of Medicago truncatula.

Establishment of symbiosis between legumes and nitrogen-fixing rhizobia depends on bacterial Nod factors (NFs) that trigger symbiosis-related NF signaling in host plants. NFs are modified oligosaccharides of chitin with a fatty acid moiety. NFs can be cleaved and inactivated by host enzymes, such as MtNFH1 (MEDICAGO TRUNCATULA NOD FACTOR HYDROLASE1). In contrast to related chitinases, MtNFH1 hydrolyzes neither chitin nor chitin fragments, indicating a high cleavage preference for NFs. Here, we provide evidence for a role of MtNFH1 in the symbiosis with Sinorhizobium meliloti Upon rhizobial inoculation, MtNFH1 accumulated at the curled tip of root hairs, in the so-called infection chamber. Mutant analysis revealed that lack of MtNFH1 delayed rhizobial root hair infection, suggesting that excess amounts of NFs negatively affect the initiation of infection threads. MtNFH1 deficiency resulted in nodule hypertrophy and abnormal nodule branching of young nodules. Nodule branching was also stimulated in plants expressing MtNFH1 driven by a tandem CaMV 35S promoter and plants inoculated by a NF-overproducing S. meliloti strain. We suggest that fine-tuning of NF levels by MtNFH1 is necessary for optimal root hair infection as well as for NF-regulated growth of mature nodules.

Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/ß-catenin signaling pathway.

BACKGROUND: The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC). METHODS: The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/ß-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo. RESULTS: In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/ß-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo. CONCLUSIONS: Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.

Familial Risk of Appendicitis: A Nationwide Population Study.

OBJECTIVE: To investigate the familial risk of appendicitis in the general population. STUDY DESIGN: A nationwide, cross-sectional study consisting of 24 349 599 Taiwan National Health Insurance beneficiaries in 2015 was conducted. Among them, 788 042 individuals had at least 1 first-degree relative with appendicitis. The familial relative risks (RRs) of appendicitis and familial transmission were estimated. RESULTS: The overall RR (95% CI) of appendicitis in individuals with any affected first-degree relatives was 1.67 (1.64-1.71) compared with the general population. The RRs for individuals with an affected twin, sibling, offspring, and parent were 3.40 (2.66-4.35), 1.98 (1.92-2.04), 1.55 (1.51-1.59), and 1.54 (1.50-1.58), respectively. The RRs for individuals with 1, 2, 3 or more affected first-degree relatives were 1.65 (1.62-1.68), 2.63 (2.37-2.91), and 6.70 (4.22-10.63), respectively. Furthermore, there was an age-dependent trend of the RRs, with the greatest RR in the youngest group. The estimated familial transmission (genetic plus shared environmental contribution to the total phenotypic variance of appendicitis) was 23.2%. CONCLUSION: Individuals with a family history of appendicitis have an increased risk of appendicitis. This risk is age-dependent and related to the genetic distance and numbers of affected relatives.

Risk of stroke in patients with dengue fever: a population-based cohort study.

BACKGROUND: Stroke is a severe neurologic complication of dengue fever, described in only a few case reports. The incidence and risk factors for stroke in patients with dengue remain unclear. We conducted a population-based retrospective cohort study to investigate the risk of stroke in patients with dengue. METHODS: Using data from the Taiwan National Health Insurance Research Database, we included a total of 13 787 patients with dengue newly diagnosed between 2000 and 2012. The control cohort consisted of patients who did not have dengue, matched 1:1 by demographic characteristics and stroke-related comorbidities. We calculated the cumulative incidences and hazard ratios (HRs) of stroke in both cohorts using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: The overall incidence rate of stroke was 5.33 per 1000 person-years in the dengue cohort and 3.72 per 1000 person-years in the control cohort, with an adjusted HR of 1.16 (95% confidence interval [CI] 1.01-1.32). The risk of stroke among patients with dengue was highest in the first 2 months after diagnosis (25.53 per 1000 person-years, adjusted HR 2.49, 95% CI 1.48-4.18). INTERPRETATION: Dengue fever was associated with an increased risk of stroke in the first few months after diagnosis. The effect of dengue on stroke may be acute rather than chronic.

Stromal derived factor-1α in hippocampus radial glial cells in vitro regulates the migration of neural progenitor cells.

Stromal derived factor-1α (SDF-1α), a critical chemokine that promotes cell homing to target tissues, was presumed to be involved in the traumatic brain injury cortex. In this study, we determined the expression of SDF-1α in the hippocampus after transection of the fimbria fornix (FF). Realtime PCR and ELISA showed that mRNA transcription and SDF-1α proteins increased significantly after FF transection. In vitro, the expression of SDF-1α in radial glial cells (RGCs) incubated with deafferented hippocampus extracts was observed to be greater than in those incubated with normal hippocampus extracts. The co-culture of neural progenitor cells (NPCs) and RGCs indicated that the extracts of deafferented hippocampus induced more NPCs migrating toward RGCs than the normal extracts. Suppression or overexpression of SDF-1α in RGCs markedly either decreased or increased, respectively, the migration of NPCs. These results suggest that after FF transection, SDF-1α in the deafferented hippocampus was upregulated and might play an important role in RGC induction of NPC migration; therefore, SDF-1α is a target for additional research for determining new therapy for brain injuries.

Cognitive control in honesty and dishonesty under different conflict scenarios: insights from reaction time.

This study investigated the role of cognitive control in moral decision-making, focusing on conflicts between financial temptations and the integrity of honesty. We employed a perceptual task by asking participants to identify which side of the diagonal contained more red dots within a square to provoke both honest and dishonest behaviors, tracking their reaction times (RTs). Participants encountered situations with no conflict, ambiguous conflict, and clear conflict. Their behaviors in the clear conflict condition categorized them as either "honest" or "dishonest." Our findings suggested that, in ambiguous conflict situations, honest individuals had significantly longer RTs and fewer self-interest responses than their dishonest counterparts, suggesting a greater need for cognitive control to resolve conflicts and a lesser tendency toward self-interest. Moreover, a negative correlation was found between participants' number of self-interest responses and RTs in ambiguous conflict situations (r = -0.27 in study 1 and r = -0.66 in study 2), and a positive correlation with cheating numbers in clear conflict situations (r = 0.36 in study 1 and r = 0.82 in study 2). This suggests less cognitive control was required for self-interest and cheating responses, bolstering the "Will" hypothesis. We also found that a person's self-interest tendency could predict their dishonest behavior. These insights extend our understanding of the role of cognitive control plays in honesty and dishonesty, with potential applications in education, policy-making, and business ethics.

Paget's disease of the nipple with underlying occult invasive carcinoma detected by magnetic resonance imaging and second-look ultrasound: Case report.

INTRODUCTION: Paget's disease of the nipple (PDN) is a rare and often misdiagnosed condition characterized by the infiltration of adenocarcinoma cells into the nipple epidermis. It poses substantial diagnostic and therapeutic challenges due to its similarity to benign dermatological conditions and its association with in situ or invasive carcinoma. CASE PRESENTATION: This report details the case of a 47-year-old woman with persistent nipple itching, rash, and occasional bloody discharge. No abnormalities were seen on the mammogram and ultrasound scans; punch biopsy was performed to confirm PDN. A small lesion missed by other imaging methods was detected via breast magnetic resonance imaging (MRI). A second-look ultrasound with needle localization enabled precise surgery. The pathology report after breast-conserving surgery (BCS) revealed invasive ductal carcinoma with no metastasis in the sentinel lymph node biopsy. DISCUSSION: PDN often mimics benign skin conditions, leading to delayed diagnosis. Furthermore, timely identification is crucial as PDN is frequently associated with underlying breast malignancies. Additional imaging, such as breast MRI, is essential for comprehensive evaluation, as it can reveal hidden lesions previously undetected by conventional mammography and ultrasound. A second-look ultrasound guided needle placement for tumor localization, enhancing surgical precision, aesthetics, and reducing patient harm. Surgical management, including mastectomy, BCS with radiotherapy, and oncoplastic surgery, offers suitable options without affecting recurrence or survival in selected patients. CONCLUSION: This case emphasizes the importance of employing additional imaging tools, such as breast MRI and second-look ultrasound for the early detection and surgical management of PDN.

Mitochondria-Targeting Metallodrugs for Cancer Therapy: Perspectives from Cell Death Modes.

Mitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continuous advancement, giving rise to a diverse array of metallodrugs characterized by variations in ligand types, metal center properties, and oxidation states. By specifically targeting mitochondria, these metallodrugs exhibit the remarkable ability to elicit various programmed cell death pathways, encompassing apoptosis, autophagy, and ferroptosis. This review primarily focuses on recent developments in transition metal-based mitochondria-targeting agents, offering a comprehensive exploration of their capacity to induce distinct cell death modes. The aim is not only to disseminate knowledge but also to stimulate an active field of research toward new clinical applications and novel anticancer mechanisms.

Beyond monetary value: how reward type drives cheating in a gender-judgment task.

Background: Investigating the effects of monetary incentives on dishonest behavior provides valuable insights into human integrity and ethical decision-making processes. This study is conducted through the lens of self-concept maintenance theory. Aim: The aim of this study is to examine the influence of different types of rewards (score-based vs. monetary) and their magnitude on dishonest behavior within a gender judgment task. Method: Using a quantitative experimental design, this study involved 116 participants who were randomly assigned to conditions that differed in reward type (score or money) and magnitude (10 yuan vs. 50 yuan). Dishonest behavior was assessed using a gender judgment task with mechanisms to simulate conditions conducive to planned cheating. Results: Results revealed significant differences in dishonesty rates between score and money conditions, with a higher proportion of dishonest participants observed in the score condition compared to the money condition. The timing of initial cheating was earlier in the score condition compared to the money condition. No significant differences were found in the proportion of dishonest participants, the cheating rate, or the timing of initial cheating across reward levels within either condition. The rate of cheating increased over time, suggesting a temporal dynamic in unethical decision making. Conclusion: The study demonstrates that the nature of rewards significantly influences the likelihood of dishonest behavior, with intangible score-based rewards facilitating rationalizations for dishonesty more readily than tangible financial incentives. These findings enrich the understanding of moral psychology by highlighting the complex interplay between reward types, ethical rationalization, and the dynamics of dishonest behavior.

Path planning optimization for swine manure-cleaning robots through enhanced slime mold algorithm with cellular automata.

One of the primary challenges for robotic manure cleaners in pig farming is to plan the shortest path to designated cleaning points under specified conditions with minimal processing cost and time, while avoiding collisions. However, pigs are randomly distributed in actual pig farms, which obstructs the robots' movement and complicates the rapid determination of optimal solutions. To address these issues, this study introduces the concept of interaction among cellular automaton cell neighborhoods and proposes the Cellular Automata Slime Mold Algorithm (CASMA). This enhanced slime mold algorithm accelerates convergence speed and improves search accuracy. To validate its effectiveness, CASMA was compared with four metaheuristic algorithms (ACO, FA, PSO, and WPA) through performance tests and simulated experiments. Results demonstrate that in complex pigsty environments with varying numbers of pigs, CASMA reduces average step consumption by 8.03%, 1.61%, 0.99%, and 4.26% compared with these algorithms and saves processing time by averages of 13.20%, 20.11%, 10.86%, and 6.4%, respectively. In addition, in dynamic obstacle experiments, CASMA achieved average time savings of 48.27% and 56.28% compared with A* and TS, respectively, while reducing step consumption. Overall, CASMA enhances the efficiency of manure-cleaning robots in pig farms, thereby improving animal welfare.

Renal angiomyolipoma with coexistent hemorrhagic aneurysm formation and fatty thrombus in inferior vena cava: a rare presentation.

Angiomyolipoma (AML) is known as the most common benign mesenchymal tumor of kidney. Usually AMLs present as benign lesions without local invasion or complication. However, few cases of renal AML have been reported with complications such as tumor thrombus extension into inferior vena cava (IVC) or hemorrhagic aneurysm formation. We report a complicated case of renal AML with CT and angiography evidence of hemorrhagic aneurysm formation and IVC thrombus, treated by a combination of selective arterial embolization, radical nephrectomy and thrombectomy. Radiologists and clinicians should be aware that AMLs could have such aggressive behaviors.

Performance of Ir(III)-Based Anticancer Agents in the Treatment of Cisplatin-Resistant Cancer Cells.

The resistance of cancer cells to cisplatin has dramatically blocked the further application of this drug in practical treatment settings. The generation of cisplatin resistance is a complex physiological process, and several mechanisms have been reported for this. New metal-based agents with distinct anticancer mechanisms are still highly desired. In this concept article, we describe Ir(III)-based anticancer agents and their underlying anticancer mechanisms, which could inhibit the proliferation of cisplatin-resistant tumors. This work could be beneficial in developing more effective Ir(III)-based agents to combat cisplatin resistance.

Association Between Antibiotic Treatment of Leptospirosis Infections and Reduced Risk of Dementia: A Nationwide, Cohort Study in Taiwan.

Background: To explore the association between leptospirosis, the risk of dementia, and the potential protective role of antibiotic treatment. Methods: We conducted a retrospective cohort nationwide, population-based study, from Taiwan's National Health Insurance Research Database (NHIRD). We enrolled 1,428 subjects aged 50 years or above, in the index year of 2000, which included those retrieved from the NHIRD record. Dementia diagnosis and incidence over 16 years follow-up was retrieved from the NHIRD records. The Fine and Gray survival analysis was used to determine the risk of dementia, and the results were presented as a sub-distribution hazard ratio (SHR) with a 95% confidence interval. Results: In the study period, 43 of the 357 leptospirosis patients developed dementia, as compared to 103 of the control group (930.90 vs. 732.49 per 105 person-years). By the Fine and Gray survival analysis, the leptospirosis was associated with the risk of dementia, and the adjusted SHR was 1.357 (95% confidence interval [CI]: 1.213-1.519, P < 0.001), across 16-year of the follow-up period. To exclude the protopathic bias, the sensitivity analysis was conducted. This analysis revealed that the leptospirosis was associated with the increased risk of dementia, even after excluding the dementia diagnosis within the first year (adjusted SHR = 1.246, 95%CI: 1.114-1.395, P < 0.001) or within the first 5 years (adjusted SHR = 1.079, 95%CI: 1.023-1.152, P = 0.028), antibiotic treatment for leptospirosis was associated with the reduced risk of dementia (P = 0.001). Conclusion: Leptospirosis was associated with an increased risk for dementia, and antibiotic treatment was associated with a reduced risk. Further research will be necessary to explore the underlying mechanisms of this association.

Multimodal Treatment with Cognitive Behavioral Therapeutic Intervention Plus Bladder Treatment Is More Effective than Monotherapy for Patients with Interstitial Cystitis/Bladder Pain Syndrome-A Randomized Clinical Trial.

(1) Background: Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) not only induces physiological damage but also greatly affects psychological stress. Multidisciplinary therapy has been recommended for IC/BPS treatment, but clinical trial data of combined bladder therapy and cognitive behavioral therapy (CBT) are lacking. This study evaluated CBT efficacy in patients with IC/BPS. (2) Methods: Patients with IC/BPS were randomized to the bladder monotherapy (BT) or combined CBT (CBT) group. The primary endpoint was the self-reported outcome by global response assessment (GRA). Secondary endpoints included IC symptoms and problem index, bladder pain score, Beck's anxiety inventory (BAI), and depression inventory, and objective parameters were also compared. (3) Result: A total of 30 patients receiving BT and 30 receiving CBT therapy were enrolled. Significant improvement of the BAI at 8 (p = 0.045) and 12 weeks (p = 0.02) post-treatment was observed in the CBT group, with significantly greater GRA scores at 12 weeks (p < 0.001). Repeated measures analysis of variance showed a significant effect within the CBT group on IC/BPS patients' self-reported treatment outcomes (p = 0.001) and anxiety severity BAI scores (p = 0.033). (4) Conclusion: A multimodal treatment of CBT combined with suitable bladder treatment more effectively improves anxiety severity and treatment outcomes in patients with IC/BPS.

The co-transduction of Nurr1 and Brn4 genes induces the differentiation of neural stem cells into dopaminergic neurons.

Fetal brain tissue can be used in cell replacement therapy for PD (Parkinson's disease), but there is a poor donor supply of this tissue. NSCs (neural stem cells) may overcome this problem as they can be isolated and expanded in vitro. However, the usage of NSCs is limited because the differentiation of NSCs into specific dopaminergic neurons has proven difficult. In the present study, we investigated the effect of Nurr1 (nuclear receptor related factor 1), a transcription factor specific for the development and maintenance of the midbrain dopaminergic neurons on inducing the differentiation of NSCs into TH (tyrosine hydroxylase) immunoreactive dopaminergic neurons. Nonetheless, these cells exhibited an immature neuronal morphology with small cell bodies and short neurite processes, and they seldom expressed DAT (dopamine transporter), a late marker of mature dopaminergic neurons. However, forced co-expression of Nurr1 with Brn4, a member of the POU domain family of transcription factors, caused immature Nurr1-induced dopaminergic neurons to differentiate into morphologically and phenotypically more mature neurons. Thus the enriched generation of mature dopaminergic neurons by forced expression of Nurr1 with Brn4 may be of future importance in NSC-based cell replacement therapy for PD.