Racial and ethnic disparities in Acute Myeloid Leukemia: 15-year experience at a safety net hospital system.

Despite recent therapeutic advances, ethnic minorities in the U.S. continue to have disproportionately poor outcomes in many hematologic malignancies including AML. We identified 162 adult AML patients treated at a non-transplant safety net hospital from 2007 to 2022 and evaluated differences in disease characteristics, treatment and clinical outcomes based on race and ethnicity. Our cohort consisted of 82 (50.6%) Hispanic, 36 (22.2%) non-Hispanic black and 44 (27.2%) non-Hispanic white and Asian patients. Median age at diagnosis was 42.5, 49.0 and 52.5 years respectively (p=0.025). Hispanics had higher rates of intermediate and high-risk disease (p=0.699) and received high intensity induction and consolidation chemotherapy at lower rates (p=0.962), although differences did not reach statistical significance. Despite this, similar remission rates were achieved. Hispanics with high-risk disease had longer overall survival (OS) than the combined non-Hispanic cohort (mOS 14 m vs 7 m, p=0.030). Multivariate regression analysis showed that OS was negatively associated with age (HR 1.023, p=0.006), intermediate (HR 3.431, p=0.0003) and high-risk disease (HR 4.689, p<0.0001) and positively associated with Hispanic ethnicity (HR 0.614, p=0.026). This report suggests that contrary to other studies, Hispanics, particularly those with high-risk AML, may have improved OS compared to other ethnic groups. These results are unique to our safety net hospital setting where common barriers to medical care and healthcare disparities are largely mitigated.

Perivascular adipose tissue and adipocyte-derived exosomal miRNAs maintain vascular homeostasis.

Perivascular adipose tissue (PVAT), a fat layer that provides structural support to the blood vessels, is a cushion protecting the vessel wall from neighbouring tissues during contraction and relaxation. PVAT actively regulates vascular tone by secreting vasoactive (vasodilatory and vasoconstrictive) factors (e.g., adipokines, batokines, and lipokines) or microRNA (miRNA)-containing exosomes to reduce the hyperreactivity induced by obesity. Of particular interest are adipocyte-derived exosomal miRNAs, which act as crucial regulators, counteracting the detrimental effects of obesity on cardiovascular well-being. These exosomes serve as potent messengers, facilitating the transport of miRNAs and other bioactive molecules involved in intercellular communication. Undoubtedly, the unique function of exosomal miRNAs promotes vascular homeostasis by fine-tuning endothelial function, vascular remodelling, and inflammatory environment, thereby preventing cardiovascular disease. The collective findings comprehensively explain their protective functions by exploring the intricate mechanisms through which PVAT and adipocyte-derived exosomal miRNAs collaboratively orchestrate vascular health. Taken together, this review strategically focuses on PVAT, exosomes, and adipocyte-derived miRNAs, offering valuable insights that can potentially inform the development of targeted interventions for cardiovascular diseases.

Effect of acupressure on alleviating constipation among inpatients with stroke during the acute phase: A randomized controlled trial.

BACKGROUND AND PURPOSE: This study aimed to explore the effects of acupressure in alleviating constipation among inpatients with stroke in neurological departments. MATERIAL AND METHODS: This was a two-arm, parallel, randomized, controlled trial conducted between September 2020 and August 2021. In total, 128 inpatients with stroke at the acute phase from neurological departments were randomly assigned at a 1:1 ratio to either an acupressure group (ST25, CV12, and CV6) or a sham acupressure group for twice-daily therapy at 4 min per intervention for 7 days. The Bristol Stool Form Scale and Constipation Assessment Scale (CAS) were assessed at the beginning and completion of the study. A generalized estimating equation was used for data analyses. RESULTS: The mean ages were 63.8 ± 19.1 and 66.2 ± 16.0 years, and the average National Institutes of Health Stroke Scale scores were 7.2 ± 5.6 and 8.1 ± 6.3 points for the acupressure and sham acupressure groups, respectively. The acupressure group demonstrated gradually lower scores on the CAS over time than the sham acupressure group. Patients who received acupressure had a lower likelihood of requiring defecation medication and were more likely to have normal bowel movements and a decreased risk of their stool appearing as a hard lump than those who received sham acupressure over time. CONCLUSION: Traditional Chinese medicine-based acupressure can help alleviate constipation and reduce the use of defecation medication among inpatients with stroke who have been admitted to neurological departments. TRIAL AND PROTOCOL REGISTRATION: ClinicalTrials.gov, NCT05612646.

Exploration and biological evaluation of 7-methoxy-3-methyl-1H-chromeno[4,3-c]pyrazol-4-one as an activating transcription factor 3 inducer for managing metabolic syndrome.

The induction of activating transcription factor 3 (ATF3) was identified as a promising therapeutic mechanism to overcome metabolic syndrome. Hence, a structure-activity relationship campaign on the chiral lead (1b) was conducted with a scaffold-hopping approach, whereby achiral 7-methoxy-3-methyl-1H-chromeno[4,3-c]pyrazol-4-one (16c) was recognized as a potential ATF3 inducer with a lipid-lowering feature in a pre-differentiated 3T3-L1 cell model. Also, in a high-fat diet scenario, mice subjected to 16c demonstrated robust weight loss with shrinkage of the white adipose mass and fewer hypertrophic adipocytes, accompanied by a preferable glycemic profile compared to 1b. Additionally, the biochemical analysis revealed that 16c further ameliorated the liver function and improved the plasma triglyceride profile that were absent from mice treated with 1b. Taken together, 16c shows promise as an ATF3 stimulant for further development to alleviate metabolic syndrome.

Role of PVAT in obesity-related cardiovascular disease through the buffering activity of ATF3.

Thoracic aortic perivascular adipose tissue (PVAT) is an adipose organ exhibiting similarities to brown adipose tissue (BAT), including cellular morphology and thermogenic gene expression. However, whether the PVAT phenotype is indistinguishable from the BAT phenotype in physiological vasculature remains unclear. We demonstrated that PVAT is distinguishable from classical BAT, given its specific vessel-tone-controlling function. Activating transcription factor 3 (ATF3) is a key factor in hypertension. Compared with wild-type mice, ATF3-deficient (ATF3 -/- ) mice fed a high-fat diet exhibited elevated mean arterial pressure, increased monocyte chemoattractant protein-1 expression and hypertrophy, plus abnormal fatty tissue accumulation in the thoracic aortic PVAT, and enhanced vascular wall tension and vasoconstrictive responses of potassium chloride, U46619, and norepinephrine in isolated aortic rings, which were restored after administration of adeno-associated ATF3 vector. We suggest that PVAT, not BAT, modulates obesity-related vascular dysfunction. ATF3 within PVAT could provide new insights into the pathophysiology of obesity-related cardiovascular diseases.

An Optimization-Based Technology Applied for Face Skin Symptom Detection.

Face recognition segmentation is very important for symptom detection, especially in the case of complex image backgrounds or noise. The complexity of the photo background, the clarity of the facial expressions, or the interference of other people's faces can increase the difficulty of detection. Therefore, in this paper, we have proposed a method to combine mask region-based convolutional neural networks (Mask R-CNN) with you only look once version 4 (YOLOv4) to identify facial symptoms by this new method. We use the face image dataset from the public image databases DermNet and Freepic as the training source for the model. Face segmentation was first applied with Mask R-CNN. Then the images were imported into ResNet-101, and the facial features were fused with region of interest (RoI) in the feature pyramid networks (FPN) structures. After removing the non-face features and noise, the face region has been accurately obtained. Next, the recognized face area and RoI data were used to identify facial symptoms (acne, freckle, and wrinkles) with YOLOv4. Finally, we use Mask R-CNN, and you only look once version 3 (YOLOv3) and YOLOv4 are matched to perform the performance analysis. Although, the facial images with symptoms are relatively few. We still use a limited amount of data to train the model. The experimental results show that our proposed method still achieves 57.73%, 60.38%, and 59.75% of mean average precision (mAP) for different amounts of data. Compared with other methods, the mAP was more than about 3%. Consequently, using the method proposed in this paper, facial symptoms can be effectively and accurately identified.

The Utility of Breast Cancer Index (BCI) Over Clinical Prognostic Tools for Predicting the Need for Extended Endocrine Therapy: A Safety Net Hospital Experience.

INTRODUCTION: Extended endocrine therapy (EET) benefits select patients with early-stage hormone-receptor positive (HR+) breast cancer (BC) but also incurs side effects and cost. The Clinical Treatment Score at Five Years (CTS5) is a free tool that estimates risks of late relapse in estrogen-receptor positive (ER+) BC using clinicopathologic factors. The Breast Cancer Index (BCI) incorporates 2 genomic assays to estimate late relapse risk and likelihood of benefit from EET. This retrospective study assesses the utility of BCI in selecting EET candidates in a safety net hospital. MATERIALS AND METHODS: We performed a retrospective chart review on 69 women with early-stage HR+, HER2- BC diagnosed at our institution from December 2009 to February 2016 on whom BCI was submitted. The CTS5 score was also calculated to assess clinical risk of late relapse. RESULTS: Median age was 53 years. All patients included in our analysis had early ER+ HER2-negative BC. Roughly half of the patients (55%) were postmenopausal and 61% were of Hispanic origin. A total of 34 patients (49%) were deemed high-risk (>5%) for late relapse by CTS5, compared to 42 (61%) by BCI. BCI identified 31 (45%) patients that would benefit from EET and of those, 74%% were advised EET. 16 (47%) clinical high-risk patients were advised against EET due to low benefit predicted by BCI. In the clinical low risk group, 9 (26%) were recommended EET based on high benefit predicted by BCI. CONCLUSION: BCI is reasonable to consider in early-stage HR+ BC and offered clinically relevant information over clinical pathologic information alone.

Multifaceted and Intricate Oncogenic Mechanisms of NDRG1 in Head and Neck Cancer Depend on Its C-Terminal 3R-Motif.

N-Myc downstream-regulated 1 (NDRG1) has inconsistent oncogenic functions in various cancers. We surveyed and characterized the role of NDRG1 in head and neck cancer (HNC). Cellular methods included spheroid cell formation, clonogenic survival, cell viability, and Matrigel invasion assays. Molecular techniques included transcriptomic profiling, RT-qPCR, immunoblotting, in vitro phosphorylation, immunofluorescent staining, and confocal microscopy. Prognostic significance was assessed by Kaplan-Meier analysis. NDRG1 participated in diverse oncogenic functions in HNC cells, mainly stress response and cell motility. Notably, NDRG1 contributed to spheroid cell growth, radio-chemoresistance, and upregulation of stemness-related markers (CD44 and Twist1). NDRG1 facilitated cell migration and invasion, and was associated with modulation of the extracellular matrix molecules (fibronectin, vimentin). Characterizing the 3R-motif in NDRG1 revealed its mechanism in the differential regulation of the phenotypes. The 3R-motif displayed minimal effect on cancer stemness but was crucial for cell motility. Phosphorylating the motif by GSK3b at serine residues led to its nuclear translocation to promote motility. Clinical analyses supported the oncogenic function of NDRG1, which was overexpressed in HNC and associated with poor prognosis. The data elucidate the multifaceted and intricate mechanisms of NDRG1 in HNC. NDRG1 may be a prognostic indicator or therapeutic target for refractory HNC.

Salvia miltiorrhiza Extract and Individual Synthesized Component Derivatives Induce Activating-Transcription-Factor-3-Mediated Anti-Obesity Effects and Attenuate Obesity-Induced Metabolic Disorder by Suppressing C/EBPα in High-Fat-Induced Obese Mice.

Pharmacological studies indicate that Salvia miltiorrhiza extract (SME) can improve cardiac and blood vessel function. However, there is limited knowledge regarding the effects (exerted through epigenetic regulation) of SME and newly derived single compounds, with the exception of tanshinone IIA and IB, on obesity-induced metabolic disorders. In this study, we administered SME or dimethyl sulfoxide (DMSO) as controls to male C57BL/J6 mice after they were fed a high-fat diet (HFD) for 4 weeks. SME treatment significantly reduced body weight, fasting plasma glucose, triglyceride levels, insulin resistance, and adipogenesis/lipogenesis gene expression in treated mice compared with controls. Transcriptome array analysis revealed that the expression of numerous transcriptional factors, including activating transcription factor 3 (ATF3) and C/EBPα homologous protein (CHOP), was significantly higher in the SME group. ST32db, a novel synthetic derivative similar in structure to compounds from S. miltiorrhiza extract, ameliorates obesity and obesity-induced metabolic syndrome in HFD-fed wild-type mice but not ATF3-/- mice. ST32db treatment of 3T3-L1 adipocytes suppresses lipogenesis/adipogenesis through the ATF3 pathway to directly inhibit C/EBPα expression and indirectly inhibit the CHOP pathway. Overall, ST32db, a single compound modified from S. miltiorrhiza extract, has anti-obesity effects through ATF3-mediated C/EBPα downregulation and the CHOP pathway. Thus, SME and ST32db may reduce obesity and diabetes in mice, indicating the potential of both SME and ST32db as therapeutic drugs for the treatment of obesity-induced metabolic syndrome.

Emergent Roles of Circular RNAs in Metabolism and Metabolic Disorders.

Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attracted attention again according to the progress in high-throughput sequencing in recent years. circRNAs are genome transcripts produced from pre-messenger (m)RNA regions in a specific process called "back-splicing," which forms covalently closed continuous loops. Due to their lack of a 5' cap and 3' poly-adenylated tails, circRNAs are remarkably more stable than linear RNAs. Functionally, circRNAs can endogenously sponge to microRNAs, interact with RNA-binding proteins (RBPs), or translate themselves. Moreover, circRNAs can be expressed in cell type- or tissue-specific expression patterns. Therefore, they are proposed to play essential roles in fine-tuning our body's homeostasis by regulating transcription and translation processes. Indeed, there has been accumulating emergent evidence showing that dysregulation of circRNAs can lead to metabolic disorders. This study explored the current knowledge of circRNAs that regulate molecular processes associated with glucose and lipid homeostasis and related pathogeneses of metabolic disorders. We also suggest the potential role of circRNAs as disease biomarkers and therapeutic targets.

Novel Three-Dimensional Bladder Reconstruction Model from B-Mode Ultrasound Image to Improve the Accuracy of Bladder Volume Measurement.

Traditional bladder volume measurement from B-mode (two-dimensional) ultrasound has been found to produce inaccurate results, and thus in this work we aim to improve the accuracy of measurement from B-mode ultrasound. A total of 75 electronic medical records including ultrasonic images were reviewed retrospectively from 64 patients. We put forward a novel bladder volume measurement method, in which a three-dimensional (3D) reconstruction model was established from conventional two-dimensional (2D) ultrasonic images to estimate the bladder volume. The differences and relationships were analyzed among the actual volume, the traditional estimated volume, and the new reconstruction model estimated volume. We also compared the data in different volume groups from small volume to high volume. The mean actual volume is 531.8 mL and the standard deviation is 268.7 mL; the mean percentage error of traditional estimation is -28%. In our new bladder measurement method, the mean percentage error is -10.18% (N = 2), -4.72% (N = 3), -0.33% (N = 4), and 2.58% (N = 5). There is no significant difference between the actual volume and our new bladder measurement method (N = 4) in all data or the divided four groups. The estimated volumes from the traditional method or our new method are highly correlated with the actual volume. Our data show that the three-dimensional bladder reconstruction model provides an accurate measurement from conventional B-mode ultrasonic images compared with the traditional method. The accuracy is seen across different groups of volume, and thus we can conclude that this is a reliable and economical volume measurement model that can be applied in general software or in apps on mobile devices.

Clinicopathological Features and Outcomes in Individuals with Breast Cancer and ATM, CHEK2, or PALB2 Mutations.

INTRODUCTION: The moderate-penetrance germline mutations ATM, CHEK2, and PALB2 are implicated in an increased risk of the development of breast cancer. Whether these mutations provide clinical utility to guide treatment strategies and prognosis remains unknown. METHODS: A retrospective case-control study from a tertiary institution compared patients with stage 0-III breast cancer, and positive for ATM, CHEK2, or PALB2 mutations, with a matched cohort selected by randomization and negative for mutations. Data acquisition included demographics, histopathologic, treatment, and clinical outcome variables. RESULTS: A total of 145 patients with breast cancer (144 female and 1 male) were analyzed-74 mutation-positive patients (24 ATM, 26 CHEK2, 24 PALB2) and 71 mutation-negative patients. Mutation-positive patients compared with mutation-negative patients had increased family history of breast cancer (79.7 vs. 52.9%, p < 0.001) and tumor size > 2.0 cm (63.1% vs. 42.3%, p = 0.015). Patients with prior knowledge of mutational status were more likely to proceed with total mastectomy and prophylactic mastectomy (74.5% vs. 25.5%, p < 0.02; and 65.5% vs. 34.5%, p < 0.001, respectively). The unadjusted recurrence rate was higher in mutation-positive patients compared with mutation-negative patients (24.3 vs. 8.5%, p = 0.01), although mutation status was not predictive for recurrence in Cox regression analysis. CONCLUSIONS: Patients positive for ATM, CHEK2, or PALB2 mutations had increased tumor size and were more likely to undergo extensive surgeries. Mutation status was not predictive of recurrence, although this lack of effect may have been mitigated by lower rates of recurrence in those who pursued total mastectomy. Further studies are needed to confirm these findings.

Lightweight and Resource-Constrained Learning Network for Face Recognition with Performance Optimization.

Despite considerable progress in face recognition technology in recent years, deep learning (DL) and convolutional neural networks (CNN) have revealed commendable recognition effects with the advent of artificial intelligence and big data. FaceNet was presented in 2015 and is able to significantly improve the accuracy of face recognition, while also being powerfully built to counteract several common issues, such as occlusion, blur, illumination change, and different angles of head pose. However, not all hardware can sustain the heavy computing load in the execution of the FaceNet model. In applications in the security industry, lightweight and efficient face recognition are two key points for facilitating the deployment of DL and CNN models directly in field devices, due to their limited edge computing capability and low equipment cost. To this end, this paper provides a lightweight learning network improved from FaceNet, which is called FN13, to break through the hardware limitation of constrained computational resources. The proposed FN13 takes the advantage of center loss to reduce the variations of the between-class features and enlarge the difference of the within-class features, instead of the triplet loss by using FaceNet. The resulting model reduces the number of parameters and maintains a high degree of accuracy, only requiring few grayscale reference images per subject. The validity of FN13 is demonstrated by conducting experiments on the Labeled Faces in the Wild (LFW) dataset, as well as an analytical discussion regarding specific disguise problems.

Inhibition of miR-155 potentially protects against lipopolysaccharide-induced acute lung injury through the IRF2BP2-NFAT1 pathway.

Sepsis-induced lung injury is a lethal complication with no effective treatment options, affecting millions of people worldwide. Oroxylin A (OroA) is a natural flavonoid with potent anticancer effects, but its modulating effect on inflammation through microRNAs (miRs) is not apparent. In this report, we investigated the target genes of the miR pathway mediated by OroA and assessed the potential for novel treatments of septic lung injury. An miR array screening and quantitative polymerase chain reaction identified that miR-155-5p could be a candidate regulated by OroA. Bioinformatics analysis indicated that interferon regulatory factor-2-binding protein-2 (IRF2BP2) might be a target of miR-155-5p, and this hypothesis was verified through reporter assays. In addition, an immunoprecipitation assay demonstrated that OroA increased the binding activity of IRF2BP2 to the nuclear factor of activated T-cells 1 (NFAT1), causing inducible nitric oxide synthase to cause an inflammatory reaction. Finally, the direct injection of short hairpin RNA (shRNA)-miR-155-5p into the bone marrow of mice ameliorated LPS-induced acute lung injury and inflammation in mice. Our results provide new mechanistic insights into the role of the OroA-induced miR-155-5p-IRF2BP2-NFAT1 axis in sepsis, demonstrating that direct bone marrow injection of lentivirus containing shRNA-155-5p could prove to be a potential future clinical application in alleviating sepsis-induced acute lung injury.

MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury.

Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such as contrast medium), is identified by an abrupt decline in kidney function and is associated with high morbidity and mortality. Despite decades of efforts, the pathogenesis of AKI remains poorly understood, and effective therapies are lacking. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level to control cell differentiation, development, and homeostasis. Additionally, extracellular miRNAs might mediate cell-cell communication during various physiological and pathological processes. Recently, mounting evidence indicates that miRNAs play a role in the pathogenesis of AKI. Moreover, emerging research suggests that because of their remarkable stability in body fluids, microRNAs can potentially serve as novel diagnostic biomarkers of AKI. Of note, our previous finding that miR-494 is rapidly elevated in urine but not in serum provides insight into the ultimate role of urine miRNAs in AKI. Additionally, exosomal miRNAs derived from stem cells, known as the stem cell secretome, might be a potential innovative therapeutic strategy for AKI. This review aims to provide new data obtained in this field of research. It is hoped that new studies on this topic will not only generate new insights into the pathophysiology of urine miRNAs in AKI but also might lead to the precise management of this fatal disease.

Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3.

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3-/- ) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate adipokine genes and induce adipocyte browning by suppressing the carbohydrate-responsive element-binding protein-stearoyl-CoA desaturase-1 axis. Furthermore, ST32da increased white adipose tissue browning and reduced lipogenesis in HFD-induced obese mice. The anti-obesity efficacy of oral ST32da administration was similar to that of the clinical drug orlistat. Our study identified the ATF3 inducer ST32da as a promising therapeutic drug for treating diet-induced obesity and related metabolic disorders.

Reducing Hospitalizations: Institution of Outpatient Infusional EPOCH-Based Chemotherapy at a Safety Net Hospital.

PURPOSE: EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) -based chemotherapy is traditionally administered inpatient because of its complex 96-hour protocol and number of involved medications. These routine admissions are costly, disruptive, and isolating to patients. Here, we describe our experience transitioning from inpatient to outpatient ambulatory EPOCH-based chemotherapy in a safety-net hospital, associated cost savings, and patient perceptions. METHODS AND MATERIALS: Guidelines for chemotherapy administration and educational materials were developed by a multidisciplinary team of physicians, nurses, and pharmacists. Data were collected via chart review and costs via the finance department. Patient satisfaction with chemotherapy at home compared with hospitalization was measured on a Likert-type scale via direct-to-patient survey. RESULTS: From January 30, 2017, through January 30, 2018, 87 cycles of EPOCH-based chemotherapy were administered to 23 patients. Sixty-one ambulatory cycles (70%) were administered to 18 patients. Of 26 cycles administered in the hospital, 18 (69%) were the first cycle of treatment. Rates of inappropriate prophylactic antimicrobial prescription and laboratory testing were lower in the outpatient setting. Eight of nine patients surveyed preferred home chemotherapy to inpatient chemotherapy. Per-cycle drug costs were 57.6% lower in outpatients as a result of differences in the acquisition cost in the outpatient setting. In total, the transition to ambulatory EPOCH-based chemotherapy yielded 1-year savings of $502,030 and an estimated 336 days of avoided hospital confinement. CONCLUSION: Multiday ambulatory EPOCH-based regimens were successfully and safely administered in our safety-net hospital. Outpatient therapy was associated with significant savings through avoided hospitalizations and reductions in drug acquisition cost and improved patient satisfaction.