Identification of Dalbergiae Odoriferae Lignum active ingredients and potential mechanisms in the treatment of adriamycin-induced cardiotoxicity based on network pharmacology and experimental verification.

The purpose of this study is to investigate the ingredients and mechanisms through which Dalbergiae Odoriferae Lignum (DOL) reduces adriamycin-induced cardiotoxicity. DOL's ingredients and drug targets were acquired from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and adriamycin-induced cardiotoxicity disease targets were gathered from GeneCards and National Center for Biotechnology Information (NCBI). The therapeutic targets of DOL against adriamycin-induced cardiotoxicity were identified by intersecting drug and disease targets. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted using R. Subsequently, core targets were determined and used for molecular docking with DOL ingredients. In vitro and in vivo experiments validated DOL's primary ingredients against adriamycin-induced cardiotoxicity efficacy. Western blot and immunohistochemistry verified its impact on target protein. After intersecting 530 drug targets and 51 disease targets, 19 therapeutic targets for DOL alleviated adriamycin-induced cardiotoxicity were received. Molecular docking demonstrated that DOL primary ingredient formononetin had a robust binding affinity for nitric oxide synthase 3 (NOS3). Experimental results showed that formononetin effectively mitigated adriamycin-induced cardiotoxicity. Additionally, western blot and immunohistochemistry showed that formononetin improved NOS3 expression. The network pharmacology and experimentation suggest that the primary ingredient of DOL, formononetin, may target NOS3 to act as a therapeutic agent for adriamycin-induced cardiotoxicity.

Establishment and study of a rat internal haemorrhoid model.

To establish a relatively stable internal haemorrhoid model in rats. A total of 48 SPF SD rats were selected and randomly divided into a blank group of 16 and a model group of 32. The model was created by croton oil-mixed liquid stimulation combined with standing and swimming experiments, and the modelling times were 1 week and 2 weeks, respectively. By observing the symptoms and signs of rats, pathological morphology and immunohistochemical staining of anorectal tissue, anorectal laser speckle blood-flow imaging and defecation contrast, etc., the effect of different modelling times was evaluated. The stability of the model was evaluated after feeding for 2 weeks. Both model-formation times caused rats to produce local symptoms of tissue bulging in the haemorrhoid area. Microscopy showed that the rectal submucosal interstitial blood vessels were dilated, and inflammatory cell infiltration and other manifestations were observed. Laser speckle blood-flow imaging revealed increased anorectal blood perfusion and capillary dilatation, and defecography showed a longitudinal and continuous rectal mucosa. After 2 weeks of normal feeding, lifting of the haemorrhoidal tissue was still present. The effect of modelling for 1 week was most in line with the clinical manifestations of internal haemorrhoids. The 1-week modelling scheme in this study can effectively establish a rat internal haemorrhoid model that closely approximates clinical internal haemorrhoid symptoms and pathological manifestations. The operation is simple, the success rate is high, and the model has certain stability. This model can be used as an important basis for studying various treatment methods for internal haemorrhoids.

Integrated transcriptome and metabolome revealed the drought responsive metabolic pathways in Oriental Lily (Lilium L.).

Objective: Lily is an essential ornamental flowering species worldwide. Drought stress is a major constraint affecting the morphology and physiology and lily leaves and flowers. Therefore, understanding the molecular mechanism underlying lily response to drought stress is important. Method: Transcriptome and metabolome analysis were performed on Oriental Lily subjected to drought stress. Result: Most transcription factors and metabolites yielded by the conjoint analysis displayed a downregulated expression pattern. Differential genes and metabolites mainly co-enriched in glycolic pathways related to sugars, such as galactose, and sucrose, glycolysis and gluconeogenesis, indicating that drought stress reduced the sugar metabolism level of Oriental Lily. Combined with transcriptome and metabolome data, nine pairs of differentially expressed metabolites and the genes (p < 0.05) were obtained. Interestingly, a gene named TRINITY_DN2608 (encoding a type of alpha-D-glucose) cloned and its overexpression lines in Arabidopsis thaliana was generated. Overexpression of TRINITY_DN2608 gene elevated the susceptibility to drought stress possibly by suppressing the glucose level. Conclusion: The enrichment of sugar-related pathways advocates the potential role of glucose metabolism in drought stress. Our study provides theoretical information related to the glucose-mediated drought response and would be fruitful in future lily breeding programs.

A narrative review on the applications of intracavitary contrast-enhanced ultrasonography in pediatric lower genitourinary anomalies.

Purpose: We mainly aimed to perform a narrative review of clinical applications of the three intracavitary contrast-enhanced ultrasonography (CEUS) including contrast-enhanced voiding urosonography (ceVUS), contrast-enhanced retrograde urethrosonography (ceRUG), and contrast-enhanced genitosonography (ceGS) in pediatric lower genitourinary anomalies. Method: A literature search in the PubMed and Web of Science databases was conducted up to 1 July 2022 on all studies published in English using the search terms "contrast-enhanced voiding urosonography", "contrast-enhanced retrograde urethrosonography", and "contrast-enhanced genitosonography". Trials were limited to pediatric subjects (ages ≤18 years) with no time restrictions. The inclusion criteria were studies on ceVUS, ceRUG, and ceGS to evaluate pediatric lower genitourinary anomalies. Two independent authors summarized the included articles. Results: Finally, a total of 48 original articles and 6 case reports or case series were included, of which 50 (93%) were only relevant to ceVUS, 3 (5%) articles involved ceGS, while only one (2%) article involved ceRUG, and 87% of the applications of ceVUS were focused on vesicoureteral reflux (VUR). We also searched 24 related reviews, of which 20 involved ceVUS in diagnosing VUR and 4 involved ceRUG and ceGS for other lower genitourinary anomalies. Conclusion: Intracavitary CEUS including ceVUS, ceRUG, and ceGS in pediatrics has many advantages over other radiological examinations in diagnosing lower genitourinary anomalies. Although ceVUS is widely used in detecting VUR, ceRUG and ceGS have also become promising techniques for evaluating the urethral pathologies and urogenital sinus.

Dynamics of heavy metals during the development and decomposition of leaves of Avicennia marina and Kandelia obovata in a subtropical mangrove swamp.

In mangrove wetlands, leaves make up a high proportion of the plant biomass and can accumulate heavy metals from contaminated sediment. Despite this, it is still unclear how heavy metal concentrations in leaves change as they develop and how metals in senescence leaves are recycled back into the mangrove ecosystems during decomposition. The present study aims to investigate the dynamics of six heavy metals (Cu, Zn, Cr, Ni, Cd, and Pb) in leaves of two common mangrove plants, Avicennia marina and Kandelia obovata, at different stages of development (young, mature, and senescent) and leaf litter decomposition (from 0 to 20 weeks). Based on litterbag experiments in a subtropical mangrove swamp, both plant species showed similar trends in alternations of the six heavy metals during leaf development, that was, decreased in Cu and Zn but increased in Pb, while Cr, Ni, and Cd remained steady. All heavy metals in litter gradually increased in concentration during decomposition. By the end of the 20-weeks decomposition, the concentrations of Cu, Zn, and Cd in decayed leaves were comparable to those in sediment, with Cu, Zn, and Cd at approximately 18, 75, and 0.2 mg·kg-1, respectively, while Cr (66 mg·kg-1), Ni (65 mg·kg-1), and Pb (55 mg·kg-1) were lower than those in sediment, indicating that metals were not retained in litter but recycled back to the sediment. Tannins in mangrove leaf litter might chelate heavy metals, affecting their migration and transformation of heavy metals in estuarine mangrove wetlands. The findings of our study provide insight into the interactions between toxic heavy metals and mangrove plant species during leaf development, representing the first example of how most metals would be retained in leaf litter during decomposition, thereby reducing their release to estuarine and marine ecosystems.

Artificial intelligence in liver ultrasound.

Artificial intelligence (AI) is playing an increasingly important role in medicine, especially in the field of medical imaging. It can be used to diagnose diseases and predict certain statuses and possible events that may happen. Recently, more and more studies have confirmed the value of AI based on ultrasound in the evaluation of diffuse liver diseases and focal liver lesions. It can assess the severity of liver fibrosis and nonalcoholic fatty liver, differentially diagnose benign and malignant liver lesions, distinguish primary from secondary liver cancers, predict the curative effect of liver cancer treatment and recurrence after treatment, and predict microvascular invasion in hepatocellular carcinoma. The findings from these studies have great clinical application potential in the near future. The purpose of this review is to comprehensively introduce the current status and future perspectives of AI in liver ultrasound.

Interrupted Time-Series Analysis of Stereotactic Radiosurgery for Brain Metastases Before and After the Affordable Care Act.

The 2010 Patient Protection and Affordable Care Act was aimed at reducing healthcare costs, improving healthcare quality, and expanding health insurance coverage among uninsured individuals in the United States. We examined trends in the utilization of radiation therapies and stereotactic radiosurgery before and after its implementation among U.S. adults hospitalized with brain metastasis. Interrupted time-series analyses of data on 383,934 Nationwide Inpatient Sample hospitalizations (2005-2010 and 2011-2013) were performed, whereby yearly and quarterly cross-sectional data were evaluated and Affordable Care Act implementation was considered the main exposure variable, stratifying by patient and hospital characteristics. Overall, we observed a declining trend in radiation therapy over time, with an upward shift post-Affordable Care Act. A downward shift in radiation therapy post-Affordable Care Act was observed among Northeastern and rural hospitals, whereas an upward shift was noted among specific patient (females, 18-39 or ≥ 65 years of age, Charlson Comorbidity Index (CCI) ≥10, non-elective admissions, Medicare, self-pay, no pay or other insurance) and hospital (Midwestern, Western, non-teaching urban) subgroups. Stereotactic radiosurgery utilization among recipients of radiation therapy increased over time among Hispanics, elective admissions, and rural hospitals, whereas post-Affordable Care Act was associated with increased stereotactic radiosurgery among African-Americans and non-elective admissions and decreased stereotactic radiosurgery among elective admissions, and rural hospitals. Whereas hospitalized adults in the United States utilized less radiation therapy over the nine-year period, utilization of radiation therapy, in general, and stereotactic radiosurgery, in particular, were not consistent among distinct subgroups defined by patient and hospital characteristics, with some traditionally underserved populations more likely to receive healthcare services post-Affordable Care Act. The Affordable Care Act may be helpful at closing the gap in access to technological advances such as stereotactic radiosurgery for treating brain metastases.

Ultrasound, CT, and MR Imaging for Evaluation of Cystic Renal Masses.

Cystic renal masses are often encountered during abdominal imaging. Although most of them are benign simple cysts, some cystic masses have malignant characteristics. The Bosniak classification system provides a useful way to classify cystic masses. The Bosniak classification is based on the results of a well-established computed tomography protocol. Over the past 30 years, the classification system has been refined and improved. This paper reviews the literature on this topic and compares the advantages and disadvantages of different screening and classification methods. Patients will benefit from multimodal diagnosis for lesions that are difficult to classify after a single examination.

Hospitalization outcomes among brain metastasis patients receiving radiation therapy with or without stereotactic radiosurgery from the 2005-2014 Nationwide Inpatient Sample.

The purpose of this study was to compare hospitalization outcomes among US inpatients with brain metastases who received stereotactic radiosurgery (SRS) and/or non-SRS radiation therapies without neurosurgical intervention. A cross-sectional study was conducted whereby existing data on 35,199 hospitalization records (non-SRS alone: 32,981; SRS alone: 1035; SRS + non-SRS: 1183) from 2005 to 2014 Nationwide Inpatient Sample were analyzed. Targeted maximum likelihood estimation and Super Learner algorithms were applied to estimate average treatment effects (ATE), marginal odds ratios (MOR) and causal risk ratio (CRR) for three distinct types of radiation therapy in relation to hospitalization outcomes, including length of stay (' ≥ 7 days' vs. ' < 7 days') and discharge destination ('non-routine' vs. 'routine'), controlling for patient and hospital characteristics. Recipients of SRS alone (ATE = - 0.071, CRR = 0.88, MOR = 0.75) or SRS + non-SRS (ATE = - 0.17, CRR = 0.70, MOR = 0.50) had shorter hospitalizations as compared to recipients of non-SRS alone. Recipients of SRS alone (ATE = - 0.13, CRR = 0.78, MOR = 0.59) or SRS + non-SRS (ATE = - 0.17, CRR = 0.72, MOR = 0.51) had reduced risks of non-routine discharge as compared to recipients of non-SRS alone. Similar analyses suggested recipients of SRS alone had shorter hospitalizations and similar risk of non-routine discharge when compared to recipients of SRS + non-SRS radiation therapies. SRS alone or in combination with non-SRS therapies may reduce the risks of prolonged hospitalization and non-routine discharge among hospitalized US patients with brain metastases who underwent radiation therapy without neurosurgical intervention.

Investigating the effects of chronic perinatal alcohol and combined nicotine and alcohol exposure on dopaminergic and non-dopaminergic neurons in the VTA.

The ventral tegmental area (VTA) is the origin of dopaminergic neurons and the dopamine (DA) reward pathway. This pathway has been widely studied in addiction and drug reinforcement studies and is believed to be the central processing component of the reward circuit. In this study, we used a well-established rat model to expose mother dams to alcohol, nicotine-alcohol, and saline perinatally. DA and non-DA neurons collected from the VTA of the rat pups were used to study expression profiles of miRNAs and mRNAs. miRNA pathway interactions, putative miRNA-mRNA target pairs, and downstream modulated biological pathways were analyzed. In the DA neurons, 4607 genes were differentially upregulated and 4682 were differentially downregulated following nicotine-alcohol exposure. However, in the non-DA neurons, only 543 genes were differentially upregulated and 506 were differentially downregulated. Cell proliferation, differentiation, and survival pathways were enriched after the treatments. Specifically, in the PI3K/AKT signaling pathway, there were 41 miRNAs and 136 mRNAs differentially expressed in the DA neurons while only 16 miRNAs and 20 mRNAs were differentially expressed in the non-DA neurons after the nicotine-alcohol exposure. These results depicted that chronic nicotine and alcohol exposures during pregnancy differentially affect both miRNA and gene expression profiles more in DA than the non-DA neurons in the VTA. Understanding how the expression signatures representing specific neuronal subpopulations become enriched in the VTA after addictive substance administration helps us to identify how neuronal functions may be altered in the brain.

Sex Differences in Patterns of Sleep Disorders Among Hospitalizations With Parkinson's Disease: 2004-2014 Nationwide Inpatient Sample.

OBJECTIVE: This study aimed to examine patterns of sleep disorders among hospitalized adults 65 years and older as related to Parkinson's disease (PD) status and to evaluate sex differences in the associations between PD with sleep disorders. METHODS: A cross-sectional study was conducted using 19,075,169 hospital discharge records (8,169,503 men and 10,905,666 women) from the 2004-2014 Nationwide Inpatient Sample databases. PD and sleep disorder diagnoses were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification coding. Logistic regression models were constructed for each sleep disorder as a correlate of PD status; adjusted odds ratios (aOR) with their 95% confidence intervals (CIs) were calculated taking into account patient and hospital characteristics. RESULTS: Period prevalences of PD and sleep disorder were estimated to be 2.1% and 8.1%, respectively. Most sleep disorder types, with the exception of sleep-related breathing disorders, were positively associated with PD diagnosis. Statistically significant interactions by sex were noted for associations of insomnia (men: aOR = 1.29, 95% CI = 1.24-1.36; women: aOR = 1.17, 95% CI = 1.12-1.22), parasomnia (men: aOR = 3.74, 95% CI = 3.44-4.07; women: aOR = 2.69, 95% CI = 2.44-2.96), sleep-related movement disorder (men: aOR = 1.09, 95% CI = 1.07-1.11; women: aOR = 1.22, 95% CI = 1.20-1.25), and any sleep disorder (men: aOR = 1.06, 95% CI = 1.05-1.08; women: aOR = 1.15, 95% CI = 1.13-1.17) with PD status. CONCLUSIONS: Overall, hospitalized men are more likely to experience PD with insomnia or parasomnia, whereas hospitalized women are more likely to experience PD with sleep-related movement disorder or any sleep disorder. Prospective cohort studies are needed to replicate these cross-sectional findings.

Insomnia as a predictor of diagnosed memory problems: 2006-2016 Health and Retirement Study.

OBJECTIVE: To evaluate the longitudinal relationship in insomnia symptoms over time with incident memory problems and dementia diagnoses among U.S. adults aged 65 years and older. METHODS: Secondary analyses were performed on 9518 elderly participants (≥65 years) who completed the 2006 wave of the Health and Retirement Study (HRS) and were followed-up to determine if insomnia symptom scores (2006-2014) were associated with time-to-onset of [1] physician-diagnosed "memory-related disease", "Alzheimer's disease" and/or "dementia, senility or any other serious memory impairment" and [2] diagnosis of dementia based on HRS-specific criteria. Cox proportional hazards models were constructed adjusting for socio-demographic, lifestyle, and health characteristics. RESULTS: In fully adjusted models, severe insomnia symptoms were associated with increased risk of physician-diagnosed memory problems. Individuals reporting any change (increase or decrease) in insomnia symptoms during the 2006-2010 period were more likely to be diagnosed with dementia based on HRS criteria. Finally, those who experienced an increase in the severity of insomnia symptoms over time exhibited 41-72% increased risks of physician-diagnosed memory problems and 45-58% increased risks of dementia diagnosis based on HRS criteria. CONCLUSIONS: When severe insomnia symptoms increased over time, physician-diagnosed memory problems and dementia diagnoses also increased among U.S. elderly people over a 10-year follow-up period. More studies are required to confirm these findings using large prospective cohort designs and validated tools.

Ontogenetic resource use and trophic dynamics of endangered juvenile Tachypleus tridentatus among diversified nursery habitats in the northern Beibu Gulf, China.

Horseshoe crabs, the most well-known example of "living fossils", are iconic and ecologically important macroinvertebrates in coastal and estuarine ecosystems. Their blood is a crucial resource for manufacturing Limulus or Tachypleus amebocyte lysate to detect bacterial endotoxins or fungal contamination in drug and medical devices. An enhanced understanding of their ecological roles and trophic interactions in the food webs is fundamental to facilitate resource management for the declining populations in Asia. Foraging information of the Asian species, however, is mainly derived from preliminary, scattered reports from a limited number of study locations. In this study, resource utilization, trophic niche dynamics, and trophic interaction of the juvenile tri-spine horseshoe crab, Tachypleus tridentatus (instars 1-12, approximately 0.5-8 years old) across ontogeny was assessed in diversified nursery habitats along the northern Beibu Gulf, China, using carbon and nitrogen stable isotopes. Our results suggest that: (i) T. tridentatus are ecological generalists given the vast range of carbon isotopic values and trophic niche width estimates exhibited between multiple instar groups; (ii) juvenile T. tridentatus across most habitat types predominantly assimilated energy from a variety of basal production sources in the food web, but primarily depended on sedimentary organic matter and seagrass resource pools; (iii) ontogenetic shifts in juvenile dietary proportions were evident, with decreased reliance on sedimentary organic matter, coupled with increased reliance on benthic macroinvertebrate grazers, detritivores, and omnivores with age; and (iv) nearly all juvenile instars occupied similar trophic positions in the food web with slight shifts in trophic position present with increasing size. Our findings indicate that resource availability and ontogenetic diet shifts strongly influence horseshoe crab trophic dynamics, and age should be accounted when formulating habitat conservation measures based on resource use for Asian horseshoe crabs.

Investigating the influence of perinatal nicotine and alcohol exposure on the genetic profiles of dopaminergic neurons in the VTA using miRNA-mRNA analysis.

Nicotine and alcohol are two of the most commonly used and abused recreational drugs, are often used simultaneously, and have been linked to significant health hazards. Furthermore, patients diagnosed with dependence on one drug are highly likely to be dependent on the other. Several studies have shown the effects of each drug independently on gene expression within many brain regions, including the ventral tegmental area (VTA). Dopaminergic (DA) neurons of the dopamine reward pathway originate from the VTA, which is believed to be central to the mechanism of addiction and drug reinforcement. Using a well-established rat model for both nicotine and alcohol perinatal exposure, we investigated miRNA and mRNA expression of dopaminergic (DA) neurons of the VTA in rat pups following perinatal alcohol and joint nicotine-alcohol exposure. Microarray analysis was then used to profile the differential expression of both miRNAs and mRNAs from DA neurons of each treatment group to further explore the altered genes and related biological pathways modulated. Predicted and validated miRNA-gene target pairs were analyzed to further understand the roles of miRNAs within these networks following each treatment, along with their post transcription regulation points affecting gene expression throughout development. This study suggested that glutamatergic synapse and axon guidance pathways were specifically enriched and many miRNAs and genes were significantly altered following alcohol or nicotine-alcohol perinatal exposure when compared to saline control. These results provide more detailed insight into the cell proliferation, neuronal migration, neuronal axon guidance during the infancy in rats in response to perinatal alcohol/ or nicotine-alcohol exposure.

Berberine Attenuates Cardiac Hypertrophy Through Inhibition of mTOR Signaling Pathway.

PURPOSE: Berberine was reported to exert beneficial effects on cardiac hypertrophy. However, its cellular and molecular mechanisms still remained unclear. METHODS: Cardiac hypertrophy was induced in male Sprague-Dawley (SD) rats by transverse aorta constriction (TAC), with or without 6-week treatment of berberine. Echocardiography was performed to evaluate cardiac function. Rats were then sacrificed for histological assay, with detection for proteins and mRNA. H9c2 cells were pretreated with berberine of different concentrations (0, 1 µM, and 10 µM), followed by treatment with 2 µM norepinephrine (NE). Cells of different groups were measured for cell surface area, with mRNA detected by qRT-PCR and proteins by western blot. RESULTS: Compared with the sham group, rats of the TAC group showed significantly increased cardiac hypertrophy and fibrosis, which could be ameliorated by treatment with berberine. Western blot showed that mammalian target of rapamycin (mTOR) signaling-related protein expressions, including phospho-mTOR, phospho-4EBP1, and phospho-p70 S6K (Thr389), but not phospho-p70 S6K (Ser371), were significantly increased in the TAC group, which were inhibited by berberine treatment. H9c2 cells were treated with NE to induce hypertrophy with increased cell surface area and mRNA expressions of anp and bnp. Berberine of 10 µM, but not 1 µM, significantly ameliorated NE-induced hypertrophy and inhibited protein expressions of mTOR signaling pathway similar to those in the rat model. CONCLUSIONS: Berberine can exert cardioprotective effects on both pressure-overloaded cardiac hypertrophy and failure in vivo and NE-induced hypertrophy in vitro. Our results suggest berberine could be a potential treatment for patients with cardiac hypertrophy and failure.

Long-term Success and Survival of Endodontic Microsurgery.

INTRODUCTION: Healed rates of endodontic microsurgery (EMS) may decrease over time, but research on the long-term outcomes is scarce. The aims of this retrospective cohort study were to evaluate the 5- to 9-year healed and survival rates of EMS, to identify associations between prognostic factors and healing status, and to compare the short-term (1- to 2-year) with long-term (5- to 9-year) outcomes. METHODS: One hundred fifty-one eligible patients (166 teeth) who underwent EMS in 2007-2010 were invited for a follow-up examination. Eighty-three patients (94 teeth) participated in the study. Survival status and reasons for extraction of all teeth were determined, and survival rates were calculated by Kaplan-Meier analyses. Outcomes were determined on the basis of clinical and radiographic findings and associated with potential prognostic variables via multivariate Cox regression analyses. RESULTS: Thirty-two teeth were extracted: 6 because of endodontic failure, 20 for unrelated reasons, and 6 for unknown reasons. Outcomes were categorized as healed and not healed. Multivariate analysis revealed that adjusted hazard ratio for failure was 5.95 times higher (95% confidence interval, 1.54-22.91) for teeth treated with intermediate restorative material than with mineral trioxide aggregate and 3.38 times higher (95% confidence interval, 1.05-10.9) for teeth with no known history of nonsurgical retreatment. Teeth classified as healed in the 1- to 2-year review mostly remained healed at 5- to 9-year review (45/48 teeth); those with uncertain healing had varied outcomes at long-term review. CONCLUSIONS: EMS results in high long-term healed (78.3%, 72/92 teeth) and survival (95.2%) rates. Root-end filling material and nonsurgical retreatment before EMS may influence the long-term outcome.

Lymph Node Metastasis Prediction from Primary Breast Cancer US Images Using Deep Learning.

Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer. Materials and Methods A data set of US images in patients with primary breast cancer with clinically negative axillary lymph nodes from Tongji Hospital (974 imaging studies from 2016 to 2018, 756 patients) and an independent test set from Hubei Cancer Hospital (81 imaging studies from 2018 to 2019, 78 patients) were collected. Axillary lymph node status was confirmed with pathologic examination. Three different convolutional neural networks (CNNs) of Inception V3, Inception-ResNet V2, and ResNet-101 architectures were trained on 90% of the Tongji Hospital data set and tested on the remaining 10%, as well as on the independent test set. The performance of the models was compared with that of five radiologists. The models' performance was analyzed in terms of accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. Results The best-performing CNN model, Inception V3, achieved an AUC of 0.89 (95% confidence interval [CI]: 0.83, 0.95) in the prediction of the final clinical diagnosis of axillary lymph node metastasis in the independent test set. The model achieved 85% sensitivity (35 of 41 images; 95% CI: 70%, 94%) and 73% specificity (29 of 40 images; 95% CI: 56%, 85%), and the radiologists achieved 73% sensitivity (30 of 41 images; 95% CI: 57%, 85%; P = .17) and 63% specificity (25 of 40 images; 95% CI: 46%, 77%; P = .34). Conclusion Using US images from patients with primary breast cancer, deep learning models can effectively predict clinically negative axillary lymph node metastasis. Artificial intelligence may provide an early diagnostic strategy for lymph node metastasis in patients with breast cancer with clinically negative lymph nodes. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Bae in this issue.

Mediating-Moderating Effect of Allostatic Load on the Association between Dietary Approaches to Stop Hypertension Diet and All-Cause and Cause-Specific Mortality: 2001-2010 National Health and Nutrition Examination Surveys.

This secondary analysis of survey data examined mediating-moderating effects of allostatic load score (calculated using the Rodriquez method) on the association between nutrient-based Dietary Approaches to Stop Hypertension (DASH) diet score (Mellen Index) and the all-cause and cause-specific mortality risks among 11,630 adults ≥ 30 years of age from the 2001-2010 National Health and Nutrition Examination Surveys with no history of cardiovascular disease or cancer at baseline, and who were followed-up for ~9.35 years. Multivariable models were adjusted for demographic, socioeconomic, lifestyle, and health characteristics. All-cause, cardiovascular disease, and cancer-specific mortality rates were estimated at 6.5%, 1.1%, and 1.9%, respectively. The median DASH total score was 3.0 (range: 1-8) (with 78.3% scoring < 4.5), whereas the median allostatic load score was 3 (range: 0-9). The DASH diet, fiber, and magnesium were negatively correlated with allostatic load, whereas allostatic load predicted higher all-cause mortality, irrespective of the DASH diet. Whereas protein was protective, potassium increased all-cause mortality risk, irrespective of allostatic load. Potassium was protective against cardiovascular disease-specific mortality but was a risk factor for cancer-specific mortality. Although no moderating effects were observed, mediation by the allostatic load on cardiovascular disease-specific mortality was observed for DASH total score and selected component scores. Direct (but not indirect) effects of DASH through the allostatic load were observed for all-cause mortality, and no direct or indirect effects were observed for cancer-specific mortality. From a public health standpoint, the allostatic load may be a surrogate for the preventive effects of the DASH diet and its components on cardiovascular disease-specific mortality risk.

Size Specific Transfection to Mammalian Cells by Micropillar Array Electroporation.

Electroporation serves as a promising non-viral gene delivery approach, while its current configuration carries several drawbacks associated with high-voltage electrical pulses and heterogeneous treatment on individual cells. Here we developed a new micropillar array electroporation (MAE) platform to advance the electroporation-based delivery of DNA and RNA probes into mammalian cells. By introducing well-patterned micropillar array texture on the electrode surface, the number of pillars each cell faces varies with its plasma membrane surface area, despite their large population and random locations. In this way, cell size specific electroporation is conveniently carried out, contributing to a 2.5~3 fold increase on plasmid DNA transfection and an additional 10-55% transgene knockdown with siRNA probes, respectively. The delivery efficiency varies with the number and size of micropillars as well as their pattern density. As MAE works like many single cell electroporation are carried out in parallel, the electrophysiology response of individual cells is representative, which has potentials to facilitate the tedious, cell-specific protocol screening process in current bulk electroporation (i.e., electroporation to a large population of cells). Its success might promote the wide adoption of electroporation as a safe and effective non-viral gene delivery approach needed in many biological research and clinical treatments.