Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of ALDH6A1 as a Potential Molecular Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome.

Various liver diseases, including hepatocellular carcinoma (HCC), have been linked to mitochondrial dysfunction, reduction of reactive oxygen species (ROS) and elevation of nitric oxide (NO). In this study, we subjected the human liver mitochondrial proteome to an extensive quantitative proteomic profiling analysis and molecular characterization to identify potential signatures indicative of cancer cell growth and progression. A sequential proteomic analysis identified 2452 mitochondrial proteins, of which 1464 and 2010 were classified as non-tumor and tumor (HCC) mitochondrial proteins, respectively, with 1022 overlaps. Further metabolic mapping of the HCC mitochondrial proteins narrowed our biological characterization to four proteins, namely ALDH4A1, LRPPRC, ATP5C1 and ALDH6A1. The latter protein, a mitochondrial methylmalonate semialdehyde dehydrogenase (ALDH6A1), was most strongly suppressed in HCC tumor regions (~10-fold decrease) in contrast to LRPPRC (~6-fold increase), and was predicted to present in plasma. Accordingly, we selected ALDH6A1 for a functional analysis and engineered Hep3B cells to overexpress this protein, called ALDH6A1-O/E cells. Since ALDH6A1 is predicted to be involved in mitochondrial respiration, we assessed changes in the levels of NO and ROS in the overexpressed cell lines. Surprisingly, in ALDH6A1-O/E cells, NO was decreased nearly 50% but ROS was increased at the similar level, while the former was restored by treatment with S-nitroso-N-acetyl-penicillamine. The lactate levels were also decreased relative to control cells. Propidium iodine staining suggested that the decrease in NO and increase in ROS in ALDH6A1-O/E cells could be caused by depolarization of the mitochondrial membrane potential (ΔΨ). Taken together, our results suggest that hepatic neoplastic transformation appear to suppress the expression of ALDH6A1, which is accompanied by a respective increase and decrease in NO and ROS in cancer cells. Given the close link between ALDH6A1 suppression and abnormal cancer cell growth, this protein may serve as a potential molecular signature or biomarker of hepatocarcinogenesis and treatment responses. Mass spectrometry data are available via ProteomeXchange with identifier PXD014252.
Regional Patterns of Fluid and Fat Accumulation in Patients with Lower Extremity Lymphedema Using Magnetic Resonance Angiography

Background: Fat accumulation is frequently observed in patients with lymphedema but is not accounted for in existing staging systems. In addition, the specific regional patterns of fat and fluid accumulation remain unknown and might affect outcomes following medical or surgical intervention. The purpose of this study was to evaluate fluid and fat distribution in patients with lower extremity lymphedema using magnetic resonance angiography. Methods: Magnetic resonance angiographic examinations of patients with lower extremity lymphedema were reviewed. Fluid-fat grade and location were assessed by three observers. Three-point scales were developed to grade fluid (0 = no fluid, 1 = reticular pattern of fluid, and 2 = continuous stripe of subcutaneous fluid) and fat (0 = normal, 1 = subcutaneous thickness less than twice that of the unaffected side, and 2 = subcutaneous thickness greater than twice that of the unaffected side) accumulation. Results: In total, 76 magnetic resonance angiographic examinations were evaluated. Using the proposed grading system, there was good interobserver agreement for fat and fluid accumulation location (91.5 percent; κ = 0.9), fluid accumulation grade (95.7 percent; κ = 0.95), and fat accumulation grade (87.2 percent; κ = 0.86). Patients with International Society of Lymphology stage 2 lymphedema had a wide range of fluid and fat grades (normal to severe). The most common location of fluid accumulation was the lateral lower leg, whereas the most common location of fat accumulation was the medial and lateral lower leg. Conclusion: The proposed magnetic resonance angiographic grading system may help stratify patients with International Society of Lymphology stage 2 lymphedema on the basis of tissue composition. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.
Agonistic anti-CD148 monoclonal antibody attenuates diabetic nephropathy in mice.

CD148 is a transmembrane protein tyrosine phosphatase (PTP) that is expressed in renal vasculature including the glomerulus. Previous studies have shown that CD148 plays a role in negative regulation of growth factor signals (including EGF and VEGF), suppressing cell proliferation and transformation. However, the role of CD148 in kidney disease remains unknown. Here, we have generated an agonistic anti-CD148 antibody and evaluated its effects in murine diabetic nephropathy (DN). Monoclonal antibodies (mAbs) against the mouse CD148 ectodomain sequence were generated by immunizing CD148 knockout (KO) mice. The mAbs that increase CD148 activity were selected by biological (proliferation) and biochemical (PTP activity) assays. The mAb (18E1) that showed strong agonistic activity was injected (10 mg/kg, i.p.) into streptozotocin-induced wild-type (WT) and CD148KO diabetic mice for 6 weeks, then renal phenotype was assessed. The effects of 18E1 mAb in podocyte growth factor signals were also assessed in culture. Compared to control IgG, 18E1 mAb significantly decreased albuminuria and mesangial expansion without altering hyperglycemia and blood pressure in WT diabetic mice. Immunohistochemical evaluation showed that 18E1 mAb significantly prevents the reduction of podocyte number and nephrin expression and decreases glomerular fibronectin expression and renal macrophage infiltration. The 18E1 mAb showed no effects in CD148KO diabetic mice. Furthermore, we demonstrate that 18E1 mAb reduces podocyte EGFR signals in culture and in diabetic mice. These findings suggest that agonistic anti-CD148 mAb attenuates DN in mice, in part by reducing EGFR signals in podocytes. This antibody may be used for the treatment of early DN.
Digest: Exposing the role of rare alleles in inbreeding depression in monkeyflower *

Outcrossing is maintained in many hermaphroditic species despite theoretical work suggesting that alleles increasing selfing should invade outcrossing populations. Brown and Kelly (2019) identify reasons why this may not have occurred in an outcrossing population of monkeyflower, namely that inbreeding depression causes strong reductions in fitness, resulting in selection for the maintenance of outcrossing. They find that genetic load imposed by rare alleles is inversely correlated with fitness‐associated traits, providing evidence that recessive, deleterious alleles contribute to inbreeding depression.
Clinical Scenarios for Which Cervical Mobilization and Manipulation Are Considered by an Expert Panel to Be Appropriate (and Inappropriate) for Patients With Chronic Neck Pain

Supplemental Digital Content is available in the text. Objectives: Cervical mobilization and manipulation are 2 therapies commonly used for chronic neck pain (CNP). However, safety, especially of cervical manipulation, is controversial. This study identifies the clinical scenarios for which an expert panel rated cervical mobilization and manipulation as appropriate and inappropriate. Methods: An expert panel, following a well-validated modified-Delphi approach, used an evidence synthesis and clinical acumen to develop and then rate the appropriateness of cervical mobilization and manipulation for each of an exhaustive list of clinical scenarios for CNP. Key patient characteristics were identified using decision tree analysis (DTA). Results: Three hundred seventy-two clinical scenarios were defined and rated by an 11-member expert panel as to the appropriateness of cervical mobilization and manipulation. Across clinical scenarios more were rated inappropriate than appropriate for both therapies, and more scenarios were rated inappropriate for manipulation than mobilization. However, the number of patients presenting with each scenario is not yet known. Nevertheless, DTA indicates that all clinical scenarios that included red flags (eg, fever, cancer, inflammatory arthritides, or vasculitides), and some others involving major neurological findings, especially if previous manual therapy was unfavorable, were rated as inappropriate for both cervical mobilization and manipulation. DTA also identified the absence of cervical disk herniation, stenosis, or foraminal osteophytosis on additional testing as the most important patient characteristic in predicting ratings of appropriate. Conclusions: Clinical guidelines for CNP should include information on the clinical scenarios for which cervical mobilization and manipulation were found inappropriate, including those with red flags, and others involving major neurological findings if previous manual therapy was unfavorable.
Nutraceutical Augmentation Strategies for Depression: A Narrative Review

Abstract Context Depression is one of the most commonly diagnosed psychiatric disorders, but antidepressant pharmacotherapy often fails to achieve remission, leading health care professionals and researchers to consider various augmentation strategies to improve clinical outcomes. Objective To assess the safety, tolerability, and efficacy of nutraceutical augmentation for depression. Methods Nutraceutical-focused systematic reviews and clinical practice guidelines identified the more commonly studied augmentation strategies for depression. Results S-adenosylmethionine, l-methylfolate, omega-3 fatty acids, and hydroxyvitamin D have sufficient scientific evidence to support their clinical consideration in the stepped care approach to the management of depression. Conclusions Clinical remission is the goal in the management of depression, and nutraceuticals may be part of an overall treatment approach to achieve that outcome.
The Trend in Household Catastrophic Medical Expenditure according to Healthcare Coverage Types and Its Associated Factors

Abstract This study aims to examine the trend in household catastrophic medical expenditure according to the healthcare coverage types and its associated factors based on the raw data of the Korean Health Panel over the years2008 to 2011. Correspondence analysis was used to investigate the trend in the incidence rates of annual catastrophic medical expenditure and generalized estimating equation to examine the factors influencing the incidence of catastrophic medical expenditure. The annual mean incidence rates of household catastrophic medical expenditure were25.1%, 15.4%, 10.1%, 5.4% and 3.2% in the threshold levels of 10%, 15%, 20%, 30%, and 40% respectively. Theincidence rate of household catastrophic medical expenditure was higher when the total annual household income waslower, the education level of the householder was lower, the healthcare coverage type was National Health Insurance,the householder had disability, the age of the householder was older, the number of household members was smaller,the subjective health status of household members was lower, and the prevalence rate of the chronic disease of thehousehold was higher(p<0.05). Therefore, a policy for vulnerable households with older or patient members of chronicdiseases should be established.
A Real-Time 3D Laparoscopic Imaging System: Design, Method, and Validation

Objective: This paper aims to propose a 3D laparoscopic imaging system that can realize dense 3D reconstruction in real time. Methods: Based on the active stereo technique which yields high-density, accurate and robust 3D reconstruction by combining structured light and stereo vision, we design a laparoscopic system consisting of two image feedback channels and one pattern projection channel. Remote high-speed image acquisition and pattern generation lay the foundation for the real-time dense 3D surface reconstruction and enable the miniaturization of the laparoscopic probe. To enhance the reconstruction efficiency and accuracy, we propose a novel active stereo method by which the dense 3D point cloud is obtained using only five patterns, while most existing multiple-shot structured light techniques require $\text{10--40}$ patterns. In our method, dual-frequency phase-shifting fringes are utilized to uniquely encode the pixels of the measured targets, and a dual-codeword matching scheme is developed to simplify the matching procedure and achieve high-precision reconstruction. Results: Compared with the existing structured light techniques, the proposed method shows better real-time efficiency and accuracy in both quantitative and qualitative ways. Ex-vivo experiments demonstrate the robustness of the proposed method to different biological organs and the effectiveness to lesions and deformations of the organs. Feasibility of the proposed system for real-time dense 3D reconstruction is verified in dynamic experiments. According to the experimental results, the system acquires 3D point clouds with a speed of 12 frames per second. Each frame contains more than 40,000 points, and the average errors tested on standard objects are less than 0.2 mm. Significance: This paper provides a new real-time dense 3D reconstruction method for 3D laparoscopic imaging. The established prototype system has shown good performance in reconstructing surface of biological tissues.
Facilitating Erotic Connection: The Relationship Shared Values Primer (RSVP) to Sex and Relationship Therapy in the Context of Sexual Trauma History

Abstract There are few models of sex therapy designed specifically for working with relationships in which one or more partners have a history of sexual trauma. The Relationship Shared Values Primer (RSVP) to sex and relationship therapies is a pre-sex therapy psychoeducation with the goal of promoting buy-in and reducing attrition by fostering safety and connection prior to beginning the therapeutic work through a dialogue of four key values: (1) Intimate Justice, (2) Non-linear Healing, (3) Mindful Acceptance, and (4) Erotic Empathy. We discuss research support for the rationale of the RSVP, how the RSVP can mitigate current obstacles to working with this population, and present a case study of the RSVP application.
Increased Incidence but Lack of Association Between Cardiovascular Risk Factors in Adults Born Preterm

Supplemental Digital Content is available in the text. Preterm birth incurs an increased risk of early cardiovascular events and death. In the general population, cardiovascular risk factors cluster in the context of inflammation and oxidative stress. Whether this also occurs in young adults born preterm is unknown. We analyzed 101 healthy young adults (ages 18–29) born preterm (≤29 weeks of gestation) and 105 full-term controls, predominantly (90%) white. They underwent a comprehensive clinical and biological evaluation, including measurement of blood pressure, lung function (spirometry), glucose metabolism (fasting glucose, glycated hemoglobin, and oral glucose tolerance test), as well as biomarkers of inflammation and oxidative stress. Individuals born preterm were at higher risk than those born full-term of stage ≥1 hypertension (adjusted odds ratio, 2.91 [95% CI, 1.51–5.75]), glucose intolerance (adjusted odds ratio, 2.22 [95% CI, 1.13–4.48]), and airflow limitation (adjusted odds ratio, 3.47 [95% CI, 1.76–7.12]). Hypertension was strongly associated with adiposity and with glucose intolerance in participants born full-term but not in those born preterm. We did not find any group difference in levels of biomarkers of inflammation and oxidative stress. In individuals born preterm, inflammation, and oxidative stress were not related to hypertension or glucose intolerance but were associated with adiposity. In those born preterm, cardiovascular risk factors were not related to each other suggesting different pathophysiological pathways leading to the development of cardiovascular risk following preterm birth. Clinicians should consider screening for these abnormalities irrespectively of other risk factors in this at-risk population. Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT03261609.
Longitudinal relationships between lung cancer mortality rates, smoking, and ambient air quality: a comprehensive review and analysis

Abstract Lung cancer mortality (LCM) has been associated with smoking and air pollution. This article draws on smoking relationships to clarify air pollution relationships. We analyzed cohort and population-based smoking studies and identified effects of latency and cumulative exposures. We found cogent relationships through longitudinal rather than cross-sectional analysis, thus involving historical data. We also considered passive smoking, occupational exposures, radon, and established carcinogens. We found stable nonsmoking LCM rates during periods of improving ambient air quality. We considered 59 cross-sectional studies of lung cancer and air pollution and found similar statistically significant relative risks for PM2.5, PM10, EC, NO2, SO2, SO2−4, and O3, and minimal risks for benzo(alpha)pyrene and trace metals. Most air pollution studies did not consider latency, exposure duration, or temporal trends; none included estimates of smoking risks implied by their models. We conclude that while LCM studies of smoking, radon, and occupational exposures appropriately considered latency and cumulative exposures; ambient air quality studies have not. Lung cancer has a long memory and exposure histories are required. Effects of cumulative exposures after pollution abatement include substantially reduced risk estimates, delayed health benefits, inability to show accountability for the abatement. However, associations of lung cancer with ambient air pollution cannot be ruled out, especially for historic periods when much higher exposures persisted. Given the major reductions in air quality and smoking habits that have been realized since the Clean Air Act, new studies of LCM and air pollution, including smoking histories and exposure data decades before diagnosis, are needed. Highlights Lifetime cigarette consumption is a good predictor of lung cancer risk. The latent period for lung cancer ranges from about 10 to 30 y. Lung cancer risks for nonsmokers have been stable during the period when ambient air quality improved substantially. Risks of established airborne carcinogens may have been important in the past but not under current conditions. Radon can be important. Air pollution-lung cancer risks should be evaluated jointly with smoking risks but are sensitive to their accuracy. When cumulative exposures to conventional air pollutants are considered rather than concurrent, the applicable risk estimates may decrease by an order of magnitude and abatement benefits will not be readily apparent. Most of the recent cross-sectional studies of lung cancer and regulated air pollutants did not consider latency, duration of exposure, or established carcinogens and their findings have been misinterpreted. Effects of smoking on LCM are now well established as are the spatial distributions of ambient air pollution; however, linkages among the three parameters remain uncertain.
The gut microbiota and its interactions with cardiovascular disease

The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.
Comparison of Commercial Kits for Recovery and Analysis of Bacterial DNA From Fingerprints

In forensic science, fingerprints are a common source of evidentiary information. However, latent examination is not always successful and trace human DNA cannot always be obtained. Thus, examining the fingerprint microbiome may offer a suitable alternative to more traditional methods of forensic identification. The Zymo Research ZR Bacterial/Fungal DNA MicroPrep™ Kit, Qiagen QIAmp® DNA Mini Kit, Promega Wizard® Genomic DNA Purification Kit, and the MPBio FastDNA® Spin Kit were compared for their ability to yield a sufficient amount of bacterial DNA for next‐generation sequencing in order to obtain a microbiome profile. Prints were deposited onto slides, allowed to sit for up to 1 month, and total DNA isolated and quantified using each kit. The kit from Zymo Research yielded the most concentrated DNA sample (0.0084 ng/µL) in the least amount of time as compared to other kits examined. Although this amount of DNA was far below the recommended DNA concentration threshold recommended for next‐generation sequencing, a microbiome profile was successfully obtained. As interest in using the microbiome of an individual as a forensic tool continues to increase, there is the possibility that the microbiome of a fingerprint could complement traditional human DNA profiling in the future. This study provides evidence that trace amounts of bacterial DNA from fingerprints is quantifiable and sufficient for microbiome analysis.
Copper and Zinc Levels in Myelodysplastic Syndrome Patients versus Healthy Subjects

Background: Myelodysplastic syndrome (MDS) is a heterogeneous hematological disease and certain serum factors are assumed to be involved in its pathogenesis and progression. Given this, our aim was to comparatively investigate the copper, zinc, and iron levels in MDS patients and healthy individuals. Methods: This case-control study was conducted on 31 patients with MDS (according to the WHO criteria after investigating laboratory tests such as peripheral blood smear and bone marrow aspiration) attending Bahonar Hospital, Kerman, Iran, and 31 healthy subjects from 2016 to 2018. The levels of copper, ceruloplasmin, zinc, ferritin, and iron were compared between the two groups. Results: Among the MDS patients, five individuals (16.13%) had low serum copper level (mean: 67.8 ± 4.35 µg/dl). Serum copper level was 111.3 ± 27.7 and 138.3 ± 26.6 in case and control groups, respectively (P = 0.0001). The serum zinc level and bone marrow iron level were also significantly different between the two groups (P < 0.05). Conclusion: Overall, it can be concluded that because only a small proportion of the MDS patients enrolled in this study were found to have lower copper levels compared with the MDS patients population, further studies with a larger sample size and also clinical trials in MDS patients with serum zinc, and copper deficiency are recommended, and post-treatment hematological reassessment would also be beneficial to achieving more definitive results.