Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood CDKN 2 A Gene Expression in Aging and Neurodegenerative Diseases

10 Background: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging. 11 Objective: This study assessed the utility of blood CDKN2A mRNA expression levels and methylation status as a potential biomarker for aging and the pathogenesis of Alzheimer’s disease (AD). 12 13 Methods: The correlation between CDKN2A mRNA expression levels and age was examined in 45 healthy subjects, after which mRNA expression levels were compared among 46 AD patients, 20 mild cognitive impairment due to AD patients, 21 Parkinson’s disease patients, 21 dementia with Lewy bodies patients, and 55 older healthy controls. The methylation rates of the second exon of the CDKN2A gene, known to influence its expression levels, was also examined. 14
Depression predicts chronic pain interference in racially-diverse, low-income patients

ABSTRACT Background Chronic pain is one of the most common reasons adults seek medical care in the US, with estimates of prevalence ranging from 11% to 40%. Mindfulness meditation has been associated with significant improvements in pain, depression, physical and mental health, sleep, and overall quality of life. Group medical visits are increasingly common and are effective at treating myriad illnesses including chronic pain. Integrative Medical Group Visits (IMGV) combine mindfulness techniques, evidence based integrative medicine, and medical group visits and can be used as adjuncts to medications, particularly in diverse underserved populations with limited access to non-pharmacological therapies. Objective and Design The objective of the present study was to use a blended analytical approach of machine learning and regression analyses to evaluate the potential relationship between depression and chronic pain in data from a randomized clinical trial of IMGV in socially diverse, low income patients suffering from chronic pain and depression. Methods This approach used machine learning to assess the predictive relationship between depression and pain and identify and select key mediators, which were then assessed with regression analyses. It was hypothesized that depression would predict the pain outcomes of average pain, pain severity, and pain interference. Results Our analyses identified and characterized a predictive relationship between depression and chronic pain interference. This prediction was mediated by high perceived stress, low pain self-efficacy, and poor sleep quality, potential targets for attenuating the adverse effects of depression on functional outcomes. Conclusions In the context of the associated clinical trial and similar interventions, these insights may inform future treatment optimization, targeting, and application efforts in racially diverse, low income populations, demographics often neglected in studies of chronic pain.
Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review.

BACKGROUND Identification of biomarkers that predict severe Crohn's disease is an urgent unmet research need, but existing research is piecemeal and haphazard. OBJECTIVE To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn's disease. DESIGN This was a prognostic systematic review with meta-analysis reserved for those potential predictors with sufficient existing research (defined as five or more primary studies). DATA SOURCES PubMed and EMBASE searched from inception to 1 January 2016, updated to 1 January 2018. REVIEW METHODS Eligible studies were studies that compared biomarkers in patients who did or did not subsequently develop severe Crohn's disease. We excluded biomarkers that had insufficient research evidence. A clinician and two statisticians independently extracted data relating to predictors, severe disease definitions, event numbers and outcomes, including odds/hazard ratios. We assessed risk of bias. We searched for associations with subsequent severe disease rather than precise estimates of strength. A random-effects meta-analysis was performed separately for odds ratios. RESULTS In total, 29,950 abstracts yielded just 71 individual studies, reporting 56 non-overlapping cohorts. Five clinical biomarkers (Montreal behaviour, age, disease duration, disease location and smoking), two serological biomarkers (anti-Saccharomyces cerevisiae antibodies and anti-flagellin antibodies) and one genetic biomarker (nucleotide-binding oligomerisation domain-containing protein 2) displayed statistically significant prognostic potential. Overall, the strongest association with subsequent severe disease was identified for Montreal B2 and B3 categories (odds ratio 4.09 and 6.25, respectively). LIMITATIONS Definitions of severe disease varied widely, and some studies confounded diagnosis and prognosis. Risk of bias was rated as 'high' in 92% of studies overall. Some biomarkers that are used regularly in daily practice, for example C-reactive protein, were studied too infrequently for meta-analysis. CONCLUSIONS Research for individual biomarkers to predict severe Crohn's disease is scant, heterogeneous and at a high risk of bias. Despite a large amount of potential research, we encountered relatively few biomarkers with data sufficient for meta-analysis, identifying only eight biomarkers with potential predictive capability. FUTURE WORK We will use existing data sets to develop and then validate a predictive model based on the potential predictors identified by this systematic review. Contingent on the outcome of that research, a prospective external validation may prove clinically desirable. STUDY REGISTRATION This study is registered as PROSPERO CRD42016029363. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 45. See the NIHR Journals Library website for further project information.
Reflections of parents of children with 22q11.2 Deletion Syndrome on the experience of receiving psychiatric genetic counseling: ‘Awareness to Act’

Individuals with 22q11.2 deletion syndrome (22qDS) have a 25%–41% risk for a psychotic disorder. Although early intervention for psychiatric conditions leads to the best long‐term outcomes, healthcare providers often provide inadequate information about these issues and psychiatric services are underused by this population. We conducted semi‐structured interviews with parents of children with 22qDS a month after they received psychiatric genetic counseling (pGC), to evaluate outcomes and perceived value of pGC with respect to parents’ needs. Using grounded theory, we generated a theoretical framework of the process of building parental awareness of psychiatric risks associated with 22qDS and protective and management strategies for mental health (MH). Parents described how after their child's diagnosis with 22qDS, a variety of barriers stalled their building awareness of psychiatric risk and protective/management strategies: dealing with the immediate symptoms of 22qDS; child's young age; parental fear and stigma; and missing MH guidance. These barriers led them to carry the burden of worrying over missing emerging psychiatric symptoms and the stress over advocating for their child's MH. Parents indicated pGC was beneficial in that led them to achieve an ‘awareness to act,’ feeling confident in being alert and equipped to protect and/or manage their child's MH.
Psychometric properties of the self-report instrument for somatic symptoms in general hospitals

Medical University, Beijing 100088, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China; Department of Clinical Psychology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Department of Clinical Psychology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Department of Clinical Psychology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; Menzies Health Institute Queensland and School of Medicine, Griffith University, Queensland, Australia.
Cortico-autonomic local arousals and heightened somatosensory arousability during NREMS of mice in neuropathic pain

Frequent nightly arousals typical for sleep disorders cause daytime fatigue and present health risks. As such arousals are often short, partial, or occur locally within the brain, reliable characterization in rodent models of sleep disorders and in human patients is challenging. We found that the EEG spectral composition of non-rapid eye movement sleep (NREMS) in healthy mice shows an infraslow (~50 s) interval over which microarousals appear preferentially. NREMS could hence be vulnerable to abnormal arousals on this time scale. Chronic pain is well-known to disrupt sleep. In the spared nerve injury (SNI) mouse model of chronic neuropathic pain, we found more numerous local cortical arousals accompanied by heart rate increases in hindlimb primary somatosensory, but not in prelimbic, cortices, although sleep macroarchitecture appeared unaltered. Closed-loop mechanovibrational stimulation further revealed higher sensory arousability. Chronic pain thus preserved conventional sleep measures but resulted in elevated spontaneous and evoked arousability. We develop a novel moment-to-moment probing of NREMS vulnerability and propose that chronic pain-induced sleep complaints arise from perturbed arousability.
STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases.

AIMS Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis. METHODS AND RESULTS Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP. CONCLUSION Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.
Ontogenetic dependence of Nile crocodile (Crocodylus niloticus) isotope diet-to-tissue discrimination factors.

RATIONALE The diet of wild Nile crocodiles (Crocodylus niloticus) is difficult to assess because they are cryptic, nocturnal predators that are extremely sensitive to disturbance by observers, and stomach content analysis is challenging, especially in large specimens. Stable light isotope analysis provides a means of assessing their diet but diet-to-tissue discrimination factors have yet to be established for the species. METHODS Isotope ratio (15 N/14 N and 13 C/12 C expressed as δ15 N and δ13 C) analyses of scutes, claws and blood of farmed crocodile of a range of sizes were compared with the isotope values of their lifelong diet, which comprises chickens from a single supplier. RESULTS Systematic size dependence in the diet-to-tissue discrimination factors for scute collagen, scute keratin, and claw keratin, is described in regression relationships against the snout to vent length. Fixed values are presented for erythrocytes and blood plasma because blood was not sampled from juveniles. CONCLUSIONS The diet-to-tissue discrimination factors allow an assessment of the diet of wild crocodiles. The diet of crocodiles from Lake Flag Boshielo shows a clear ontogenic shift, as has been seen in other studies, and the results strongly indicate a dependence on the terrestrial food web rather than a fish diet. That this population may exploit a terrestrial diet highlights potential conflicts for conserving Nile crocodiles outside of protected areas.
Body composition techniques in health and disease: Application of dual-energy X-ray absorptiometry and related techniques to the assessment of bone and body composition

Introduction The development of absorptiometric techniques has revolutionised our ability to measure the mineral content of the human skeleton in living individuals. The first technique to be introduced was single-photon absorptiometry (SPA), capable of the precise measurement of bone mineral in the appendicular skeleton (Cameron et al. , 1962; Cameron & Sorenson, 1963; Sorenson & Cameron, 1967). Some years later, dual-photon absorptiometry (DPA) was developed for the measurement of bone in the axial skeleton (Mazess, 1971; Roos & Skoldborn, 1974). Versions of these instruments are capable of scanning the entire body and these provide a measure of whole-body fat and lean masses in addition to total-body bone mineral content. The photon beams required for SPA and DPA are produced by gamma-emitting radioisotopes. In recent years, X-ray technology has replaced the use of gamma-rays and the instruments are referred to as single- or dual-energy X-ray absorptiometers (SXA, DXA). Absorptiometric techniques are known by a variety of names. For example, bone densitometry refers to any absorptiometric method which measures bone mineral content; X-ray absorptiometry (XRA), quantitative digital radiography (QDR) and X-ray spectrophotometry are synonyms for DXA, and there is a continuing debate as to whether the accepted abbreviation for dual-energy X-ray absorptiometry should be DXA or DEXA. Currently, the principal application of absorptiometry is for the measurement of bone mineral content in clinical practice (Johnston et al. , 1991). This includes screening for osteoporosis, either as a primary condition or secondary to a number of disease states, and long-term monitoring of therapies and drugs known to affect bone. Imaging of prostheses and stones is possible with the latest DXA instruments.
Extractive Distillation with a Mixture of Organic Solvent and Ionic Liquid as Entrainer

A mixture of organic solvent and ionic liquid (IL) was proposed as entrainer for the ethanol/water separation by extractive distillation. The vapor–liquid equilibrium (VLE) experimental results showed that the relative volatility of ethanol to water is significantly enhanced using the ethylene glycol (EG) and [EMIM]+[Ac]− mixed entrainers when compared to that of the benchmark solvent EG. The nonrandom-two-liquid model parameters were correlated using the measured ternary and quaternary experimental VLE data. On this basis, process simulation was carried out to evaluate the improvement of the proposed mixed entrainers. It was found that for the ethanol/water separation using the mixed entrainers, the overall heat duties on reboilers in the processes without and with heat integration (HI) decrease 11.53% and 10.34%, respectively, when compared to the conventional benchmark solvent EG. Moreover, the presented process intensification method is easily achieved in practice by substituting the proposed mixed en.
固相萃取-超高效液相色谱-串联质谱法检测保健食品中9种人参皂苷

建立了以固相萃取结合超高效液相色谱-串联质谱(UPLC-MS/MS)同时检测保健食品中9种原人参二醇型和原人参三醇型人参皂苷的方法。 保健食品中人参皂苷经过提取后,通过Alumina-N/XAD-2 SPE柱净化,在Hypersil Gold C18色谱柱(100 mm×2.1 mm, 1.9 μm)上分离,利用乙酸铵溶液(含0.1%甲酸)和乙腈作为流动相进行梯度洗脱,采用负离子扫描,多反应监测模式测定,外标法定量。 研究通过对不同填料的固相萃取小柱的考察,最终选择了Alumina-N/XAD-2复合填料,其能对保健食品复杂基质中的人参皂苷进行有效富集和净化;通过考察人参皂苷的电离裂解过程,确定人参皂苷一级质谱准分子离子和相应的碎片离子,并经过色谱条件的优化,使质谱条件下一级质谱准分子离子和相应的碎片离子均一致的3种原人参二醇型人参皂苷Rb2、Rb3、Rc同分异构体实现完全分离。 结果表明,9种人参皂苷在0. 005~0.5 μg/mL范围内具有很好的线性关系,相关系数均大于0. 9950。 方法的加标回收率为81. 1%~114.2%,相对标准偏差为0. 4%~8.0%。 所建立的方法采用XAD-2大孔吸附树脂和中性氧化铝的复合固相萃取材料,保健食品经过简单提取可直接作为固相萃取的上样溶液进行人参皂苷的富集和净化,通过超高效液相色谱-串联质谱不仅缩短了分析时间,也能对复杂基质样品中含量相对较低的人参皂苷进行准确定性和定量。 该方法通量高,简单快速,重复性好,适用于保健食品中9种人参皂苷的定性和定量分析。
Antioxidant Activity of Novel Casein-Derived Peptides with Microbial Proteases as Characterized via Keap1-Nrf2 Pathway in HepG2 Cells

Casein-derived antioxidant peptides by using microbial proteases have gained increasing attention. Combination of two microbial proteases, Protin SD-NY10 and Protease A “Amano” 2SD, was employed to hydrolyze casein to obtain potential antioxidant peptides that were identified by LCMS/ MS, chemically synthesized and characterized in a oxidatively damaged HepG2 cell model. Four peptides, YQLD, FSDIPNPIGSEN, FSDIPNPIGSE, YFYP were found to possess high 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability. Evaluation with HepG2 cells showed that the 4 peptides at low concentrations (< 1.0 mg/ml) protected the cells against oxidative damage. The 4 peptides exhibited different levels of antioxidant activity by stimulating mRNA and protein expression of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as nuclear factor erythroid-2-related factor 2 (Nrf2), but decreasing the mRNA expression of Kelch-like ECH-associated protein 1 (Keap1). Furthermore, these peptides decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), but increased glutathione (GSH) production in HepG2 cells. Therefore, the 4 casein-derived peptides obtained by using microbial proteases exhibited different antioxidant activity by activating the Keap1-Nrf2 signaling pathway, and they could serve as potential antioxidant agents in functional foods or pharmaceutic preparation.
Apparent diffusion coefficients (ADC) in response assessment of transarterial radioembolization (TARE) for liver metastases of neuroendocrine tumors (NET): a feasibility study

Background In patients with hepatic neuroendocrine tumors (NETs) locoregional therapies such as transarterial radioembolization (TARE) are increasingly applied. Response evaluation remains challenging and previous studies assessing response with diffusion-weighted imaging (DWI) have been inconclusive. Purpose To perform a feasibility study to evaluate if response assessment with quantitative apparent diffusion coefficient (ADC) in patients with liver metastases of NETs after TARE will be possible. Material and Methods Retrospectively, 43 patients with 120 target lesions who obtained abdominal magnetic resonance imaging (MRI) with DWI 39±28 days before and 74±46 days after TARE were included. Intralesional ADC (ADCmin, ADCmax, and ADCmean) were measured for a maximum number of three lesions per patient on baseline and post-interventional DWI. Tumor response was categorized according to RECIST 1.1 and mRECIST. Results TARE resulted in partial remission (PR) in 23% (63%), in stable disease (SD) in 73% (23%), in progressive disease (PD) in 5% (7%) and in complete response (CR) in 0% (1%) according to RECIST 1.1 (mRECIST, respectively). ADC values increased significantly (P<0.005) after TARE in the PR group whereas there was no significant change in the PD group. Post-therapeutic ADC values of SD lesions increased significantly when evaluated by RECIST 1.1 but not if evaluated by mRECIST. Percentual changes of ADCmean values were slightly higher for responders compared to non-responders (P<0.05). Conclusion ADC values seem to represent an additional marker for treatment response evaluation after TARE in patients with secondary hepatic NET. A conclusive study seems feasible though patient-based evaluation and overall survival and progression free survival as alternate primary endpoints should be considered.
Normalized intraplaque hemorrhage signal on MP-RAGE as a marker for acute ischemic neurological events

Purpose This study sought to validate whether the signal intensity ratio (SIR) of carotid intraplaque hemorrhage (IPH) was associated with acute ischemic neurologic events. Methods A retrospective review was completed of consecutive patients that underwent neck magnetic resonance angiography using magnetization prepared-rapid gradient echo (MP-RAGE) and T1-CUBE sequences between 2017 and 2020. Patients with magnetic resonance evidence of IPH were included. SIRs were measured by comparing the maximum IPH signal with the mean intramuscular signal from the adjacent sternocleidomastoid. Patients were stratified into ischemic or non-ischemic groups based on the presence of acute ipsilateral ischemic events (stroke, retinal artery occlusion). Logistic regression analysis was performed to determine if increasing IPH SIR was associated with an increased risk of ipsilateral ischemic events. Results Of 85 included patients (85 arteries), 66 were male (77.6%). Mean age was 71.0 (SD ± 11.1). There were 70 arteries with IPH that were ipsilateral to an ischemic event, and 15 that belonged to patients without an ischemic event. No association was found between increasing IPH SIR seen on MP-RAGE (odds ratio (OR): 0.82; 95% confidence interval (CI): 0.58–1.4; P = 0.43) or T1-CUBE sequences (OR: 0.85; 95% CI: 0.53–1.5; P = 0.56). Conclusions There was no association between the SIR of IPH and acute ischemia on either MP-RAGE or T1-CUBE sequences. Further investigation is required prior to widespread acceptance of SIR as a predictive imaging marker of symptomatic carotid plaque.
Voluntary exercise blocks ongoing pain and diminishes bone remodeling while sparing protective mechanical pain in a rat model of advanced osteoarthritis pain.

ABSTRACT Exercise is the most common treatment recommended by health care providers for treatment of musculoskeletal pain. We examined whether voluntary running wheel exercise improves pain and bone remodeling in rats with monosodium iodoacetate (MIA)-induced unilateral knee joint pain. During acquisition of wheel running prior to OA treatment, rats separated into two groups characterized by either high or low levels of voluntary wheel running as indicated by distance and peak speed. Following induction of knee joint OA, all rats showed diminished voluntary wheel running throughout the study. Voluntary wheel running failed to alter evoked nociceptive responses evaluated as weight asymmetry or hindpaw tactile thresholds at any time-point of the study. In contrast, relief of ongoing pain was demonstrated by conditioned place preference produced by lidocaine injection into the MIA-treated knee in high but not low running rats. Both high and low voluntary runners showed diminished trabecular bone loss compared to sedentary controls. These observations indicate that both high and low intensity exercise is beneficial in protecting against bone remodeling in advanced OA. The data suggest that similar to clinical observation, bone remodeling does not correlate with pain. Additionally, these results suggest that higher intensity exercise may relieve persistent ongoing OA pain while maintaining movement-evoked nociception. The relief of ongoing pain can potentially offer significant improvement in quality of life while preservation of responses to movement-evoked pain may be especially important in protecting the joint from damage due to overuse.