Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemoprotective effects of dietary grape powder on ultraviolet B radiation-mediated skin carcinogenesis in SKH-1 hairless mice

Skin cancer is the most frequently diagnosed cancer in the US, and solar ultraviolet (UV) radiation is an established causative factor for ~90% of these cases. Despite efforts aimed at UV protection, including use of sunscreen and clothing, annual cases of skin cancers continue to rise. Here, we report that dietary grape powder (GP) mitigates UVB-mediated skin carcinogenesis in SKH-1 hairless mouse model. Employing a UVB initiation-promotion protocol, where mice were exposed to 180 mJ/cm 2 UVB 2x/week for 28 weeks, we determined the effects of GP-fortified diet (3% or 5%) on skin carcinogenesis. GP consumption at both doses resulted in marked inhibition in tumor incidence, as well as a delay in onset of tumorigenesis. Molecular analyses of skin and tumor tissue demonstrated that GP-mediated protective response against UVB-induced skin cancer was accompanied by enhanced DNA damage repair, reduced proliferation, increased apoptosis and modulations in several oxidative stress markers specifically related to inhibition of oxidative stress and increased ROS metabolism. Interestingly, NRF2, an activator of cellular antioxidant response, was decreased by GP feeding, suggesting a supportive role in tumor cell survival. Overall, our study suggested that dietary grape, containing several antioxidants in natural amalgamation, may protect against UVB-mediated skin carcinogenesis. of polyphenol One suggest
Glutathione S -Transferase P Influences Redox Homeostasis and Response to Drugs that Induce the Unfolded Protein Response in Zebrafish s

We have created a novel glutathione S -transferase p 1 ( gstp1 ) knockout (KO) zebrafish model and used it for comparative analyses of redox homeostasis and response to drugs that cause endoplasmic reticulum (ER) stress and induce the unfolded protein response (UPR). Under basal conditions, gstp1 KO larvae had higher expression of antioxidant nuclear factor erythroid 2 – related factor 2 (Nrf2) accompanied by a more reduced larval environment and a status consistent with reductive stress. Compared with wild type, various UPR markers were decreased in KO larvae, but treatment with drugs that induce ER stress caused greater toxicities and increased expression of Nrf2 and UPR markers in KO. Tunicamycin and 0 2 -{2,4-dinitro-5-[4-( N N , 1-ium-1,2-diolate (PABA/nitric oxide) activated inositol-requiring protein-1/X-box binding protein 1 pathways, whereas thap- sigargin caused greater activation of protein kinase-like ER kinase/activating transcription factor 4/CHOP pathways. These results suggest that this teleost model is useful for predicting howGSTPregulatesorganismalmanagementofoxidative/reductivestressandisadeterminantofresponsetodrug-inducedERstressandtheUPR.
Post-operative Complications and Risk of Mortality Following Laparotomy in a Resource-Limited Setting

Introduction: Despite increases in surgical capacity in Malawi, minimal data exist on postoperative complications. Identifying surgical management gaps and targeting quality improvement requires detailed, longitudinal complications and outcome data that assess surgical safety and efficacy. Methods: We conducted a six-month prospective, observational study of patients >12 years following laparotomy at a tertiary hospital in Lilongwe, Malawi. Outcomes included postoperative complications and mortality. The senior-most rounding physician determined complication diagnoses. Bivariate and Poisson regression analyses identified predictors of mortality. Results: Only patients undergoing emergent laparotomy (77.8%) died before discharge, so analysis excluded elective cases. Of 189 patients included, the median age was 33.5 (IQR 22– 50.5), 22 (12.2%) had prior abdominal surgery, and 11 (12.1%) were HIV-positive. Gastrointestinal perforation was the most common diagnosis (35.5%). The most common procedures were primary gastrointestinal repair (24.9%), diverting ostomy (21.2%), and bowel resection with anastomosis (16.4%). Overall post-operative mortality was 14.8%. Intraabdominal complication occurred in 17 (9.0%) patients, of whom 8 (47.1%) died. Older age (RR 1.05, 95% CI 1.02–1.08, p<0.001) and intraabdominal complication (RR 2.88, 95% CI 1.28–6.46, p=0.01) increased the relative risk of mortality. Preoperative diagnosis, surgical intervention type, and symptom-to-surgery time did not increase the relative risk of mortality. Conclusions: The incidence of complications and mortality following laparotomy at a large referral hospital in Malawi is high. Older age and intraabdominal complications increase the risk of death. Strategies to improve operative mortality in Malawi should prioritize post-operative surveillance and management and continued outcomes reporting.
Brain tumors in children with neuro(cid:142) bromatosis: Additional neuropsychological morbidity? 1

Neuro(cid:142)bromatosis type 1 is a common autosomal dominant genetic disorder associated with numerous physical anomalies and an increased incidence of neuropsychological impairment. Tumors of the CNS occur in approximately 15% of children with neuro(cid:142)bromatosis, presenting additional risk for cognitive impairment. This study examines the impact of an additional diagnosis of brain tumor on the cognitive pro(cid:142)le of children with neuro(cid:142)bro-matosis. A comprehensive battery of neuropsychological tests was administered to 149 children with neuro(cid:142)bro-matosis. Thirty-six of these children had a codiagnosis of brain tumor. A subset of 36 children with neuro(cid:142)bro-matosis alone was matched with the group of children diagnosed with neuro(cid:142)bromatosis and brain tumor. Although mean scores of the neuro(cid:142)bromatosis plus brain tumor group were, in general, lower than those of the neu-ro(cid:142)bromatosis alone group, these differences were not statistically signi(cid:142)cant. Children in the neuro(cid:142)bromatosis plus brain tumor group who received cranial irradiation ( n = 9) demonstrated weaker academic abilities than did children with brain tumor who had not received that treatment. These results suggest that neuro(cid:142)bromatosis points (WRAT-3, arithmetic). Discrepancies were statistically signi(cid:142)cant for the general academic achievement
Neprilysin-2 Is an Important (cid:1) -Amyloid Degrading Enzyme

Proteases that degrade the amyloid- (cid:1) peptide (A (cid:1) ) are important in protecting against Alzheimer’s disease (AD), and understanding these proteases is critical to understanding AD pathology. Endopeptidases sensitive to inhibition by thiorphan and phosphoramidon are especially important, because these inhibitors induce dramatic A (cid:1) accumulation ( (cid:1) 30- to 50-fold) and pathological deposition in rodents. The A (cid:1) -degrading enzyme neprilysin (NEP) is the best known target of these inhibitors. However, genetic ablation of NEP results in only modest increases ( (cid:1) 1.5- to 2-fold) in A (cid:1) , indicating that other thiorphan/phosphoramidon-sensitive endopeptidases are at work. Of particular interest is the NEP homolog neprilysin 2 (NEP2), which is thiorphan/ phosphoramidon-sensitive and degrades A (cid:1) . We investigated the role of NEP2 in A (cid:1) degradation in vivo through the use of gene knockout and transgenic mice. Mice deficient for the NEP2 gene showed significant elevations in total A (cid:1) species in the hippocampus and brainstem/diencephalon
Development and Progression of Radiologic Abnormalities in Individuals at Risk for Familial ILD.

RATIONALE The pre-clinical natural history of progressive lung fibrosis is poorly understood. OBJECTIVES Our goal was to identify risk factors for interstitial lung abnormalities (ILA) on high-resolution computed tomography (HRCT) scans, and determine progression towards clinical interstitial lung disease (ILD) among participants in a longitudinal cohort of self-reported unaffected first-degree relatives of patients with familial interstitial pneumonia. METHODS Enrollment evaluation included health/exposure questionnaire and HRCT, which were categorized by visual assessment as no ILA, early/mild ILA, or extensive ILA. The study endpoint was met when ILA were extensive or when ILD was diagnosed clinically. Among subjects with adequate study-time to complete a 5-year follow-up HRCT, the proportion with ILD events (endpoint met or radiographic ILA progression) was calculated. MEASUREMENTS AND MAIN RESULTS Among 336 subjects, the mean age was 53.1 (SD 9.9) years. Those with ILA [early/mild (n=74) or extensive (n=3)] were older, more likely ever-smokers, had shorter peripheral-blood mononuclear cell telomeres, and more likely carried the MUC5B risk allele. Self-reported environmental/occupational exposures, including aluminum smelting, lead, birds, and mold were independently associated with ILA. Among 129 subjects with sufficient study-time, 25 (19.4%) had an ILD event by 5 years post-enrollment [12 met the study endpoint and another 13 had radiologic progression of ILA]. ILD events were more common among those with early/mild ILA at enrollment (63.3% vs 6.1%, p<0.0001). CONCLUSIONS Rare and common environmental exposures are independent risk factors for radiologic abnormalities. In 5 years, progression of ILA occurred in most individuals with early ILA detected at enrollment.
Non Ruminant Nutrition Estimation of the net energy and protein requirements for maintenance of male arctic foxes ( Alopex lagopus ) during the growth period

The maintenance requirements of net energy and net protein were assumed to represent the most accurate and important values totally for the animal’s utilization. The objective of this experiment was to determine the net energy and net protein requirements for maintenance of growing arctic foxes. The experiments was evaluated using regression models estimated from data collected by means of indirect calorimetry, nitrogen balance trials, and digestion and metabolism experiments. Thirty-six growing arctic foxes (3 487 ± 261.7 g) at the age of 85 days were randomly assigned to four groups with 9 animals in each group. Arctic foxes were fed a complete formula diet at four intake levels (100%, or 80%, 60%, and 40% of feed requirements) from 24 July 2017 to 23 September 2017. Arctic foxes in each treatment were kept individually in respiration chambers after 1-d adaptation at day 2 for a 3-d balance trial and then at day 5 followed by a 3-d fasting period. The metabolizable energy intake ( MEI ), heat production in the fed state ( HP ), and retained energy ( RE ) of arctic foxes significantly decreased ( P < 0.01) as the feed intake level decreased. Fasting heat production (FHP) of arctic foxes was not influenced by feed intake level ( P > 0.05). The metabolizable energy maintenance requirement ( ME m ) and net energy maintenance requirement (NE m ) estimated from the linear relationship between RE and MEI were 230 and 217 kJ/kg of body weight BW 0.75 /d, respectively. The ME m and NE m estimated by logarithmic regression of HP on MEI were 225 and 209 kJ/kg BW 0.75 /d, respectively. The net N maintenance requirement ( NN m ) and net protein maintenance requirement ( NP m ) estimated from the linear relationship between retained nitrogen ( RN ) and daily nitrogen intake ( NI ) were 179.6 mg/kg BW 0.75 /d and 1.123 g/kg BW 0.75 /d, respectively. It is concluded that NEm and NPm values obtained fill the net energy and protein requirements shortage, and provide the basic data for establishing the standard of nutrition demand of breeding arctic foxes in China.
Facilitation of the Cognitive Enhancing Effects of Working Memory Training Through Conjoint Voluntary Aerobic Exercise

Increases in performance on tests of attention and learning are often observed shortly after a period of aerobic exercise, and evidence suggests that humans who engage in regular exercise are partially protected from age-related cognitive decline. However, the cognitive benefits of exercise are typically short-lived, limiting the practical application of these observations. We explored whether physical exercise would induce lasting changes in general cognitive ability if that exercise was combined with working memory training, which is purported to broadly impact on cognitive performance. Mice received either exercise (six weeks of voluntary running wheel access), working memory training, both treatments, or various control treatments. Near the completion of this period of exercise, working memory training (in a dual radial-arm maze) was initiated (alternating with days of exercise), and was continued for several weeks. Upon completion of these treatments, animals were assessed (2–4 weeks later) for performance on four diverse learning tasks, and the aggregate performance of individual animals across all four learning tasks was estimated. Working memory training alone promoted small increases in general cognitive performance, although any beneficial effects of exercise alone had dissipated by the time of learning assessments. However, the two treatments in combination more than doubled the improvement in general cognitive performance supported by working memory training alone. Unlike the transient effects that acute aerobic exercise can have on isolated learning tasks, these results indicate that an acute period of exercise combined with working memory training can have synergistic and lasting impact on general cognitive performance. Disclaimer: This a PDF file of an unedited manuscript accepted publication. As a to our customers we are providing this early version of the manuscript. The manuscript will copyediting, typesetting, and review of the resulting proof is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
long-term effects Influence of alternate nostril breathing on heart rate variability in non-practitioners of

Jan-Jun-2012 66 of this technique on the cardiovascular and autonomic nervous systems in healthy and clinical populations and many of these studies have suggested that ANB leads to a shift in sympathovagal balance toward parasympathetic dominance. [2-5] For example, Pal et al . [2] found a reduced basal heart rate and a reduced heart rate response to standing, suggesting enhanced parasympathetic outflow in response to a three-month ANB intervention. Thereafter, Upadhyay Dhungel et al . [4] found that a four-week ANB intervention led to reduced heart rate and blood pressure, whereas Mourya et al . [5] reported reduced blood pressure and improved autonomic reactivity to a series of autonomic tests following a three-month ANB intervention in individuals with stage-1 hypertension. On the other hand, there less information autonomic system function time immediately a heart rate (HRV), Original Article Background: Long-term alternate nostril breathing (ANB) has been shown to enhance autonomic control of the heart by increasing parasympathetic modulation. However, there is no information on the immediate effects of ANB on autonomic control compared to paced breathing (PB) at the same rate in individuals who are inexperienced with yogic breathing. Aim: To examine cardiac autonomic modulation following ANB in comparison to that following PB in individuals who were inexperienced in ANB. Materials and Methods: Twenty healthy individuals (22.3 ± 2.9 years) with no prior experience with ANB engaged in 30 min of both ANB and PB which were preceded and followed by 5 min of normal breathing (PRE, post-ANB, and post-PB, respectively). Mean arterial pressure (MAP) and heart rate variability (HRV) were assessed during all conditions. HRV was reported as spectral power in the total (lnTP), low-(lnLF), and high-frequency (lnHF) ranges and were natural log (ln) transformed. Results: Analysis of covariance revealed lnTP, lnLF and lnHF were greater during both post-ANB and post-PB compared to PRE ( P< 0.05). MAP and lnLF/lnHF did not significantly differ between conditions. Conclusions: These data suggest that there was an immediate increase in cardiac autonomic modulation following ANB and PB without a shift in autonomic balance in individuals inexperienced with yogic breathing. To our knowledge, this is the first investigation to investigate the autonomic effects of ANB in this population and also to compare the effects of ANB and PB at the same yogic
Lung Screen Uptake Trial (LSUT): Randomized Controlled Clinical Trial Testing Targeted Invitation Materials

Rationale: Low uptake of low-dose computed tomography (LDCT) lung cancer screening, particularly by current smokers of a low socioeconomic position, compromises effectiveness and equity. Objectives: To compare the effect of a targeted, low-burden, and steppedinvitationstrategyversuscontrolonuptakeofhospital-basedLungHealthCheckappointmentsofferingLDCTscreening. Methods: In a two-arm, blinded, between-subjects, randomized controlledtrial,2,012participantswereselectedfrom16primarycarepracticesusingthesecriteria: 1 ) aged 60 to 75 years, 2 ) recorded as a current smoker within the last 7 years, and 3 ) no prespeci ﬁ ed exclusion criteria contraindicating LDCT screening. Both groups received a stepped sequence of preinvitation, invitation, and reminder letters from their primary care practitioner offering prescheduled appointments. The key manipulation was the accompanying lea ﬂ et. The intervention group ’ s lea ﬂ et targeted psychological barriers and provided low-burden information, mimicking the concept of the U.K. Ministry of Transport ’ s annual vehicle test ( “ M.O.T. For Your Lungs ” ). Measurements and Main Results: Uptake was 52.6%, with no difference between intervention (52.3%) and control (52.9%) groups in unadjusted (odds ratio [OR], 0.98; 95% con ﬁ dence interval [CI], 0.82 – 1.16) or adjusted (OR, 0.98; 95% CI, 0.82 – 1.17) analyses. Currentsmokerswerelesslikelytoattend(adjustedOR,0.70;95%CI,0.56 0.86) than former smokers. Socioeconomic deprivation was signi ﬁ cantly associated with lower uptake for the control group only ( P , 0.01). Conclusions: The intervention did not improve uptake. Regardless of trial arm, uptake was considerably higher than previous clinical and real-world studies, particularly given that the samples were predominantly lower socioeconomic position smokers. Strategies common to both groups, including a Lung Health Check approach, could represent a minimum standard. Registered
Glutamate NMDA receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure

Background— Despite widely reported clinical and preclinical studies of rapid antidepressant actions of glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonists, there has been very little work examining the effects of these drugs in stress models of depression that require chronic administration of antidepressants, or the molecular mechanisms that could account for the rapid responses. Methods— We used a rat 21-day chronic unpredictable stress (CUS) model to test the rapid actions of NMDA receptor antagonists on depressant-like behavior, neurochemistry, and spine density and synaptic function of prefrontal cortex (PFC) neurons. Results— The results demonstrate that acute treatment with the non-competitive NMDA channel blocker ketamine or the selective NR2B antagonist Ro 25-6981 rapidly ameliorates CUS-induced anhedonia and anxiogenic behaviors. We also find that CUS exposure decreases the expression levels of synaptic proteins and spine number and the frequency/amplitude of synaptic currents (EPSCs) in layer V pyramidal neurons in the PFC, and that these deficits are rapidly reversed by ketamine. Blockade of the mammalian target of rapamycin (mTOR) protein synthesis cascade abolishes both the behavioral and biochemical effects of ketamine. Conclusions— The results indicate that the structural and functional deficits resulting from long-term stress exposure, which could contribute to the pathophysiology of depression, are rapidly reversed by NMDA receptor antagonists in an mTOR-dependent manner.
Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus Study, the Canadian Cohort of HIV+ Slow Progressors, the Canadian HIV and Aging Cohort Groups

REG3α been identified as a gut damage marker in bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. predict non-AIDS comorbidity risks in PWH.
Computed tomography densitometry and morphology of radiofrequency ablated Stage IA non-small cell lung cancer: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial

Purpose: Evaluate tumor and ablation zone morphology and densitometry, related to recurrence in participants with stage IA non-small cell lung cancer undergoing radiofrequency ablation in a prospective, multicenter trial. Materials and methods: Forty-five participants (median age 76; 25 women, 20 men) from 16 sites were followed for 2 years (December 2006 to November 2010) with CT densitometry. Imaging findings before and after ablation were recorded, including maximum CT attenuation [Hounsfield units (HU)] at precontrast, 45, 90, 180, and 300 seconds post contrast. Results: Every 1cm increase in largest axial diameter of the ablation zone at three-month follow-up compared to the index tumor, reduced odds of two-year recurrence by 52% (p= 0.02). A 1cm difference performed best (sensitivity 0.56, specificity 0.93, positive likelihood ratio 8). CT densitometry precontrast and at 45 seconds showed significantly different enhancement patterns when comparing pretreated lung cancer (delta=+61.2 HU), tumor recurrence (delta=+ 57 HU), and treated tumor/ablation zone (delta=+16.9 HU), (p<0.0001). Densitometry from 45–300 seconds was also different among pretreated tumor (delta=−6.8 HU), recurrence (delta=−11.2 HU), and treated tumor (delta= +12.1 HU), (p=0.01). Untreated and residual tumor demonstrated washout, whereas treated tumor demonstrated increased attenuation. Conclusion: An ablation zone ≥1 cm larger than initial tumor on 3-month follow-up imaging is recommended to decrease odds of recurrence. CT densitometry can delineate tumor versus treatment zone.
Phosphoinositide-3 Kinase–Rac1–c-Jun NH2-terminal Kinase Signaling Mediates Collagen I–induced Cell Scattering and Up-Regulation of N-Cadherin Expression in Mouse Mammary Epithelial Cells□D

During epithelial-to-mesenchymal transitions (EMTs), cells must change their interactions with one another and with their extracellular matrix in a synchronized manner. To characterize signaling pathways cells use to coordinate these changes, we used NMuMG mammary epithelial cells. We showed that these cells become fibroblastic and scattered, with increased N-cadherin expression when cultured on collagen I. Rac1 and c-Jun NH2-terminal kinase (JNK) were activated when cells were plated on collagen I, and dominant inhibitory Rac1 (RacN17) or inhibition of JNK signaling prevented collagen I–induced morphological changes and N-cadherin up-regulation. Furthermore, inhibiting phosphoinositide-3 kinase (PI3K) activity prevented Rac1 and JNK activation as well as collagen I–induced N-cadherin up-regulation. These data implicate PI3K–Rac1–JNK signaling in collagen I–induced changes in NMuMG cells. To establish a role for N-cadherin in collagen I–induced cell scattering, we generated N-cadherin overexpressing and knockdown NMuMG cells and showed that knocking down N-cadherin expression prevented collagen I–induced morphological changes. Motility assays showed that cells overexpressing N-cadherin were significantly more motile than mock-transfected cells and that N-cadherin-mediated motility was collagen I dependent. In addition, we showed that cord formation and branching in three-dimensional culture (EMT-dependent events) required N-cadherin expression and PI3K–Rac1–JNK signaling.