Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term Outcomes of Laparoscopy-assisted Gastrectomy for T4a Advanced Gastric Cancer: A Single-center Retrospective Study

Background: Laparoscopy-assisted gastrectomy (LAG) has been proven to be feasible and oncologically safe for early gastric cancer. Despite the rapid increase in the number of LAG cases, there are few reports on the long-term outcomes of T4a (serosalinvasion) gastric cancer after LAG. The aim of the present study was to evaluate the long-term clinical outcomes in patients with stage T4a gastric cancer after laparoscopic gastrectomy. Materials and Methods: A total of 578 patients with gastric cancer were treated with LAG between February 2004 and December 2014. Among these patients, 224 patients were pathologically confirmed with T4a advanced gastric cancer. The clinical and follow-up data were retrospectively analyzed, the survival rates were estimated using the Kaplan-Meier method, and the risk factors for overall and disease-free survival (DFS) were evaluated by Cox regression. Results: Among these 224 patients, 129 patients were above 60 years old, and the male-to-female ratio was 157:67. Furthermore, among these patients, 125 patients received laparoscopy-assisted distal gastrectomy, whereas 99 patients received laparoscopy-assisted total gastrectomy. Forty (17.90%) patients experienced postoperative complications according to the Clavien-Dindo classification. Median follow-up time was 32 months. Recurrence was observed in 99 (44.20%) patients. The cumulative 5-year overall survival (OS) and DFS rates were 47.20% and 43.60%, respectively. The 5-year OS and DFS rates were 72.50% and 70.00% for stage N0, 57.00% and 53.90% for stage N1, 41.60% and 37.00% for stage N2, and 23.30% and 21.30% for stage N3, respectively. In the univariate analysis, tumor size, tumor location, N stage and metastatic lymph node ratio (MLR) were correlated with OS and DFS. The MLR was identified as an independent predictor for OS (P<0.05; hazard ratio=1.828; 95% confidence interval, 1.353-2.469) and DFS (P<0.05; hazard ratio=1.197; 95% confidence interval, 0.945-1.516). Conclusions: The long-term outcomes of LAG for T4a (M0) gastric cancer were acceptable, compared with previous reports. Therefore, this treatment could be considered as an alternative operative approach for T4a gastric cancer. The MLR was an independent predictor for OS and DFS.
The influence of dietary leucine above recommendations and fixed ratios to isoleucine and valine on muscle protein synthesis and degradation pathways in broilers

This study investigated the hypothesis that dietary supplementation of leucine (Leu) above actual recommendations activates protein synthesis and inhibits protein degradation pathways on the molecular level and supports higher muscle growth in broilers. Day-old male Cobb-500 broilers (n = 180) were allotted to 3 groups and phase-fed 3 different corn-wheat-soybean meal-based basal diets during periods 1 to 10, 11 to 21, and 22 to 35 D. The control group (L0) received the basal diet which met the broiler's requirements of nutrients and amino acids for maintenance and growth. Groups L1 and L2 received basal diets supplemented with Leu to exceed recommendations by 35 and 60%, respectively, and isoleucine (Ile) and valine (Val) were supplemented to keep Leu: Ile and Leu: Val ratios fixed. Samples of liver and breast muscle and pancreas were collected on days 10, 21, and 35. The gene expression and abundance of total and phosphorylated proteins involved in the mammalian target of rapamycin pathway of protein synthesis, in the ubiquitin-proteasome pathway and autophagy-lysosomal pathway of protein degradation, in the general control nonderepressible 2/eukaryotic translation initiation factor 2A pathway involved in the inhibition of protein synthesis, and in the myostatin–Smad2/3 pathway involved in myogenesis were evaluated in the muscle, as well as expression of genes involved in the growth hormone axis. Growth performance, feed intake, the feed conversion ratio, and carcass weights did not differ between the 3 groups (P > 0.05). Plasma concentrations of Leu, Ile, and Val and of their keto acids, and the activity of the branched-chain α-keto acid dehydrogenase in the pancreas increased dose dependently with increasing dietary Leu concentrations. In the breast muscle, relative mRNA abundances of genes and phosphorylation of selected proteins involved in all investigated pathways were largely uninfluenced by dietary Leu supplementation (P > 0.05). In summary, these data indicate that excess dietary Leu concentrations do not influence protein synthesis or degradation pathways, and subsequently do not increase muscle growth in broilers at fixed ratios to Ile and Val.
Pyocyanin, a Metabolite of Pseudomonas Aeruginosa, Exhibits Antifungal Drug Activity Through Inhibition of a Pleiotropic Drug Resistance Subfamily FgABC3

Abstract The fungus Fusarium graminearum is the causative agent of economically significant plant diseases such as Fusarium Healed Blight (FHB) of cereals, its mycotoxins as deoxynivalenol (DON), Nivalenol (NIV) and Zearalenone (ZEN) contaminate wheat and other grains. The objectives of the present study were to determine the mechanism by which the bacterium Pseudomonas aeruginosa inhibits the growth of F. graminearum. Our results indicate that P. aeruginosa metabolites as pyocyanin has effective antifungal properties. Pyocyanin was produced by P. aeruginosa when cultured on mineral salt medium and reached a maximum concentration after 72 h. Pyocyanin significantly decreased mycotoxins of F. graminearum, a 25 mg/ml of pyocyanin for 72 h decreased DON by 68.7% and NIV by 57.7%. Real-Time PCR analysis demonstrated that the antifungal effect is mediated by downregulation of the Pleiotropic Drug Resistance (PDR) subfamily FgABC3. 25 mg/ml of pyocyanin decreased FgABC3-mRNA by 60%, inhibited the fungal growth and decreased the area of mycelial growth at 12, 24, 36 and 72 h post incubation by 40–50%. Deletion of FgABC3 led to enhanced accumulation of DON and NIV by 40 and 60%, respectively. The data presented in this report may have significance in understanding mechanism by which certain bacterial metabolites exert a beneficial effect and for developing antifungal drugs.
A 2.55 NEF 76 dB CMRR DC-Coupled Fully Differential Difference Amplifier Based Analog Front End for Wearable Biomedical Sensors

High input impedance, low noise, high common mode rejection ratio (CMRR), and ultralow power are the most important performance indicators in the design of analog front end (AFE) for wearable biomedical sensors. This paper presents a fully differential difference amplifier based AFE that employs dc-coupled input stage to increase the input impedance and improve CMRR. A parasitic capacitor reuse technique is proposed to improve the noise/area efficiency and CMRR. An on-body dc bias scheme is introduced to deal with the input dc offset. Implemented in 0.35 μm CMOS process with an area of 0.405 mm2, the proposed AFE consumes 0.9 μW at 1.8 V and shows excellent noise effective factor of 2.55, and CMRR of 76 dB. Experiment shows the proposed AFE not only picks up clean ECG signal with electrodes placed as close as 2 cm under both resting and walking conditions, but also obtain the distinct α-wave after eye blink from EEG recording.
Impact of gastrointestinal conditions, restrictive diets and mental health on health-related quality of life: cross-sectional population-based study in Australia

Objectives To assess the relationship between gastrointestinal conditions, restrictive diets, mental health and health-related quality of life (HRQoL). Design Cross-sectional population-based face-to-face survey. Setting South Australia. Participants A representative sample of 2912 consenting adults (48.9±18.1 years; 50.9% females) investigated in 2015. Primary and secondary outcome measures Participants self-reported diagnosis of gastrointestinal conditions, mental health and current use of restrictive diets. The physical component score (PCS) and mental component score (MCS) of HRQoL were investigated (Study Short Form 12 V.1 questionnaire). Linear regression models were used to test the associations, adjusting for (1) sociodemographic variables, (2) mental health status and (3) lifestyle and body mass index. Results The prevalence of restrictive diets (36.1%; 95% CI 33.9 to 38.3) was higher among those with any self-reported gastrointestinal condition (60.7% vs 31.3% for those without these conditions; p<0.001). PCS was lower among those with a gastrointestinal condition (mean difference=−3.4; 95% CI −4.5 to −2.4) or on a restrictive diet (mean difference=−1.9; 95% CI −2.7 to −1.1), with a similar pattern, but with a smaller effect, observed for MCS. Being on a restrictive diet did not modify the relationship between having a gastrointestinal condition and reduced HRQoL. However, having a gastrointestinal condition was associated with a 2.4 points lower PCS (95% CI −3.5 to −1.3) among those without a mental health problem, while for those affected by a mental health condition this reduction was greater (mean difference=−5.9; 95% CI −8.7 to −3.1). For MCS, there was no evidence of interaction between mental health and gastrointestinal conditions. Conclusions One-third of Australian adults are restricting their diet, and this is associated with lower HRQoL. Being on a restrictive diet was not associated with a better HRQoL among individuals with a gastrointestinal condition. Mental health problems were associated with a stronger adverse relationship between gastrointestinal diseases and physical HRQoL. Health professionals should be alert to these associations when trying to improve health outcomes for patients.
Preadmission Statin Use and 90-day Mortality in the Critically Ill: A Retrospective Association Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC Randomized controlled trials evaluating the potential value of statin administration for intensive care unit patients have not observed a benefitHowever, the chronic preadmission use of statins among patients admitted to the intensive care unit has not been robustly studied WHAT THIS ARTICLE TELLS US THAT IS NEW: Single-center retrospective data suggest that preadmission statin use may be associated with decreased 90-day mortality among some intensive care unit patientsSpecific statin agents and noncardiovascular mortality may demonstrate a stronger signal for further study BACKGROUND:: This study aimed to examine the association between preadmission statin use and 90-day mortality in critically ill patients and to investigate whether this association differed according to statin type and dose. We hypothesized that preadmission statin use was associated with lower 90-day mortality. METHODS This retrospective cohort study analyzed the medical records of all adult patients admitted to the intensive care unit in a single tertiary academic hospital between January 2012 and December 2017. Data including preadmission statin use, statin subtype, and daily dosage were collected, and the associations between these variables and 90-day mortality after intensive care unit admission were examined. The primary endpoint was 90-day mortality. RESULTS A total of 24,928 patients (7,396 statin users and 17,532 non-statin users) were included. After propensity score matching, 5,354 statin users and 7,758 non-statin users were finally included. The 90-day mortality rate was significantly higher in non-statin users (918 of 7,758; 11.8%) than in statin users (455 of 5,354; 8.5%; P < 0.001). In Cox regression analysis, the 90-day mortality rate was lower among statin users than among non-statin users (hazard ratio: 0.70, 95% CI: 0.63 to 0.79; P < 0.001). Rosuvastatin use was associated with 42% lower 90-day mortality (hazard ratio: 0.58, 95% CI: 0.47 to 0.72; P < 0.001). There were no specific significant differences in the association between daily statin dose and 90-day mortality. In competing risk analysis, the risk of noncardiovascular 90-day mortality in statin users was 32% lower than that in non-statin users (hazard ratio: 0.68, 95% CI: 0.60 to 0.78; P < 0.001). Meanwhile, cardiovascular 90-day mortality was not significantly associated with statin use. CONCLUSIONS Preadmission statin use was associated with a lower 90-day mortality. This association was more evident in the rosuvastatin group and with noncardiovascular 90-day mortality; no differences were seen according to daily dosage intensity.
Neural correlates of sparse coding and dimensionality reduction

Supported by recent computational studies, there is increasing evidence that a wide range of neuronal responses can be understood as an emergent property of nonnegative sparse coding (NSC), an efficient population coding scheme based on dimensionality reduction and sparsity constraints. We review evidence that NSC might be employed by sensory areas to efficiently encode external stimulus spaces, by some associative areas to conjunctively represent multiple behaviorally relevant variables, and possibly by the basal ganglia to coordinate movement. In addition, NSC might provide a useful theoretical framework under which to understand the often complex and nonintuitive response properties of neurons in other brain areas. Although NSC might not apply to all brain areas (for example, motor or executive function areas) the success of NSC-based models, especially in sensory areas, warrants further investigation for neural correlates in other regions.
Populations and Dynamics of Guanine Radicals in DNA strands—Direct versus Indirect Generation

Guanine radicals, known to be involved in the damage of the genetic code and aging, are studied by nanosecond transient absorption spectroscopy. They are generated in single, double and four-stranded structures (G-quadruplexes) by one and two-photon ionization at 266 nm, corresponding to a photon energy lower than the ionization potential of nucleobases. The quantum yield of the one-photon process determined for telomeric G-quadruplexes (TEL25/Na+) is (5.2 ± 0.3) × 10−3, significantly higher than that found for duplexes containing in their structure GGG and GG sequences, (2.1 ± 0.4) × 10−3. The radical population is quantified in respect of the ejected electrons. Deprotonation of radical cations gives rise to (G-H1)• and (G-H2)• radicals for duplexes and G-quadruplexes, respectively. The lifetimes of deprotonated radicals determined for a given secondary structure strongly depend on the base sequence. The multiscale non-exponential dynamics of these radicals are discussed in terms of inhomogeneity of the reaction space and continuous conformational motions. The deviation from classical kinetic models developed for homogeneous reaction conditions could also be one reason for discrepancies between the results obtained by photoionization and indirect oxidation, involving a bi-molecular reaction between an oxidant and the nucleic acid.
The epileptic network and cognition: What functional connectivity is teaching us about the childhood epilepsies

Our objective was to summarize and evaluate the rapidly expanding body of literature studying functional connectivity in childhood epilepsy. In the self‐limited childhood epilepsies, awareness of cognitive comorbidities has been steadily increasing, and recent advances in our understanding of the network effects of these disorders promise insights into the underlying neurobiology. We reviewed publications addressing functional connectivity in children with epilepsy with an emphasis on studies of children with self‐limited childhood epilepsies. The majority of studies have been published in the past 10 years and predominantly examine childhood epilepsy with centrotemporal spikes and childhood absence epilepsy. Cognitive network alterations are commonly observed across the childhood epilepsies. Some of these effects appear to be nonspecific to epilepsy syndrome or even to category of neurological disorder. Other patterns, such as changes in the connectivity of cortical language areas in childhood epilepsy with centrotemporal spikes, provide clues to the underlying cognitive deficits seen in affected children. The literature to date is dominated by general observations of connectivity patterns without a priori hypotheses. These data‐driven studies build an important foundation for hypothesis generation and are already providing useful insights into the neuropathology of the childhood epilepsies. Future work should emphasize hypothesis‐driven approaches and rigorous clinical correlations to better understand how the knowledge of network alterations can be applied to guidance and treatment for the children in our clinics.
Thromboelastography On-the-Go: Evaluation of the TEG 6s Device During Ground and High-Altitude Aeromedical Evacuation with Extracorporeal Life Support.

BACKGROUND Coagulation monitoring capabilities during transport are limited. Thromboelastography (TEG) is a whole-blood clotting test measuring clot formation, stabilization and fibrinolysis; and is traditionally performed in a laboratory. We evaluated a new point-of-care TEG analyzer, TEG 6s (Haemonetics; Braintree, MA), in a large animal model of combat-relevant trauma managed with extracorporeal life support (ECLS) during ground and high-altitude aeromedical evacuation. The objective was to compare TEG 6s used during transport vs. the predicate device, TEG 5000, used in the laboratory. We hypothesized that TEG 6s would be comparable to TEG 5000 during dynamically changing transport conditions. METHODS TEG parameters (R, K, Angle, MA, LY30) derived by TEG 6s and TEG 5000 were compared during transport of 8 swine. TEG 6s was transported with animals during ground transport and flight. TEG 5000 was stationary in an adjacent building. TEG 6s activated clotting time (ACT) was compared to a Hemochron Junior ACT analyzer (Accriva Diagnostics; San Diego, CA). Statistics were performed using SAS 9.4 with Deming regressions, Spearman correlations and average differences compared. RESULTS Correlation between devices was stronger at sea-level (R r=0.7413, K r=0.7115, Angle r=0.7192, MA r=0.8386, LY30 r=0.9099) than during high-altitude transport (R r=0.4787, K r=0.4007, Angle r =0.3706, MA r=0.6573, LY30 r=0.8481). Method agreement was comparable during stationary operation (R r=0.7978, K r=0.7974, Angle r=0.7574, MA r=0.7841, LY30 r=0.9140) vs. ground transport (R r=0.7927, K r=0.6246, Angle r=0.6967, MA r=0.9163, LY30 r=0.8603). TEG 6s ACT trended higher than Hemochron ACT when subjects were heparinized (average difference=1442±1703 sec) without a methodological difference by Deming regression. CONCLUSIONS Mobile TEG 6s during ground and altitude transport is feasible and provides unprecedented information to guide coagulation management. Future studies should assess the precision and accuracy of TEG 6s during transport of critically ill. LEVEL OF EVIDENCE Basic science paper, does not require level of evidence.
Rounding the corner on residual risk: Implications of REDUCE‐IT for omega‐3 polyunsaturated fatty acids treatment in secondary prevention of atherosclerotic cardiovascular disease

Patients with established atherosclerotic cardiovascular (CV) disease remain at increased risk of major adverse cardiovascular events even during optimal lipid‐lowering therapy. Recent studies using the methods of Mendelian randomization, as well as analyses of data from large statin trials, have concluded that elevated triglyceride (TG) levels contribute to that increased risk. Omega‐3 polyunsaturated fatty acids (omega‐3 PUFAs) from fish and shellfish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) reduce TG levels when added to the diet in sufficient amounts, and they have favorable effects on several other markers of CV risk. However, trials of omega‐3 PUFAs have had inconsistent findings regarding CV risk reduction. Recently, the REDUCE‐IT (Reduction of Cardiovascular Events with EPA‐Intervention Trial) trial reported that treatment of such high‐risk patients with icosapent ethyl, a purified and stabilized ethyl ester of EPA, reduced the risk of the trial's primary CV endpoint by 25% (95% confidence intervals [CI], 32%‐17%; P < .001). To appreciate the clinical implications of this result, it is important to understand how the REDUCE‐IT trial differed from previous trials, especially with regard to patient enrollment criteria and treatment dosing. We discuss these design features relative to other trials. TG lowering can account for only part of the risk reduction seen with icosapent ethyl; we also consider other potential contributory mechanisms.
Visual Cortical Plasticity in Retinitis Pigmentosa

Purpose Retinitis pigmentosa is a family of genetic diseases inducing progressive photoreceptor degeneration. There is no cure for retinitis pigmentosa, but prospective therapeutic strategies are aimed at restoring or substituting retinal input. Yet, it is unclear whether the visual cortex of retinitis pigmentosa patients retains plasticity to react to the restored visual input. Methods To investigate short-term visual cortical plasticity in retinitis pigmentosa, we tested the effect of short-term (2 hours) monocular deprivation on sensory ocular dominance (measured with binocular rivalry) in a group of 14 patients diagnosed with retinitis pigmentosa with a central visual field sparing greater than 20° in diameter. Results After deprivation most patients showed a perceptual shift in ocular dominance in favor of the deprived eye (P < 0.001), as did control subjects, indicating a level of visual cortical plasticity in the normal range. The deprivation effect correlated negatively with visual acuity (r = −0.63, P = 0.015), and with the amplitude of the central 18° focal electroretinogram (r = −0.68, P = 0.015) of the deprived eye, revealing that in retinitis pigmentosa stronger visual impairment is associated with higher plasticity. Conclusions Our results provide a new tool to assess the ability of retinitis pigmentosa patients to adapt to altered visual inputs, and suggest that in retinitis pigmentosa the adult brain has sufficient short-term plasticity to benefit from prospective therapies.
(F)uridylylated Peptides Linked to VPg1 of Foot-and- Mouth Disease Virus (FMDV): Design, Synthesis and X-Ray Crystallography of the Complexes with FMDV RNA-Dependent RNA Polymerase

Foot-and-mouth disease virus (FMDV) is an RNA virus belonging to the Picornaviridae family that contains three small viral proteins (VPgs), named VPg1, VPg2 and VPg3, linked to the 5′-end of the viral genome. These VPg proteins act as primers for RNA replication, which is initiated by the consecutive binding of two UMP molecules to the hydroxyl group of Tyr3 in VPg. This process, termed uridylylation, is catalyzed by the viral RNA-dependent RNA polymerase named 3Dpol. 5-Fluorouridine triphosphate (FUTP) is a potent competitive inhibitor of VPg uridylylation. Peptide analysis showed FUMP covalently linked to the Tyr3 of VPg. This fluorouridylylation prevents further incorporation of the second UMP residue. The molecular basis of how the incorporated FUMP blocks the incorporation of the second UMP is still unknown. To investigate the mechanism of inhibition of VPg uridylylation by FUMP, we have prepared a simplified 15-mer model of VPg1 containing FUMP and studied its x-ray crystal structure in complex with 3Dpol. Unfortunately, the fluorouridylylated VPg1 was disordered and not visible in the electron density maps; however, the structure of 3Dpol in the presence of VPg1-FUMP showed an 8 Å movement of the β9-α11 loop of the polymerase towards the active site cavity relative to the complex of 3Dpol with VPg1-UMP. The conformational rearrangement of this loop preceding the 3Dpol B motif seems to block the access of the template nucleotide to the catalytic cavity. This result may be useful in the design of new antivirals against not only FMDV but also other picornaviruses, since all members of this family require the uridylylation of their VPg proteins to initiate the viral RNA synthesis.