Miracle-dz/UniFAR-FTUs huggingface dataset:
In-DRAM Cache Management for Low Latency and Low Power 3D-Stacked DRAMs

Recently, 3D-stacked dynamic random access memory (DRAM) has become a promising solution for ultra-high capacity and high-bandwidth memory implementations. However, it also suffers from memory wall problems due to long latency, such as with typical 2D-DRAMs. Although there are various cache management techniques and latency hiding schemes to reduce DRAM access time, in a high-performance system using high-capacity 3D-stacked DRAM, it is ultimately essential to reduce the latency of the DRAM itself. To solve this problem, various asymmetric in-DRAM cache structures have recently been proposed, which are more attractive for high-capacity DRAMs because they can be implemented at a lower cost in 3D-stacked DRAMs. However, most research mainly focuses on the architecture of the in-DRAM cache itself and does not pay much attention to proper management methods. In this paper, we propose two new management algorithms for the in-DRAM caches to achieve a low-latency and low-power 3D-stacked DRAM device. Through the computing system simulation, we demonstrate the improvement of energy delay product up to 67%.
Resting‐state fMRI effective connectivity between the bed nucleus of the stria terminalis and amygdala nuclei

The bed nucleus of the stria terminalis (BNST) and the laterobasal nucleus (LB), centromedial nucleus (CM), and superficial nucleus (SF) of the amygdala form an interconnected dynamical system, whose combined activity mediates a variety of behavioral and autonomic responses in reaction to homeostatic challenges. Although previous research provided deeper insight into the structural and functional connections between these nuclei, studies investigating their resting‐state functional magnetic resonance imaging (fMRI) connectivity were solely based on undirected connectivity measures. Here, we used high‐quality data of 391 subjects from the Human Connectome Project to estimate the effective connectivity (EC) between the BNST, the LB, CM, and SF through spectral dynamic causal modeling, the relation of the EC estimates with age and sex as well as their stability over time. Our results reveal a time‐stable asymmetric EC structure with positive EC between all amygdala nuclei, which strongly inhibited the BNST while the BNST exerted positive influence onto all amygdala nuclei. Simulation of the impulse response of the estimated system showed that this EC structure shapes partially antagonistic (out of phase) activity flow between the BNST and amygdala nuclei. Moreover, the BNST‐LB and BNST‐CM EC parameters were less negative in males. In conclusion, our data points toward partially separated information processing between BNST and amygdala nuclei in the resting‐state.
Effect of the comprehensive smoke-free law on time trends in smoking behaviour in primary healthcare patients in Spain: a longitudinal observational study

Objective This study aimed to analyse the impact of comprehensive smoke-free legislation (SFL) on the prevalence and incidence of adult smoking in primary healthcare (PHC) patients from three Spanish regions, overall and stratified by sex. Design Longitudinal observational study conducted between 2008 and 2013. Setting 66 PHC teams in Catalonia, Navarre and the Balearic Islands (Spain). Participants Population over 15 years of age assigned to PHC teams. Primary and secondary outcomes measures Quarterly age-standardised prevalence of non-smoker, smoker and ex-smoker and incidence of new smoker, new ex-smoker and ex-smoker relapse rates were estimated with data retrieved from PHC electronic health records. Joinpoint analysis was used to analyse the trends of age-standardised prevalence and incidence rates. Trends were expressed as annual percentage change and average annual percent change. Results The overall standardised smoker prevalence rate showed a significant downward trend (higher in men than women) and the overall standardised ex-smoker prevalence rate showed a significant increased trend (higher in women than men) in the three regions. Standardised smoker and ex-smoker prevalence rates were higher for men than women in all regions. With regard to overall trends of incidence rates, new smokers decreased significantly in Catalonia and Navarre and similarly in men and women, new ex-smokers decreased significantly and more in men in Catalonia and the Balearic Islands, and ex-smoker relapse increased in Catalonia (particularly in women) and decreased in Navarre. Conclusions Trends in smoking behaviour in PHC patients remain unchanged after the implementation of comprehensive SFL. The impact of the comprehensive SFL might have been lessened by the effect of the preceding partial SFL.
Dose dependency PM2.5 aggravated airway inflammation in asthmatic mice via down-regulating expression of ITGB4.

OBJECTIVE We aimed to investigate whether PM2.5 has the potential to exacerbate neutrophil airway inflammation and to analyze the underlying mechanisms. MATERIALS AND METHODS The high-volume air sampler (Laoying 2033B, Qingdao, China) was used to collect PM2.5 from January 01, 2016 to December 21, 2016 in Yantai, Shandong Province, China. BALB/c mice were divided into the following four groups: control group, ovalbumin (OVA) group, low-dose PM2.5 group and high-dose PM2.5 group. Mice except for control group were sensitized and challenged by OVA, and those in low-dose PM2.5 group and high-dose PM2.5 group were intranasally administered by PM2.5 suspension. Airway responsiveness of mice was measured. Enzyme-linked immunosorbent assay (ELISA) kit was used to evaluate the expressions of interleukin 17 (IL-17) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and serum samples. Cell counting in BALF and histological examination were measured to explore PM2.5-induced airway inflammation. Protein expression of Integrin β4 (ITGB4) was assessed by Western blot. RESULTS Airway hyperresponsiveness (AHR) exacerbated in PM2.5 exposed asthmatic mice in progressively increased doses of acetylcholine chloride (ACH). Levels of IL-17 and TNF-αin BALF and serum increased significantly in PM2.5 groups compared with other groups with significant differences between two PM2.5 groups. PM2.5 exposure exacerbated inflammatory cell infiltration and mucus secretion in airways of asthmatic mice. Percentage of neutrophils in PM2.5 groups was significantly higher in dose-dependent manner. OVA and PM2.5 co-exposure inhibited the expression of ITGB4. In particular, ITGB4 expression in mice of high-dose PM2.5 group was significantly lowered than the low-dose PM2.5 group. CONCLUSIONS We showed that PM2.5 exposure exacerbates neutrophil airway inflammation in asthmatic mice though up-regulating expressions of IL-17 and TNF-α but down-regulating the expression of ITGB4.
Dermoscopic findings of umbilical granuloma

Dermoscopic findings in umbilical granuloma are vascular polymorphism comprised of linear irregular and arborizing vessels with structureless areas distributed over a milky‐red background. The increase of angiogenesis and neovascularization is represented by the linear irregular and arborizing vessels. Structureless areas over an irregularly milky‐red background are originated by the proliferation of vascular endothelial cells and fibroblasts, with capillary and granulation tissue formation.
The Human Ventromedial Prefrontal Cortex: Sulcal Morphology and Its Influence on Functional Organization

The ventromedial prefrontal cortex (vmPFC), which comprises several distinct cytoarchitectonic areas, is a key brain region supporting decision-making processes, and it has been shown to be one of the main hubs of the Default Mode Network, a network classically activated during resting state. We here examined the interindividual variability in the vmPFC sulcal morphology in 57 humans (37 females) and demonstrated that the presence/absence of the inferior rostral sulcus and the subgenual intralimbic sulcus influences significantly the sulcal organization of this region. Furthermore, the sulcal organization influences the location of the vmPFC peak of the Default Mode Network, demonstrating that the location of functional activity can be affected by local sulcal patterns. These results are critical for the investigation of the function of the vmPFC and show that taking into account the sulcal variability might be essential to guide the interpretation of neuroimaging studies. SIGNIFICANCE STATEMENT The ventromedial prefrontal cortex (vmPFC) is one of the main hubs of the Default Mode Network and plays a central role in value coding and decision-making. The present study provides a complete description of the interindividual variability of anatomical morphology of this large portion of prefrontal cortex and its relation to functional organization. We have shown that two supplementary medial sulci predominantly determine the organization of the vmPFC, which in turn affects the location of the functional peak of activity in this region. Those results show that taking into account the variability in sulcal patterns might be essential to guide the interpretation of neuroimaging studies of the human brain and of the vmPFC in particular.
Intrauterine growth restriction and neonatal hypoxic ischemic brain injury causes sex‐specific long‐term neurobehavioral abnormalities in rats

There is a lack of knowledge of factors preventing an adequate response to moderate hypothermia after hypoxic ischemic (HI) brain injury. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to have a worse outcome with HI brain injury. IUGR was induced by placental insufficiency in dams at 14 days of gestation. HI was induced at postnatal day (P) 10 by permanent right carotid artery ligation followed by 90 min of hypoxia (8% oxygen). Tests for early brain injury and neurobehavioral outcomes were subsequently done. All statistical analysis was done using Two‐way ANOVA; post hoc Holm‐Sidak test. HI in control and IUGR groups decreased the success rate of the contralateral vibrissa‐elicited forelimb test, increased response latency in movement initiation test and increased the time to finish elevated beam walk test at P40 and P60. IUGR augmented HI‐induced abnormality in vibrissa‐elicited forelimb test at P40 but showed higher success rate when compared to HI only group at P60. IUGR’s negative effect on HI‐induced changes on the elevated beam walk test was sex‐specific and exaggerated in P60 males. Increased TUNEL positive cells in the cortex were noted at 72 h after in HI in control but not in IUGR groups. In conclusion, the consequences of IUGR on subsequent neonatal HI varied based on age, sex and outcomes examined, and overall, male sex and IUGR had worse effects on the long‐term neurobehavioral outcomes following HI.
Breast Cancer in Lean Postmenopausal Women Might Have Specific Pathological Features

Background/Aim: The rate of obesity, an independent risk factor for breast cancer in post-menopausal women, is quite low in Japan, indicating breast cancer in lean women to be more common in the Japanese than in Westerners. However, biological characteristics of such breast cancers have not been adequately investigated. Patients and Methods: We retrospectively investigated clinicopathological breast cancer features of 566 postmenopausal Japanese women, who underwent curative surgery, in relation to patient physique based on the body mass index. Results: There were no differences in several factors examined such as tumour size according to patient physique. On the other hand, mean values of the Ki67 labelling index were significantly higher in lean compared to obese patients (p=0.027). Likewise, HER2-positive tumours were more often observed in lean patients (p=0.051). Conclusion: Lean postmenopausal women had more aggressive tumours, apparently contradicting the widely held view for breast cancer in obese women.
Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation

Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.
Quantifying Range of Motion and Stress Patterns at the Transitional Lumbosacral Junction: Pilot Study Using a Computational Model for Load-Bearing at Accessory L5-S1 Articulation

ABSTRACT Background: Symptomatic or asymptomatic transitional anomalies at the lumbosacral junction are common occurrences in the population. Lumbosacral (L5-S1) accessory articulations are the most common presentations of transitional anomalies at this region. Such anatomical alterations are believed to be associated with biomechanical changes of load-bearing and movement restrictions leading to low back pain. This study attempts to use computational models of a normal and a lumbosacral transitional vertebrae (LSTV) accessory articulation to analyze and compare the range of motion and loading patterns at the lumbosacral articulations. Methods: Three-dimensional Finite Element computational models of normal and accessory L5-S1 articulated sacrum were created. These models were tested for range of motion and stress patterns generated at the lumbosacral articulations using similar loading and motion simulation to elicit different moments/excursions at the lumbosacral junctions. Results: Compared to the normal variant, the transitional model exhibited different range of motion and divergent patterns of stress generation at the lumbosacral and accessory articulations with equal and physiological magnitudes of loading applied to both the models. Conclusions: The finite element modeling approach can be used for biomechanical investigations in LSTV variants. However, larger sample studies with different LSTV models may be required to statistically compare movement and loading patterns at LSTV-affected lumbosacral and sacroiliac junctions, and to recommend definitive treatment strategies in these situations.
Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer

PURPOSE PROSTVAC, a viral vector–based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This phase III study further investigated those findings. PATIENTS AND METHODS Patients were randomly assigned to PROSTVAC (Arm V; n = 432), PROSTVAC plus granulocyte-macrophage colony-stimulating factor (Arm VG; n = 432), or placebo (Arm P; n = 433), stratified by prostate-specific antigen (less than 50 ng/mL v 50 ng/mL or more) and lactate dehydrogenase (less than 200 v 200 U/L or more). Primary end point was OS. Secondary end points were patients alive without events (AWE)—namely, radiographic progression, pain progression, chemotherapy initiation, or death—at 6 months and safety. The study design was a superiority trial of PROSTVAC (Arm V or Arm VG) versus Arm P. Three interim analyses were planned. RESULTS At the third interim analysis, criteria for futility were met and the trial was stopped early. Neither active treatment had an effect on median OS (Arm V, 34.4 months; hazard ratio, 1.01; 95% CI, 0.84 to 1.20; P = .47; Arm VG, 33.2 months; hazard ratio, 1.02; 95% CI, 0.86 to 1.22; P = .59; Arm P, 34.3 months). Likewise, AWE at 6 months was similar (Arm V, 29.4%; odds ratio, 0.96; 95% CI, 0.71 to 1.29; Arm VG, 28.0%; odds ratio, 0.89; 95% CI, 0.66 to 1.20; placebo, 30.3%). Adverse events were similar for the treatment and placebo groups, with the most common being injection site reactions (62% to 72%) and fatigue (21% to 24%). Arrhythmias were the most common cardiac-related events (1.4% to 3.5%). There were no reports of either myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients. CONCLUSION Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.
Volatile emissions from thawing permafrost soils are influenced by meltwater drainage conditions

Vast amounts of carbon are bound in both active layer and permafrost soils in the Arctic. As a consequence of climate warming, the depth of the active layer is increasing in size and permafrost soils are thawing. We hypothesize that pulses of biogenic volatile organic compounds are released from the near‐surface active layer during spring, and during late summer season from thawing permafrost, while the subsequent biogeochemical processes occurring in thawed soils also lead to emissions. Biogenic volatile organic compounds are reactive gases that have both negative and positive climate forcing impacts when introduced to the Arctic atmosphere, and the knowledge of their emission magnitude and pattern is necessary to construct reliable climate models. However, it is unclear how different ecosystems and environmental factors such as drainage conditions upon permafrost thaw affect the emission and compound composition. Here we show that incubations of frozen B horizon of the active layer and permafrost soils collected from a High Arctic heath and fen release a range of biogenic volatile organic compounds upon thaw and during subsequent incubation experiments at temperatures of 10°C and 20°C. Meltwater drainage in the fen soils increased emission rates nine times, while having no effect in the drier heath soils. Emissions generally increased with temperature, and emission profiles for the fen soils were dominated by benzenoids and alkanes, while benzenoids, ketones, and alcohols dominated in heath soils. Our results emphasize that future changes affecting the drainage conditions of the Arctic tundra will have a large influence on volatile emissions from thawing permafrost soils – particularly in wetland/fen areas.
Development and performance evaluation of the Medicines Optimisation Assessment Tool (MOAT): a prognostic model to target hospital pharmacists’ input to prevent medication-related problems

Background Medicines optimisation is a key role for hospital pharmacists, but with ever-increasing demands on services, there is a need to increase efficiency while maintaining patient safety. Objective To develop a prediction tool, the Medicines Optimisation Assessment Tool (MOAT), to target patients most in need of pharmacists’ input in hospital. Methods Patients from adult medical wards at two UK hospitals were prospectively included into this cohort study. Data on medication-related problems (MRPs) were collected by pharmacists at the study sites as part of their routine daily clinical assessments. Data on potential risk factors, such as number of comorbidities and use of ‘high-risk’ medicines, were collected retrospectively. Multivariable logistic regression modelling was used to determine the relationship between risk factors and the study outcome: preventable MRPs that were at least moderate in severity. The model was internally validated and a simplified electronic scoring system developed. Results Among 1503 eligible admissions, 610 (40.6%) experienced the study outcome. Eighteen risk factors were preselected for MOAT development, with 11 variables retained in the final model. The MOAT demonstrated fair predictive performance (concordance index 0.66) and good calibration. Two clinically relevant decision thresholds (ie, the minimum predicted risk probabilities to justify pharmacists’ input) were selected, with sensitivities of 90% and 66% (specificity 30% and 61%); these equate to positive predictive values of 47% and 54%, respectively. Decision curve analysis suggests that the MOAT has potential value in clinical practice in guiding decision-making. Conclusion The MOAT has potential to predict those patients most at risk of moderate or severe preventable MRPs, experienced by 41% of admissions. External validation is now required to establish predictive accuracy in a new group of patients.
Effects of Bupivacaine Versus Bupivacaine Plus Dexamethasone-Soaked Nasal Packing After Endoscopic Nasal Surgery.

BACKGROUND The aim of this randomized prospective study was to investigate the postoperative analgesic effectiveness of bupivacaine versus bupivacaine plus dexamethasone-soaked nasal packing in patients scheduled for endoscopic nasal surgery. METHODS Sixty American Society of Anesthesiologists groups I and II patients aged 18 to 65 years and scheduled for endoscopic nasal surgery were assigned into 2 groups. Group B received 8 mL 0.5% bupivacaine and 2 mL saline, and group BD received 8 mL 0.5% bupivacaine and 8 mg (2 mL) dexamethasone-soaked nasal packing. In the postoperative period, 1000 mg paracetamol was administered and repeated every 6 hours. Postoperative pain scores, additional analgesia requirements and nausea-vomiting were recorded. RESULTS Postoperative pain scores were significantly lower in group BD than in group B at 1, 2, 4, 8, and 12 hours, and during tampon removal (P < 0.05), but there was no difference between the groups' 24-hour visual analog scale scores (P = 0.115). Postoperative additional analgesia use was statistically significantly higher in group B than in group BD (25/30 versus 13/30 respectively, P = 0.001). Postoperative nausea and vomiting was statistically higher in group B than in group BD (11/30 versus 4/30 respectively, P = 0.037). CONCLUSION The addition of dexamethasone to bupivacaine via soaked nasal packing in endoscopic nasal surgery reduced postoperative pain scores, additional analgesia requirements, and PONV. The authors recommended a combination of bupivacaine plus dexamethasone-soaked nasal packing after endoscopic nasal surgery.
The ABCD of Obesity: An EASO Position Statement on a Diagnostic Term with Clinical and Scientific Implications

Obesity is a frequent, serious, complex, relapsing, and chronic disease process that represents a major public health problem. The coining of obesity as an adiposity-based chronic disease (ABCD) is of particular relevance being in line with EASO’s proposal to improve the International Classification of Diseases ICD-11 diagnostic criteria for obesity based on three dimensions, namely etiology, degree of adiposity, and health risks. The body mass index as a unique measurement of obesity does not reflect the whole complexity of the disease. Obesity complications are mainly determined by 2 pathological processes, i.e., physical forces (fat mass disease) as well as endocrine and immune responses (sick fat disease), which are embedded in a cultural and physical context leading to a specific ABCD stage.