Miracle-dz/UniFAR-FTUs huggingface dataset:
Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC

BACKGROUND An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression‐free survival, as compared with placebo, among patients with stage III, unresectable non–small‐cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival. METHODS We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression‐free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety. RESULTS Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow‐up was 25.2 months. The 24‐month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two‐sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression‐free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events. CONCLUSIONS Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461.)
Altered Cervical Spinal Cord Resting‐State Activity in Fibromyalgia

Altered afferent input and central neural modulation are thought to contribute to fibromyalgia symptoms, and these processes converge within the spinal cord. We undertook this study to investigate the hypothesis that, using resting‐state functional magnetic resonance imaging (rs‐fMRI) of the cervical spinal cord, we would observe altered frequency‐dependent activity in fibromyalgia.
Visual Curiosity: Learning to Ask Questions to Learn Visual Recognition

In an open-world setting, it is inevitable that an intelligent agent (e.g., a robot) will encounter visual objects, attributes or relationships it does not recognize. In this work, we develop an agent empowered with visual curiosity, i.e. the ability to ask questions to an Oracle (e.g., human) about the contents in images (e.g., What is the object on the left side of the red cube? ) and build visual recognition model based on the answers received (e.g., Cylinder). In order to do this, the agent must (1) understand what it recognizes and what it does not, (2) formulate a valid, unambiguous and informative language query (a question) to ask the Oracle, (3) derive the parameters of visual classifiers from the Oracle response and (4) leverage the updated visual classifiers to ask more clarified questions. Specifically, we propose a novel framework and formulate the learning of visual curiosity as a reinforcement learning problem. In this framework, all components of our agent, visual recognition module (to see), question generation policy (to ask), answer digestion module (to understand) and graph memory module (to memorize), are learned entirely end-to-end to maximize the reward derived from the scene graph obtained by the agent as a consequence of the dialog with the Oracle. Importantly, the question generation policy is disentangled from the visual recognition system and specifics of the environment. Consequently, we demonstrate a sort of double generalization. Our question generation policy generalizes to new environments and a new pair of eyes, i.e., new visual system. Trained on a synthetic dataset, our results show that our agent learns new visual concepts significantly faster than several heuristic baselines, even when tested on synthetic environments with novel objects, as well as in a realistic environment.
P2.03 - Abscheidung von Langasit mittels Laserablation zur Herstellung hochtemperaturstabiler piezoelektrischer Sensorschichten

Effektive Energiewandlungsprozesse erfordern hohe Temperaturen und damit entsprechend stabile Sensoren. Ein wesentlicher Bestandteil miniaturisierter Hochtemperatur-Sensoren sind piezoelektrische Funktionsschichten. Aus diesem Grund wird die epitaktische Abscheidung von hochtemperaturstabilen, piezoelektrischen Langasitschichten systematisch untersucht. Im Gegensatz zu herkömmlichen Herstellungsverfahren wird Langasit mittels einer Kombination aus gepulster Laserablation und thermischer Behandlung während des Ablationsprozesses epitaktisch auf Langasit (Homoepitaxie) und anderen Substratmaterialien (Heteroepitaxie) abgeschieden. Dabei werden die Qualität der Funktionsschichten und die Temperaturabhängigkeit der elektromechanischen Eigenschaften des Systems aus Schicht und Substrat untersucht. Als Beispiel für einen piezoelektrischen Wandler wird ein monolithischer Dickenscherschwinger vorgestellt. Dabei werden Elektroden durch die epitaktische Abscheidung von dotiertem Langasit hergestellt. Die elektrischen und elektromechanischen Eigenschaften des Messelements werden bis zu einer Temperatur von 1000 °C untersucht. Mit diesen Ergebnissen wird die weitere Entwicklung miniaturisierter, piezoelektrischer Bauelemente und Sensoren bei hohen Temperaturen auf der Basis von Langasit vorangetrieben.
A sampling framework for counting temporal motifs

Pattern counting in graphs is fundamental to network science tasks, and there are many scalable methods for approximating counts of small patterns, often called motifs, in large graphs. However, modern graph datasets now contain richer structure, and incorporating temporal information in particular has become a critical part of network analysis. Temporal motifs, which are generalizations of small subgraph patterns that incorporate temporal ordering on edges, are an emerging part of the network analysis toolbox. However, there are no algorithms for fast estimation of temporal motifs counts; moreover, we show that even counting simple temporal star motifs is NP-complete. Thus, there is a need for fast and approximate algorithms. Here, we present the first frequency estimation algorithms for counting temporal motifs. More specifically, we develop a sampling framework that sits as a layer on top of existing exact counting algorithms and enables fast and accurate memory-efficient estimates of temporal motif counts. Our results show that we can achieve one to two orders of magnitude speedups with minimal and controllable loss in accuracy on a number of datasets.
Maternal age and cardiovascular and metabolic disease outcomes: a retrospective cohort study using data from population-based electronic medical records

Abstract Objective: To evaluate whether a woman’s age at first birth is associated with cardiovascular risk and metabolic health outcomes (cardiometabolic outcomes) by age 45. Methods: This is a retrospective, population-based cohort study that uses electronic health record data from the largest health fund in Israel. Women aged 34–39 at baseline (2004–2006) free of chronic diseases were identified as nulliparous at baseline and were followed up to 10 years (through 2016). The cohort was divided into three groups based on their age at first birth: younger parturients (ages 35–39), older parturients (ages 40–44), and never had children. The percentage of adverse pregnancy events and cardiometabolic outcomes at age 45 were compared across these three groups as well as to women in the general population. Cardiovascular risk and metabolic health outcomes were defined as: Type 2 diabetes, obesity, hypertension, cardiovascular disease, and Framingham risk score. Methods and results: Out of a group of 126,121 women aged 34–39 at baseline, 9979 were nulliparous and free of comorbidities. Over the course of the follow-up, there were 952 younger parturients and 673 older parturients who had their first birth, and 8354 women who remained persistent nulliparous. While older parturients had more adverse pregnancy events, there was no difference in rates of cardiometabolic outcomes between the two parturient groups, and they both had lower rates than the persistent nulliparous and the general population. Conclusions: Parturients free of major chronic diseases who give birth at a later age do not have increased cardiometabolic outcomes in midlife as compared to a general population of women in a large retrospective cohort. Our results may support clinicians when counseling healthy women who are seeking advice regarding delaying their first pregnancy without a tradeoff on health outcomes.
Multimodal MRI suggests that male homosexuality may be linked to cerebral midline structures

The neurobiology of sexual preference is often discussed in terms of cerebral sex dimorphism. Yet, our knowledge about possible cerebral differences between homosexual men (HoM), heterosexual men (HeM) and heterosexual women (HeW) are extremely limited. In the present MRI study, we addressed this issue investigating measures of cerebral anatomy and function, which were previously reported to show sex difference. Specifically, we asked whether there were any signs of sex atypical cerebral dimorphism among HoM, if these were widely distributed (providing substrate for more general ‘female’ behavioral characteristics among HoM), or restricted to networks involved in self-referential sexual arousal. Cortical thickness (Cth), surface area (SA), subcortical structural volumes, and resting state functional connectivity were compared between 30 (HoM), 35 (HeM) and 38 (HeW). HoM displayed a significantly thicker anterior cingulate cortex (ACC), precuneus, and the left occipito-temporal cortex compared to both control groups. These differences seemed coordinated, since HoM also displayed stronger cortico-cortical covariations between these regions. Furthermore, functional connections within the default mode network, which mediates self- referential processing, and includes the ACC and precuneus were significantly weaker in HoM than HeM and HeW, whereas their functional connectivity between the thalamus and hypothalamus (important nodes for sexual behavior) was stronger. In addition to these singular features, HoM displayed ‘female’ characteristics, with a similar Cth in the left superior parietal and cuneus cortices as HeW, but different from HeM. These data suggest both singular and sex atypical features and motivate further investigations of cerebral midline structures in relation to male homosexuality.
TRILO: A Traffic Indication-Based Downlink Communication Protocol for LoRaWAN

LPWAN (Low-Power Wide Area Network) technologies such as LoRa and SigFox are emerging as a technology of choice for the Internet of Things (IoT) applications where tens of thousands of untethered devices are deployed over a wide area. In such operating environments, energy conservation is one of the most crucial concerns and network protocols adopt various power saving schemes to lengthen device lifetimes. For example, to avoid idle listening, LoRaWAN restricts downlink communications. However, the confined design philosophy impedes the deployment of IoT applications that require asynchronous downlink communications. In this paper, we design and implement an energy efficient downlink communication mechanism, named TRILO, for LoRaWAN. We aim to make TRILO be energy efficient while obeying an unavoidable trade-off that balances between latency and energy consumption. TRILO adopts a beacon mechanism that periodically alerts end-devices which have pending downlink frames. We implement the proposed protocol on top of commercially available LoRaWAN components and confirm that the protocol operates properly in real-world experiments. Experimental results show that TRILO successfully transmits downlink frames without losses while uplink traffic suffers from a slight increase in latency because uplink transmissions should halt during beacons and downlink transmissions. Computer simulation results also show that the proposed scheme is more energy efficient than the legacy LoRaWAN downlink protocol.
Cmah-dystrophin deficient mdx mice display an accelerated cardiac phenotype that is improved following peptide-PMO exon skipping treatment

Abstract Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin protein, leading to progressive muscle weakness and premature death due to respiratory and/or cardiac complications. Cardiac involvement is characterized by progressive dilated cardiomyopathy, decreased fractional shortening and metabolic dysfunction involving reduced metabolism of fatty acids—the major cardiac metabolic substrate. Several mouse models have been developed to study molecular and pathological consequences of dystrophin deficiency, but do not recapitulate all aspects of human disease pathology and exhibit a mild cardiac phenotype. Here we demonstrate that Cmah (cytidine monophosphate‐sialic acid hydroxylase)‐deficient mdx mice (Cmah−/−;mdx) have an accelerated cardiac phenotype compared to the established mdx model. Cmah−/−;mdx mice display earlier functional deterioration, specifically a reduction in right ventricle (RV) ejection fraction and stroke volume (SV) at 12 weeks of age and decreased left ventricle diastolic volume with subsequent reduced SV compared to mdx mice by 24 weeks. They further show earlier elevation of cardiac damage markers for fibrosis (Ctgf), oxidative damage (Nox4) and haemodynamic load (Nppa). Cardiac metabolic substrate requirement was assessed using hyperpolarized magnetic resonance spectroscopy indicating increased in vivo glycolytic flux in Cmah−/−;mdx mice. Early upregulation of mitochondrial genes (Ucp3 and Cpt1) and downregulation of key glycolytic genes (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabolism and shift towards glucose utilization in Cmah−/−;mdx mice. Moreover, we show long‐term treatment with peptide‐conjugated exon skipping antisense oligonucleotides (20‐week regimen), resulted in 20% cardiac dystrophin protein restoration and significantly improved RV cardiac function. Therefore, Cmah−/−;mdx mice represent an appropriate model for evaluating cardiac benefit of novel DMD therapeutics.
The acute effect of training fire exercises on fire service instructors

Abstract Fire service instructors (FSI) regularly experience different types of fire exercises, however the strain experienced from these scenarios is not well understood. This study aims to identify the physiological and perceptual strain of Fire Service Instructors (FSI) to three training exercises: DEMO, ATTACK, COMPARTMENT, and the different roles performed: SETTER, INSTRUCTOR. The study also aims to assess the effect that different exercise patterns over a day (BOX, MULTI, COMBINATION) have on immunological responses. Sixteen FSI (age: 41 ± 8 years, body mass: 83.7 ± 6.7 kg, height: 177.0 ± 6.7 cm) were recruited, with 10 FSI completing the three exercises. Physiological and perceptual measures were collected prior to and immediately post each exercise. Venous blood samples were collected at the beginning and end of each day. One-way analysis of variance (ANOVA) were conducted to assess differences in physiological variables between exercise types, independent samples t-tests were conducted between roles. Day changes in hematological variables were assessed by paired sample t-tests and analyzed by one-way ANOVAs to identify differences between exercise patterns. The COMPARTMENT exercise resulted in a greater change in rectal temperature (ΔTre) (0.49 ± 0.28 °C) than both the DEMO (0.23 ± 0.19 °C, p = 0.045) and ATTACK (0.27 ± 0.22 °C, p = 0.016). Within the COMPARTMENT exercise, the SETTER resulted in a greater ΔTre and rating of perceived exertion than the INSTRUCTOR (0.67 ± 0.29 °C vs. 0.43 ± 0.18 °C, p = 0.027 and 14 ± 2 vs. 11 ± 2, p = 0.001, respectively). Following a day of fire exercises white blood cells (WBC), neutrophils, lymphocytes (LYMPH), monocytes (MONO), platelets (PLT), mean platelet volume (MPV), Interleukin (IL)-6, and cardiac troponin T (cTnT) all increased (p < 0.05). Exercise patterns containing a COMPARTMENT exercise resulted in greater PLT, MPV, and IL-6. Total daily variation in ΔTre was correlated with post-exercise WBC, MONO, and LYMPH. COMPARTMENT exercises produce the greatest physiological strain, with the SETTER role within this exercise causing the greatest ΔTre. Although predominately physiological responses remain within safe limits. Exercise patterns that include a COMPARTMENT exercise also generate a greater inflammatory response.
GRIN2D variants in three cases of developmental and epileptic encephalopathy

N‐methyl‐d‐aspartate (NMDA) receptors are glutamate‐activated ion channels that are widely distributed in the central nervous system and essential for brain development and function. Dysfunction of NMDA receptors has been associated with various neurodevelopmental disorders. Recently, a de novo recurrent GRIN2D missense variant was found in two unrelated patients with developmental and epileptic encephalopathy. In this study, we identified by whole exome sequencing novel heterozygous GRIN2D missense variants in three unrelated patients with severe developmental delay and intractable epilepsy. All altered residues were highly conserved across vertebrates and among the four GluN2 subunits. Structural consideration indicated that all three variants are probably to impair GluN2D function, either by affecting intersubunit interaction or altering channel gating activity. We assessed the clinical features of our three cases and compared them to those of the two previously reported GRIN2D variant cases, and found that they all show similar clinical features. This study provides further evidence of GRIN2D variants being causal for epilepsy. Genetic diagnosis for GluN2‐related disorders may be clinically useful when considering drug therapy targeting NMDA receptors.
Medium‐chain glycerides affect gut morphology, immune‐ and goblet cells in post‐weaning piglets: In vitro fatty acid screening with Escherichia coli and in vivo consolidation with LPS challenge

The influence of medium-chain glycerides on performance and gastrointestinal well-being in weaning piglets was assessed. First, caproic (C6), caprylic (C8) and capric (C10) acid activity against Escherichia coli was screened in vitro. Pig flora of the whole small intestine was used as inoculum. Seven in vitro incubations were done in duplicate at pH = 3 and 5: C10 (15 mM), C8 (12 mM), C6 (15, 12, 10 mM), a non-incubated-negative control and incubated negative control. Culture suspensions were plated on E. coli-selective agar. Controls showed bacterial growth. C6 and C8 showed no growth at both pH-values, where C10 showed growth at pH = 5. Secondly, an in vivo study was done with 80 weaned piglets over 42 days, housed in pens of eight animals (five pens/treatment), fed a basal diet containing broken rice/soya bean meal/fish meal and supplemented with C6 and C8 in medium-chain glyceride form (MCT6/8, 0.175%) or antibiotic growth promoter (AGP, 0.020%) (Kasetsart University, Thailand) serving as control. Feed intake, daily gain and feed-to-gain ratio did not differ between MCT6/8 and AGP. Per replicate, two random selected piglets were challenged intravenously with E. coli-lipopolysaccharide (LPS) or saline solution (S) at Days 21 and 28. All challenged animals were sacrificed; blood and digestive tract samples (jejunum/ileum) were collected at Day 35. LPS challenge consistently reduced villus height and crypt depth for MCT6/8 and AGP. However, LPS-challenged piglets supplemented with MCT6/8 restored villus height, where AGP did not. MCT6/8 piglets had higher serum IgA, more jejunal IgA-positive plasma cells and goblet cells than AGP. At the ileal level, results were similar, though less pronounced. The present study offers new insight in the benefits of MCT6/8 over AGP in the post-weaning period. There is in vitro anti-microbial action of C6 and C8 on E. coli. In vivo, MCT6/8 also has protective effects in the small intestine that may result in growth promotion.
Drug-Coated Balloon Treatment of Femoropopliteal Lesions Typically Excluded From Clinical Trials: 12-Month Findings From the IN.PACT Global Study

Purpose: To report a post hoc analysis comparing outcomes between subjects who would have been included in the IN.PACT SFA randomized controlled trial vs those who would have been excluded. Methods: The 1406 subjects enrolled in the IN.PACT Global Study (ClinicalTrials.gov identifier NCT01609296) were retrospectively assigned to a standard-use group (n=281) based on the inclusion and exclusion criteria from the randomized IN.PACT SFA trial; the remaining 1125 patients were assigned to the broader-use group. Freedom from clinically-driven target lesion revascularization (CD-TLR) was evaluated at 12 months. The composite primary safety endpoint was freedom from 30-day device- and procedure-related death plus freedom from 12-month target limb major amputation and clinically-driven target vessel revascularization (CD-TVR). Functional outcomes were evaluated with dedicated questionnaires. Results: Compared with the standard-use cohort, the broader-use lesions were longer, more calcified, and had more popliteal involvement, bilateral disease, and in-stent restenosis (p<0.001 for all). Freedom from 12-month CD-TLR by Kaplan-Meier analysis was 96.6% for the standard-use group and 91.6% for the broader-use group (p=0.005). The safety endpoint was 96.2% in the standard-use group and 91.0% in the broader-use group (p=0.003). The 12-month CD-TLR (3.4% standard-use vs 8.5% broader-use, p=0.004) and CD-TVR (4.2% standard-use vs 9.1% broader-use, p=0.008) were increased in the broader-use group. Twelve-month all-cause mortality was not increased (3.8% standard-use vs 3.4% broader-use, p=0.852). Conclusion: Post hoc analysis of the IN.PACT Global Study of real-world patients demonstrated consistent outcomes with significant clinical improvement to 12 months in subjects with complex lesions typically excluded from a randomized controlled trial.