Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer

Purpose: This single-arm, open-label phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer. Patients and Methods: Patients received 6-mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for PIK3CA mutations. Adverse events (AE) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1. Results: Median treatment duration was 4.6 (range: 0.9–40.5) months. All patients experienced ≥1 AE, 30 (50.0%) had grade ≥3 AEs, and 19 (31.7%) experienced 35 serious AEs. Forty-seven of 60 patients had evaluable tissue for central PIK3CA mutation testing [20 had mutations, 27 had no mutation detected (MND)]. In patients with baseline measurable disease, clinical activity was observed in tumors with PIK3CA mutations [best confirmed response rate: 38.5% (5/13; 95% CI, 13.9–68.4); clinical benefit rate (CBR): 38.5% (5/13; 95% CI, 13.9–68.4)], PIK3CA-MND [best confirmed response rate: 14.3% (3/21; 95% CI, 3.0–36.3); CBR: 23.8% (5/21; 95% CI, 8.2–47.2)], and unknown PIK3CA mutation status [best confirmed response rate: 20.0% (2/10; 95% CI, 2.5–55.6); CBR: 30.0% (3/10; 95% CI, 6.7–65.2)]. Conclusions: Taselisib plus fulvestrant had clinical activity irrespective of PIK3CA mutation status, with numerically higher objective response rate and CBR in patients with PIK3CA-mutated (vs. -MND) locally advanced or metastatic HER2-negative, HR-positive breast cancer. No new safety signals were reported. A confirmatory phase III trial is ongoing. Clin Cancer Res; 24(18); 4380–7. ©2018 AACR.
A Central Role for Heme Oxygenase-1 in the Control of Intestinal Epithelial Chemokine Expression

In mucosal inflammatory disorders, the protective influence of heme oxygenase-1 (HO-1) and its metabolic byproducts, carbon monoxide (CO) and biliverdin, is a topic of significant interest. Mechanisms under investigation include the regulation of macrophage function and mucosal cytokine expression. While there is an increasing recognition of the importance of epithelial-derived factors in the maintenance of intestinal mucosal homeostasis, the contribution of intestinal epithelial cell (IEC) HO-1 on inflammatory responses has not previously been investigated. We examined the influence of modulating HO-1 expression on the inflammatory response of human IECs. Engineered deficiency of HO-1 in Caco-2 and T84 IECs led to increased proinflammatory chemokine expression in response to pathogenic bacteria and inflammatory cytokine stimulation. Crosstalk with activated leukocytes also led to increased chemokine expression in HO-1-deficient cells in an IL-1β dependent manner. Treatment of Caco-2 cells with a pharmacological inducer of HO-1 led to the inhibition of chemokine expression. Mechanistic studies suggest that HO-1 and HO-1-related transcription factors, but not HO-1 metabolic products, are partly responsible for the influence of HO-1 on chemokine expression. In conclusion, our data identify HO-1 as a central regulator of IEC chemokine expression that may contribute to homeostasis in the intestinal mucosa.
Fructo-Oligosaccharide (DFA III) Feed Supplementation for Mitigation of Mycotoxin Exposure in Cattle—Clinical Evaluation by a Urinary Zearalenone Monitoring System

The potential effect of difructose anhydride III (DFA III) supplementation in cattle feed was evaluated using a previously developed urinary-zearalenone (ZEN) monitoring system. Japanese Black cattle from two beef herds aged 9–10 months were used. DFA III was supplemented for two weeks. ZEN concentrations in feed were similar in both herds (0.27 and 0.22 mg/kg in roughage and concentrates, respectively), and below the maximum allowance in Japan. ZEN, α-zearalenol (α-ZOL), and β-ZOL concentrations in urine were measured using LC/MS/MS the day before DFA III administration, 9 and 14 days thereafter, and 9 days after supplementation ceased. Significant differences in ZEN, α-ZOL, β-ZOL, and total ZEN were recorded on different sampling dates. The concentration of inorganic phosphate in DFA III-supplemented animals was significantly higher than in controls on day 23 (8.4 vs. 7.7 mg/dL), suggesting a possible role of DFA III in tight junction of intestinal epithelial cells. This is the first evidence that DFA III reduces mycotoxin levels reaching the systemic circulation and excreted in urine. This preventive effect may involve an improved tight-junction-dependent intestinal barrier function. Additionally, our practical approach confirmed that monitoring of urinary mycotoxin is useful for evaluating the effects of dietary supplements to prevent mycotoxin adsorption.
Worldwide Prevalence of Brugada Syndrome: A Systematic Review and Meta-Analysis.

Background Brugada syndrome (BrS) is considered to be an inherited arrhythmic disease associated with fatal complications and premature sudden unexpected death. The prevalence of the Brugada electrocardiogram pattern (BrP) has been reported in several countries. Nonetheless, the specific worldwide prevalence of BrS has not been reported. Objective We estimated the worldwide prevalence of BrS and Type-2/3 BrP in general adult populations using a systematic review and meta-analysis of the existing literature. Methods We thoroughly searched MEDLINE and SCOPUS databases up to March 2017. Included studies were population-based electrocardiogram studies in which prevalence was presented or could be calculated from available data. Pooled prevalence by country/region and/or ethnicity was estimated using a random-effect model. Results Twenty-eight articles with atotal population of 369,068 were included in this study. The worldwide pooled prevalence of BrS was 0.5 per 1,000 [95% confidence interval (CI): 0.3-0.7]. The highest prevalence was reported in Southeast Asia (1.8 per 1,000, 95% CI: 0.5-6.6); the lowest was found in North Africa (0 per 1,000). BrS in Asians was nine times more common than in Caucasians and 36 times more common than in Hispanics. The worldwide pooled prevalence of Type-2/3 BrP was 6.1 per 1,000 (95% CI: 5.0-7.1). The highest prevalence was also reported in Southeast Asia (35.5 per 1,000, 95% CI: 17.1-53.9). Conclusions This study revealed a significant difference in the worldwide prevalence of BrS and Type-2/3 BrP. Brugada electrocardiogram patterns are highly prevalent in Southeast Asia.
Performance comparison between Hadoop and Spark frameworks using HiBench benchmarks

Big Data has become one of the major areas of research for cloud service providers due to a large amount of data produced every day and the inefficiency of traditional algorithms and technologies to handle these large amounts of data. Big Data with its characteristics such as volume, variety, and veracity (3V) requires efficient technologies to process in real time. To solve this problem and to process and analyze this vast amount of data, there are many powerful tools like Hadoop and Spark, which are mainly used in the context of Big Data. They work following the principles of parallel computing. The challenge is to specify which Big Data's tool is better depending on the processing context. In this paper, we present and discuss a performance comparison between two popular Big Data frameworks deployed on virtual machines. Hadoop MapReduce and Apache Spark are used to efficiently process a vast amount of data in parallel and distributed mode on large clusters, and both of them suit for Big Data processing. We also present the execution results of Apache Hadoop in Amazon EC2, a major cloud computing environment. To compare the performance of these two frameworks, we use HiBench benchmark suite, which is an experimental approach for measuring the effectiveness of any computer system. The comparison is made based on three criteria: execution time, throughput, and speedup. We test Wordcount workload with different data sizes for more accurate results. Our experimental results show that the performance of these frameworks varies significantly based on the use case implementation. Furthermore, from our results we draw the conclusion that Spark is more efficient than Hadoop to deal with a large amount of data in major cases. However, Spark requires higher memory allocation, since it loads the data to be processed into memory and keeps them in caches for a while, just like standard databases. So the choice depends on performance level and memory constraints.
A Materials Roadmap to Functional Neural Interface Design

Advancements in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, and optogenetics are revolutionizing scientific understanding of the brain while enabling treatments and preventative measures for a variety of neurological disorders. The grand challenge in neural interface engineering is to seamlessly integrate the interface between neurobiology and engineered technology to record from and modulate neurons over chronic timescales. However, the biological inflammatory response to implants, neural degeneration, and long‐term material stability diminishes the quality of the interface overtime. Recent advances in functional materials are aimed at engineering solutions for chronic neural interfaces, yet, the development and deployment of neural interfaces designed from novel materials have introduced new challenges that have been largely unaddressed. Many engineering efforts that solely focus on optimizing individual probe design parameters, such as softness or flexibility, downplay critical multidimensional interactions between different physical properties of the device that contribute to overall performance and biocompatibility. Moreover, the use of these new materials present substantial new difficulties that must be addressed before regulatory approval for use in human patients is achievable. In this review, the interdependence of different electrode components is highlighted to demonstrate the current material‐based challenges facing the field of neural interface engineering.
Enhancing the usability of low-cost eye trackers for rehabilitation applications

Eye tracking is one of the most widely used technique for assessment, screening and human-machine interaction related applications. There are certain issues which limit the usage of eye trackers in practical scenarios, viz., i) need to perform multiple calibrations and ii) presence of inherent noise in the recorded data. To address these issues, we have proposed a protocol for one-time calibration against the “regular” or the “multiple” calibration phases. It is seen that though it is always desirable to perform multiple calibration, the one-time calibration also produces comparable results and might be better for individuals who are not able to perform multiple calibrations. In that case, “One-time calibration” can also be done by a participant and the calibration results are used for the rest of the participants, provided the chin rest and the eye tracker positions are unaltered. The second major issue is the presence of the inherent noise in the raw gaze data, leading to systematic and variable errors. We have proposed a signal processing chain to remove these two types of errors. Two different psychological stimuli-based tasks, namely, recall-recognition test and number gazing task are used as a case study for the same. It is seen that the proposed approach gives satisfactory results even with one-time calibration. The study is also extended to test the effect of long duration task on the performance of the proposed algorithm and the results confirm that the proposed methods work well in such scenarios too.
Integrating artificial intelligence with real-time intracranial EEG monitoring to automate interictal identification of seizure onset zones in focal epilepsy

Objective. An ability to map seizure-generating brain tissue, i.e. the seizure onset zone (SOZ), without recording actual seizures could reduce the duration of invasive EEG monitoring for patients with drug-resistant epilepsy. A widely-adopted practice in the literature is to compare the incidence (events/time) of putative pathological electrophysiological biomarkers associated with epileptic brain tissue with the SOZ determined from spontaneous seizures recorded with intracranial EEG, primarily using a single biomarker. Clinical translation of the previous efforts suffers from their inability to generalize across multiple patients because of (a) the inter-patient variability and (b) the temporal variability in the epileptogenic activity. Approach. Here, we report an artificial intelligence-based approach for combining multiple interictal electrophysiological biomarkers and their temporal characteristics as a way of accounting for the above barriers and show that it can reliably identify seizure onset zones in a study cohort of 82 patients who underwent evaluation for drug-resistant epilepsy. Main results. Our investigation provides evidence that utilizing the complementary information provided by multiple electrophysiological biomarkers and their temporal characteristics can significantly improve the localization potential compared to previously published single-biomarker incidence-based approaches, resulting in an average area under ROC curve (AUC) value of 0.73 in a cohort of 82 patients. Our results also suggest that recording durations between 90 min and 2 h are sufficient to localize SOZs with accuracies that may prove clinically relevant. Significance. The successful validation of our approach on a large cohort of 82 patients warrants future investigation on the feasibility of utilizing intra-operative EEG monitoring and artificial intelligence to localize epileptogenic brain tissue. Broadly, our study demonstrates the use of artificial intelligence coupled with careful feature engineering in augmenting clinical decision making.
CD44 and ALDH1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma

BACKGROUND Tumour metastasis has been associated with cancer stem cells, a small population with stem-like cells properties, higher rate of migration and metastatic potential compared to cells from the tumour bulk. Our aim was to evaluate the immunoexpression of the putative cancer stem cell biomarkers ALDH1 and CD44 in primary tumour and corresponding metastatic lymph nodes. METHODS Tumour tissue specimens (n = 50) and corresponding metastatic lymph nodes (n = 25) were surgically obtained from 50 patients with oral squamous cell carcinoma and submitted to immunohistochemistry. CD44 and ALDH1 were semi-quantitatively scored according to the proportion and intensity of positive cells within the invasive front and metastatic lymph nodes as a whole. A combined score was obtained by multiplying both parameters and later dichotomized into a final score classified as low (≤2) or high (>2) immunoexpression. RESULTS ALDH1 immunoexpression and CD44 immunoexpression were detected in both tumour sites, although the means of ALDH1 (P = .0985) and CD44 (P = .4220) cells were higher in metastasis compared to primary tumours. ALDH1high was positively associated (P = .0184) with angiolymphatic invasion, while CD44high was positively associated (P = .0181) with metastasis (N+). At multivariate analysis, CD44 significantly increased the odds of lymph node metastasis, regardless of T stage (OR = 8.24; 1.64-65.64, P = .0088). CONCLUSIONS CD44 immunoexpression was a significant predictor of lymph node metastasis, while ALDH1high immunostaining was associated with angiolymphatic invasion. Altogether, it suggests that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with oral squamous cell carcinoma invasion and metastasis.
NSC 95397 Suppresses Proliferation and Induces Apoptosis in Colon Cancer Cells through MKP-1 and the ERK1/2 Pathway

NSC 95397, a quinone-based small molecule compound, has been identified as an inhibitor for dual-specificity phosphatases, including mitogen-activated protein kinase phosphatase-1 (MKP-1). MKP-1 is known to inactivate mitogen-activated protein kinases by dephosphorylating both of their threonine and tyrosine residues. Moreover, owing to their participation in tumorigenesis and drug resistance in colon cancer cells, MKP-1 is an attractive therapeutic target for colon cancer treatment. We therefore investigated the inhibitory activity of NSC 95397 against three colon cancer cell lines including SW480, SW620, and DLD-1, and their underlying mechanisms. The results demonstrated that NSC 95397 reduced cell viability and anchorage-independent growth of all the three colon cancer cell lines through inhibited proliferation and induced apoptosis via regulating cell-cycle-related proteins, including p21, cyclin-dependent kinases, and caspases. Besides, by using mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126, we provided mechanistic evidence that the antineoplastic effects of NSC 95397 were achieved via inhibiting MKP-1 activity followed by ERK1/2 phosphorylation. Conclusively, our results indicated that NSC 95397 might serve as an effective therapeutic intervention for colon cancer through regulating MKP-1 and ERK1/2 pathway.
A values‐driven self‐organization mechanism for automating multiagent coordination

In distributed and open environments, MASs (multiagent systems) generally have no mechanisms for prior coordination and self‐organization has been believed to be the necessary selection to achieve the coordination of agents. This paper first presents a values‐driven model for self‐organization in which the expected emergent properties of a system are specified as the social values while the social values are realized via implicitly inducing members to regulate their individual values and adjust their behaviors to fit the expectations of the system. Based on the values‐driven self‐organization, this paper proposes an automated coordination mechanism for decentralized MASs. In this mechanism, by indirectly changing the difficulties in acquiring resources (which may be delegated to some special agents since MASs generally do not have substantial bodies), MASs can lead agents to regulate their values to be consistent with the social values of MASs so that the coordination of MASs can spontaneously emerge from the local behaviors of agents. Finally, this paper implements a simulation traffic system using the coordination mechanism based on values‐driven self‐organization to validate the emergence of coordination among multiple agents.
The Development of Peptide-based Antimicrobial Agents against Dengue Virus

Dengue fever has become an imminent threat to international public health because of global warming and climate change. The World Health Organization proclaimed that more than 50% of the world’s population is at risk of dengue virus (DENV) infection. Therefore, developing a clinically ap-proved vaccine and effective therapeutic remedy for treating dengue fever is imperative. Peptide drug de-velopment has become a novel pharmaceutical research field. This article reviews various peptides-based antimicrobial agents targeting three pathways involved in the DENV lifecycle. Specifically, they are peptide vaccines from immunomodulation, peptide drugs that inhibit virus entry, and peptide drugs that interfere with viral replication. Many antiviral peptide studies against DENV have been conducted in animal model trials, and progression to clinical trials for these promising peptide drugs is anticipated.
Sleep Disorders and Attention Deficit: A Consequence of Proinflammatory State?

Journal of Clinical Sleep Medicine, Vol. 14, No. 6 June 15, 2018 Attention-deficit hyperactivity disorder (ADHD) is common neuropsychiatric disorder in children and adults. Sleep disorders and restless legs are related to the presence of ADHD. Wynchank et al.1 have recently reported in the Journal of Clinical Sleep Medicine the results of a large survey of adults. The authors found that within the group with clinically relevant ADHD symptoms, 43% reported significant insomnia symptoms and 41% reported short sleep duration. A consensus group recently implicated arousal dysregulation in the pathological mechanism of attention in ADHD.2 In this context, this letter is a plea to investigators in this journal to evaluate the association between enhanced lowgrade inflammation, sleep disorders, and ADHD. This mechanism has been proposed by the investigators of the Turkish Adult Risk Factor (TARF) study to underlie diverse chronic diseases,3 including type 2 diabetes, coronary heart disease, chronic kidney disease, and rheumatic diseases. It postulates that in individuals with proinflammatory state due to obesity or circulating excess oxidized phospholipid content of lipoprotein [Lp](a),4 protective plasma proteins such as adiponectin5 become converted to an inflammatory protein, with concomitant slower clearance of the protein from plasma. Some support for this notion having a potential relevance for ADHD may be derived from Li et al.’s study that reported nondiabetic men with restless legs syndrome (RLS) have a higher risk of early death.6 Li et al. emphasized that the elevated mortality risk was not associated with the usual known risk factors but rather with endocrine, nutritional/metabolic, and immunological disorders. RLS may be another manifestation of the basic process of enhanced proinflammatory state and autoimmune activation. The TARF cohort revealed that metabolic syndrome, a constellation of proinflammatory state, was associated significantly with obstructive sleep apnea in nondiabetic individuals.7 In summary, we believe that investigations directed to proinflammatory state may be fruitful to identify mechanisms underlying sleep disorders and ADHD. LETTERS TO THE EDITOR
Ovarian folliculogenesis in the oviparous Mexican lizard Ctenosaura pectinata

The ovarian follicles of Ctenosaura pectinata exhibit a clear seasonal cycle in morphology. Early in development, each oocyte is surrounded by a granulosa composed of a single layer of cuboidal or squamous cells and thin thecal layers. As folliculogenesis progresses, the granulosa becomes multilayered and composed of three distinct cell types. After vitellogenesis begins and active sequestration of yolk into the ooplasm is initiated, the granulosa is reduced to a single cell type. We observed a striking change in the appearance of the ooplasm during folliculogenesis. Early ovarian development is characterized by an ooplasm with homogeneously distributed fine fibrils, but as development progresses, the ooplasm contains dense clumps of fibers aggregated into distinctive bundles. The ooplasm displays further complexity in morphology as previtellogenic growth continues and as different regions exhibit various combinations of fibers and vacuoles. Yolk platelet formation is complex, with distinctive stages generating platelets with varying morphologies. © 1996 Wiley‐Liss, Inc.
La relation innovation-emploi dans les services: un bilan et un agenda de recherche

Cet article est consacre a la difficile question de la relation entre l'innovation et l'emploi dans les services. Il propose une relecture, a la lumiere de la question de l'emploi, des travaux consacres a l'innovation dans les services. Il s'agit d'evaluer dans quelle mesure et sous quelle forme cette question y est implicitement ou explicitement presente ou merite d'y etre introduite. Ce projet constitue a la fois un bilan de la litterature nationale et internationale et un agenda de recherche. On explorera ainsi successivement les deux themes suivants : 1) les approches technologistes et la question de l'emploi ; 2) la question de l'emploi dans les approches servicielles.