Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneity in Cancer Metabolism: New Concepts in an Old Field

Abstract Significance: In the last years, metabolic reprogramming, fluctuations in bioenergetic fuels, and modulation of oxidative stress became new key hallmarks of tumor development. In cancer, elevated glucose uptake and high glycolytic rate, as a source of adenosine triphosphate, constitute a growth advantage for tumors. This represents the universally known Warburg effect, which gave rise to one major clinical application for detecting cancer cells using glucose analogs: the positron emission tomography scan imaging. Recent Advances: Glucose utilization and carbon sources in tumors are much more heterogeneous than initially thought. Indeed, new studies emerged and revealed a dual capacity of tumor cells for glycolytic and oxidative phosphorylation (OXPHOS) metabolism. OXPHOS metabolism, which relies predominantly on mitochondrial respiration, exhibits fine-tuned regulation of respiratory chain complexes and enhanced antioxidant response or detoxification capacity. Critical Issues: OXPHOS-dependent cancer cells use alternative oxidizable substrates, such as glutamine and fatty acids. The diversity of carbon substrates fueling neoplastic cells is indicative of metabolic heterogeneity, even within tumors sharing the same clinical diagnosis. Metabolic switch supports cancer cell stemness and their bioenergy-consuming functions, such as proliferation, survival, migration, and invasion. Moreover, reactive oxygen species-induced mitochondrial metabolism and nutrient availability are important for interaction with tumor microenvironment components. Carcinoma-associated fibroblasts and immune cells participate in the metabolic interplay with neoplastic cells. They collectively adapt in a dynamic manner to the metabolic needs of cancer cells, thus participating in tumorigenesis and resistance to treatments. Future Directions: Characterizing the reciprocal metabolic interplay between stromal, immune, and neoplastic cells will provide a better understanding of treatment resistance. Antioxid. Redox Signal. 26, 462–485.
Prediction of fluoroscopic angulations for transcatheter aortic valve implantation by CT angiography: influence on procedural parameters

Aims Repeated angiograms to achieve an exactly orthogonal visualization of the aortic valve plane can substantially contribute to the total contrast amount required for transcatheter aortic valve implantation (TAVI). We investigated whether pre-procedural identification of an optimal fluoroscopic projection by cardiac computed tomography (CT) can significantly reduce the amount of a procedure-related contrast agent compared with angiographic determination of suitable angulations. Methods and results Eighty consecutive patients (81 ± 5 years, 55% male) with symptomatic severe aortic valve stenosis and normal renal function who underwent cardiac CT prior to TAVI were prospectively randomized. In 40 patients, a CT-predicted suitable angulation was used for the first aortic angiogram (CT cohort); in the other 40 patients, the first aortogram was acquired at LAO 10°/cranial 10 (angiography cohort). Additional aortograms were performed if no satisfactory view of the aortic valve plane was obtained. The number of aortograms needed to achieve a satisfactory fluoroscopic projection (1.2 ± 0.6 vs. 3.2 ± 1.7; P < 0.001) and the total amount of contrast agent per TAVI procedure were significantly lower in the CT cohort (95 ± 21 vs. 125 ± 36 mL; P < 0.001). Incidence of acute kidney injury was not significantly different. There was no significant difference regarding radiation dose, time of procedure, degree of post-procedural aortic regurgitation, complications and 30-day mortality between the cohorts. Conclusion Pre-procedural identification of a suitable fluoroscopic projection by cardiac CT significantly reduces a procedural contrast agent volume required for TAVI.
cAMPr: A single-wavelength fluorescent sensor for cyclic AMP

A genetically encoded sensor of cAMP enables detection of this second messenger in live cells and tissues. Live-cell imaging of cAMP The second messenger cAMP is found in many cell types and organisms. Increases in the cytosolic concentration and localization of cAMP mediate various cellular functions through the activation of the kinase PKA and the transcription factor CREB; thus, the ability to detect and image cAMP in live cells would help to understand its mechanism of action. Hackley et al. developed a genetically encoded fluorescent sensor of cAMP (cAMPr), which was expressed in mammalian neurons and in the Drosophila brain and responded to stimulation of adenylyl cyclase, the enzyme that generates cAMP. Furthermore, cAMPr was used together with a fluorescent Ca2+ sensor to simultaneously detect cAMP and Ca2+ in the Drosophila brain through two-photon imaging, suggesting its potential use to study cAMP signaling in diverse tissues and organisms. Genetically encoded fluorescent sensors enable cell-specific measurements of ions and small molecules in real time. Cyclic adenosine monophosphate (cAMP) is one of the most important signaling molecules in virtually all cell types and organisms. We describe cAMPr, a new single-wavelength cAMP sensor. We developed cAMPr in bacteria and embryonic stem cells and validated the sensor in mammalian neurons in vitro and in Drosophila circadian pacemaker neurons in intact brains. Comparison with other single-wavelength cAMP sensors showed that cAMPr improved the quantitative detection of cAMP abundance. In addition, cAMPr is compatible with both single-photon and two-photon imaging. This enabled us to use cAMPr together with the red fluorescent Ca2+ sensor RCaMP1h to simultaneously monitor Ca2+ and cAMP in Drosophila brains. Thus, cAMPr is a new and versatile genetically encoded cAMP sensor.
Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis

Abstract The association of interleukin-6 (IL-6)-174G > C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G > C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G > C SNP with increased RA risk: allelic (OR = 3.750, 95% CI = 1.800–7.813, p < 0.001); dominant (OR = 2.800, 95% CI = 1.167–6.721, p = 0.021); and recessive (OR = 36.72, 95% CI = 2.004–672.7, p = 0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G > C SNP in overall population: allelic (OR = 1.650, 95% CI = 1.169–2.329, p = 0.004); homozygous (OR = 1.380, 95% CI = 0.906–2.101, p = 0.133); heterozygous (OR = 1.559, 95% CI = 1.001–2.428, p = 0.049); dominant (OR = 1.663, 95% CI = 1.078–2.567, p = 0.022); and recessive (OR = 1.366, 95% CI = 0.964–1.935, p = 0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR = 3.724, 95% CI = 1.361–10.190, p = 0.010); dominant (OR = 3.823, 95% CI = 1.320–11.074, p = 0.013); and recessive (OR = 4.357, 95% CI = 1.634–11.623, p = 0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G > C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.
In vivo anti-ulcerogenic effect of okra (Abelmoschus esculentus) on ethanol-induced acute gastric mucosal lesions

Abstract Context: Okra, Abelmoschus esculentus (L.) (Malvaceae), is a medicinal plant widely used in Turkish traditional medicine for the treatment of various diseases such as ulcers and gastritis. Objective: In the present study, we evaluated the gastroprotective effect of okra against ethanol-induced acute gastric mucosal injury in animal models. Materials and methods: Wistar rats were treated with 500, 250 or 100 mg/kg okra; 20 mg/kg famotidine (Fam); and 75 mg/kg quercetin (Que). Following a 60 min period, all the rats were given 1 mL of ethanol (80%). One hour after the administration of ethanol, all groups were sacrificed. Results: At 5000 mg/kg, the extract produced (okra) no signs of toxicity in animals. Okra 500, 250, 100, Fam 20 and Que 75 inhibited ulcer formation by 81.0, 67.5, 67.0, 76.3 and 72.4%, respectively. Okra 500 significantly decreased edema, hemorrhage and inflammation scores compared with the ethanol group (p < 0.05). The oxidant levels decreased significantly in the all study groups compared within ethanol group (p < 0.001). Serum β-carotene and retinol levels significantly increased 40.2 and 45.4% in the okra 500 group. In okra 500, 250 and Fam 20 groups, apoptosis significantly decreased (p < 0.001), while okra 500, 250 and Fam 20 groups showed a higher percentage of cell proliferation compared with the ethanol group (p < 0.001). Discussion and conclusions: Our in vivo data indicate that okra has a gastroprotective effect against ethanol and could reduce the gastric ulcer as seen from biochemical and histopathological results. We suggest that okra could be a possible therapeutic antiulcer agent.
Brazil: Self-Inflicted Pain

The Brazilian economy grew 7.5% in 2010, when Mr. Lula finished his second mandate as president with a popularity rate of 85%. Six years later, his successor, Ms. Rousseff, is suspended from the presidency under an impeachment trial, while the economy endures a recession of 3.8% of the GDP for the second consecutive year. In this article I argue that the current economic crisis is the result of ill-advised economic policies. Ms. Rousseff’s government altered each one of the tripod of policies implemented by Mr. Cardoso in the 1990s, which had been successful in maintaining macroeconomic stability (namely, the inflation targeting regime, the floating exchange rate and the fiscal austerity). Also, Ms. Rousseff’s government greatly expanded the improperly designed industrial policies that were reintroduced in Brazil during the second mandate of Mr. Lula, which created distortions in the economy and a large fiscal burden for the government. The acting president, Mr. Temer faces great difficulties to put the economy back in order, since unpopular measures are required that are very hard to be implemented in the midst of the current political turmoil.
Safe Medicine Recommendation via Medical Knowledge Graph Embedding

Most of the existing medicine recommendation systems that are mainly based on electronic medical records (EMRs) are significantly assisting doctors to make better clinical decisions benefiting both patients and caregivers. Even though the growth of EMRs is at a lighting fast speed in the era of big data, content limitations in EMRs restrain the existed recommendation systems to reflect relevant medical facts, such as drug-drug interactions. Many medical knowledge graphs that contain drug-related information, such as DrugBank, may give hope for the recommendation systems. However, the direct use of these knowledge graphs in the systems suffers from robustness caused by the incompleteness of the graphs. To address these challenges, we stand on recent advances in graph embedding learning techniques and propose a novel framework, called Safe Medicine Recommendation (SMR), in this paper. Specifically, SMR first constructs a high-quality heterogeneous graph by bridging EMRs (MIMIC-III) and medical knowledge graphs (ICD-9 ontology and DrugBank). Then, SMR jointly embeds diseases, medicines, patients, and their corresponding relations into a shared lower dimensional space. Finally, SMR uses the embeddings to decompose the medicine recommendation into a link prediction process while considering the patient's diagnoses and adverse drug reactions. To our best knowledge, SMR is the first to learn embeddings of a patient-disease-medicine graph for medicine recommendation in the world. Extensive experiments on real datasets are conducted to evaluate the effectiveness of proposed framework.
Toward sustainable publishing and querying of distributed Linked Data archives

Purpose The purpose of this paper is to detail a low-cost, low-maintenance publishing strategy aimed at unlocking the value of Linked Data collections held by libraries, archives and museums (LAMs). Design/methodology/approach The shortcomings of commonly used Linked Data publishing approaches are identified, and the current lack of substantial collections of Linked Data exposed by LAMs is considered. To improve on the discussed status quo, a novel approach for publishing Linked Data is proposed and demonstrated by means of an archive of DBpedia versions, which is queried in combination with other Linked Data sources. Findings The authors show that the approach makes publishing Linked Data archives easy and affordable, and supports distributed querying without causing untenable load on the Linked Data sources. Research limitations/implications The proposed approach significantly lowers the barrier for publishing, maintaining, and making Linked Data collections queryable. As such, it offers the potential to substantially grow the distributed network of queryable Linked Data sources. Because the approach supports querying without causing unacceptable load on the sources, the queryable interfaces are expected to be more reliable, allowing them to become integral building blocks of robust applications that leverage distributed Linked Data sources. Originality/value The novel publishing strategy significantly lowers the technical and financial barriers that LAMs face when attempting to publish Linked Data collections. The proposed approach yields Linked Data sources that can reliably be queried, paving the way for applications that leverage distributed Linked Data sources through federated querying.
BAFS: Bundle Adjustment With Feature Scale Constraints for Enhanced Estimation Accuracy

We propose to incorporate within bundle adjustment (BA) a new type of constraint that uses feature scale information, leveraging the scale invariance property of typical image feature detectors (e.g., SIFT). While feature scales play an important role in image matching, they have not been utilized thus far for estimation purposes in a BA framework. Our approach exploits the already-available feature scale information and uses it to enhance the accuracy of BA, especially along the optical axis of the camera in a monocular setup. Importantly, the mentioned feature scale constraints can be formulated on a frame to frame basis and do not require loop closures. We study our approach in synthetic environments and the real-imagery KITTI dataset, demonstrating significant improvement in positioning error.
Initial Results of a Safety and Feasibility Study of Auditory Brainstem Implantation in Congenitally Deaf Children.

OBJECTIVE To determine the safety and feasibility of the auditory brainstem implant (ABI) in congenitally deaf children with cochlear aplasia and/or cochlear nerve deficiency. STUDY DESIGN Phase I feasibility clinical trial of surgery in 10 children, ages 2 to 5 years, over a 3-year period. SETTING Tertiary children's hospital and university-based pediatric speech/language/hearing center. INTERVENTION(S) ABI implantation and postsurgical programming. MAIN OUTCOME MEASURE(S) The primary outcome measure is the number and type of adverse events during ABI surgery and postsurgical follow-up, including behavioral mapping of the device. The secondary outcome measure is access to and early integration of sound. RESULTS To date, nine children are enrolled. Five children have successfully undergone ABI surgery and postoperative behavioral programming. Three children were screen failures, and one child is currently undergoing candidacy evaluation. Expected adverse events have been documented in three of the five children who received the ABI. One child experienced a cerebral spinal fluid leak, which resolved with lumbar drainage. One child demonstrated vestibular side effects during device programming, which resolved by deactivating one electrode. One child experienced postoperative vomiting resulting in an abdominal radiograph. Four children have completed their 1-year follow-up and have speech detection thresholds of 30 to 35 dB HL. Scores on the IT-MAIS/MAIS range from 8 to 31 (out of a total of 40), and the children are demonstrating some ability to discriminate between closed-sets words that differ by number of syllables (pattern perception). CONCLUSION ABI surgery and device activation seem to be safe and feasible in this preliminary cohort.
Design for testability of high‐order OTA‐C filters

A study of oscillation‐based test for high‐order Operational Transconductance Amplifier‐C (OTA‐C) filters is presented. The method is based on partition of a high‐order filter into second‐order filter functions. The opening Q‐loop and adding positive feedback techniques are developed to convert the second‐order filter section into a quadrature oscillator. These techniques are based on an open‐loop configuration and an additional positive feedback configuration. Implementation of the two testability design methods for nth‐order cascade, IFLF and leapfrog (LF) filters is presented, and the area overhead of the modified circuits is also discussed. The performances of the presented techniques are investigated. Fourth‐order cascade, inverse follow‐the‐leader feedback (IFLF) and LF OTA‐C filters were designed and simulated for analysis of fault coverage using the adding positive feedback method based on an analogue multiplexer. Simulation results show that the oscillation‐based test method using positive feedback provides high fault coverage of around 97%, 96% and 95% for the cascade, IFLF and LF OTA‐C filters, respectively. Copyright © 2016 John Wiley & Sons, Ltd.
Psychological prognosis after newly diagnosed chronic conditions: socio-demographic and clinical correlates

ABSTRACT Background: This study was aimed toward discerning depressive symptom trajectories associated with different chronic conditions and toward finding modifiable factors associated with those trajectories. Methods: Data were drawn from the 1996–2007 Taiwan Longitudinal Study on Aging. Nine chronic conditions were selected, and mood trajectories were measured with the Center of Epidemiological Studies-Depression scale. Results: Among the nine chronic conditions we examined, four patterns of depressive symptom trajectories were identified: (1) elevated depressive symptoms and worsened over time after diagnosed with heart disease (n = 681), arthritis (n = 850), or hypertension (n = 1,207); (2) elevated depressive symptoms without worsening over time after diagnosed with stroke (n = 160), lung diseases (n = 432), gastric conditions (n = 691), or liver diseases (n = 234); (3) no elevated depressive symptoms after diagnosis but an increase in depressive symptoms over time for participants with diabetes (n = 499); and (4) no significant patterns after diagnosed with cancer (n = 57). Cumulative psychological burden over time was significant for participants with hypertension, diabetes, heart diseases, or arthritis. However, these effects disappeared after controlling for comorbidities and physical limitations. Moreover, psychiatric condition was found to play an important role in baseline depressive symptoms among participants diagnosed with lung diseases, arthritis, or liver diseases. Conclusions: Findings from this study provide information in addressing psychological burden at different times for different conditions. In addition, minimizing the incidence of comorbidities, physical limitations, or psychiatric conditions may have the prospective effect of avoiding the trend of increased depressive symptoms, especially when adults diagnosed with hypertension, diabetes, heart diseases, arthritis, lung diseases, arthritis, or liver diseases.
Mutational analysis of KRAS and its clinical implications in cervical cancer patients

Objective The predictive and prognostic role of KRAS mutations in cervical cancer remains inconclusive. The aim of this study was to explore the clinicopathological and prognostic relevance of KRAS mutations in invasive cervical cancers (ICC). Methods Reverse transcription polymerase chain reaction (PCR) and Sanger sequencing were employed to detect KRAS mutations in 876 ICC patients. Quantitative real-time PCR was used to detect human papillomavirus (HPV) 16 and HPV 18. Results Non-synonymous mutations of KRAS were identified in 30 (3.4%) patients. These mutations were more common in non-squamous cell carcinoma than in squamous cell carcinoma (SCC) (8.2% vs. 2.2%, respectively, p<0.001) and were associated with HPV 18 infection (p=0.003). The prevalence of mutations was highest (18.2%) in the uncommon histological subtypes followed by adenocarcinoma (AC, 7.3%) and adenosquamous carcinoma (ASC, 5.8%). During the median follow-up of 55 months, compared to patients with wild-type KRAS, a greater percentage of patients with mutant KRAS relapsed (20.0% vs. 42.9%, respectively, p=0.007). The 3-year relapse-free survival was poorer in patients with mutant KRAS than in patients without KRAS mutations (57.1% vs. 81.9%, respectively, p=0.001). Furthermore, the multivariate analysis showed that the presence of a KRAS mutation was an independent predictor for disease recurrence (hazard ratio [HR]=2.064; 95% confidence interval [CI]=1.125–3.787; p=0.019). Conclusion KRAS mutations were predominant in non-SCCs of the cervix and were associated with HPV 18 infection. A combination of KRAS mutation detection and HPV genotyping would be useful in identifying patient with poor prognosis for further interventions.
Cure cycle simulations of composites with temperature and cure dependent anisotropic viscoelastic properties

Complete 3 D anisotropic degree of cure and temperature dependent thermal properties and viscoelastic constitutive relations are formulated to describe composites during curing in autoclaves. Sensitivity studies were undertaken to determine the influences of time step and mesh size on the convergence of the finite element analysis of temperature and degree of cure. Expressions for the probability of tunes to delaminate during cure under combined stresses are derived and delamination onset survival times of laminated composites in the autoclave during manufacture are investigated in detail. Specific experimental areas are identified where needed deterministic and stochastic data for thermal, viscoelastic and failure properties during manufacturing cycles are unavailable.