Miracle-dz/UniFAR-FTUs huggingface dataset:
Jadomycin breast cancer cytotoxicity is mediated by a copper-dependent, reactive oxygen species–inducing mechanism

Jadomycins are natural products biosynthesized by the bacteria Streptomyces venezuelae which kill drug‐sensitive and multidrug‐resistant breast cancer cells in culture. Currently, the mechanisms of jadomycin cytotoxicity are poorly understood; however, reactive oxygen species (ROS)–induced DNA cleavage is suggested based on bacterial plasmid DNA cleavage studies. The objective of this study was to determine if and how ROS contribute to jadomycin cytotoxicity in drug‐sensitive MCF7 (MCF7‐CON) and taxol‐resistant MCF7 (MCF7‐TXL) breast cancer cells. As determined using an intracellular, fluorescent, ROS‐detecting probe, jadomycins B, S, SPhG, and F dose dependently increased intracellular ROS activity 2.5‐ to 5.9‐fold. Cotreatment with the antioxidant N‐acetyl cysteine lowered ROS concentrations to below baseline levels and decreased the corresponding cytotoxic potency of the four jadomycins 1.9‐ to 3.3‐fold, confirming a ROS‐mediated mechanism. Addition of CuSO4 enhanced, whereas addition of the Cu(II)‐chelator d‐penicillamine reduced, the ROS generation and cytotoxicity of each jadomycin. Specific inhibitors of the antioxidant enzymes, superoxide dismutase 1, glutathione S‐transferase, and thioredoxin reductase, but not catalase, enhanced jadomycin‐mediated ROS generation and anticancer activity. In conclusion, the results indicate that jadomycin cytotoxicity involves the generation of cytosolic superoxide via a Cu(II)‐jadomycin reaction, a mechanism common to all jadomycins tested and observed in MCF7‐CON and drug‐resistant MCF7‐TXL cells. The superoxide dismutase 1, glutathione, and peroxiredoxin/thioredoxin cellular antioxidant enzyme pathways scavenged intracellular ROS generated by jadomycin treatment. Blocking these antioxidant pathways could serve as a strategy to enhance jadomycin cytotoxic potency in drug‐sensitive and multidrug‐resistant breast cancers.
Normalizing Flows on Riemannian Manifolds

We consider the problem of density estimation on Riemannian manifolds. Density estimation on manifolds has many applications in fluid-mechanics, optics and plasma physics and it appears often when dealing with angular variables (such as used in protein folding, robot limbs, gene-expression) and in general directional statistics. In spite of the multitude of algorithms available for density estimation in the Euclidean spaces $\mathbf{R}^n$ that scale to large n (e.g. normalizing flows, kernel methods and variational approximations), most of these methods are not immediately suitable for density estimation in more general Riemannian manifolds. We revisit techniques related to homeomorphisms from differential geometry for projecting densities to sub-manifolds and use it to generalize the idea of normalizing flows to more general Riemannian manifolds. The resulting algorithm is scalable, simple to implement and suitable for use with automatic differentiation. We demonstrate concrete examples of this method on the n-sphere $\mathbf{S}^n$.
Characterizing gene sets using discriminative random walks with restart on heterogeneous biological networks

Motivation: Analysis of co-expressed gene sets typically involves testing for enrichment of different annotations or ‘properties’ such as biological processes, pathways, transcription factor binding sites, etc., one property at a time. This common approach ignores any known relationships among the properties or the genes themselves. It is believed that known biological relationships among genes and their many properties may be exploited to more accurately reveal commonalities of a gene set. Previous work has sought to achieve this by building biological networks that combine multiple types of gene–gene or gene–property relationships, and performing network analysis to identify other genes and properties most relevant to a given gene set. Most existing network-based approaches for recognizing genes or annotations relevant to a given gene set collapse information about different properties to simplify (homogenize) the networks. Results: We present a network-based method for ranking genes or properties related to a given gene set. Such related genes or properties are identified from among the nodes of a large, heterogeneous network of biological information. Our method involves a random walk with restarts, performed on an initial network with multiple node and edge types that preserve more of the original, specific property information than current methods that operate on homogeneous networks. In this first stage of our algorithm, we find the properties that are the most relevant to the given gene set and extract a subnetwork of the original network, comprising only these relevant properties. We then re-rank genes by their similarity to the given gene set, based on a second random walk with restarts, performed on the above subnetwork. We demonstrate the effectiveness of this algorithm for ranking genes related to Drosophila embryonic development and aggressive responses in the brains of social animals. Availability and Implementation: DRaWR was implemented as an R package available at veda.cs. illinois.edu/DRaWR. Contact: blatti@illinois.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Synthetic Bone Substitute Engineered with Amniotic Epithelial Cells Enhances Bone Regeneration after Maxillary Sinus Augmentation

Background Evidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined. Aim In the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC), loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT) technique, was evaluated in an animal study. Material And Methods Two blocks of synthetic bone substitute (∼0.14 cm3), alone or engineered with 1×106 ovine AEC (oAEC), were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.). Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT), morphological, morphometric and biochemical analyses. Results And Conclusions The obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation), data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their ability to switch-on the expression of a specific bone-related protein (osteocalcin, OCN) when transplanted into host tissues.
Machine Learning for Outcome Prediction of Acute Ischemic Stroke Post Intra-Arterial Therapy

Introduction Stroke is a major cause of death and disability. Accurately predicting stroke outcome from a set of predictive variables may identify high-risk patients and guide treatment approaches, leading to decreased morbidity. Logistic regression models allow for the identification and validation of predictive variables. However, advanced machine learning algorithms offer an alternative, in particular, for large-scale multi-institutional data, with the advantage of easily incorporating newly available data to improve prediction performance. Our aim was to design and compare different machine learning methods, capable of predicting the outcome of endovascular intervention in acute anterior circulation ischaemic stroke. Method We conducted a retrospective study of a prospectively collected database of acute ischaemic stroke treated by endovascular intervention. Using SPSS®, MATLAB®, and Rapidminer®, classical statistics as well as artificial neural network and support vector algorithms were applied to design a supervised machine capable of classifying these predictors into potential good and poor outcomes. These algorithms were trained, validated and tested using randomly divided data. Results We included 107 consecutive acute anterior circulation ischaemic stroke patients treated by endovascular technique. Sixty-six were male and the mean age of 65.3. All the available demographic, procedural and clinical factors were included into the models. The final confusion matrix of the neural network, demonstrated an overall congruency of ∼80% between the target and output classes, with favourable receiving operative characteristics. However, after optimisation, the support vector machine had a relatively better performance, with a root mean squared error of 2.064 (SD: ±0.408). Discussion We showed promising accuracy of outcome prediction, using supervised machine learning algorithms, with potential for incorporation of larger multicenter datasets, likely further improving prediction. Finally, we propose that a robust machine learning system can potentially optimise the selection process for endovascular versus medical treatment in the management of acute stroke.
An Experimental Study of Combination

The crowd is emerging as a new source of innovation, and here a new way of organizing the crowd to produce new ideas is discussed: an idea generation system using combination in which participants synthesize new designs from the efforts of their peers. A crowd generates designs; then another crowd combines the designs of the previous crowd. In an experiment with 540 participants, the combined designs are compared to the initial designs, and to a control condition in which fresh idea generation rather than combination is used. The results show that designs become more creative in later generations of the combination system, and the combination produces more creative ideas than the fresh idea generation. The model of crowdsourced idea generation discussed here may be used to instantiate systems that can be applied to a wide range of design problems. The work has pragmatic implications, and also theoretical implications: new forms of coordination are now possible, and, using the crowd, it is possible to build and test existing and emerging theories of coordination and design.
Title Hope-based intervention for individuals susceptible to colorectal cancer: a pilot study

Individuals undergoing genetic testing for hereditary colorectal cancer (HCRC) are prone to develop psychological problems. This study investigated the shortterm efficacy of a hope-based intervention program in increasing hope levels and decreasing psychopathology among HCRC genetic testing recipients. A longitudinal study was carried out on HCRC genetic testing recipients recruited by the Hereditary Gastrointestinal Cancer Registry. Participants joined a hope-based intervention program consisting of six sessions of weekly closed group therapy. Psychological questionnaires were administered immediately before the first and after the last sessions of the program measuring hope, anxiety and depression levels of the participants. There were 22 participants (7 men and 15 women) at a mean age of 49.4 ± 9.6 years. Women tended to have higher level of anxiety than men at pre-intervention. Paired sample t tests were conducted. Hope levels increased significantly from preto post-intervention (pre-total hope score = 5.56; post-total hope score = 6.07; t(1) = -0.281, p \ 0.05). Anxiety level also decreased significantly from preto post-intervention (pre-anxiety score = 7.38; postanxiety score = 5.90; t (1) = 2.35, p \ 0.05). Our findings imply that hope-based intervention program would be effective in enhancing hope in HCRC genetic testing recipients. The program may also be more effective in alleviating anxiety than depression in these individuals.
A novel diagnostic tool reveals mitochondrial pathology in human diseases and aging

The inherent complex and pleiotropic phenotype of mitochondrial diseases poses a significant diagnostic challenge for clinicians as well as an analytical barrier for scientists. To overcome these obstacles we compiled a novel database, www.mitodb. com, containing the clinical features of primary mitochondrial diseases. Based on this we developed a number of qualitative and quantitative measures, enabling us to determine whether a disorder can be characterized as mitochondrial. These included a clustering algorithm, a disease network, a mitochondrial barcode and two scoring algorithms. Using these tools we detected mitochondrial involvement in a number of diseases not previously recorded as mitochondrial. As a proof of principle Cockayne syndrome, ataxia with oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and ataxia-telangiectasia have recently been shown to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders. We next evaluated mitochondrial involvement in aging and detected two distinct categories of accelerated aging disorders, one of them being associated with mitochondrial dysfunction. Normal aging seemed to associate stronger with the mitochondrial diseases than the non-mitochondrial partially supporting a mitochondrial theory of aging.
The UK Wage Curve: New Evidence from the British Household Panel Survey

This paper investigates the UK wage curve using longitudinal micro data drawn from the first eight waves of the British Household Panel Survey (BHPS). We estimate a fixed-effects model that controls for observed and unobserved individual-specific heterogeneity. Our results suggest that there is evidence of a negative relationship in wage-unemployment space. The estimated unemployment elasticity of pay for UK males is approximately ? 0.14 and this elasticity is robust to a number of alternative specifications. There is no evidence of a significant wage curve for women. These findings are consistent with panel studies reported for other countries. They contrast with previous studies for the UK, however, in that they reject the inclusion of higher order polynomial terms for unemployment. The main findings of the paper, therefore, are that the wage-unemployment relationship is robust but not as non-linear as has been previously thought.
Creoles are typologically distinct from non-creoles

In creolist circles, there has been a long-standing debate whether creoles differ structurally from non-creole languages and thus would form a special class of languages with specific typological properties. This debate about the typological status of creole languages has severely suffered from a lack of systematic empirical study. This paper presents for the first time a number of large-scale empirical investigations of the status of creole languages as a typological class on the basis of different and well-balanced samples of creole and non-creole languages. Using statistical modeling (multiple regression) and recently developed computational tools of quantitative typology (phylogenetic trees and networks), this paper provides robust evidence that creoles indeed form a structurally distinguishable subgroup within the world's languages. The findings thus seriously challenge approaches that hold that creole languages are structurally indistinguishable from non-creole languages.
Bayesian Hypothesis Testing: a Reference Approach

For any probability model M={p(x|θ, ω), θεΘ, ωεΩ} assumed to describe the probabilistic behaviour of data xεX, it is argued that testing whether or not the available data are compatible with the hypothesis H0={θ=θ0} is best considered as a formal decision problem on whether to use (a0), or not to use (a0), the simpler probability model (or null model) M0={p(x|θ0, ω), ωεΩ}, where the loss difference L(a0, θ, ω) –L(a0, θ, ω) is proportional to the amount of information δ(θ0, ω), which would be lost if the simplified model M0 were used as a proxy for the assumed model M. For any prior distribution π(θ, ω), the appropriate normative solution is obtained by rejecting the null model M0 whenever the corresponding posterior expectation ∫∫δ(θ0, θ, ω)π(θ, ω|x)dθdω is sufficiently large.
Markers of T Cell Infiltration and Function Associate with Favorable Outcome in Vascularized High-Grade Serous Ovarian Carcinoma

Background When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL) could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. Methodology and Principal Findings In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3)) and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1)) correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049–5.106); p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF) expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097–5.799); p = 0.0294]. Significance Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.
PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma

Purpose: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic α (PIK3CA) gene in several human solid tumors. Although gene amplifications of PIK3CA have been reported in head and neck squamous cell carcinoma (HNSCC), small mutation of the gene has not been evaluated in HNSCC previously. In this study, we examined the mutation frequency of PIK3CA in HNSCC. Experimental Design: More than 75% of the somatic mutations of PIK3CA are clustered in the helical (exon 9) and kinase domains (exon 20). To investigate the possible role of PIK3CA in HNSCC tumorigenesis, exons 1, 4, 5, 6, 7, 9, and 20 of the gene were analyzed by direct genomic DNA sequencing in 38 HNSCC specimens. Results: We identified four missense mutations in the seven exons of PIK3CA from 38 HNSCC specimens (11%). Three of the four mutations (i.e., H1047R, E542K, and E545K) have been previously reported as hotspot mutations. The remaining novel mutation, Y343C, is identified at exon 4 nucleotide 1028 A → G. Three of the four mutations were shown to be somatic, whereas the fourth mutation (H1047R) was identified in a cell line. Interestingly, three of the four mutations identified were in pharyngeal cancer samples. Conclusions: These data provide evidence that oncogenic properties of PIK3CA contribute to the carcinogenesis of human head and neck cancers, especially in pharyngeal cancer. A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular.
A sequential Monte Carlo approximation of the HISP filter

A formulation of the hypothesised filter for independent stochastic populations (hisp) is proposed, based on the concept of association measure, which is a measure on the set of observation histories. Using this formulation, a particle approximation is introduced at the level of the association measure for handling the exponential growth in the number of underlying hypotheses. This approximation is combined with a sequential Monte Carlo implementation for the underlying single-object distributions to form a mixed particle association model. Finally, the performance of this approach is compared against a Kalman filter implementation on simulated data based on a finite-resolution sensor.
Comparison of Analgesic Efficacy between Single Interscalene Block Combined with a Continuous Intra-bursal Infusion of Ropivacaine and Continuous Interscalene Block after Arthroscopic Rotator Cuff Repair

Background This study evaluated the effectiveness of a continuous interscalene block (CISB) by comparing it with that of a single interscalene block combined with a continuous intra-bursal infusion of ropivacaine (ISB-IB) after arthroscopic rotator cuff repair. Methods Patients who had undergone CISB (CISB group; n = 25) were compared with those who had undergone ISB-IB (ISB-IB group; n = 25) for more than 48 hours after surgery. The visual analog scale (VAS) for pain, motor and/or sensory deficit, supplementary analgesics and adverse effects were recorded. Results There were no significant differences between the postoperative VAS of the CISB and ISB-IB groups, except at 1 hour after surgery. Their supplementary analgesics of the two groups were similar. Transient motor weakness (52%) and sensory disturbance (40%) of the affected arm were observed in patients in the CISB group. The catheters came out accidentally in 22% of the CISB group but in only 4% of the ISB-IB group. Conclusions ISB-IB provides similar analgesia to CISB. However, the ISB-IB group had a lower incidence of neurological deficits and better catheter retention.
Medical Guidelines , Quality of Care and Physician Density : Evidence from German SHARE Data

In this paper we use German SHARE data to study the relationship between district general practitioner density and the quality of medical care provided to older adults. We measure physician quality of care as the degree of adherence to medical guidelines (for the diagnosis and treatment of obesity and falls) as reported by patients (i.e., respondents). Contrary to our expectations, we find only weak and insignificant effects of physician density on quality of care. Our results shed some doubt on the notion that increasing physician supply will increase the quality of care provided in Germany’s present health care system.