Miracle-dz/UniFAR-FTUs huggingface dataset:
Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications the example of oncology trials

Background Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. Method We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. Results We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [&kgr; = 0.53, 95% confidence interval (0.25–0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. Conclusion In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes.
Pressure exposure and catheter impingement affect the recorded pressure in the Manoscan 360™ system

The accuracy of pressure measurements by Manoscan high‐resolution manometry (HRM) system is affected by pressure drift (PD). The PD is partly related to temperature and study duration, but other factors that contribute to errant pressure recording have not been systematically evaluated. The aim of this study was to investigate and quantify contributing factors to pressure recording error.
MicroRNA-503 inhibits the proliferation and invasion of breast cancer cells via targeting insulin-like growth factor 1 receptor

MicroRNAs (miRs), a class of non-coding RNAs that are 18–25 nucleotides in length, serve as key regulators in the development and progression of human cancers. Previously, miR-503 has been implicated in breast cancer. However, the underlying mechanism of miR-503 in regulating the proliferation and invasion of breast cancer cells remains largely unknown. In the present study, reverse transcription-quantitative polymerase chain reaction analysis indicated that the expression of miR-503 was significantly reduced in breast cancer tissues compared with their matched adjacent normal tissues. Furthermore, miR-503 expression levels were markedly reduced in T2-T4 stage breast cancer, compared with T1 stage. Insulin-like growth factor 1 receptor (IGF-1R) was further identified as a novel target of miR-503. Overexpression of miR-503 significantly suppressed the protein expression levels of IGF-1R. Furthermore, it inhibited the proliferation and invasion of human breast cancer MCF-7 cells, as assessed by MTT and Transwell assays, respectively. However, restoration of IGF-1R expression markedly ameliorated the suppressive effects of miR-503 overexpression on MCF-7 cell proliferation and invasion, indicating that miR-503 inhibits breast cancer cell proliferation and invasion at least partially via directly targeting IGF-1R. Furthermore, the mRNA and protein expression levels of IGF-1R were demonstrated to be significantly increased in breast cancer tissues compared with their matched adjacent normal tissues. In addition, IGF-1R mRNA expression levels were reversely correlated with miR-503 expression levels in breast tumors, suggesting that the upregulation of IGF-1R may be due to downregulation of miR-503 in breast cancer. In conclusion, the present study expanded the understanding of the regulatory mechanism of miR-503 in breast cancer, and implicates the miR-503/IGF-1R axis as a potential therapeutic target for breast cancer.
FK506 binding protein 51 integrates pathways of adaptation

This review portraits FK506 binding protein (FKBP) 51 as “reactivity protein” and collates recent publications to develop the concept of FKBP51 as contributor to different levels of adaptation. Adaptation is a fundamental process that enables unicellular and multicellular organisms to adjust their molecular circuits and structural conditions in reaction to environmental changes threatening their homeostasis. FKBP51 is known as chaperone and co‐chaperone of heat shock protein (HSP) 90, thus involved in processes ensuring correct protein folding in response to proteotoxic stress. In mammals, FKBP51 both shapes the stress response and is calibrated by the stress levels through an ultrashort molecular feedback loop. More recently, it has been linked to several intracellular pathways related to the reactivity to drug exposure and stress. Through its role in autophagy and DNA methylation in particular it influences adaptive pathways, possibly also in a transgenerational fashion.
Sensor Array Optimization of Electronic Nose for Detection of Bacteria in Wound Infection

In order to identify the bacteria in wound infection, an electronic nose system with a sensor array of 34 sensors was designed. Eight kinds of samples were detected, i.e., culture medium, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and their mixture with different concentration. Using support vector machine as the classifier and without sensor array optimization, the recognition rate is up to 86.54%. To simplify the sensor array and improve the recognition rate for bacteria samples, Wilks’ lambda statistic (Wilks’ Λ-statistic), Mahalanobis distance, principal component analysis (PCA), linear discriminant analysis (LDA), and genetic algorithm are used to optimize the sensor array. It is shown that the sensor array optimization may be realized efficiently by these methods except PCA. After sensor array optimization by Wilks’ Λ-statistic and LDA, both of their recognition rates are the highest and up to 96.15%, while the numbers of sensors in optimized sensor arrays are 22 and 20, respectively. Under the limitation of ten sensors, the recognition rate optimized by Wilks’ Λ-statistic and LDA may still reach 95.19%.
Novel function of ceramide for regulation of mitochondrial ATP release in astrocytes[S]

We reported that amyloid β peptide (Aβ42) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ42 induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro-sphingosine (pacFACer), a bifunctional ceramide analog, and binding of tubulin to ceramide-linked agarose beads. Ceramide-associated tubulin (CAT) translocated from the perinuclear region to peripheral CEMAMs and mitochondria, which was prevented in nSMase2-deficient or FB1-treated astrocytes. Proximity ligation and coimmunoprecipitation assays showed that ceramide depletion reduced association of tubulin with voltage-dependent anion channel 1 (VDAC1), an interaction known to block mitochondrial ADP/ATP transport. Ceramide-depleted astrocytes contained higher levels of ATP, suggesting that ceramide-induced CAT formation leads to VDAC1 closure, thereby reducing mitochondrial ATP release, and potentially motility and resistance to Aβ42. Our data also indicate that inhibiting ceramide generation may protect mitochondria in Alzheimer’s disease.
Definition of Superhydrophobic States

We have recently published a paper entitled “Superhydro-phobic Aligned Polystyrene Nanotube Films with High Adhe-sive Force” in Advanced Materials . [1] This work reported the preparation of superhydrophobic aligned polystyrene (PS) nanotube films with a high static contact angle (CA) of about 162° and a high adhesive force. The as-prepared films have been used to transfer small water droplets without mass loss, as assessed by a high-sensitivity microelectromechanical balance system. Indeed, the results point to the occurrence of a new superhydrophobic phenomenon. Some readers have been perplexed by these results and have raised several questions about this new superhydrophobic phenomenon. [2] Moreover, other researchers have expressed a different opinion about whether a superhydrophobic surface should exhibit a low CA hysteresis. [3] Considering the current confusion in understanding superhydrophobicity, we attempt here to clarify the definition of superhydrophobic states. We hope that this clarification will help readers obtain a better understanding of interesting superhydrophobic phenomena on solid surfaces. In general, surfaces with a static CA higher than 150° are defined as superhydrophobic surfaces. As for the details of CA hysteresis, [4–8] five states are possible for superhydrophobic surfaces (Fig. 1): Wenzel’s state, Cassie’s state, the so-called “Lotus” state, the transitional state between Wenzel’s and Cassie’s states, and the “Gecko” state.
Distortion and Signal Loss in Medial Temporal Lobe

Background The medial temporal lobe (MTL) contains subregions that are subject to severe distortion and signal loss in functional MRI. Air/tissue and bone/tissue interfaces in the vicinity of the MTL distort the local magnetic field due to differences in magnetic susceptibility. Fast image acquisition and thin slices can reduce the amount of distortion and signal loss, but at the cost of image signal-to-noise ratio (SNR). Methodology/Principal Findings In this paper, we quantify the severity of distortion and signal loss in MTL subregions for three different echo planar imaging (EPI) acquisitions at 3 Tesla: a conventional moderate-resolution EPI (3×3×3 mm), a conventional high-resolution EPI (1.5×1.5×2 mm), and a zoomed high-resolution EPI. We also demonstrate the advantage of reversing the phase encode direction to control the direction of distortion and to maximize efficacy of distortion compensation during data post-processing. With the high-resolution zoomed acquisition, distortion is not significant and signal loss is present only in the most anterior regions of the parahippocampal gyrus. Furthermore, we find that the severity of signal loss is variable across subjects, with some subjects showing negligible loss and others showing more dramatic loss. Conclusions/Significance Although both distortion and signal loss are minimized in a zoomed field of view acquisition with thin slices, this improvement in accuracy comes at the cost of reduced SNR. We quantify this trade-off between distortion and SNR in order to provide a decision tree for design of high-resolution experiments investigating the function of subregions in MTL.
Thermomechanical response of laser processed nickel-titanium shape memory alloy

The exciting thermomechanical properties of nickel-titanium shape memory alloys have sparked significant research efforts seeking to exploit their exotic capabilities. Until recently, the performance capabilities of nickel-titanium devices have been inhibited by the retention of only one thermomechanical characteristic. However, laser processing technology promises to deliver enhanced material offerings which are capable of multiple functional responses. Presented in this thesis, is an investigation of the effects of laser processing on the thermomechanical behaviour of nickel-titanium shape memory alloys. In the context of this work, laser processing refers to removal of alloy constituents, as in the case of laser ablation, or alternatively, addition of elements through laser alloying. The effects of laser ablation on the composition, crystallography and phase transformation temperatures of a nickel-titanium strip have been studied. Application of laser energy was shown to ablate nickel constituents, induce an austenite-martensite phase change and cause an increase in phase transformation onset temperatures, which correlated well with reported findings. Laser processing of a nickel-titanium wire was shown to locally embed an additional thermomechanical response which manifested as unique shape memory and pseudoelastic properties. Localized alloying of ternary species via laser processing of nickel-titanium strip was investigated. Synthesis of a ternary shape memory intermetallic within the laser processing region was achieved through melting of copper foils. Results from thermoanalytical testing indicated that the ternary compound possessed a higher phase transformation temperature and reduced transformation hysteresis in comparison to the reference alloy. Indentation testing was used to demonstrate the augmented thermomechanical characteristics of the laser processed shape memory alloy. In order to demonstrate the enhanced functionality of laser processed nickel-titanium shape memory alloys, a self-positioning nickel-titanium microgripper was fabricated. The microgripper was designed to actuate through four different positions, corresponding to activation of three embedded shape memory characteristics. Thermoanalytical and tensile testing instrumentations were used to characterize the thermomechanical performance of the laser processed nickel-titanium microgripper. Results indicated that each of the laser processed microgripper components possessed unique mechanical and shape memory recovery properties.
Explorer Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

Background: Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD). Methods: Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression. Results: There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype. Conclusion: This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease. Background Variant CJD is one of the prion diseases, which affect both humans and animals. It is an acquired disease associated with infection with bovine spongiform encephalopathy (BSE), mainly through the ingestion route [1,2], although three cases have resulted from human-to-human blood transfusion. [3-5] It is most prevalent in the UK, where 163 confirmed cases have been reported, but has also been found in smaller numbers in other countries including France (24 cases, see Availability and requirements Published: 21 April 2008 BMC Medical Genetics 2008, 9:31 doi:10.1186/1471-2350-9-31 Received: 13 December 2007 Accepted: 21 April 2008 This article is available from: http://www.biomedcentral.com/1471-2350/9/31 © 2008 Bishop et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. BMC Medical Genetics 2008, 9:31 http://www.biomedcentral. com/1471-2350/9/31
Tau‐based fluorescent protein fusions to visualize microtubules

The ability to visualize cytoskeletal proteins and their dynamics in living cells has been critically important in advancing our understanding of numerous cellular processes, including actin‐ and microtubule (MT)‐dependent phenomena such as cell motility, cell division, and mitosis. Here, we describe a novel set of fluorescent protein (FP) fusions designed specifically to visualize MTs in living systems using fluorescence microscopy. Each fusion contains a FP module linked in frame to a modified phospho‐deficient version of the MT‐binding domain of Tau (mTMBD). We found that expressed and purified constructs containing a single mTMBD decorated Xenopus egg extract spindles more homogenously than similar constructs containing the MT‐binding domain of Ensconsin, suggesting that the binding affinity of mTMBD is minimally affected by localized signaling gradients generated during mitosis. Furthermore, MT dynamics were not grossly perturbed by the presence of Tau‐based FP fusions. Interestingly, the addition of a second mTMBD to the opposite terminus of our construct caused dramatic changes to the spatial localization of probes within spindles. These results support the use of Tau‐based FP fusions as minimally perturbing tools to accurately visualize MTs in living systems.
On the importance of Legal Catchphrases in Precedence Retrieval

This paper presents our working notes for FIRE 2017, Information Retrieval from Legal documents -Task 2 (Precedence retrieval). Common Law Systems around the world recognize the importance of precedence in Law. In making decisions, Judges are obliged to consult prior cases that had already been decided to ensure that there is no divergence in treatment of similar situations in different cases. Our approach was to investigate the effectiveness of using legal catchphrases in precedence retrieval. To improve retrieval performance, we incorporated term dependency in our retrieval. In addition, we investigate the effects of deploying query expansion on the retrieval performance. Our results show an improvement in the retrieval performance when we incorporate term dependence in scoring and ranking prior cases. However, we see a degradation in the retrieval performance when we deploy query expansion.
Intelligent RDD Management for High Performance In-Memory Computing in Spark

Spark is a pervasively used in-memory computing framework in the era of big data, and can greatly accelerate the computation speed by wrapping the accessed data as resilient distribution datasets (RDDs) and storing these datasets in the fast accessed main memory. However, the space of main memory is limited, and Spark does not provide an intelligent mechanism to store reasonable RDDs in the limited memory. In this paper, we propose a fine-grained RDD checkpointing and kick-out selection strategy, by which Spark can intelligently select the reasonable RDDs to maximize the memory usage. The experiment is conducted on a server with four nodes. Experimental results demonstrate that the proposed techniques can effectively accelerate the execution speed.
Proximity of Cytomegalovirus-Specific CD8+ T Cells to Replicative Senescence in Human Immunodeficiency Virus-Infected Individuals

Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, age-related morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other age-related morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIV-infected individuals seropositive for anti-CMV antibodies. Our study cohort consists mainly of middle aged men who have sex with men (MSM) and heterosexuals who are stable under long-term ART. Median levels of IL-6, TNF-α, and CRP were significantly higher in those coinfected with CMV. Lymphocyte telomere length in general correlated with age, but for 32/32 subjects tested, there was a consistent hierarchy of telomere lengths with CD8+ T cells’ shorter than the general lymphocyte population, CD57+CD8+ T cells’ shorter than CD8+ T cells’ and CMV-specific CD57+CD8+ T cells’ the shortest of all. Telomeres of HIV-specific CD8+ T cells were longer than those of CMV-specific CD8+ T cells in all cases tested and over 10 years, CMV-specific CD8+ T cell telomeres of two HIV-infected individuals eroded faster than those of HIV-specific CD8+ T cells. These data indicate that CMV-specific CD8+ T cells of HIV-infected individuals are the lymphocytes closest to telomere-imposed replicative senescence. Exhaustive proliferation of CMV-specific CD8+ T cells in HIV-infected individuals is a potential source of senescent lymphocytes affecting systemic immune function and inflammation.
A low‐complexity add‐on score for protein remote homology search with COMER

Motivation: Protein sequence alignment forms the basis for comparative modeling, the most reliable approach to protein structure prediction, among many other applications. Alignment between sequence families, or profile‐profile alignment, represents one of the most, if not the most, sensitive means for homology detection but still necessitates improvement. We aim at improving the quality of profile‐profile alignments and the sensitivity induced by them by refining profile‐profile substitution scores. Results: We have developed a new score that represents an additional component of profile‐profile substitution scores. A comprehensive evaluation shows that the new add‐on score statistically significantly improves both the sensitivity and the alignment quality of the COMER method. We discuss why the score leads to the improvement and its almost optimal computational complexity that makes it easily implementable in any profile‐profile alignment method. Availability and implementation: An implementation of the add‐on score in the open‐source COMER software and data are available at https://sourceforge.net/projects/comer. The COMER software is also available on Github at https://github.com/minmarg/comer and as a Docker image (minmar/comer). Supplementary information: Supplementary data are available at Bioinformatics online.