Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomization-based inference for Bernoulli trial experiments and implications for observational studies

We present a randomization-based inferential framework for experiments characterized by a strongly ignorable assignment mechanism where units have independent probabilities of receiving treatment. Previous works on randomization tests often assume these probabilities are equal within blocks of units. We consider the general case where they differ across units and show how to perform randomization tests and obtain point estimates and confidence intervals. Furthermore, we develop rejection-sampling and importance-sampling approaches for conducting randomization-based inference conditional on any statistic of interest, such as the number of treated units or forms of covariate balance. We establish that our randomization tests are valid tests, and through simulation we demonstrate how the rejection-sampling and importance-sampling approaches can yield powerful randomization tests and thus precise inference. Our work also has implications for observational studies, which commonly assume a strongly ignorable assignment mechanism. Most methodologies for observational studies make additional modeling or asymptotic assumptions, while our framework only assumes the strongly ignorable assignment mechanism, and thus can be considered a minimal-assumption approach.
Super-resolution for sequence series data using long-short term memory network

Sequence Series Data (SSD) refers to multi-dimensional data involving measurements over sequences, which can be ordered. This type of data is frequently encountered in genomic data sets and text sentiment analysis data sets, but collecting them can be time-consuming and labour-intensive. These factors result in low-resolution data sets. Therefore, we employed six machine learning regression methods to perform SSD super-resolution, i.e. to recover high-resolution data sets using self-similarity in low-resolution data sets. Furthermore, we propose a novel Long-Short Term Memory (LSTM) network, namely Interaction Encoded LSTM (IELSTM) network, which is capable of handling multiple distant interactions among sequences. IELSTM network generally shows better overall reconstruction quality when compared with ridge regression, LASSO regression, orthogonal matching pursuit regression, multilayer perceptron regression, and random forest regression, on four genomic data sets.
Vitamin C promotes oligodendrocytes generation and remyelination

Oligodendrocyte‐formed myelin sheaths play important roles in the neuronal functions in the central nervous system. In demyelinating diseases, such as Multiple Sclerosis, the myelin sheaths are damaged and the remyelinating process is somehow hindered. Restoration of the myelin sheaths requires the differentiation of the oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). To discover small molecule compounds that might promote the OPC to OL differentiation, a high‐throughput screening system is established and L‐ascorbyl‐2‐phosphate (As‐2P), a stable form of Vitamin C (Vc), is found to greatly enhance the OPC to OL differentiation. As‐2P promotes gradual expression of OL lineage markers, including O4, CNPase and MBP, in a dose‐ and time‐dependent manner. It also facilitates the formation of myelin sheaths in OPC‐neuron co‐culture. As‐2P also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone‐mediated demyelination animal model. Interestingly, As‐2P's function in promoting OPC differentiation is not related to its antioxidant activity. And an intracellular rather than an extracellular mechanism might be involved. Considering the safe use of Vc as a dietary supplement for many years, it might also be used as an alternative medicine for CNS demyelinating diseases.
The influence of in vitro hemoglobin modification on hemoglobinuric nephrosis in rabbits.

Abstract The influence of intravenous injection of old hemoglobin, modified hemoglobin, and methemoglobin on pigment cast formation was studied in three groups of rabbits. Hemoglobin of different ages stored up to 330 days was not toxic, nor did aging exert any appreciable influence on urine excretion in nine rabbits. Oxyhemoglobin which was modified by acidification and neutralization prior to intravenous injection was toxic. Seven of fourteen animals became extremely weak, one died, and two refused to eat. In spite of the immediate toxic effects, modified hemoglobin did not predispose to an accumulation of pigment casts. In the last group of ten animals significant. numbers of pigment casts and increases in kidney weight were observed in five with aciduria following intravenous methemoglobin injection. Of the remaining five with alkalinuria there were significant increases in kidney weight without many pigment casts. Of the three pigments analyzed, methemoglobin is the most nephrotoxie. The mechanism by which methemoglobin exerts such a nephrotoxic. effect is not apparent from these studies.
Experimental nonlinear identification of a lab-scale helicopter system using MLP neural network

Artificial Neural Networks (ANN) are justified to be used as universal function approximators. That is to say, with the proper structure, ANN can approximate any nonlinear dynamics and describe the required input-output mapping. This paper introduces an experimental investigation of this concept, where a Multi-Layer Perceptron (MLP) network is used to model the entire dynamics of a nonlinear complex structure. An empirical modelling approach using MLP is established and applied to model a real-time Flexible Manoeuvring System (FMS). Various modified versions of the essential back-propagation learning algorithm are used to train the MLP model. Results are investigated and validated in both time and frequency domains; networks that are trained with the Levenberg-Marquardt (LM) algorithm conducted the best performance. Then, the validation checks indicate rapid improvements in the obtained model using the introduced MLP approach.
4-Bromo-2,5-dimethoxyphenylisopropylamine, a new centrally active amphetamine analog.

A new centrally active halo-amine, 4-bromo-2,5 dimethoxyphenylisopropylamine, is described. In clinical evalua tion it proved to enhance effectively both emotional and in tellectual perception, without the imagery and perceptual distortions commonly encountered with many of the chemically related psychotomimetics. These properties suggest a potential valuable role in conjunction with psychotherapy.
Assessment of Fibrin–Fibrinogen Degradation Products (Accu–Dx) Test in Bladder Cancer Patients

Objectives: Measurement of urine fibrin–fibrinogen degradation products has been reported to be a useful marker for bladder malignancies. This is a simple, noninvasive and rapid method in the diagnosis and follow–up of bladder cancer. We performed a prospective study to evaluate the reliability of the Accu–Dx test which detects urinary fibrin and fibrinogen products associated with bladder cancer. Material and Methods: 97 patients were included in this study. 55 patients with bladder cancer were under surveillance, and 35 were evaluated as primary cases. The Accu–Dx test was performed in 7 additional patients presenting with hematuria due to benign disorders. Urine cytology specimens were collected in all, whereas bladder pathology specimens were obtained in 93. The Accu–Dx test was evaluated with regard to the results of urine cytology and pathological assessment, which constituted the gold standard. Results: According to pathology, 69 patients had carcinoma of the bladder. In 48 (69.6%), the Accu–Dx test was positive whereas urine cytology was positive in only 31 (44.9%; p<0.001). Specificity rates were 67.9 and 96.4%, respectively. With higher stages and higher tumor grades, the Accu–Dx test yielded higher positive rates (50% in Ta versus 100% in T2 or higher and 42.9% in G1 versus 94.1% in G3). On the other hand, the test was positive in 6 patients with cystitis of various etiologies. The overall accuracy rate for Accu–Dx was 69%. Conclusions: The Accu–Dx test is a simple, rapid, reproducible and more importantly a noninvasive method in the detection of bladder malignancies. But it seems inadequate to replace conventional cystoscopy plus pathologic assessment due to its relatively low accuracy and specificity rates. It may be helpful in selecting patients who should be evaluated with rigid endoscopes together with bladder biopsies.
Surrogate Endpoint Biomarkers for Clinical Trials of Prostate Cancer Chemoprevention

High-grade prostatic intraepithelial neoplasia is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence. It has a high predictive value as a marker for adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. Androgen deprivation therapy and radiation therapy decrease its prevalence and extent, suggesting a role in chemopre-
Application of a Thermodynamic Concept for the Analysis of Structural Degradation of Soap Thickened Lubricating Greases

Lubricating greases are special lubricants with a wide range of application. The tribologically stressed grease is used as tribological system and finally modeled as an open thermodynamic system. This study investigated the phenomenon of self-optimization and applied to the process of shearing a grease. The conditions for self-optimization and the consequences of created dissipative structures are investigated according to the interpreted literature.
Tacrine Treatment of Alzheimer’s Disease: Many Expectations,Few Certainties

Quality of life and behavioral functions are severely reduced in patients affected by Alzheimer’s disease (AD). Among the drugs employed in the treatment of this invalidating degenerative dementia, tacrine (THA) seemed to play a possible therapeutic role. Our study was aimed to evaluate the efficacy of THA in the treatment of AD, performing a comparison with lecithin and/or placebo treatment. Five randomized controlled trials on tacrine versus lecithin and/or placebo treatment were randomly selected. Mantel-Haenszel-Peto method was applied. Patients treated with tacrine achieved better results than control subjects (overall OR = 2.34; 95% CI 1.42–3.85); but long-term treatment with tacrine was not significantly more efficacious than placebo. Statistical significance in favor of THA versus other drugs employed was obtained in MMSE and ADAS-Cog tests in the studies carried out by Eagger et al. and Knapp et al. Moreover, Fitten et al. administered the highest tolerated THA dose to only a few patients enrolled in the study. The presence of broad CIs observed in the 5 meta-analytic studies infer non homogeneity of effects of treatment. Solely few patients improved, whereas the clinical conditions of the majority remained stationary. Between 5 and 10% of the outpatients in each single study presented reversible side effects calling for suspension of THA treatment. The optimal dose ranged between 80 and 160 mg THA, but often produced side effects. Comparative trials revealed the reduced efficacy and elevated toxicity of THA treatment, dampening the initial enthusiasm concerning the usefulness of this drug in AD. Furtermore, tacrine-induced side effects provoked many dropouts in all studies investigated. The effectiveness of tacrine treatment in AD disease was not fully confirmed. Other studies are required to identify doses and modalities of administration of this drug in AD.
Modified capacity enhanced PF (MCE-PF) downlink scheduling algorithm for heterogeneous LTE-Advanced Networks

This Scheduling in heterogeneous LTE-Advanced Networks is a very important approach where using the effective scheduler helps to enhance the overall system performance. There are different scheduling algorithms developed in downlink LTE system. The main improvement of this current paper is to design a Modified Capacity Enhanced PF (MCE-PF) Downlink Scheduling Algorithm for heterogeneous networks that achieves better performance in terms of throughput and spectral efficiency compared to the original PF and to other methods for scheduling. The new algorithm is, however, applied on the two types of networks heterogeneous and homogeneous networks to quantify its performance using simulation.
A retrospective analysis of blood gases with two different insulin infusion protocols in patients undergoing cardiovascular surgery.

AIM Intraoperative blood glucose concentration is known to be an independent risk factor for morbidity and mortality in patients undergoing cardiovascular surgery. Arterial blood gas analysis is an important investigation to monitor the acid-base balance and gas exchange in these patients. Hyperglycemia leads to a series of metabolic changes which affect acid-base balance and serum electrolytes. In this study, we aimed to look into the effect of glycemic control on arterial blood gas parameters, serum electrolytes, and hemoglobin (Hb). MATERIALS AND METHODS We collected data from diabetic patients who underwent cardiovascular surgery between 2010 and 2014. The patients were divided into two groups according to the insulin infusion protocols applied such as with conventional (180-250 mg/dl) (n = 17) (Group 1) and tighter glycemic targets (121-180 mg/dl) (n = 51) (Group 2). We retrospectively analyzed arterial blood gas results taken at different perioperative time points from these patients. RESULTS We found that pH HCO3and base excess, serum sodium, potassium, calcium, and Hb were similar in both groups. CONCLUSION Our study showed that a tighter intraoperative glycemic control does not affect arterial blood gas parameters, serum electrolytes, or Hb when compared to the conventional glycemic control.
Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon‐like peptide‐1 secretion

To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic polypeptide, glucose, insulin, C‐peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake.
Metabolic stress regulates ERK activity by controlling KSR‐RAF heterodimerization

Altered cell metabolism is a hallmark of cancer, and targeting specific metabolic nodes is considered an attractive strategy for cancer therapy. In this study, we evaluate the effects of metabolic stressors on the deregulated ERK pathway in melanoma cells bearing activating mutations of the NRAS or BRAF oncogenes. We report that metabolic stressors promote the dimerization of KSR proteins with CRAF in NRAS‐mutant cells, and with oncogenic BRAF in BRAFV600E‐mutant cells, thereby enhancing ERK pathway activation. Despite this similarity, the two genomic subtypes react differently when a higher level of metabolic stress is induced. In NRAS‐mutant cells, the ERK pathway is even more stimulated, while it is strongly downregulated in BRAFV600E‐mutant cells. We demonstrate that this is caused by the dissociation of mutant BRAF from KSR and is mediated by activated AMPK. Both types of ERK regulation nevertheless lead to cell cycle arrest. Besides studying the effects of the metabolic stressors on ERK pathway activity, we also present data suggesting that for efficient therapies of both genomic melanoma subtypes, specific metabolic targeting is necessary.
Hepatic fibrosis and its serum markers: a review.

Hepatic fibrosis is characterized by a progressive increase in extracellular matrix in the liver, formed by collagens, proteoglycans and glycoproteins, qualitatively similar but quantitatively different from that in normal liver. A great number of matrix-related substances have been investigated in serum in order to identify reliable serum markers of liver fibroplasia. Among the various cleavage products of collagen precursor, the NPIIIP collagen is at present considered the most reliable serum marker of active fibrogenesis in liver, useful in monitoring the progression of fibrosis and in assessing the therapeutic efficacy of antifibrotic drugs. Lam-P1 and type IV collagen are now regarded as putative markers of basement membrane formation and sinusoids capillarization, an important pathological process in fibrosing disease, related to the impairment of hepatic circulation. Other serum-measured matrix-related substances, e.g. enzymes involved in collagen metabolism, fibronectin and proteoglycans, have not proved to reflect liver fibroplasia reliably. In spite of the availability of useful serum markers, the assessment of hepatic fibrosis is still based on liver biopsy.
Emergence of Aspergillus fumigatus azole resistance in azole‐naïve patients with chronic obstructive pulmonary disease and their homes

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34 /L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France.
Genetic and Epigenetic Alterations of the Estrogen Receptor Gene and Hormone Independence in Human Breast Cancer

The existence of hormone-independent tumors is a substantial problem for the present endocrine treatment of breast cancers. Estrogen receptor (ER) gene mutation can change the biochemical activity of the protein and can affect hormone responsiveness. However, quite a few mutations of significance have been described in breast cancer. Recently, numerous variant ERs have been detected at the mRNA level with alternative splicing, yielding deletion of exon 3, 5, or 7. The truncated ER protein induced from variant mRNA could mainly be exhibited as a repressor through dominant negative effects on normal ER protein. The mechanism of the loss of hormone dependency is, however, still very complex. Further work to assess the correlation between clinical behavior and ER variants is required to determine whether these variants play a role in hormone-resistant disease. Additionally, the DNA methylation of the ER gene itself may control ER expression. These epigenetic changes can play an important role in the loss of hormone dependence in breast cancer.
Comparative diffusion study of two nitrosoureas: carmustine and fotemustine in normal rat brain, human and rat brain biopsies.

In order to assess the apparent diffusion coefficient of two nitrosoureas (carmustine and fotemustine) in the brain, a model of planar diffusion was used in the rat brain and in rat and human brain biopsies. Drugs were deposed on the brain surface at a constant concentration for 30 min. At the end of the diffusion time, the concentration gradient was determined with microelectrodes using voltammetry at 5 different depths in the extracellular space of the gray matter (0-304 microns). Voltammetry with microelectrodes measured quantitatively intact drug in the brain extracellular space (CV 4% for the 2 drugs) in the range studied. The same procedure was used for human and rat brain biopsies which were held in a small cup. The apparent diffusion coefficients in living animals were 0.49 x 10(-6) cm2.s-1 for carmustine and 0.23 x 10(-6) cm2.s-1 for fotemustine; in human biopsies, they were 0.84 x 10(-6) cm2.s-1 for carmustine and 0.37 x 10(-6) cm2.s-1 for fotemustine. Significant differences in the apparent diffusion coefficients of the drugs were accounted for by the fact that the intracellular penetration of fotemustine was better than that of carmustine.
Learning and adaptation: neural and behavioural mechanisms behind behaviour change

ABSTRACT This special issue presents perspectives on learning and adaptation as they apply to a number of cognitive phenomena including pupil dilation in humans and attention in robots, natural language acquisition and production in embodied agents (robots), human-robot game play and social interaction, neural-dynamic modelling of active perception and neural-dynamic modelling of infant development in the Piagetian A-not-B task. The aim of the special issue, through its contributions, is to highlight some of the critical neural-dynamic and behavioural aspects of learning as it grounds adaptive responses in robotic- and neural-dynamic systems.
Human studies with microneedles for evaluation of their efficacy and safety

ABSTRACT Introduction: During the past two decades, many studies have documented the development of microneedles (MNs) as a feasible technique for the effective administration of drugs. More and more human studies have been done with MNs to bridge the gap between research and market applications that provide efficacious techniques for clinical implementation. Areas covered: The aim of this review is provide a brief description of the status of human study with MNs and to demonstrate progress for the right use of microneedle arrays in clinical settings. It also describes the considerations for clinical application with each type of MNs. Expert opinion: Microneedle systems were introduced to overcome the limitations of conventional methods of drug administration. Lots of microneedle systems have undergone clinical evaluation to determine their efficacy and safety, and many studies have demonstrated positive results. The successful clinical use of the microneedle in vaccine therapy is remarkable and supports the importance of conducting further tests in a wide range of medical applications. Self-administered MNs appeared to be an attractive alternative method that needs further research to become a reality in the near future.