Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating the Pharmacodynamic Effect of Antimalarial Drugs in Clinical Trials by Quantitative PCR

ABSTRACT The ongoing development of new antimalarial drugs and the increasing use of controlled human malaria infection (CHMI) studies to investigate their activity in early-stage clinical trials require the development of methods to analyze their pharmacodynamic effect. This is especially so for studies where quantitative PCR (qPCR) is becoming the preferred method for assessing parasite clearance as the study endpoint. We report the development and validation of an analytic approach for qPCR-determined parasite clearance data. First, in a clinical trial with the licensed antimalarial combination sulfadoxine-pyrimethamine (S/P), qPCR data were collected from 12 subjects and used to determine qPCR replicate variability and to identify outliers. Then, an iterative analytic approach based on modeling the log-linear decay of parasitemia following drug treatment was developed to determine the parasite reduction ratio (PRR) and parasite clearance half-life, both measures of parasite clearance. This analytic approach was then validated with data from 8 subjects enrolled in a second study with the licensed antimalarial drug mefloquine. By this method, the PRR and parasite clearance half-lives for S/P and Mefloquine were determined to be 38,878 (95% confidence interval [95% CI], 17,396 to 86,889) at 3.15 (95% CI, 2.93 to 3.41) days and 157 (95% CI, 130 to 189) at 6.58 (95% CI, 6.35 to 6.83) days for the respective studies. No serious adverse events occurred in the two trials, and pharmacokinetic values were within expected ranges for sulfadoxine and pyrimethamine. The robust statistical method that we have developed to analyze qPCR-derived pharmacodynamic data from CHMI studies will facilitate the assessment of the activity of a range of experimental antimalarial drugs now entering clinical trials. (This trial was registered with the Australian New Zealand Clinical Trials Registry under registration numbers ACTRN12611001203943 and ACTRN12612000323820.)
A prospective study of the risk of tuberculosis among HIV‐infected patients

ObjectiveTo evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1 -infected patients. MethodsProspective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration ≥5mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl—Neelsen stains or grown in Lowenstein—Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. ResultsActive TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 $pM 11 months (range, 2–52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3–27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 $pM 103 $$ 106/I (range/ −1–400 $$ 106/l). ConclusionsAmong HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 $$ 106/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.
Effect of NaF, SnF2, and TiF4 Toothpastes on Bovine Enamel and Dentin Erosion-Abrasion In Vitro

The aim of this study was to compare the effect of toothpastes containing TiF4, NaF, and SnF2 on tooth erosion-abrasion. Bovine enamel and dentin specimens were distributed into 10 groups (n = 12): experimental placebo toothpaste (no F); NaF (1450 ppm F); TiF4 (1450 ppm F); SnF2 (1450 ppm F); SnF2 (1100 ppm F) + NaF (350 ppm F); TiF4 (1100 ppm F) + NaF (350 ppm F); commercial toothpaste Pro-Health (SnF2—1100 ppm F + NaF—350 ppm F, Oral B); commercial toothpaste Crest (NaF—1.500 ppm F, Procter & Gamble); abrasion without toothpaste and only erosion. The erosion was performed 4 × 90 s/day (Sprite Zero). The toothpastes' slurries were applied and the specimens abraded using an electric toothbrush 2 × 15 s/day. Between the erosive and abrasive challenges, the specimens remained in artificial saliva. After 7 days, the tooth wear was evaluated using contact profilometry (μm). The experimental toothpastes with NaF, TiF4, SnF2, and Pro-Health showed a significant reduction in enamel wear (between 42% and 54%). Pro-Health also significantly reduced the dentin wear. The toothpastes with SnF2/NaF and TiF4/NaF showed the best results in the reduction of enamel wear (62–70%) as well as TiF4, SnF2, SnF2/NaF, and TiF4/NaF for dentin wear (64–79%) (P < 0.05). Therefore, the experimental toothpastes containing both conventional and metal fluoride seem to be promising in reducing tooth wear.
On the Notion of Framing in Computational Creativity

In most domains, artefacts and the creativity that went into their production is judged within a context; where a context may include background information on how the creator feels about their work, what they think it expresses, how it fits in with other work done within their community, their mood before, during and after creation, and so on. We identify areas of framing information, such as motivation, intention, or the processes involved in creating a work, and consider how these areas might be applicable to the context of Computational Creativity. We suggest examples of how such framing information may be derived in existing creative systems and propose a novel dually-creative approach to framing, whereby an automated story generation system is employed, in tandem with the artefact generator, to produce suitable framing information. We outline how this method might be developed and some longer term goals.
Prediction of protein-ligand interactions from paired protein sequence motifs and ligand substructures

Identification of small molecule ligands that bind to proteins is a critical step in drug discovery. Computational methods have been developed to accelerate the prediction of protein-ligand binding, but often depend on 3D protein structures. As only a limited number of protein 3D structures have been resolved, the ability to predict protein-ligand interactions without relying on a 3D representation would be highly valuable. We use an interpretable confidence-rated boosting algorithm to predict protein-ligand interactions with high accuracy from ligand chemical substructures and protein 1D sequence motifs, without relying on 3D protein structures. We compare several protein motif definitions, assess generalization of our model’s predictions to unseen proteins and ligands, demonstrate recovery of well established interactions and identify globally predictive protein-ligand motif pairs. By bridging biological and chemical perspectives, we demonstrate that it is possible to predict protein-ligand interactions using only motif-based features and that interpretation of these features can reveal new insights into the molecular mechanics underlying each interaction. Our work also lays a foundation to explore more predictive feature sets and sophisticated machine learning approaches as well as other applications, such as predicting unintended interactions or the effects of mutations.
Cold blooded.

In undergoing this life, many people always try to do and get the best. New knowledge, experience, lesson, and everything that can improve the life will be done. However, many people sometimes feel confused to get those things. Feeling the limited of experience and sources to be better is one of the lacks to own. However, there is a very simple thing that can be done. This is what your teacher always manoeuvres you to do this one. Yeah, reading is the answer. Reading a book as this cold blooded and other references can enrich your life quality. How can it be?
Clinical Evaluation of Parkinson's‐Related Dysphonia

Objectives: Nearly one third of patients with idiopathic Parkinson's disease (IPD) cite dysphonia, characterized subjectively as causing a harsh and breathy voice, as their most debilitating deficit. Medical or behavioral treatments may lead to voice improvement. The purpose of this study was 1) to determine whether vocal fold injection of Cymetra (micronized form of collagen, elastin, proteoglycans; Lifecell Co.) is associated with changes in dysphonic voice characteristics in subjects with IPD, as judged perceptually using a standard instrument Consensus Auditory‐Perceptual Evaluation of Voice (CAPE‐V), and (2) which acoustic and aerodynamic measurements of voice are most reflective of any observed perceptual changes in voice.
Fast Logo Detection and Recognition in Document Images

The scientific significance of automatic logo detection and recognition is more and more growing because of the increasing requirements of intelligent document image analysis and retrieval. In this paper, we introduce a system architecture which is aiming at segmentation-free and layout-independent logo detection and recognition. Along with the unique logo feature design, a novel way to ensure the geometrical relationships among the features, and different optimizations in the recognition process, this system can achieve improvements concerning both the recognition performance and the running time. The experimental results on several sets of real-word documents demonstrate the effectiveness of our approach.
Electrical stimulation of the supplementary eye fields in the head-free macaque evokes kinematically normal gaze shifts.

The supplementary eye fields (SEFs), located on the dorsomedial surface of the frontal cortex, are involved in high-level aspects of saccade generation. Some reports suggest that the same area could also be involved in the generation of motor commands for the head. If so, it is important to establish whether this structure encodes eye and head commands separately or gaze commands that give rise to coordinated eye-head movements. Here we systematically stimulated (50 microA, 300 Hz, 200 ms) the SEF of two head-free (head unrestrained) macaques while recording three-dimensional eye and head rotations. A total of 55 sites were found to consistently elicit saccade-like gaze movements, always in the contralateral direction with variable vertical components, and ranging in average amplitude from 5 to 60 degrees. These movements were always a combination of eye-in-head saccades and head-in-space movements. We then performed a comparison between these movements and natural gaze shifts. The kinematics of the elicited movements (i.e., their temporal structure, their velocity-amplitude relationships, and the relative contributions of the eye and the head as a function of movement amplitude) were indistinguishable from those of natural gaze shifts. Additionally, they obeyed the same three-dimensional constraints as natural gaze shifts (i.e., eye-in-head movements obeyed Listing's law, whereas head- and eye-in-space movements obeyed Donders' law). In summary, gaze movements evoked by stimulating the SEF were indistinguishable from natural coordinated eye-head gaze shifts. Based on this we conclude that the SEF explicitly encodes gaze and that the kinematics aspects of eye-head coordination are implicitly specified by mechanisms downstream from the SEF.
SPARSE REGRESSION

Yuan an Lin (2004) proposed the grouped LASSO, which achieves shrinkage and selection simultaneously, as LASSO does, but works on blocks of covariates. That is, the grouped LASSO provides a model where some blocks of regression coefficients are exactly zero. The grouped LASSO is useful when there are meaningful blocks of covariates such as polynomial regression and dummy variables from categorical variables. In this paper, we propose an extension of the grouped LASSO, called ‘Blockwise Sparse Regression’ (BSR). The BSR achieves shrinkage and selection simultaneously on blocks of covariates similarly to the grouped LASSO, but it works for general loss functions including generalized linear models. An efficient computational algorithm is developed and a blockwise standardization method is proposed. Simulation results show that the BSR compromises the ridge and LASSO for logistic regression. The proposed method is illustrated with two datasets.
Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat.

BACKGROUND--The short chain fatty acid (SCFA) butyrate provides energy for colonocytes, stimulates colonic fluid and electrolyte absorption and is recognised as an effective treatment for multiple types of colitis. AIM--To examine the impact of butyrate enema therapy on the clinical course, severity of inflammation, and SCFA stimulated Na+ absorption in a chronic experimental colitis. METHODS--Distal colitis was induced in rats with a trinitrobenzenesulphonic acid (TNBS) enema. Five days after induction, rats were divided into groups to receive: no treatment, saline enemas, or 100 mM Na-butyrate enemas daily. On day 24, colonic damage score and tissue myeloperoxidase (MPO) activity were evaluated. Colon was mounted in Ussing chambers and Na+ transport and electrical activities were measured during a basal period and after stimulation with 25 mM butyrate. RESULTS--In the untreated and the saline enema treated TNBS groups, diarrhoea and extensive colonic damage were seen, associated with increased tissue MPO activities and absent butyrate stimulated Na+ absorption. In contrast, in the butyrate enema treated TNBS group, diarrhoea ceased, colonic damage score improved, and tissue MPO activity as well as butyrate stimulated Na+ absorption recovered to control values. CONCLUSION--Butyrate enema therapy stimulated colonic repair, as evidenced by clinical recovery, decreased inflammation, and restoration of SCFA stimulated electrolyte absorption.
Research on the Diagnosis of Rotor Coupling Fault Based on Wavelet Packet and Local Fisher Discriminant

this article is for the coupling fault diagnosis of rotor system, and does in-depth analysis of the rotor unbalance and misalignment, and the fault formed by the coupling of these two. Through research, Rotor Coupling was found filled with rich features. In this paper, Wavelet packet de-noising ideas being introduced to the local Fisher discriminant analysis (LFDA), a new method of fault diagnosis based on Wavelet Packet and Local Fisher Discriminant is proposed. The technology of information fusion is applied to the data processing with coupling faults. By comparing and analyzing the algorithms effect of LE, LPP, FDA, LFDA and IOLFA through experiment, it shows that LE and LPP are unable to identify the fault, while FDA, LFDA has better identification, and Wavelet Packet and Local Fisher discriminant has the best effect. Copyright © 2014 IFSA Publishing, S. L.
Pathologies of body, self, and space

This special issue of Cognitive Neuropsychiatry is devoted to accounts of some of the most bizarre and disturbing abnormalities of human experience precipitated by neurological and neuropsychiatric disorder. All but one of these papers derives from The First Sheffield Psychopathology Symposium, which took place 21 June 2001. The meeting was particularly concerned with those phenomena arising when body and self, soma and psyche become dissociated within or beyond the body’s surface. These conditions share a propensity for changing the subjective sense of the body and its relation either to the mind or the surrounding physical environment. There is some resemblance also in their neurological substrates (where these have been investigated) and certainly a recurrent theme is the complex functioning of the parietal cortex. However, as we shall see, there is by no means universal acceptance of the pathological status of some of these phenomena (see Halligan, this issue), nor is there necessarily an acceptance that a cognitive paradigm (as currently applied) can be used to explain all these symptoms adequately (see Thornton, this issue). We hope readers will find much that is intellectually stimulating as well as clinically relevant in these assembled contributions. In the opening two papers, we were interested in contemporary accounts of spatial neglect and dissociation syndromes, where, for neurological or psychological reasons, awareness of the body is compromised. In each, there is a relative constriction of bodily awareness, disturbing and often reducing the
The Costs of Texting in the Classroom

Many college students seem to find it impossible to resist the temptation to text on electronic devices during class lectures and discussions. One common response of college professors is to yield to the inevitable and try to ignore student texting. However, research indicates that because of limited cognitive capacities, even simple texting can reduce comprehension of class material at a rate of 10–20%. We review that research and present our study of the effects of texting on comprehension. Proposed alternatives to ignoring texting or outright bans include using smartphones for classroom exercises, educating students about the dangers of multitasking, and the use of “technology breaks. ”
Mechanism of the Blood Pressure—Raising Effect of Cocaine in Humans

Background—Although the sympathomimetic actions and cardiovascular complications of cocaine are ascribed to inhibition of norepinephrine (NE) reuptake, this hypothesis has not been tested in humans. We asked (a) whether cocaine can inhibit NE reuptake in the human peripheral circulation and (b) whether the NE-mediated peripheral vasoconstriction is the main mechanism mediating blood pressure-raising effect of cocaine. Methods and Results—In 15 healthy cocaine-naive subjects, we measured blood pressure, forearm blood flow, and forearm venous NE concentration during administration of (a) intrabrachial cocaine (0.15 and 15 mg), which produced no systemic neurohormonal effects, and (b) intranasal cocaine (2 mg/kg). Intrabrachial cocaine (0.15 mg) increased venous forearm NE concentration by 82% and vascular resistance by 71% (P <0.01). Increasing the intrabrachial cocaine dose by 100-fold to match the venous cocaine level of massive cocaine overdose caused a small additional increase in venous forearm NE concentration without causing significant additional vasoconstriction. Although intranasal cocaine (2 mg/kg) matched the venous cocaine concentrations caused by 0.15 mg of intrabrachial cocaine, venous NE concentration was unchanged as sympathetic nerve activity (SNA) decreased reflexively as the result of an increase in blood pressure. When SNA was restored to baseline by blunting the cocaine-induced rise in blood pressure (baroreflex activation) with nitroprusside, venous NE concentration increased to the same level caused by intrabrachial cocaine. Conclusions—In healthy cocaine-naive individuals, cocaine can inhibit NE reuptake in the human peripheral circulation. However, this mechanism does not contribute importantly to the blood pressure-raising effect of cocaine because activation of baroreceptor reflexes decreases SNA, the neural stimulus for NE release.
A vibro-tactile system for image contour display

This paper presents the design and testing of an image contour display system with vibrotactile array. The tactile image display system is attached on the user's back. It produces non-visual image and permits subjects to determine the position, size, shape of visible objects through vibration stimulus. The system comprises three parts: 1) a USB camera; 2) 48 (6×8) vibrating motors; 3) ARM micro-controlled system. Image is captured with the camera and the 2D contour is extracted and transformed into vibrotactile stimulus with a “contour following” (time-spatial dynamic coding) pattern. With this system subjects could identify the shape of object without special training; meanwhile fewer vibrotactile actuators are adopted. Preliminary experiments were carried out and the results demonstrated that the prototype was satisfactory and efficient for the visually impaired in seeing aid and environment perception.
MRI, CT, and PET/CT for ovarian cancer detection and adnexal lesion characterization.

OBJECTIVE The purpose of this article is to describe the role of MR, CT, and PET/CT in the detection of ovarian cancer and the evaluation of adnexal lesions. CONCLUSION The goal of imaging in ovarian cancer detection is to expeditiously distinguish benign adnexal lesions from those requiring further pathologic evaluation for malignancy. For lesions indeterminate on ultrasound, MRI increases the specificity of imaging evaluation, thus decreasing benign resections. CT is useful in diagnosis and treatment planning of advanced cancer. Although (18)F-FDG-avid ovarian lesions in postmenopausal women are considered suspicious for malignancy, PET/CT is not recommended for primary cancer detection because of high false-positive rates.
Myocardial passive shear wave detection

We studied the mechanical waves after mitral and aortic valve closure in the septal wall of 34 pigs (18 diabetic for heart failure and 16 controls), using high frame rate imaging on a programmable commercial ultrasound machine. The wave pattern was extracted from the data through a local tissue velocity estimator based on phase correlation. The wave propagation velocity was determined by manual estimates, cross-correlation, and Radon and Fourier transforms resulting in waves propagation velocities between 1.5 and 9 m/s, with spectral contents in the audible range of the heart tones. The Fourier analysis showed that the propagation velocity increases with frequency, which is consistent with asymmetric Lamb waves as can be expected from the geometry of the septal wall surrounded by blood.