Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of tenofovir's population pharmacokinetic parameters without reliable dosing histories and application to tracing dosing history using simulation strategies

The objectives of this analysis were to develop a population pharmacokinetic model (PPK) for tenofovir without using potentially unreliable patient reported dosing records and to retrace patient dosing history using pharmacokinetic simulations conditioned on protocol design constraints to assess patient adherence. MTN‐001 is a multi‐center, open label, 3‐way cross over study comparing oral, vaginal and combination (oral and vaginal) administration of tenofovir in healthy women. It was reported that self‐reported adherence in this study was high (94%), but serum concentrations indicated only 64% of participants used tablets consistently. A method based on superposition was applied to develop the population PPK considering only observable clinic visit dosing information. A two compartment model described the data well and the parameters agree with the literature reported values. Race was not a significant covariate on clearance. Retracing of the dosing history with 3‐past dose resolution was not successful. Trial simulations with full adherence assumption predict a median Cmin of 68 ng/mL, which is in agreement with literature reports. Non‐adherence at 25% resulted in 37–51% reduction in Cmin using one coin and two coin models, respectively. Population analyses should consider some method of correction for non‐adherence to avoid biased estimates.
Differential modes of photosensitisation in cancer cells by berberine and coralyne

Abstract In this study, we demonstrated that the cytotoxicity of the protoberberine alkaloids such as coralyne, berberine and jatrorrhizine to several human cancer cell lines can be improved significantly in combination with UVA exposure. However, the phototoxic property of coralyne was much higher than that of the other two alkaloids. The combination of coralyne and UVA (designated as CUVA) induced oxygen-independent cytotoxicity in the human lung cancer A549 cells by producing more lethal DNA double-strand breaks, and the effect was mediated via the replication machinery. In comparison, the berberine-induced phototoxicity to the A549 cells was mediated by reactive oxygen species generation, mitochondrial membrane permeabilisation and caspase-9/caspase-3 activation.
Suicide attempts among adolescents in northeastern Slovenia: A 25 year report

UNLABELLED Slovenia is one of the countries with the highest national suicide rates (30/100,000/year). The rate of suicide attempts is accordingly high, for both adolescents and adults. Suicidal children and adolescents from the four North-eastern regions of Slovenia are hospitalised at the Child and Adolescent Psychiatry Unit of the General Hospital Maribor. The aim of this study was to show the pattern of changes in these hospitalisations along 25 years. METHOD The data was collected retrospectively, using chart review of this unit by a psychiatrist for the years 1978 through 2004. RESULTS The data consists of two different samples. The first sample contains gender distribution (n = 774) from 1978 to mid 2004 with 664 girls and 110 boys, and the second sample (n = 1,477) consisted of suicide attempts as well as alcohol (n = 772) and drug abuse (n = 115) data for the last decade. The number of hospitalisations was increasing in a wavy curve with average 7,5 times more admitted girls than boys. In 98%, the suicide method was intoxication, and most were additionally diagnosed with "adolescent crisis" (ICD-10: F93.8). CONCLUSION The rise in the number of admitted suicidal adolescents was partly consequent to the improvement of their detection maybe because 25 years ago most of these cases were recorded as "accidental poisonings" and did not include the diagnosis of a suicide attempt. The socio-economic changes characteristic of a country in transition also contributed to this increase, as did the development of the Unit with more trained staff and advanced treatment.
Slovak Vegetation Database

The Slovak Vegetation Database (or Central Database of Phytosociological Samples – CDF; EU-SK-001) was established in 1995 at the Institute of Botany, Slovak Academy of Sciences. The aim was to assemble all available phytosociological releves from the territory of Slovakia and adjacent areas with the objective of producing a vegetation overview of all vegetation types and plant communities of Slovakia. The database provides information not only about the locality, floristic composition and variability of individual vegetation types but also on several environmental variables such as inclination, aspect, geology or soil type, characteristics for individual releves. The Slovak vegetation database is providing the basis for national and supra-national classification overviews and other scientific studies. It can be linked to any international database, and supports not only the exchange of data, but mainly the possibility of bior multilateral projects, vegetation overviews of supra-regional areas (e.g. Carpathians) and supra-regional analyses of vegetation data that will enable a better insight into the functioning and distribution of plant communities, as well as evaluating local and global changes. The current structure of the database used as a basis of Slovak Vegetation Database reflects the experiences and suggestions of the users after years of using the programme TURBOVEG. Very important is also the non-commercial use of the database not only by scientists (botanists, zoologists, ecologists etc.), but also by nature conservation institutions, since it contains high-quality floristic records of both vascular and non-vascular plants with exact localisation and basic environmental characteristics.
Time course of release of pheromonally active gonadal steroids and their conjugates by ovulatory goldfish.

Previous studies have demonstrated that ovulatory goldfish synthesize and release a variety of steroids into the water, where some of them function as sex pheromones. Among the steroids which have been measured are free androstenedione, testosterone, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P), 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (17,20 beta,21-P), 17 alpha-hydroxy-4-pregnene-3,20-dione (17-P), 11-deoxycortisol (17,21-P), and 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P), glucuronidated testosterone, 17,20 beta-P, and 17,20 beta,21-P, and sulfated 17,21-P, 17,20 beta-P, and 17,20 beta,21-P. This study reports the changes in the amounts of these steroids released into the water, at 3-hr intervals, by 12 female goldfish injected with human chorionic gonadotrophin (HCG). Eight fish ovulated. The amounts of steroids released into the water were significantly higher in the fish which ovulated than in those which did not. The peak rate of release (ng per hour) of free androstenedione (91), glucuronidated testosterone (143), and sulfated 17,21-P (33) occurred at ca. 4 hr postinjection; free 17-P (163) and free 17,21-P (217) at ca. 6 hr. ; free 17,20 beta-P (58) and free 17,20 beta,21-P (58) at ca. 7.5 hr; and glucuronidated 17,20 beta-P (96), glucuronidated 17,20 beta,21-P (264), sulfated 17,20 beta-P (64) and sulfated 17,20 beta,21-P (153) at ca. 9 hr. Amounts of all of the steroids were at their lowest between 12 and 15 hr and, in the ovulated fish, had risen significantly again between 18 and 21 hr. The amounts of glucuronidated testosterone, 17,20 beta-P and 17,20 beta,21-P, and of sulfated 17,20 beta-P and 17,20 beta,21-P, in water exceeded those of free steroid. Elevated levels of free and glucuronidated steroids were also found in the blood plasma of HCG-injected fish. Considerably more androstenedione than testosterone was released into the water. Assessment of the "pheromonal effectiveness" of each steroid indicated that the free and sulfated forms of 17,20 beta-P and 17,20 beta,21-P, and androstenedione were the most important pheromonal steroids released by female goldfish.
On the Space-Time Structure of Human Interlimb Co-Ordination

In three experiments we show, using behavioural measures of movement outcome, as well as movement trajectory information and resultant kinematic profiles, that there is a strong tendency for the limbs to be co-ordinated as a unitary structure even under conditions where the movements are of disparate difficulty. Environmental constraints (an obstacle placed in the path of one limb, but not in the other) are shown to modulate the space-time behaviour of both limbs (Experiment II). Our results obtain for symmetrical (Experiment I) as well as asymmetrical movements that involve non-homologous muscle groups (Experiment III). These findings suggest that in multi-joint limb movements, the many degrees of freedom are organised to function temporarily as a single coherent unit that is uniquely specific to the task demands placed on it. For movements in general, and two-handed movements in particular, such units are revealed in a partitioning of the relevant force demands for each component (a force scaling characteristic) and a preservation of the internal “topology” of the action, as indexed by the relative timing among components. These features, as well as systematic deviations from perfect synchrony between the limbs can be rationalised by a model that assumes the limbs behave qualitatively like non-linear oscillators.
Computer-assisted minimally invasive total knee arthroplasty compared with standard total knee arthroplasty. A prospective, randomized study.

BACKGROUND There is little information on the feasibility of computer navigation when using a minimally invasive approach for total knee arthroplasty, during which the anatomic landmarks for registration may be obscured. The purpose of the present study was to determine the radiographic accuracy of this technique and to compare the rate of functional recovery between patients who underwent computer-assisted minimally invasive arthroplasty and those who underwent conventional total knee arthroplasty. METHODS One hundred and eight consecutive patients were randomized to undergo computer-assisted minimally invasive total knee arthroplasty or conventional total knee arthroplasty. Perioperative pain management was standardized. The clinical parameters, long-leg radiographs, and functional assessment scores were evaluated for six months postoperatively. RESULTS Patients who underwent computer-assisted minimally invasive total knee arthroplasty had a significantly longer operative time (by a mean of twenty-four minutes) and a significantly shorter inpatient stay (3.3 compared with 4.5 days) in comparison with those who underwent conventional arthroplasty (p </= 0.001). Significantly more patients in the computer-assisted minimally invasive total knee arthroplasty group were able to walk independently for more than thirty minutes at one month (p = 0.04). The percentage of patients with a coronal tibiofemoral angle within +/-3 degrees of the ideal was 92% for the computer-assisted minimally invasive total knee arthroplasty group, compared with 68% for the conventional total knee arthroplasty group (p = 0.003). CONCLUSIONS Although specific clinical parameters reflect an early increased rate of functional recovery in association with computer-assisted minimally invasive total knee arthroplasty within the first postoperative month, the main advantage of this technique over conventional total knee arthroplasty is improved postoperative radiographic alignment without increased short-term complications.
Complex interventions: how “out of control” can a randomised controlled trial be?

Complex interventions are more than the sum of their parts, and interventions need to be better theorised to reflect this Many people think that standardisation and randomised controlled trials go hand in hand. Having an intervention look the same as possible in different places is thought to be paramount. But this may be why some community interventions have had weak effects. We propose a radical departure from the way large scale interventions are typically conceptualised. This could liberate interventions to be responsive to local context and potentially more effective while still allowing meaningful evaluation in controlled designs. The key lies in looking past the simple elements of a system to embrace complex system functions and processes. The suitability of cluster randomised trials for evaluating interventions directed at whole communities or organisations remains vexed.1 It need not be.2 Some health promotion advocates (including the WHO European working group on health promotion evaluation) believe randomised controlled trials are inappropriate because of the perceived requirement for interventions in different sites to be standardised or look the same.1 3 4 They have abandoned randomised trials because they think context level adaptation, which is essential for interventions to work, is precluded by trial designs. An example of context level adaptation might be adjusting educational materials to suit various local learning styles and literacy levels. Lead thinkers in complex interventions, such as the UK's Medical Research Council, also think that trials of complex interventions must “consistently provide as close to the same intervention as possible” by “standardising the content and delivery of the intervention. ”5 By contrast, however, they do not see this as a reason to reject randomised controlled trials. These divergent views have led to problems on two fronts. Firstly, the field of health promotion is being turned away from randomised …
The Measure of All Minds: Evaluating Natural and Artificial Intelligence

Are psychometric tests valid for a new reality of artificial intelligence systems, technology-enhanced humans, and hybrids yet to come? Are the Turing Test, the ubiquitous CAPTCHAs, and the various animal cognition tests the best alternatives? In this fascinating and provocative book, Jose Hernandez-Orallo formulates major scientific questions, integrates the most significant research developments, and offers a vision of the universal evaluation of cognition. By replacing the dominant anthropocentric stance with a universal perspective where living organisms are considered as a special case, long-standing questions in the evaluation of behavior can be addressed in a wider landscape. Can we derive task difficulty intrinsically? Is a universal g factor - a common general component for all abilities - theoretically possible? Using algorithmic information theory as a foundation, the book elaborates on the evaluation of perceptual, developmental, social, verbal and collective features and critically analyzes what the future of intelligence might look like.
Related TT viruses in chimpanzees.

A series of serum specimens obtained from two chimpanzees experimentally infected with hepatitis A virus (HAV), hepatitis C virus, and hepatitis G/GB-C virus were tested for TT virus (TTV) by polymerase chain reaction (PCR). All PCR fragments obtained from both animals were directly sequenced, and the nucleotide sequences were compared to each other and to all known TTV sequences. This comparison showed that both animals were infected simultaneously with four new TTV variants designated A, M1, M2, and M3. One chimpanzee was found to be infected with TTV only after HAV inoculation, whereas the other animal was infected with TTV before any experimental procedure was performed. A set of PCR primers specific for these four new TTV variants was used to amplify TTV-like sequences from nine naive chimpanzees. None of these animals was infected with the prototype TTV variant. Two of these animals, however, were infected with one of the new TTV variants, while one animal was infected with an additional new TTV variant designated T. Among 99 hepatitis patients, 29 were found to be infected with the prototype TTV variant. None of these human specimens was found to be positive by PCR specific for TTV variants A, M1, M2, and M3. Similarly, not a single specimen from a smaller subset of human serum samples was found to be positive for the TTV variant T. Phylogenetic analysis performed on all known TTV sequences demonstrated that TTV can be classified into 13 different, yet closely related TTV species, designated as TTV-I for the prototype variant through TTV-XIII. The new variants M1 and M2 were classified as two different genotypes of TTV-VI, variant M3 was classified as TTV-VII, variant A was classified as TTV-VIII, and variant T was classified as TTV-IX. Thus, the data obtained in this study suggest that TTV represents a large swarm of TTV-like species, some of which have not been detected in humans and circulate predominantly among chimpanzees.
Dynamic QoS Allocation for Multimedia Ad Hoc Wireless Networks

In this paper, we propose an approach to support QoS for multimedia applications in ad hoc wireless network. An ad hoc network is a collection of mobile stations forming a temporary network without the aid of any centralized coordinator and is different from cellular networks which require fixed base stations interconnected by a wired backbone. It is useful for some special situations, such as battlefield communications and disaster recovery. The approach we provide uses CSMA/CA medium access protocol and additional reservation and control mechanisms to guarantee quality of service in ad hoc network system. The reason we choose CSMA protocol instead of other MAC protocols is that it is used in most of currently wireless LAN productions. Via QoS routing information and reservation scheme, network resources are dynamically allocated to individual multimedia application connections.
Privacy guaranteeing execution containers: one time use of personal data by location based services

Privacy issues are becoming more and more important especially since the cyber and the real world are converging up to certain extent when using mobile devices. Means that really protect privacy are still missing. The problem is, as soon as a user provides data to a service provider the user looses control over her data. The simple solution is not to provide any data but then a lot of useful services e.g. navigation applications cannot be used. In order to remedy this problem we propose privacy guaranteeing execution containers (PGEC). Basically the concept is that the application gets access to the user data in a specially protected and certified environment, the PGEC. PGECs enable applications to access private user data locally and guarantee that the user data is deleted as soon as the service is quit. Thus, the PGEC guarantees a "one time use" of the provided private data. The PGECs also restrict the communication between the application and the service provider to what is explicitly allowed by the service user. In order to highlight the security provided by the PGEC, we discuss potential attacks such as modified execution environments as well as appropriate countermeasures.
A real‐time PCR assay for the differentiation of Candida species

Aims: We established a real‐time PCR assay for the detection and strain identification of Candida species and demonstrated the ability to differentiate between Candida albicans the most common species, and also Candida parapsilosis, Candida glabrata, Candida tropicalis and Candida dubliniensis by LightCycler PCR and melting curve analysis.
Pulmonary reperfusion injury

Pulmonary reperfusion injury is a clinical syndrome with no single and recognized pathophysiologic mechanism. It is a major cause of morbidity and mortality following lung transplantation, cardiogenic shock, or cardiopulmonary bypass. The underlying mechanisms remain uncertain. Lung inflammatory injury induced by lipopolysaccharide, characterized by rapid sequestration of neutrophils in response to inflammatory chemokines and cytokines released in the lungs is an acceptable theory. Structural or functional impairment of surfactant has been noted in pulmonary reperfusion injury. The pathological changes may include bilateral pulmonary infiltrates, reduced lung compliance and worsening of gas exchange in the immediate posttransplant period. Recruitment maneuver and high positive end-expiratory pressure can relieve postoperative respiratory failure, especially in the patient with reperfusion pulmonary edema after pulmonary thromboendarterectomy. Pharmaceutical agents, including inhaled nitric oxide, soluble complement receptor type 1, prostaglandin E1 and exogenous surfactant, attenuate pulmonary reperfusion injury through distinct mechanisms. Extracorporeal membrane oxygenation and Novalung are temporary assistance in bridging to lung transplantation, stabilization of hemodynamics during transplantation and treatment of severe lung dysfunction and primary graft failure. Modulation of heme oxygenase-1 expression, ischemic conditioning and gene therapy are future directions for pulmonary reperfusion injury management.
Expression of AmphiCoe, an amphioxus COE/EBF gene, in the developing central nervous system and epidermal sensory neurons

Summary: The COE/EBF gene family marks a subset of prospective neurons in the vertebrate central and peripheral nervous system, including neurons deriving from some ectodermal placodes. Since placodes are often considered unique to vertebrates, we have characterised an amphioxus COE/EBF gene with the aim of using it as a marker to examine the timing and location of peripheral neuron differentiation. A single COE/EBF family member, AmphiCoe, was isolated from the amphioxus Branchiostoma floridae. AmphiCoe lies basal to the vertebrate COE/EBF genes in molecular phylogenetic analysis, suggesting that the duplications that formed the vertebrate COE/EBF family were specific to the vertebrate lineage. AmphiCoe is expressed in the central nervous system and in a small number of scattered ectodermal cells on the flanks of neurulae stage embryos. These cells become at least largely recessed beneath the ectoderm. Scanning electron microscopy was used to examine embryos in which the ectoderm had been partially peeled away. This revealed that these cells have neuronal morphology, and we infer that they are the precursors of epidermal primary sensory neurons. These characters lead us to suggest that differentiation of some ectodermal cells into sensory neurons with a tendency to sink beneath the embryonic surface represents a primitive feature that has become incorporated into placodes during vertebrate evolution. genesis 38:58–65, 2004. © 2004 Wiley‐Liss, Inc.
[Central nervous system infections in neonates caused by multiresistant Klebsiella pneumoniae].

OBJECTIVE To evaluate the incidence, clinical course and outcome of central nervous system (CNS) infections caused by multiresistant Klebsiella pneumoniae (MRKP) in critically ill neonates. METHODS Retrospective study of neonates treated in Neonatal Department of Poznań University of Medical Science during a three years period from 1st January 1997 to 31st December 1999. Isolates were identified as Klebsiella pneumoniae with the ID32Gn test (bioMerieux), and antibiotic susceptibility was determined with ATBG test (bioMerieux) and with disc-diffusion technique. RESULTS In this period there were 27 cases of CNS infections in our Department 17--65.4% of which (16 meningitis, one ventriculitis and one brain abscess), were caused by Klebsiella pneumoniae. 81.25% occurred in prematures (< 31 weeks of gestational age and < 1500 grams). In 10 (58.8%) cases CNSI developed in the course of sepsis. 9 children died. In all the isolates ESBL expression in vitro was detected. Only carbapenems and fluoroquinolones were active in all the cases. Ventriculitis was treated successfully with imipenem administered intraventrically and brain abscess surgically. CONCLUSIONS CNS infections in neonates caused by MRKP are quite frequent, severe and possibly life threatening. Eradication of these strains from hospital environment by introducing adequate sanitary regime and reasonable antibiotic policies is the only method of conquering the infections.