Miracle-dz/UniFAR-FTUs huggingface dataset:
Irinotecan (CPT-11) metabolism and disposition in cancer patients.

The objective of this study was to determine the metabolic fate and disposition of the antitumor camptothecine derivative irinotecan (CPT-11). Ten patients with histological proof of malignant solid tumor received 200 mg/m2 CPT-11 as a 90-min i.v. infusion, followed by a 1.5-h i.v. infusion of cisplatin (60 or 80 mg/m2). Plasma, urine, and feces were collected for 56 h and analyzed by a specific reversed-phase high-performance liquid chromatographic assay for the parent drug and all four metabolites positively identified to date: SN-38; its beta-glucuronide conjugate, SN-38 beta-glucoronide (SN-38G); 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecine (APC); and 7-ethyl-10-[4-N-(1-piperidino)-1-amino]-carbonyloxycamptothecine (NPC). A three-exponential decline was observed in plasma for all compounds, with a clear predominance of the parent drug [25.6+/-5.71 microM x h (CPT-11) versus 15.8+/-3.51 microM x h (total metabolites)]. Total urinary excretion was 28.1+/-10.6% of the dose, with unchanged CPT-11 and SN-38G as the main excretion products. Whereas renal clearance of SN-38 was only a minor route of drug elimination, fecal concentrations of this compound were unexpectedly high (on average, 2.45% of the dose), suggestive of intestinal hydrolysis of SN-38G by bacterial beta-glucuronidase. CPT-11 and the other metabolites could also be identified from fecal extracts, with a very minor contribution overall of the cytochrome P-450-mediated compounds 7-ethyl-10-[4-N-(1-piperidino)-1-amino]-carbonyloxycamptothecine and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecine. Surprisingly, fecal excretion accounted for only 24.4+/-13.3% of the dose, leading to a total excretion of approximately 52%. These data indicate that half of the dose in urine and feces may constitute some further unknown nonextractable or nonfluorescent metabolites. The findings from this study should be of importance as a guide to further therapeutic evaluation of this drug.
CBCT Evaluation of the Upper Airway Morphological Changes in Growing Patients of Class II Division 1 Malocclusion with Mandibular Retrusion Using Twin Block Appliance: A Comparative Research

Objective The purpose of this study was to evaluate the morphological changes of upper airway after Twin Block (TB) treatment in growing patients with Class II division 1 malocclusion and mandibular retrusion compared with untreated Class II patients by cone beam computed tomography (CBCT). Materials and Methods Thirty growing patients who have completed TB treatment were recruited into TB group. The control group (n = 30) was selected from the patients with the same diagnosis and without TB treatment. CBCT scans of the pre-treatment (T1) and post-treatment (T2) data of TB group and control data were collected. After three-dimensional (3D) reconstruction and registration of T1 and T2 data, the morphological changes of upper airway during TB treatment were measured. The statistical differences between T1 and T2 data of TB group as well as T2 and control data were accessed by t-test. Results During the TB treatment, the mandible moved advanced by 3.52±2.14 mm in the horizontal direction and 3.77±2.10 mm in the vertical direction. The hyoid bone was in a more forward and inferior place. The upper airway showed a significant enlargement in nasopharynx, oropharynx and hypopharynx. In addition, the nasopharynx turned more circular, and the oropharynx became more elliptic in transverse shape. However, the transverse shape of the hypopharynx showed no significant difference. After comparison between T2 and control data, only the horizontal movement of the hyoid bone, the volumetric expansion of the oropharynx and hypopharynx, and changes of the oropharyngeal transverse shape showed significant difference. Conclusion Compared to the untreated Class II patients, the upper airway of growing patients with Class II division 1 malocclusion and mandibular retrusion showed a significant enlargement in the oropharynx and hypopharynx as well as a more elliptic transverse shape in the oropharynx, and the hyoid bone moved to an anterior position after TB treatment.
ROS-GC interlocked Ca2+-sensor S100B protein signaling in cone photoreceptors: review

Photoreceptor rod outer segment membrane guanylate cyclase (ROS-GC) is central to visual transduction; it generates cyclic GMP, the second messenger of the photon signal. Photoexcited rhodopsin initiates a biochemical cascade that leads to a drop in the intracellular level of cyclic GMP and closure of cyclic nucleotide gated ion channels. Recovery of the photoresponse requires resynthesis of cyclic GMP, typically by a pair of ROS-GCs, 1 and 2. In rods, ROS-GCs exist as complexes with guanylate cyclase activating proteins (GCAPs), which are Ca2+-sensing elements. There is a light-induced fall in intracellular Ca2+. As Ca2+ dissociates from GCAPs in the 20–200 nM range, ROS-GC activity rises to quicken the photoresponse recovery. GCAPs then progressively turn down ROS-GC activity as Ca2+ and cyclic GMP levels return to baseline. To date, GCAPs mediate the only known mechanism of ROS-GC regulation in the photoreceptors. However, in mammalian cone outer segments, cone synapses and ON bipolar cells, another Ca2+ sensor protein, S100B, complexes with ROS-GC1 and senses the Ca2+ signal with a K1/2 of 400 nM. Unlike GCAPs, S100B stimulates ROS-GC activity when Ca2+ is bound. Thus, the ROS-GC system in cones functions as a Ca2+ bimodal switch; with rising intracellular Ca2+, its activity is first turned down by GCAPs and then turned up by S100B. This presentation provides a historical perspective on the role of S100B in the photoreceptors, offers a pictorial model for the “bimodal” operation of the ROS-GC switch and projects future tasks that are needed to understand its operation. Some accounts of this review have been adopted from the original publications of these authors.
The effect of total knee replacement on employment in patients under 60 years of age.

INTRODUCTION The effect of primary total knee replacement on the employment status of 56 patients under 60 years of age was examined at a mean follow-up of 64 months. PATIENTS AND METHODS A total of 56 primary total knee replacements performed on patients under the age of 60 years by two surgeons between 1996 and 2003 were retrospectively assessed by postal questionnaire. Patients were selected from databases held at Holly House and Newham Hospital NHS Trust. RESULTS Overall, 97.5% of patients who were employed before their operation, returned to their previous work. However, in patients not working prior to total knee replacement none were employed after their operation. CONCLUSIONS Total knee replacement may be a valuable tool to help some patients to continue working but may not affect patients who are already unemployed.
KAPOSI'S SARCOMA: A REVIEW OF THE CLASSICAL AND EPIDEMIC FORMS a

Kaposi’s sarcoma (KS) represents a potential model for a virally associated human tumor. Prior to 1981, KS was considered a rare tumor occurring in cluster distribution. A sudden increase in the number of KS cases along with pneumonia caused by Pneumocystis carinii (PCP) and other opportunistic infections (01) was observed among the victims of the epidemic of acquired immune deficiency syndrome (AIDS). Initially, the cases were seen in New York and California, but now they have been reported from most large cities in the USA and many other countries. The first reports were exclusively among homosexual men and intravenous drug abusers; the disease, however, is now being observed among Haitians, hemophiliacs, and even in some children with AIDS. In this new epidemic form, KS presents with a more aggressive course involving skin, gastrointestinal tract, and lymph nodes. ’ The epidemic form of KS has a similar course to lymphadenopathic KS seen in African children. Whereas 01 have been the major cause of death in this epidemic, cases have been seen in whom KS has spread rapidly to vital organs such as lung, liver, and spleen. Much interest has been generated in the study of KS since the epidemic of AIDS. It is hoped that investigative work will provide a better insight into this interesting tumor.
Human muscle macrophages express &bgr;‐amyloid precursor and prion proteins and their mRNAs

&NA; Well‐characterized antibodies against &bgr;‐amyloid precursor protein (&bgr;APP) and prion protein (PrP), and specific cRNA probes, were used to localize &bgr;APP and PrP and their mRNAs in human muscle macrophages. Macrophages present in muscle biopsies of 51 patients with various neuromuscular disorders showed accumulation of &bgr;APP and PrP, and strongly expressed &bgr;APP and PrP mRNAs. These were present in all muscle macrophages unrelated to their localization within the muscle tissue or diagnosis. Our study provides the first demonstration that human muscle resident macrophages synthesize and accumulate &bgr;APP and PrP. We suggest that those proteins play a role in biology of muscle macrophages, including their participation in inflammatory and immune responses.
A micro RNA‐146a polymorphism is associated with coronary restenosis

The association of the miRNA‐146a polymorphism rs2910164 with atherosclerosis and restenosis was investigated. We found no association with atherosclerosis; however, we found a negative association for the G/C (P = 0.007) and a positive association for the C/C genotype with the risk of restenosis, which is the main drawback for cardiac surgery.
Influence of Calculation Method on Value of Activation Energy in Hot Forming

Abstract Influence of the methodology of mathematical processing of experimental data on the calculated value of the activation energy in hot forming was evaluated for three very different alloys: iron aluminide, low-alloyed steel and magnesium alloy. Application of the mean strain rates is appropriate but calculations with use of nominal strain rates of the plastometric tests do not give significantly different results. Calculations based on the processing of the simplified power dependence between strain rate and peak stress can give the results differing very substantially from those that were gained by the solution of the complex hyperbolic relationship. This has negative impacts, particularly at prediction of the maximum flow stress in the broad range of forming conditions, represented by the Zener-Hollomon parameter.
Voiding dysfunction due to multiple sclerosis: a large scale retrospective analysis.

PURPOSE To assess the outcome of urologic evaluation in patients with voiding dysfunction due to multiple sclerosis (MS) and to determine the relationship between urological and neurological parameters of these patients. MATERIALS AND METHODS We retrospectively reviewed the medical records of 249 consecutive patients (162 female and 87 male) with MS who were referred to our clinic between 1991 and 2006, with a median time of 4 years (range 3 months to 26 years) of MS onset. Data was analyzed with respect to patient demographics and findings of initial evaluation. Lower urinary tract symptoms were evaluated by Boyarsky symptom index. RESULTS All patients except 13 had lower urinary tract symptoms and 70% manifested mixed symptoms. Total, storage and voiding symptom scores correlated with expanded disability status scale scores (p < 0.05). Twelve patients (5%) had abnormal upper urinary tract. Ultrasound findings of lower urinary tract were abnormal in 12 patients (5%). No demographic parameters were associated with abnormal findings of upper urinary tract on univariate analysis. Urodynamic evaluation of 75 patients (30.1%) revealed detrusor overactivity with or without detrusor-sphincter dyssynergia in 56 (75%). No correlation was found between urodynamic diagnosis and upper tract deterioration and urinary symptom scores (p > 0.05). CONCLUSIONS The prevalence of mixed symptoms in patients with MS is higher than storage or voiding symptoms alone. Although detrusor overactivity and detrusor-sphincter dyssynergia were the most common urodynamic diagnoses, upper urinary tract deterioration was rare in our series.
Generating Secret Keys from Biometric Body Impedance Measurements

Growing numbers of ubiquitous electronic devices and services motivate the need for effortless user authentication and identification. While biometrics are a natural means of achieving these goals, their use poses privacy risks, due mainly to the difficulty of preventing theft and abuse of biometric data. One way to minimize information leakage is to derive biometric keys from users' raw biometric measurements. Such keys can be used in subsequent security protocols and ensure that no sensitive biometric data needs to be transmitted or permanently stored. This paper is the first attempt to explore the use of human body impedance as a biometric trait for deriving secret keys. Building upon Randomized Biometric Templates as a key generation scheme, we devise a mechanism that supports consistent regeneration of unique keys from users' impedance measurements. The underlying set of biometric features are found using a feature learning technique based on Siamese networks. Compared to prior feature extraction methods, the proposed technique offers significantly improved recognition rates in the context of key generation. Besides computing experimental error rates, we tailor a known key guessing approach specifically to the used key generation scheme and assess security provided by the resulting keys. We give a very conservative estimate of the number of guesses an adversary must make to find a correct key. Results show that the proposed key generation approach produces keys comparable to those obtained by similar methods based on other biometrics.
Parameter setting in second language phonology and syntax

This paper reports on studies of second language acquisition in two domains, phonology and syntax. The phenomena investigated were the acquisition by native speakers of Hindi, Japanese, and Korean of two areas of English: in phonology, the mastery of particular syllable onset clusters, and in syntax, the acquisition of the binding patterns of reflexive anaphors. Both these areas are ones for which multi-valued parameters have been posited to account for the range of variation across natural languages. The paper presents evidence that acquisition in these two areas is quite similar: at a certain stage of acquisition learners seem to arrive at a parameter setting that is midway between the native and the target language settings. This effect occurs both when the target language employs a less marked setting than the native language and when the target language setting is more marked than that of the native language.
Investigation of the effect of chitin nanowhiskers distribution on structural and physical properties of high impact polypropylene/chitin nanocomposites

Polymer composites have been gaining more importance in our daily lives because of the favorable properties that can be provided by these types of material. A polymer composite consists of improved properties when compared to the individual polymers that it is compiled of. The reason that composites are better than the individual polymers is mainly because composites are a combination of all the bene cial properties from the individual materials that was used to make the polymer composite. High impact polypropylene (HiPP) is a complex copolymer that was developed to overcome the restrictions of polypropylene (PP). Although PP have excellent properties at lower temperatures, it loses these advantages at elevated temperatures. High impact polypropylene has a much better impact strength and is processable at high temperatures. High impact polypropylene has been studied in depth for its applications and its superior properties such as an improved impact strength. The tensile properties, after the incorporation of a nano ller, have however not been investigated to our knowledge. Nano llers have reinforcing abilities due to the nano-scale diameters. Particles that have sizes on a nanometer range are mostly devoid of defects. Nano llers that are biopolymers have additional advantages such that can consist of antimicrobial abilities, renewability, biocompatibility and biodegradability. Composites reinforced with chitin nanowhiskers (chnw) have shown to have valuable applications in the latest medical, industrial and environmental developments. Di erent loadings of chnw were incorporated into a HiPP matrix in order to investigate the e ects that this nano ller will have on the tensile properties of HiPP. There were two challenges that required attention during the incorporation of chnw into HiPP. The rst major challenge was the poor interaction that exist between chnw and HiPP due to the hydrophobic nature of the HiPP matrix and the hydrophilic nature of chnw. The second problem was the agglomeration that can occur because of the hydrogen bonding between the chnw that is caused by the structure of the chnw chains. In order to gain the best dispersion of chnw within the HiPP matrix it was necessary to use compatibilizers and di erent methods of incorporation. The two types of compatibilizers that were chosen to improve the compatibility between the HiPP matrix and chnw were polypropylenegraft-maleic anhydride (PPgMA) and poly(ethylene-co-vinyl alcohol)(EVOH). Injection molding is typically used to process HiPP and was chosen as one of the methods for iii Stellenbosch University http://scholar.sun.ac.za
Abnormal Echogenic Findings Detected by Transesophageal Echocardiography and Cardiorespiratory Impairment during Total Knee Arthroplasty with Tourniquet

Background In patients undergoing total knee arthroplasty, intraoperative pulmonary embolic events are rare, and most occur following tourniquet deflation. This embolization can be observed using transesophageal echocardiography. However, the authors have encountered sudden decreases in arterial oxygen partial pressure while a tourniquet is still inflated. Therefore, the current investigation was designed to detect emboli during the tourniquet inflation phase and to identify the composition of the echogenic material. Methods Forty-six patients were randomly assigned to undergo total knee arthroplasty without (control, n = 24) or with a tourniquet (n = 22). Hemodynamic monitoring, blood gas analysis, and continuous transesophageal echocardiography were performed during the total knee arthroplasty procedure. Right jugular blood specimens were collected whenever echogenic material was seen in the atrium. Results In the tourniquet group, embolic events occurred in 27% of patients during femoral reaming and in 100% after tourniquet deflation. In the control group, emboli were detected in 54% of patients during femoral reaming. Most of the patients exhibited cardiopulmonary impairment after severe echogenic embolism, even while the tourniquet was inflated (two patients). None of the blood samples aspirated from the central catheters contained detectable material. Conclusions This prospective study showed that embolic events occurred during total knee arthroplasty, even while a tourniquet was inflated. An inflated tourniquet does not completely prevent pulmonary emboli.
3-Hydroxyphthalic Anhydride-Modified Chicken Ovalbumin Exhibits Potent and Broad Anti-HIV-1 Activity: a Potential Microbicide for Preventing Sexual Transmission of HIV-1

ABSTRACT Heterosexual transmission is the primary route by which women acquire human immunodeficiency virus (HIV)/AIDS. Thus, development of woman-controlled topical microbicides for prevention of sexual transmission of HIV is urgently needed. Here we report that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibits potent antiviral activity against a broad spectrum of human immunodeficiency virus type 1 (HIV-1) isolates with different genotypes and biotypes. Its antiviral activity is correlated with the percentages of the chemically modified and unmodified lysines and arginines in OVA. HP-OVA inhibits HIV-1 fusion and entry through multiple mechanisms of action, including (i) blocking gp120 binding to CD4 and (ii) interfering with gp41 six-helix bundle formation. Because of the widespread availability and established safety profile of OVA, HP-OVA has good potential to be developed as an effective, safe, and affordable microbicide for prevention of HIV sexual transmission.
Schizophrenia and suicide: systematic review of risk factors.

BACKGROUND Suicide risk is greatly increased in schizophrenia. Detection of those at risk is clinically important. AIMS To identify risk factors for suicide in schizophrenia. METHOD The international literature on case-control and cohort studies of patients with schizophrenia or related conditions in which suicide was reported as an outcome was systematically reviewed. Studies were identified through searching electronic databases and reference lists, and by consulting experts. RESULTS Twenty-nine eligible studies were identified. Factors with robust evidence of increased risk of suicide were previous depressive disorders (OR=3.03, 95% CI 2.06-4.46), previous suicide attempts (OR=4.09, 95% CI 2.79-6.01), drug misuse (OR=3.21, 95% CI 1.99-5.17), agitation or motor restlessness (OR=2.61, 95% CI 1.54-4.41), fear of mental disintegration (OR=12.1, 95% CI 1.89-81.3), poor adherence to treatment (OR=3.75, 95% CI 2.20-6.37) and recent loss (OR=4.03, 95% CI 1.37-11.8). Reduced risk was associated with hallucinations (OR=0.50, 95% CI 0.35-0.71). CONCLUSIONS Prevention of suicide in schizophrenia is likely to result from treatment of affective symptoms, improving adherence to treatment, and maintaining special vigilance in patients with risk factors, especially after losses.
Advantage of Upregulation of Succinate Dehydrogenase in Staphylococcus aureus Biofilms

ABSTRACT Previous studies have demonstrated that various tricarboxylic acid (TCA) cycle genes, particularly the succinate dehydrogenase genes (sdhCAB), are upregulated in Staphylococcus aureus biofilms. To better study the role of this enzyme complex, an sdhCAB deletion mutant (Δsdh) was constructed. Compared to the wild type (wt) the mutant was impaired in planktonic growth under aerobic conditions, excreted acetic acid could not be reused and accumulated continuously, succinate was excreted and found in the culture supernatant, and metabolome analysis with cells grown in chemically defined medium revealed reduced uptake/metabolism of some amino acids from the growth medium. Moreover, the mutant was able to counteract the steadily decreasing extracellular pH by increased urease activity. The addition of fumarate to the growth medium restored the wt phenotype. The mutant showed a small-colony variant (SCV)-like phenotype, a slight increase in resistance to various aminoglycoside antibiotics, and decreased pigmentation. The decreased growth under aerobic conditions is due to the interruption of the TCA cycle (indicated by the accumulation of succinate and acetic acid) with the consequence that many fewer reduction equivalents (NADH and FADH2) can fuel the respiratory chain. The results indicate that the TCA cycle is required for acetate and amino acid catabolism; its upregulation under biofilm conditions is advantageous under such nutrient- and oxygen-limited conditions.