Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

During the last 10-15 years, cytochrome P450 (CYP) 2C8 has emerged as an important drug-metabolizing enzyme. CYP2C8 is highly expressed in human liver and is known to metabolize more than 100 drugs. CYP2C8 substrate drugs include amodiaquine, cerivastatin, dasabuvir, enzalutamide, imatinib, loperamide, montelukast, paclitaxel, pioglitazone, repaglinide, and rosiglitazone, and the number is increasing. Similarly, many drugs have been identified as CYP2C8 inhibitors or inducers. In vivo, already a small dose of gemfibrozil, i.e., 10% of its therapeutic dose, is a strong, irreversible inhibitor of CYP2C8. Interestingly, recent findings indicate that the acyl-β-glucuronides of gemfibrozil and clopidogrel cause metabolism-dependent inactivation of CYP2C8, leading to a strong potential for drug interactions. Also several other glucuronide metabolites interact with CYP2C8 as substrates or inhibitors, suggesting that an interplay between CYP2C8 and glucuronides is common. Lack of fully selective and safe probe substrates, inhibitors, and inducers challenges execution and interpretation of drug-drug interaction studies in humans. Apart from drug-drug interactions, some CYP2C8 genetic variants are associated with altered CYP2C8 activity and exhibit significant interethnic frequency differences. Herein, we review the current knowledge on substrates, inhibitors, inducers, and pharmacogenetics of CYP2C8, as well as its role in clinically relevant drug interactions. In addition, implications for selection of CYP2C8 marker and perpetrator drugs to investigate CYP2C8-mediated drug metabolism and interactions in preclinical and clinical studies are discussed.
In Search for Boundary Conditions of Reconsolidation: A Failure of Fear Memory Interference

The presentation of a fear memory cue can result in mere memory retrieval, destabilization of the reactivated memory trace, or the formation of an extinction memory. The interaction between the degree of novelty during reactivation and previous learning conditions is thought to determine the outcome of a reactivation session. This study aimed to evaluate whether contextual novelty can prevent cue-induced destabilization and disruption of a fear memory acquired by non-asymptotic learning. To this end, fear memory was reactivated in a novel context or in the original context of learning, and fear memory reactivation was followed by the administration of propranolol, an amnestic drug. Remarkably, fear memory was not impaired by post-reactivation propranolol administration or extinction training under the usual conditions used in our lab, irrespective of the reactivation context. These unexpected findings are discussed in the light of our current experimental parameters and alleged boundary conditions on memory destabilization.
Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim.

BACKGROUND There is a misconception that elderly cancer patients cannot tolerate standard doses of chemotherapy because of the frequency and severity of myelosuppressive complications. The reactive use of colony-stimulating factors (i.e., in response to severe neutropenia) commonly observed in this setting contributes to the frequency and severity of these complications. This study evaluated the incidence of febrile neutropenia and related events in elderly cancer patients receiving pegfilgrastim beginning with cycle 1 (proactive) in comparison with pegfilgrastim initiated after cycle 1 at the physician's discretion (reactive). METHODS Patients (> or = 65 years of age) with either solid tumors or non-Hodgkin's lymphoma (NHL) were randomly assigned to receive pegfilgrastim either proactively or reactively. The primary endpoint was the proportion of patients experiencing febrile neutropenia. RESULTS There were 852 patients enrolled (median age, 72 years). Proactive pegfilgrastim use resulted in a significantly lower incidence of febrile neutropenia for both solid tumor and NHL patients compared with reactive use. Proactive pegfilgrastim use also led to fewer hospitalizations resulting from neutropenia and febrile neutropenia by approximately 50%. Antibiotic use was lower for solid tumor patients receiving proactive pegfilgrastim and equivalent in the two NHL groups. CONCLUSIONS This is the largest, randomized, prospective trial evaluating growth factor support in typical elderly cancer patients. Proactive pegfilgrastim use effectively produced a lower incidence of febrile neutropenia and related events in elderly patients with either solid tumors or NHL receiving an array of mild to moderately neutropenic chemotherapy regimens. Pegfilgrastim should be used proactively in elderly cancer patients to support the optimal delivery of standard chemotherapy.
Parental determinants of neonatal body composition.

BACKGROUND The prevalence of both childhood and adult obesity is rising in the developed world, and there is increasing interest in its underlying causes. A number of studies suggest a positive relationship between birth weight and childhood body mass index, but less is known about specific prenatal environmental influences on more direct measures of obesity. We used data from the Southampton Women's Survey to investigate parental influences on neonatal body composition ascertained by dual x-ray absorptiometry. METHODS Participating mothers were characterized in detail (anthropometry, lifestyle, diet) before and during pregnancy; information was also obtained on their partners. The offspring underwent assessment of fat and lean body mass by dual x-ray absorptiometry within 2 wk of birth. Linear regression methods were used to explore the parental determinants of neonatal body composition. RESULTS Complete data were available for 448 mother-offspring pairs. Taller women and those with higher parity had offspring with increased birth weight, fat, and lean mass (P < 0.05). Mothers who were taller, of greater parity, had greater fat stores, or walked more slowly also had offspring with greater proportionate body fat at birth (all P < 0.05). There was a weaker trend toward lower percentage fat and greater percentage lean in the offspring of mothers who smoked during pregnancy. CONCLUSION Maternal size, parity, smoking history, walking speed, and fat stores are independent determinants of neonatal body composition. If these influences are shown to have persisting effects on body composition through to adulthood, they point to novel public health interventions early in life to prevent later obesity.
Costumes and Wearables as Game Controllers

There has been a significant increase in commercial interest in wearable technologies, spearheaded by Google's Glass project, and also by the success of a new generation of fitness oriented biosensors such as the Fitbit, the Bodymedia Fit, and the Misfit Shine. Concurrently, there has been a proliferation of embodied interfaces for digital games such as Nintendo's Wii, Sony's Move controller, and Microsoft's Kinect. These technologies often only scratch the surface of the design possibility space, overlooking nuances of social and emotional experience for wearers/players that are important in other areas of design, such as theatrical costuming and fashion. We propose a studio that offers participants the chance to create wearable game controllers that afford a playful exploration of this design terrain, encouraging transformation, collaboration, and enjoyment of rich spectacle.
Testicular histomorphometry and semen quality of adult Wistar rats following juvenile oral lead intoxication

Empirical evidence has shown that childhood lead (Pb) intoxication impairs cognitive function and heightens the risk of dementia in young adult humans. However, the effects of juvenile Pb toxicity on testicular morphometry and semen quality in young adulthood require further studies. Using a rodent model, juvenile (4 weeks old) Wistar rats were randomized to receive either normal saline or lead acetate in their drinking water at 0.5% (5000 ppm), 1.5% (15000 ppm) and 2.5% (25000 ppm) for 7 weeks. At 11 weeks postnatal, young adult rats were anaesthetized and their cauda epididymides excised for sperm analysis. The left testicles were homogenized in phosphate buffer and the supernatants assayed for testosterone by the enzyme immunoassay technique. The right testicles were processed for photomicroscopy by the haematoxylin and eosin technique. Using ImageJ software, testicular sections were subjected to morphometric analysis. Our findings showed that juvenile Pb intoxication alters testicular histomorphometry in young adulthood as indicated by significant (P 0.05). These findings show that Pb intoxication initiated prior to pubescence alters testicular histomorphometry and lowers semen quality in young adult Wistar rats, and these changes were unconnected with testicular testosterone levels.
IVIG treatment for VZV-related acute inflammatory polyneuropathy in a child

Acute inflammatory polyneuropathy is an inflammatory demyelinating disease triggered by an autoimmune mechanism. It follows an infection or an immunisation after a free interval of 2–30 days. We report a case of a 14-year-old boy who develops an acute rapidly progressive paraplegia, urine incontinence and positive Lasegue a week after a characteristic chickenpox rash. Spinal MRI showed diffuse thickening and leptomeningeal enhancement of cauda equina nerve roots. Intravenous immunoglobulins were given and yielded a dramatic clinical and radiological improvement. The patient was discharged without any clinical problems 1 month after the onset of symptoms. We performed a review of the literature, discussing the different forms of varicella-zoster virus-related central and peripheral nervous system complications and management strategies for acute postinfectious encephalomyelitis/radiculitis.
Impairment Analysis of WDM-PON Based on Low-Cost Tunable Lasers

WDM-PON is considered for next-generation broadband backhaul and radio access networking. Among different implementation choices, we propose to utilize low-cost tunable lasers at the remote sites, together with a centralized wavelength locker. Practical implementations require a transparently added downstream signaling channel and upstream per-channel pilot tones for channel tagging and remote wavelength control. Together with some unavoidable crosstalk effects during tuning, all of these system-related items lead to impairments. To keep penalties below 1 dB, the modulation index of the signaling channel must be kept below 15%. Similar values result for the upstream pilot tones. In order to limit crosstalk, such systems require reduced launch power during wavelength tuning and can cover up to 40 km differential reach. These results confirm that WDM-PON based on low-cost lasers is a technically viable approach.
Surgical Treatment of Early-Stage Cervical Cancer

Surgical treatment of cervical cancer has been a cornerstone in the management of this malignancy for more than 100 years. Today, for early-stage and low-risk cervical cancer, surgery is still considered the gold standard. If the preoperative assessment of the tumor reveals a situation prompting postoperative adjuvant radiochemotherapy, the latter should be planned as the primary treatment option, being preceded by staging laparoscopy including pelvic and paraaortic lymph node dissection. As an alternative to the open approach, the definitive surgical treatment should be either performed laparoscopically, or be laparoscopic-assisted, or laparoscopically robotic-assisted.
15 Toxoplasmosis in HIV / AIDS Patients-A Living Legacy Veeranoot Nissapatorn University of Malaya Malaysia 1

The coccidian Toxoplasma gondii (T. gondii) is a ubiquitous, intracellular, protozoan parasite that causes toxoplasmosis, a cosmopolitan zoonotic disease. Toxoplasma infections are reported in approximately half of the world’s population but most are asymptomatic. T. gondii may serve as one factor that can enhance the immunodeficiency found after HIV-1 infections. Co-infection with other pathogens in humans infected with HIV-1 may enhance the progression of the disease to AIDS (Lin & Bowman, 1992). In concurrence with HIV infection, cerebral toxoplasmosis (CT) occurs primarily due to reactivation of latent Toxoplasma infection and is one of the most frequent opportunistic infections, particularly in patients with full-blown AIDS. CT is the most common clinical presentation of toxoplasmosis (Luft & Remington, 1992), and is one of the most frequent causes of focal intracerebral lesions that complicates AIDS (Nissapatorn et al, 2004). CT is undoubtedly a serious life-threatening disease but it is treatable when there is a timely diagnosis and prompt treatment, and there are no other concurrent co-infections. When HIV-infected patients develop CT this poses many diagnostic and therapeutic challenges for clinicians (Israelski & Remington, 1992), particularly in developing countries where the infrastructure is limited but the number of patients infected with HIV is increasing. This chapter focuses on the clinico-epidemiological aspects of toxoplasmosis in HIV/AIDS patients at the time of transition to treatment with highly active anti-retroviral therapy (HAART). The course of toxoplasmosis in HIV/AIDS patients should be able to provide us with a better understanding of the clinical scenario and future management of this so-called “enigmatic parasite” of the tropics.
Contraction coupling efficiency of human first dorsal interosseous muscle

During working contractions, chemical energy in the form of ATP is converted to external work. The efficiency of this conversion, called ‘contraction coupling efficiency’, is calculated by the ratio of work output to energy input from ATP splitting. Experiments on isolated muscles and permeabilized fibres show the efficiency of this conversion has a wide range, 0.2–0.7. We measured the work output in contractions of a single human hand muscle in vivo and of the ATP cost of that work to calculate the contraction coupling efficiency of the muscle. Five subjects performed six bouts of rapid voluntary contractions every 1.5 s for 42 s (28 contractions, each with time to peak force < 150 ms). The bouts encompassed a 7‐fold range of workloads. The ATP cost during work was quantified by measuring the extent of chemical changes within the muscle from 31P magnetic resonance spectra. Contraction coupling efficiency was determined as the slope of paired measurements of work output and ATP cost at the five graded work loads. The results show that 0.68 of the chemical energy available from ATP splitting was converted to external work output. A plausible mechanism to account for this high value is a substantially lower efficiency for mitochondrial ATP synthesis. The method described here can be used to analyse changes in the overall efficiency determined from oxygen consumption during exercise that can occur in disease or with age, and to test the hypothesis that such changes are due to reduced contraction coupling efficiency.
Simple switching control method changes power converter into a current source

A switching converter with an LC output filter behaves as a loose-tolerance voltage-controlled current source if each switch closure is ended when switch current reaches an adjustable threshold. This converter is then combined with an external feedback to produce a precise output voltage. By generating a fixed voltage with a current source in this manner, the converter has many advantages including continuous protection of the switches, stable and equal load sharing when several converters are operated in parallel, inherent overload protection, automatic switch symmetry correction, and fast system response.
A Novel Nonsense Mutation 6, E – X in the Protein S Gene Causes Type I Deficiency

The proband is a 38-year-old male Caucasian patient who had the first event of deep vein thrombosis (DVT) in November 1992, during the third cycle of chemotherapy for non-Hodgkin lymphoma. The amount of total and free PS antigen was reduced to 61 and 25%, respectively, and the PS anticoagulant activity was 49%, when he was not undergoing warfarin treatment, indicating type I deficiency. Protein C and antithrombin were within the normal range. Factor V Leiden was negative and he was heterozygous for the MTHR mutation (A677V). His mother had DVT and died at the age of 32 from an ischemic cerebral vascular accident. Two brothers had DVT and pulmonary embolism at the age of 25 and 26, respectively. His sister had DVT in her third pregnancy when she was 28. All three siblings demonstrated decreased PS antigen and activity. One daughter and one niece of the proband, who were asymptomatic, have PS deficiency. Another daughter of the proband was not PS deficient.
A rapid rendering method for caustics arising from refraction by transparent objects

Caustics are patterns of light formed by reflection or refraction of light from objects, and several methods have been developed to render caustics because of their visually beautiful patterns. This paper proposes a method for the rapid rendering of caustics formed by refracted light through transparent objects. First, a preprocess is used to generate sampling rays incident on each vertex of the object, and, taking refraction into account, to trace the rays until they leave the object. The position and direction of each ray that finally leaves the transparent object are obtained and stored in a lookup table. Next, in the rendering process, when the object is illuminated, the position and direction of the rays leaving the object are calculated using the lookup table. This makes it possible to render refractive caustics due to transparent objects at interactive frame rates even if the direction of the light changes and the object is translated or rotated.
Spatial diversity for off-body communications in an indoor populated environment at 5.8 GHz

Human activity in the vicinity of body-centric wireless communications systems often affects received signal characteristics. In particular, pedestrian movements may induce temporal fading and cause shadowing events in situations where an individual or group obstructs the dominant signal path. In this paper, we report results from a series of carefully controlled experiments aimed at assessing the impact of using multiple-antenna techniques to reduce the influence of pedestrian effects on off-body radio-links. Using two co-located, spatially-separated bodyworn antennas mounted on the anterior human torso, it was found that the cross-correlation coefficient value between branches was always less than 0.7, irrespective of the number of nearby pedestrians. The difference in mean signal level between receiver branches generally decreased as pedestrian numbers increased. Post-detection selection combining of the measurement data has shown that diversity gain improves with increased human traffic in the local environment.
Saturated Adaptive Robust Control for Active Suspension Systems

This paper investigates the problem of vibration control in vehicle active suspension systems, whose aim is to stabilize the attitude of the vehicle and improve ride comfort. In response to uncertainties in systems and the possible actuator saturation, a saturated adaptive robust control (ARC) strategy is proposed. Specifically, an antiwindup block is added to adjust the control strategy in a manner conducive to stability and performance preservation in the presence of saturation. Furthermore, the proposed saturated ARC approach is applied to the half-car active suspension systems, where nonlinear springs and piecewise linear dampers are adopted. Finally, the typical bump road inputs are considered as the road disturbances in order to illustrate the effectiveness of the proposed control law.
X-linked congenital ataxia: a clinical and genetic study.

We report on a family in which two males are affected with X-linked congenital ataxia (XCA). Clinical manifestations include severe hypotonia at birth, delay of early motor development, slow eye movements, and nonprogressive cerebellar ataxia. The neurological examination excluded a neuromuscular disease, mental retardation, and pyramidal tract involvement. Neuroimaging showed global cerebellar atrophy in both patients that was not evident in the first years of life. The clinical findings in this family are very similar to those in a Russian pedigree [Illarioskin et al., 1996: Ann Neurol 40:75-83] and outline a recognizable phenotype. Linkage studies in our family, using 28 highly polymorphic Généthon microsatellite markers evenly distributed along the X chromosome, excluded a 24 cM interval between DXS990 and DXS424 located within the previous candidate region of 54 cM, reducing the critical interval.
Breath‐Powered Intranasal Sumatriptan Dry Powder

A breath-powered delivery system for sumatriptan dry powder (brand name Onzetra Xsail, Alisa Viejo, CA, USA) is approved by the Food and Drug Administration (FDA) for the treatment of migraine attacks. Sumatriptan is the oldest of the triptan family. Available in the United States in tablet, liquid nasal, injectable, and skin patch forms. In general, triptan medications are taken at the onset of a migraine attack. As a group, they are a specific treatment that delivers relief by targeting the chemicals causing head pain, also treating the ill feelings that make migraines so uncomfortable. Each form of sumatriptan has its own benefit. Until now, for migraine patients who vomit with their headache attacks, or who need very rapid relief from pain, choices were limited to the inconvenient and painful pinch of the injectable formulation, liquid nasal sprays that mostly go down the throat, or the slower patch. The breath-powered device delivers 11 mg of sumatriptan dry powder into each nostril for a total dose of 22 mg. The device comes with two nosepieces per treatment (Fig. 1). First, a clear disposable nosepiece clicks into the reusable device. A white button on the device is pressed to pierce the capsule, releasing the drug into the nosepiece, which is then inserted into the nostril. The user blows forcefully into the mouthpiece, and the powder is delivered to the nasal tissue, blown high up into the nose. When one blows the powder, the back of the palate closes and prevents the powder from going down the throat. The advantage of this device over tablets is that the medicine is not absorbed through the stomach, whose function is often impaired during a migraine attack. Nasal absorption is fast and not affected by the nausea or gastrointestinal dysfunction typically present during a migraine attack. The closing of the palate when one blows the drug up the nose prevents the powder from being swallowed, which is a problem with liquid nasal sprays. Swallowing not only decreases how much sumatriptan gets in, but also the drug tastes bad, and this is reduced with the dry powder. A scientific comparison study was run to compare the sumatriptan breath–powered device with the traditional sumatriptan tablet. Migraine patients were assigned to a traditional, active sumatriptan tablet plus an inactive, sham, placebo device, or the active breath-powered device plus an inactive tablet (placebo). Of the 174 patients who completed the study, those who used the active breathpowered device had significantly greater pain relief than those who took the active tablet. This difference in favor of the device held at time points between 30 minutes and 2 hours following the treatment. After 2 hours, the degree of pain relief between the tablet and the breath-powered device merged and remained similar between 2 and 48 hours after the attack. This suggests that the device worked faster than the tablet for up to 2 hours.