Miracle-dz/UniFAR-FTUs huggingface dataset:
Progressive and Preferential Cellular Accumulation of Hydrophobic Bile Acids Induced by Cholestatic Drugs Is Associated with Inhibition of Their Amidation and Sulfation

Drug-induced intrahepatic cholestasis is characterized by cellular accumulation of bile acids (BAs), whose mechanisms remain poorly understood. The present study aimed to analyze early and progressive alterations of BA profiles induced by cyclosporine A, chlorpromazine, troglitazone, tolcapone, trovafloxacin, and tacrolimus after 4-hour, 24-hour, and 6-day treatments of differentiated HepaRG cells. In BA-free medium, the potent cholestatic drugs cyclosporine A, chlorpromazine, and troglitazone reduced endogenous BA synthesis after 24 hours, whereas the rarely cholestatic drugs tolcapone, trovafloxacin, and tacrolimus reduced BA synthesis only after 6 days. In the presence of physiologic serum BA concentrations, cyclosporine A, chlorpromazine, and troglitazone induced early and preferential cellular accumulation of unconjugated lithocholic, deoxycholic, and chenodeoxycholic acids that increased 8- to 12-fold and 47- to 50-fold after 24 hours and 6 days, respectively. Accumulation of these hydrophobic BAs resulted from strong inhibition of amidation, and in addition, for lithocholic acid reduction of its sulfoconjugation, and was associated with variable alterations of uptake and efflux transporters. Trovafloxacin also caused BA accumulation, especially after 6 days, whereas tolcapone and tacrolimus were still without effect. However, when exogenous BAs were added to the medium at cholestatic serum concentrations, a 6-day treatment with all drugs resulted in cellular BA accumulation with higher folds of chenodeoxycholic and lithocholic acids. At the tested concentration, tolcapone had the lowest effect. These results bring the first demonstration that major cholestatic drugs can cause preferential and progressive in vitro cellular accumulation of unconjugated toxic hydrophobic BAs and bring new insights into mechanisms involved in drug-induced cellular accumulation of toxic BAs.
Heart Rate Control in an Unselected Consecutive Population of Outpatients With Stable Coronary Artery Disease: Analysis of the CARDIf Study Cohort

Background: Despite increasing pharmacological and mechanical treatment options, coronary artery disease (CAD) continues to be associated with considerable mortality and morbidity. The detrimental effects of elevated heart rate (HR) on cardiac morbidity and mortality are well established. Although β-blockers represent the mainstay of treatment of patients with CAD and heart failure (HF), according to current guidelines, these drugs are most often undertitrated for various reasons despite the lack of real contraindications. This observational, cross-sectional, multicenter survey was designed to assess which clinical variables influence HR and whether HR is adequately controlled; and the rate of administration of β-blockers in patients with chronic CAD attending outpatient clinics. Methods: Over 6 months 2226 (of 2362 screened) outpatients with stable CAD and resting HR > 60 beats/min (bpm) were enrolled. Left ventricular systolic function was not a criterion of inclusion. Each patient had a full clinical examination and the past medical history, angina, or HF-related symptoms were evaluated. In each patient, the demographics and cardiovascular risk factors were assessed; weight, height, and body mass index (BMI) was calculated; sitting blood pressure and a HR by a 12-lead electrocardiogram was obtained. Results: Overall, 45.4% of patients with CAD were not under β-blocker therapy. Male patients featured a significantly lower HR than females, corrected from β-blockers use. In multiple regression analysis, which also included the use/nonuse of β-blockers as independent variable, not using β-blockers, female sex (OR 2.55), New York Heart Association (NYHA) classes I and II (OR 1.62 vs classes III-IV), smoking (OR 0.89), and increased BMI (OR 0.14) were all independent determinants of resting HR, with the lack of β-blockade therapy (OR 3.35) being the main determinant of the magnitude of HR increase. Heart rate in patients under β-blocker therapy was significantly less than in untreated patients (73.6 10.0 vs 77.1 10.4, P < .0001), although it often did not reach target values of <70 bpm. Among patients with HF symptoms, 56.6% were under β-blocker therapy. In patients free of symptoms of HF, HR was significantly less in those receiving a β-blocker (72.3 10 vs 76.7 11 bpm, P < .0001). Conclusion: This survey demonstrates that HR is poorly controlled in a broadly representative cohort of outpatients with CAD, even in those on β-blocker therapy, mainly because of undertitration of therapy—almost half of the patients with CAD and elevated resting HR are not on β-blockers. This might be related to absolute or relative controindications and to haemodynamic and chronotropic intolerance to beta-blockers.
The sodium iodide symporter and thyroid disease

The movement of a variety of species from the iodine-rich environment of the sea to the relatively iodine-deficient land has necessitated the development of mechanisms which will trap more efficiently inorganic iodide (I – ) necessary for the formation of thyroid hormones (Venturi et al. , 2000). In man as in other mammals iodide uptake by the thyroid is mediated via a TSHdependent transmembrane protein, the sodium iodide symporter (NIS), so-called because it co-transports Na + with I – into the thyroid against the concentration gradient (De La Vieja et al. , 2000). The NIS is located in the basolateral membrane of thyroid follicular cells, and accumulated I – is organified to molecular iodine (I 2 ) through the action of the enzyme thyroid peroxidase (TPO) in the presence of H 2 O 2 , which takes place mainly at the apical membrane of the follicular cell. Organified iodine iodinates the thyroid protein thyroglobulin, which when stored in the lumen of thyroid follicles represents a storage site for the hormones thyroxine (T4) and triiodothyronine (T3) (Taurog, 1996). Possession of NIS enables the thyroid to concentrate I –
Design and virtual evaluation of a customized surface-guided knee implant

Although total knee arthroplasty is generally a successful operation, many studies have shown that it results in significant alterations in the kinematics of the joint, which cause limitations in performing the activities of daily living. This study aimed to define the design features for a customized surface-guided total knee replacement and to evaluate the kinematic outcomes. Magnetic resonance imaging data of the knee joint are used to generate the design features as they relate to the functionality of the implant. The motion is guided by considering a partial ball and socket configuration on the medial condyle and varying radii of curvature on the lateral articulating surface. A virtual simulation of the behavior of the surface-guided total knee replacement was performed to investigate the motion patterns of this total knee replacement under gait and squatting loading conditions. Results of the virtual simulation show that flexion and extension of the knee make the center of the lateral condyle move more naturally in the posterior and anterior directions, in comparison to the center of the medial condyle. Such guidance is achieved as a result of the novel customized designed contact between the articulating surfaces. The proposed customized surface-guided total knee replacement provides patterns of motion close to the expected more natural target, not only during a gait cycle but also as the knee flexes to higher degrees during squatting. Major design features include location and orientation of the flexion and pivoting axes, the trace of the contact points on the tibia, and the radii of the guiding arcs on the lateral condyle.
The toxic effect of L-cysteine on the rat retina. A morphological and biochemical study.

Subcutaneous injection of L-cysteine into 4-day-old rats (1.2 mg/gm body weight) leads to permanent retinal dystrophy. When the eyes were examined 4 to 6 weeks later, there was a reduction of ganglion cells to less than 50% of the controls. The inner plexiform layer was reduced to about 60%, and the inner nuclear layer was reduced with approximately one cell layer. The photoreceptors were unaffected. The same layers were reduced in retinas from L-glutamate-treated animals which were examined for comparison. Electron microscopy showed that no single class of neurons was entirely eliminated by the cysteine treatment, and no specific changes were observed in the remaining neurons. The retinal lesion induced by L-cysteine was not accompanied by any reduction in glutamate decarboxylase activity, choline acetyltransferase activity, or in the high-affinity uptake of glutamate, which are markers for some of the retinal neurotransmitters. This is in striking contrast to the retinal lesion induced by L-glutamate, which is followed by a severe reduction in these biochemical parameters. Eyes enucleated4 hr after injection of L-cysteine showed widespread necrosis of neurons in the inner nuclear layer and of ganglion cells. In conclusion, L-cysteine, like L-glutainate, given systemically to newborn rats, affects neurons in the inner layers of retina. L-Cysteine, however, apparently affects other populations of cells than L-glutamate.
Respiratory pump contributes to increased physiological reserve for compensation during simulated haemorrhage

What is the central question of this study? The negative intrathoracic pressure created by inspiration (i.e. the respiratory pump) is associated with enhanced venous return, although its contribution as a potential mechanism of compensation during blood loss has not been quantified. What is the main finding and its importance? We demonstrated that optimizing the creation of negative intrathoracic pressure during inspiration represented a mechanism of compensation during haemorrhage that was quantifiably reflected in a reduced rate of diminution of the compensatory reserve, resulting in increased tolerance to progressive reductions in central blood volume.
Original Contribution Night-Shift Work and Breast Cancer Risk in a Cohort of Chinese Women

Shift work involving disruption of circadian rhythms has been classified as a probable cause of human cancer by the International Agency for Research on Cancer, based on limited epidemiologic evidence and abundant experimental evidence. The authors investigated this association in a population-based prospective cohort study of Chinese women. At baseline (1996–2000), information on lifetime occupational history was obtained from 73,049 women. Lifetime night-shift exposure indices were created using a job exposure matrix. During 2002–2004, selfreported data on frequency and duration of night-shift work were collected. Hazard ratios and 95% confidence intervals, adjusted for major breast cancer risk factors, were calculated. During follow-up through 2007, 717 incident cases of breast cancer were diagnosed. Breast cancer risk was not associated with ever working the night shift on the basis of the job exposure matrix (adjusted hazard ratio1⁄4 1.0, 95% confidence interval: 0.9, 1.2) or self-reported history of night-shift work (adjusted hazard ratio 1⁄4 0.9, 95% confidence interval: 0.7, 1.1). Risk was also not associated with frequency, duration, or cumulative amount of night-shift work. There were no indications of effect modification. The lack of an association between night-shift work and breast cancer adds to the inconsistent epidemiologic evidence. It may be premature to consider shift work a cause of cancer.
Cold Characteristic Development Test of a New SF6 High Voltage Circuit Breaker

Computer controlled triggering of an impulse generator was implemented in order to perform precisely timed lightning impulse voltage discharges on a new SF6 high voltage circuit breaker while performing a trip operation. Successive discharges at different time intervals would provide an envelope of dielectric withstand and travel characteristic of the specific high voltage circuit breaker. This test not only evaluates the interrupter gap design but also evaluates the gas flow effect in the dynamic dielectric recovery of the interrupter chamber. Gas flow characteristics in the interruption chamber of an SF6 breaker strongly modifies the dielectric withstand recovery rate of any design. Identifying any weakness before power test are performed not only reduces cost and time, but also simplifies design modifications required and provides an insight into the expected performance of the interrupting chamber during actual synthetic power testing. This paper presents the implementation of this testing procedure as well as the results obtained in a new design of a 245 kV, 63 kA SF6 interrupter
Dual adaptive control in continuous-time

Dual control laws offer important advantages for adaptive systems. The majority of dual control publications consider only discrete-time systems. This paper proposes a novel dual adaptive controller for nth order, parametric uncertain continuous-time linear systems that exhibits the desirable properties of discrete-time dual control in continuous-time too. These properties are verified through Monte Carlo tests.
AWARENESS OF PATIENTS REGARDING ANESTHESIA; ATTITUDE TOWARDS BASIC TYPES OF ANESTHESIA TECHNIQUES

Awareness of patients regarding anesthesia & their attitude towards basic types of anesthesia techniques. Objective: The purpose of this study was to assess the knowledge of patients regarding anesthesia, their attitudes towards basic types of anesthesia techniques and effect of previous experience of anesthesia on the awareness. Study design: Descriptive observational study. Place and duration of study: This descriptive, prospective study was conducted in the isra university hospital Hyderabad, Sindh, Pakistan from 2nd August 2013 upto 8th March 2014. Patients and Methods: Two hundred thirty one patients were included in the study after taking verbal informed consent. All patients who were scheduled for elective surgery were interviewed while patients who had refused from participation, have language barrier, psychiatric disease, had lack of sufficient mental capacity due to poor health status and patients undergoing emergency surgeries were excluded from the study. Patients were interviewed in their local language upon arrival in the preoperative area of operation theatre. Self made questionnaire was filled. All the data was entered on SPSS version 16. Frequency and percentages were calculated to show the results. Mean with SD of patients age was computed. Chi-square test was applied to assess the affect of previous experience of surgery on patient’s knowledge regarding anesthesia. P value less than 0.05 was taken as significant. Results: Total 231 patients were included in the study. Mean age of the patients was 36 ± SD 1.01. Fifty one (22.1%) patients were illiterate; while 54 (23.4%) patients were graduate. 103(44.6%) patients had previous experience of surgery/ anesthesia while 128(55.4%) patients had no experience. Out of 231 patients, 111 (48.1%) patients were aware of different type of anesthesia techniques while 120(51.9%) patients were not aware. Out of 103 patients, who had previous exposure of anesthesia, 64 patients answered correctly about different types of anesthesia techniques while 81 patients who had no previous exposure of anesthesia, answered incorrectly (P value = 0.000). Fifty three patients who had previous exposure of anesthesia answered correctly that anesthetist is a qualified doctor, while 62 patients answered incorrectly who had no previous exposure (P value=0.546). Out of 231 patients, 91 (39.39%) patients were in favor of having general anesthesia while 52(22.51%) patients were in favor of regional anesthesia, while 88(38.0%) had left the choice on surgeon. Conclusions: Results of the study show poor knowledge of patients regarding anesthesia and anesthesiologists. Majority of the patients were in favor of having general anesthesia rather regional anesthesia. There is need to correct the misconceptions of patients and to educate the public.
Characterization of the Near-Wake of an Ahmed Body Profile

In aerovehicles context, the flow around an Ahmed body profile is simulated using the velocity-vorticity formulation of the Navier-Stokes equations, associated to a penalization method for solids and Large Eddy Simulation for turbulence. The study focuses both on the ground influence on the flow and on the dissymetry of the wake, observed for a ground clearance greater than 10% of the body height H . Unsteady and mean flows are presented and analyzed. POD study completes the analysis and gives information on the most energetic structures of the flow. Keywords—Ahmed body, bi-stability, LES, near wake.
Anxiety and depression are improved by continuous positive airway pressure treatments in obstructive sleep apnea

Background Obstructive sleep apnea involves repeated nocturnal desaturation and sleep fragmentation that leads to poor sleep quality, anxiety, and depression. This study aimed to investigate short- and long-term improvements in the anxiety and depression of patients with different obstructive sleep apnea treatments. Methods This is a prospective, non-randomized hospital-based study evaluated 55 patients (46 male, 9 female) with obstructive sleep apnea. The patients were divided into three groups based on different treatment: uvulopalatopharyngoplasty group, continuous positive airway pressure group, and no treatment group (by their own decision). They completed the Beck Depression Inventory II, Beck Anxiety Inventory, and Pittsburgh Sleep Quality Index before treatment and at one and six months after treatment. Results Compared to the no treatment group, the surgery and continuous positive airway pressure groups had higher body mass index, AHI, and Epworth sleepiness scale, but no difference in Pittsburgh Sleep Quality Index, Chinese Health Questionnaire-12, Beck Depression Inventory II, and Beck Anxiety Inventory. The continuous positive airway pressure and surgery groups still had no improvements in Pittsburgh Sleep Quality Index, Chinese Health Questionnaire-12, Beck Depression Inventory II, and Beck Anxiety Inventory scores one month after treatment. At six months after treatment, the continuous positive airway pressure group had significantly decreased Pittsburgh Sleep Quality Index, Chinese Health Questionnaire-12, Beck Depression Inventory II, and Beck Anxiety Inventory, whereas the surgery group had significant difference in Beck Anxiety Inventory only and the no treatment group still had no significant difference in any of the parameters. Conclusions Continuous positive airway pressure can improve the sleep quality, quality of life, depression, and anxiety of obstructive sleep apnea patients after six months of treatment. However, surgery can significantly improve anxiety only in the same period.
Era Digitalisasi Media Pemasaran Online dalam Gugurnya Pasar Ritel Konvensional

Digital communication era has impacts on the life, one of them is in the world of marketing communications. Based on data obtained, it was started in the end of 2016 to early 2017 that became the beginning of the turmoil of the modern retail market. One by one the modern retail market fell because modern society was not only to want comfortable shopping activities and places, but also practical and efficient. This was offered by online shopping, a lot of benefits coulbe be gains, such as making people prefer to online shopping activities rather than shopping conventionally. There were many benefits that offered by online shopping, the modern retail market should anticipate and implement several programs to maintain its existence in the market. It aims to make the life of the modern retail market more exist. In the era of the development of digitalization of communication needs alternative way to anticipate unexsistansion in society. So, that was no longer the process of fall of the conventional market in the digital era.
Mobile banking adoption in an emerging economy: An empirical analysis of young Indian consumers

Purpose The purpose of this paper is to analyze the factors affecting mobile banking adoption among young Indian consumers. Design/methodology/approach The authors use a cross-sectional survey research design to empirically examine the factors affecting mobile banking adoption among young Indian consumers. The study sample consists of 269 respondents aged between 23 and 30 years from India. Findings The findings of the study suggest that perceived usefulness (PU), perceived ease of use (PEU), perceived credibility (PC) and structural assurance (SA) are strong determinants of user satisfaction (US) and behavioral intention (BI) to use the mobile banking service. US was found to partially mediate the relationship between PU, PEU, PC and SA and BI to use the service. Perceived risk was found to be statistically insignificant in terms of its relationship with BI to use the service. Research limitations/implications The results of this study provide good evidence for banks to further revamp their work practices in the area of mobile banking to enhance the overall penetration of mobile banking in India. Originality/value The study identifies factors influencing mobile banking adoption among young Indian consumers. Furthermore, this study suggests that US partially mediates the relationship between factor influencing mobile banking adoption and BI.
A Critical Organizational Analysis of Frontline Nurses’ Experience of Rapid and Continuous Change in an Acute Health Care Organization

The aim of this study was to explore the nature of frontline nurses’ experiences of living with rapid and continuous organizational change in a tertiary health care institution. The phenomenon under study was organizational change. A component of this research was also to explore the possibility of change fatigue in nurses’ discourse. Change is inevitable, and increasingly rapid and continuous in health care as organizations strive to adapt, improve and innovate in response to external pressures. These pressures challenge hospitals to strive for patient safety, quality assurance and provision of exceptional family centred care. Attending to these pressures require time, energy and money. Rapid and continuous change creates a push/pull relationship between innovation and budget. New technologies require extra resources however, simultaneous restructuring and optimization efforts see hospitals decreasing available resources. This creates a challenging workplace for nurses who must engage in organizational change activities with limited resources. Organizational change challenges health care providers in a variety of ways because it restructures how and when patient care delivery is provided, changing ways in which nurses must carry out their work. Little research has been done regarding the impact of rapid and continuous organizational change for frontline health care providers, most notably, nurses. In this study a critical hermeneutic design was applied. Guided by the theoretical framework of critical management studies, the researcher explored concepts of organizational change, experience of change, change fatigue, and power and voice. The setting was an urban pediatric teaching hospital located in eastern Ontario. The researcher sought breadth, depth, complexity and richness of data in understanding the experience of organizational change, which supported a decision to seek a sample size of ten to fifteen participants. Thick description commenced at fourteen participants. Face to face interviews were conducted using open-ended questions to understand nurses’ experiences of change. Brown and Gilligan’s Voice-centred relational