Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Pharmacokinetics of Linezolid in Patients Treated in a Compassionate-Use Program

ABSTRACT Data obtained from 318 adult patients treated under the linezolid compassionate-use protocol were used to develop a population model of the pharmacokinetics of intravenous and oral linezolid. All of the patients received 600 mg of linezolid every 12 h, intravenously and/or orally. Blood samples (2 to 10 per patient; median, 4) were obtained and assayed for linezolid by high-performance liquid chromatography. These data and patient covariates were modeled by iterative two-stage analysis, and model discrimination was done by Akaike's information criterion. Of the patient covariates considered (age, sex, ideal body weight, baseline serum albumin, hepatic or renal dysfunction, underlying malignancy, organ transplantation, surgical status, global severity of illness, site of infection, route of administration, and location of care [intensive-care unit, general floor, or outpatient]), only normalized creatinine clearance (CLCR) and body weight explained significant portions of the variance and were incorporated into the pharmacokinetic model. The final model included central and peripheral compartments with parallel capacity-limited (nonrenal) and first-order (renal [CLR]) clearances. Volumes and clearances were normalized to the ideal body weight, and CLR was modeled as proportional to CLCR. Compared to previously studied adult volunteers, intrinsic clearance was ∼60% higher and the maximum rate of metabolism was twice as high in these debilitated patients, resulting in lower area under the time-concentration curve (AUC) values (P < 0.001). The derived 24-h AUC, averaged over the first 7 days of treatment, ranged between 57 and 871 (median, 191) μg/ml · 24 h. Despite these variations, linezolid provided high rates of clinical cure, as well as microbiological success, in the patients treated in the compassionate-use program. The mechanism(s) of these pharmacokinetic differences is unknown and requires further mechanistic study.
Hydrogen sulfide alleviates uranium‐induced acute hepatotoxicity in rats: Role of antioxidant and antiapoptotic signaling

As an endogenous gaseous mediator, H2S exerts antioxidative, antiapoptotic, and cytoprotective effects in livers. This study was designed to investigate the protective role of H2S against uranium‐induced hepatotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2S production was determined in livers. The levels of endogenous H2S and H2S‐producing enzymes (CBS and CSE) were measured in liver homogenates from uranium ‐intoxicated rats. In rats injected intraperitoneally (i.p.) with uranyl acetate or NaHS (an H2S donor) alone or in combination, we examined biochemical parameters to assess liver function, revealed hepatic histopathological alteration, investigated oxidative stress markers, and explored apoptotic signaling in liver homogenates. The results suggest that uranium‐intoxication in rats decreased CBS and CSE protein expression, H2S synthesis capacity, and endogenous H2S generation. NaHS administration in uranium‐intoxicated rats produced amelioration in liver biochemical indices and histopathological effects, decreased MDA content, and increased GSH level and antioxidative enzymes activities like SOD, CAT, GPx, and GST. NaHS administration in uranium‐intoxicated rats attenuated uranium‐activated phosphorylation state of JNK. NaHS treatment in uranium‐intoxicated rats increased antiapoptotic Bcl‐2 but decreased pro‐apoptotic Bax, resulting in the rise of Bcl‐2/Bax ratio. NaHS treatment in uranium‐intoxicated rats reduced the apoptosis mediator caspase‐3 and cytochrome c release and elevated ATP contents. Taken together, these data implicate that H2S can afford protection to rat livers against uranium‐induced adverse effects mediated by up‐regulation of antioxidant and antiapoptotic signaling. The anti‐apoptotic property of H2S may be involved, at least in part, in inhibiting JNK signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 581–593, 2017.
NGOs and Corporations: Classifying NGOs: definitions, typologies and networks

The business–society interface has changed over the last decades of the twenty-first century as disparate interests within civil society have coalesced around an increasingly vocal – and powerful – nongovernmental or “third” sector. Nongovernmental organizations (NGOs) – the organizational manifestation of this movement – have gained considerable influence in government, business and within broader society. A coherent understanding of NGOs is a necessary precondition for proper consideration not only of their activities and influence, but also of the nature of the corporate–NGO interactions. In this chapter, we provide a definition of NGOs, a typology for conceptualizing the different varieties of NGOs, and discuss the importance of networks and coalitions to NGOs. Definitions of NGOs Although the term NGO is relatively recent, associations among like-minded individuals have been part of both ancient and modern history. When Tocqueville first visited the United States, he was struck by the fact that: Americans of all ages, all stations of life and all types of disposition are forever forming associations … In democratic countries knowledge of how to combine is the mother of all other forms of knowledge; on its progress depends that of all the others. There are not only commercial and industrial associations in which all take part, but others of a thousand different types – religious, moral, serious, futile, very general and very limited, immensely large and very minute … Nothing, in my view, deserves more attention than the intellectual and moral associations in America.
International Asset Allocation with Regime Switching: Evidence from the ETFs†

We develop a dynamic investment strategy with Markov regime switching (MRS) in asset allocation with international iShares exchange-traded funds (ETFs). Using daily ETF data, we show that a portfolio based on the dynamic MRS strategy outperforms one based on static mean-variance strategies after transaction costs. This dynamic investment strategy not only captures the regime shifts in the highly frequent trading process but also can be practically used with tradable ETFs. We investigate the reasons for predictive misjudgments and assess the contribution of each regime's investment strategy, providing insight into the characteristics of the MRS model and modifying our views on why the MRS strategy outperforms traditional strategies.
Credibility and Multiple SEOs: What Happens When Firms Return to the Capital Market?

Using a sample of firms that conducted multiple SEOs during 1995-2012, we examine whether firms can build credibility for subsequent SEOs by following through on their stated use of proceeds from earlier SEOs. We find that firms that previously state their intention to invest funds in projects and those that make no such statements but nevertheless make investments both have relatively more positive announcement returns around subsequent SEO announcements. Our results suggest that markets are aware of potential agency costs of equity, have a long memory, and update their beliefs as to the likely use of funds raised by firms.
A Hierarchical Contextual Attention-based GRU Network for Sequential Recommendation

Sequential recommendation is one of fundamental tasks for Web applications. Previous methods are mostly based on Markov chains with a strong Markov assumption. Recently, recurrent neural networks (RNNs) are getting more and more popular and has demonstrated its effectiveness in many tasks. The last hidden state is usually applied as the sequence's representation to make recommendation. Benefit from the natural characteristics of RNN, the hidden state is a combination of long-term dependency and short-term interest to some degrees. However, the monotonic temporal dependency of RNN impairs the user's short-term interest. Consequently, the hidden state is not sufficient to reflect the user's final interest. In this work, to deal with this problem, we propose a Hierarchical Contextual Attention-based GRU (HCA-GRU) network. The first level of HCA-GRU is conducted on the input. We construct a contextual input by using several recent inputs based on the attention mechanism. This can model the complicated correlations among recent items and strengthen the hidden state. The second level is executed on the hidden state. We fuse the current hidden state and a contextual hidden state built by the attention mechanism, which leads to a more suitable user's overall interest. Experiments on two real-world datasets show that HCA-GRU can effectively generate the personalized ranking list and achieve significant improvement.
Epithelial‐mesenchymal transition softens head and neck cancer cells to facilitate migration in 3D environments

The biological impact and signalling of epithelial‐mesenchymal transition (EMT) during cancer metastasis has been established. However, the changes in biophysical properties of cancer cells undergoing EMT remain elusive. Here, we measured, via video particle tracking microrheology, the intracellular stiffness of head and neck cancer cell lines with distinct EMT phenotypes. We also examined cells migration and invasiveness in different extracellular matrix architectures and EMT‐related signalling in these cell lines. Our results show that when cells were cultivated in three‐dimensional (3D) environments, the differences in cell morphology, migration speed, invasion capability and intracellular stiffness were more pronounced among different head and neck cancer cell lines with distinct EMT phenotypes than those cultivated in traditional plastic dishes and/or seated on top of a thick layer of collagen. An inverse correlation between intracellular stiffness and invasiveness in 3D culture was revealed. Knock‐down of the EMT regulator Twist1 or Snail or inhibition of Rac1 which is a downstream GTPase of Twist1 increased intracellular stiffness. These results indicate that the EMT regulators, Twist1 and Snail and the mediated signals play a critical role in reducing intracellular stiffness and enhancing cell migration in EMT to promote cancer cells invasion.
Measurement of Oman's Destination Image in the US

Hamed I. Al Azri Lecturer of Tourism Management, Department of Tourism, College of Arts and Social Sciences, Sultan Qaboos University, the Sultanate of Oman. e-mail: alazri@squ.edu. om Alastair M. Morrison Distinguished Professor of Hospitality and Tourism Management, School of Consumer and Family Sciences, Room 111A, Stone Hall, Purdue University, West Lafayette, Indiana 47907-2059, USA. e-mail: alastair@purdue.edu
Using group ratings to assess household food security: Empirical evidence from southern Africa

This article addresses the reliability and validity of household welfare rankings using the Group Ratings (GR) method. The GR aimed to measure the food security status of 142 households in seven villages in Malawi. Sets of informant groups rated households from their own community. Results show that the reliability of the method was no more than fair to moderate, and was particularly low for households falling in the middle category of 'intermittently food insecure'. Consensus ratings from the GR sessions were then compared with a number of alternative indicators of food security from a quantitative household survey. GR were associated with the more visible aspects of food security, such as household asset and livestock holdings, but associations with less visible aspects of food security were weaker. The strength of these associations varied from village to village.
The Effects of Public Policy on Strike Duration

Hazard-function estimates are utilized to analyze the effect of numerous public policy variables on strike duration, based on 7,546 strikes in Canada between 1967 and 1985. We find that only the mandatory strike vote substantially reduced conditional duration. However, the policy variables generally had a more favorable effect on reducing strike incidence, so that on net they tended to reduce unconditional duration (incidence times conditional duration). Specifically, reduced unconditional duration was associated with the existence of conciliation and the requirement of a mandatory strike vote, but the prohibition on replacement workers had a perverse effect.
Durable Responses With Maintenance Dose-Sparing Regimens of Romidepsin in Cutaneous T-Cell Lymphoma.

IMPORTANCE Romidepsin is a histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma (CTCL). Durable responses have been published without establishing a standard recommendation about duration of treatment. OBJECTIVE To review the long-term use of romidepsin in responders who received a dose-sparing regimen. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of medical records of patients with a diagnosis of CTCL, including mycosis fungoides (MF), Sézary syndrome (SS), or CTCL not otherwise specified seen at a multidisciplinary clinic at Northwestern University from 2009 until December 2014. EXPOSURES Doses administered and different regimens of romidepsin were reviewed. MAIN OUTCOMES AND MEASURES Duration of treatment, participants receiving dose-sparing regimen. RESULTS Of 47 patients identified, 23 had MF, 15 had SS, and 9 had other types of CTCL. None of these 9 (mostly cytotoxic lymphomas) achieved a durable response. Of the remaining 38 patients, 17 were considered long-term responders (>6 months of treatment). Nine of these patients received a dose-sparing regimen. The median (range) duration of treatment was 15 (7-34) months; the frequency of patients with SS (10 of 15) in the long-term group was significantly higher than that of patients with MF (7 of 23; P = .046). Adverse events were reported in 29 (69%) of 42 patients for whom data were available. There was no significant difference in the incidence of AEs between the short-term and long-term groups (12 of 21 vs 12 of 17; P = .50). CONCLUSIONS AND RELEVANCE Decreasing the frequency of infusions in patients with MF or SS who achieve a response with romidepsin therapy may provide a practical strategy to prolong response.
Great Horned Owl (Bubo virginianus) productivity and home range characteristics in a shortgrass prairie

We studied movements and breeding success of resident Great Horned Owls (Bubo virginianus) at the Rocky Mountain Arsenal National Wildlife Refuge from 1994-1996. We captured adult owls prior to nest initiation and outfitted them with radio transmitters. Twelve, 5, and 11 pairs nested each year, respectively. Eleven nests successfully hatched and produced 24 owlets in 1994, 3 nests produced 6 owlets in 1995, and 10 nests produced 29 owlets in 1996. We documented three cases in which a single parent successfully fledged owlets. We recorded three cases of nest site reuse. Ninety-five percent adaptive kernel mean home range size did not differ between ages or sexes.
Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases

Guillain-Barre syndrome (GBS) is the most frequent cause of acute flaccid paralysis in humans, occurring with an annual incidence of 1 to 2 cases per 100,000 people. In recent years, studies have shed new light on a number of disease aspects that have enhanced the understanding of the pathogenic
The Actualization of the Malaysian National Education Philosophy in Secondary Schools: Student and Teacher Perspectives

In the Malaysian context, all educational processes at the national level are envisioned by the National Education Philosophy (NEP). The NEP was formed in 1988 in line with the National Principles (Rukun Negara) with the ultimate aims of building a united and progressive society (Ministry of Education, 2001). However, there is uncertainty whether the NEP has been actualized in the educational processes, transmitted successfully by teachers to students and further personalized by students. This paper aims to report findings of study which analyzed the actualization of the NEP in government and private secondary schools based on student and teacher perspectives. The research followed a survey design through two sets of questionnaires; one for teachers and the other for students. The Cronbach’s Alpha reliability coefficient value for the teacher and student questionnaire was 0.96 and 0.98 respectively. A total of 185 Form 4 students and 45 teachers from both private and government secondary schools in Kuching, Sarawak, Malaysia participated in this research. 77.3% of students and 64.4% of teachers rated the level of actualization of the NEP as high, with a mean score of 7.67 and 7.28 out of 10 as rated by the students and teachers respectively. The paper further discusses the finding of the study from both teacher and student perspectives. It also provides a brief discussion on the limitations of this study and on its implications. It concludes with general implications of the study to the educational processes in the country in general and to the national education system in specific.
The use of a simultaneous integrated boost in spinal stereotactic body radiotherapy to reduce the risk of vertebral compression fractures: a treatment planning study

In the management of spinal metastases, stereotactic radiotherapy (SBRT) is an emerging technique intended to deliver a high-radiation dose precisely to the target [1]. Concern has been raised about the dose-fractionation schemes used in spinal SBRT as the risk of vertebral compression fractures (VCF) have been reported to be as high as 40% [2]. These rates are much higher compared to conventional radiotherapy, which is typically below 5% [3]. It was hypothesized that radiation effects in the form of bone and tumor necrosis compromise the ability of the vertebrae to withstand the axial loading forces, leading to an increased risk of VCF [4]. Clinicopathologic samples of spinal metastases, obtained after SBRT, showed radiation-induced tumor and osteonecrosis, giving evidence for this hypothesis [5,6]. More support for this hypothesis is provided by studies assessing VCF risk in patients receiving high-dose radiation for primary tumors in the thoracic or abdominal region, showing that vertebral fractures are mostly seen in the high-dose regions [7]. Prevention of VCF is challenging because the metastatic lesions lie within the segment at risk. A simultaneous integrated boost (SIB) dose delivery approach might mitigate the risk of SBRT-induced VCF by boosting the gross tumor volume (GTV) with the non-affected bone included in the clinical target volume (CTV). Currently, a SIB planning design has not been formally compared with a non-SIB approach. In this study, we report on the dosimetric feasibility of a SIB SBRT approach in the treatment of spinal metastases.
Minimal-path fault-tolerant approach using connection-retaining structure in Networks-on-Chip

There are many fault-tolerant approaches presented both in off-chip and on-chip networks. Regardless of all varieties, there has always been a common assumption between them. Most of all known fault-tolerant methods are based on rerouting packets around faults. Rerouting might take place through nonminimal paths which affect the performance significantly not only by taking longer paths but also by creating hotspot around a fault. In this paper, we present a fault-tolerant approach based on using the shortest paths. This method maintains the performance of Networks-on-Chip in the presence of faults. To avoid using non-minimal paths, the router architecture is slightly modified. In the new form of architecture, there is an ability to connect the horizontal and orthogonal links of a faulty router such that healthy routers are kept connected to each other. Based on this architecture, a fault-tolerant routing algorithm is presented which is obviously much simpler than traditional fault-tolerant routing algorithms. According to this algorithm, only the shortest paths are used by packets in the presence of fault. This results retains the performance of NoCs in faulty situations. This algorithm is highly reliable, for an instance, the reliability is more than 99.5% when there are six faulty routers in an 8×8 mesh network.
Airway Relaxation Effects of Water-Soluble Sclerotial Extract From Lignosus rhinocerotis

Lignosus rhinocerotis has a long history of use by the indigenous community within East Asia to treat a range of health conditions including asthma and chronic cough. To date, there is limited scientific evidence to support its therapeutic effects in relieving these airways conditions. In this study, we examined the effects of the different molecular weight fractions [high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW)] obtained from the cold water sclerotial extract (CWE) of L. rhinocerotis on airways patency using airway segments isolated from Sprague Dawley rat in an organ bath set-up. It is demonstrated that the HMW and MMW fractions exhibited higher efficacy in relaxing the pre-contracted airways when compared to the CWE and LMW fraction. In addition, the HMW fraction markedly supressed carbachol-, 5-hydroxytrptamine-, and calcium-induced airway contractions. CWE demonstrated a lower efficacy than the HMW fraction but it also significantly attenuated carbachol- and calcium-induced airway contractions. Results showed that the bronchorelaxation effect of CWE and fractions is mediated via blockade of extracellular Ca2+ influx. The composition analysis revealed the following parts of carbohydrate and proteins, respectively: HMW fraction: 71 and 4%; MMW fraction: 35 and 1%; and LMW fraction: 22 and 0.3%. Our results strongly suggest that the polysaccharide–protein complex or proteins found in the HMW and MMW fractions is likely to contribute to the bronchorelaxation effect of CWE.