Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxygen administration, cerebral blood flow velocity, and dynamic cerebral autoregulation.

INTRODUCTION Hyperoxia is reported to decrease steady-state cerebral blood flow (CBF). In addition, dynamic cerebral autoregulation would be altered. Hyperoxia may improve dynamic cerebral autoregulation, contrary to hypoxia. However, no previous studies have examined changes in steady-state CBF velocity (CBFV) and alterations of dynamic cerebral autoregulation during acute exposure to hyperoxia. We, therefore, evaluated dynamic cerebral autoregulation simultaneously with steady-state CBFV during stepwise hyperoxia under oxygen administration. METHODS There were eight healthy volunteers who were examined under normoxic (21% O2) and hyperoxic conditions in stepwise fashion to 40%, 70%, and 100% O2. Mean blood pressure (MBP) in the radial artery was measured via tonometry, and CBFV in the middle cerebral artery was measured by transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis of beat-to-beat changes in MBP and CBFV. RESULTS End-tidal CO2 decreased significantly at 70% and 100% O2. Steady-state CBFV decreased significantly at F1O2 > or = 40%, while MBP was unchanged. Associated with these changes, cerebral vascular resistance index increased at 70% and 100% O2. Transfer function gain and coherence remained unchanged at all levels of F1O2. DISCUSSION These results suggest that hyperoxemia and hypocapnia reduce steady-state CBFV and increase cerebral vascular resistance during oxygen administration. This reduction in steady-state CBFV occurs even during mild hyperoxia < or = 40% O2 and becomes obvious at 70% O2 with hypocapnia. However, dynamic cerebral autoregulation may remain unchanged during hyperoxia, even with apparent changes in steady-state CBFV.
Outcomes in elderly patients with advanced colorectal cancer treated with capecitabine: a population-based analysis.

BACKGROUND Toxicity concerns impact the delivery of palliative chemotherapy to elderly patients with advanced colorectal cancer (CRC). Capecitabine was approved for funding in the province of British Columbia in the spring of 2002 as an oral chemotherapeutic option for metastatic CRC. PATIENTS AND METHODS We conducted a population-based study to assess temporal trends in the use of systemic agents in elderly patients. Patients aged > or = 70 years with metastatic CRC diagnosed between January 1, 2000, and December 31, 2000, and between June 1, 2002, and May 31, 2003, were identified through the British Columbia Cancer Agency Registry. The time cohorts were before and after the provincial approval of capecitabine. Data were obtained regarding demographics, systemic therapies, and outcomes. RESULTS In cohort A, 35 of 89 patients (39%) were treated with chemotherapy. In the treated versus untreated groups of cohort A, 66% and 57% of patients were male, median ages were 73 years and 76 years, and liver metastasis was seen in 69% and 70% of patients, respectively. In cohort B, 36 of 78 patients (46%) were treated with systemic therapy. In the treated versus untreated groups of cohort B, 58% and 40% of patients were male, median ages were 75 years and 78.5 years, and liver metastasis was seen in 78% and 64% of patients. The most common first-line chemotherapy regimens used in cohort A included single-agent 5-FU in 66%, irinotecan-based regimens in 17%, and other regimens in 11%. First-line chemotherapy in cohort B included capecitabine in 47%, oxaliplatin-based regimens in 19%, and irinotecan-based regimens in 17%. The median times to treatment failure resulting from toxicity, disease progression, or death were 37 days in cohort A and 61 days in cohort B. Overall survival between the 2 time cohorts did not differ significantly. Toxicities resulting in dose delay and/or reduction were comparable. CONCLUSION We conclude that, in patients > or = 70 years of age with advanced CRC, single-agent 5-FU and capecitabine were the favored palliative regimens in British Columbia in 2000 and 2002, respectively. Capecitabine was well tolerated, and both treatments demonstrated similar survival. There was a trend observed toward a greater proportion of patients being offered systemic therapy in the 2002 cohort; however, the difference was not statistically significant.
Development of Farnesyltransferase Inhibitors for Clinical Cancer Therapy: Focus on Hematologic Malignancies

Farnesyltransferase inhibitors (FTIs) target and inhibit the peptide prenylating enzyme farnesyltransferase. This new class of signal transduction inhibitors is being tested clinically in diverse malignancies, with encouraging results in hematololgic malignancies and breast cancer in particuarl. Critical questions have yet to be answered, for example, optimal dose and schedule, disease subgroups most likely to respond, and appropriate combinations with standard cytotoxics and new biologics. Gene profiling studies of malignant target cells obtained during FTI clinical trials will help to identify patients who are likely to respond to FTIs and to develop mechanisms for overcoming FTI resistance. Clinical trials and correlative laboratory studies in progress and under development will define the optimal roles of FTIs in cancer patients.
Malformations of the great vessels in the neonatal rat induced by N-(2-aminoethyl)ethanolamine.

The reproductive and developmental toxicity of aminoethylethanolamine was evaluated in a standard screening study (OECD, 1995: Organisation for economic co-operation and development. Paris, France), in which groups of Wistar rats (10/sex/group) were administered the test substance by gavage at dosage levels of 50, 250, or 1000 mg/kg/day (groups 2-4, respectively). A control group received the vehicle, doubly distilled water. No live pups were delivered in group 4, and there was a higher incidence of stillborn offspring and reduced postnatal survival in group 3. Macroscopic changes in groups 2 and 3 were primarily related to the great vessels and characterized by dilations, aneurysms, and altered course of the aorta, pulmonary trunk, carotids, and the ductus arteriosus. A follow-up study was conducted to characterize the low dose-response, using dosage levels of 0, 0.2, 1, 5, or 50 mg/kg/day (groups 1-5, respectively). Given the expected scarcity of the lesions in control offspring, each group consisted of 25 animals of each sex. Macroscopic examination revealed a high incidence (18.5%) of aneurysm-bearing offspring in group 5 litters, and single offspring (0.3-0.4%) with aneurysms in groups 3 and 4. Microscopic examination revealed dissecting aneurysms in offspring from all aminoethylethanolamine treatment groups, without a clear dose-response between groups 2 and 4 (0.6%, 1.2%, and 0.3%, respectively), and focal hemorrhages in all groups including the control. In comparison, the background incidence of aneurysms in untreated 4-day old offspring was 0.2% (Treumann et al., 2011: Toxicol Pathol 39:969-974). Consequently, the findings in groups 2-4 cannot be conclusively attributed to treatment.
Using a specialized corpus and Google custom search engine ( CSE ) for enhancing L 2 teaching and learning

This study explores how teachers can enhance L2 instruction using a specialized corpus with a popular custom search engine from Google. With a focus on the learners' lexicogrammatical performance, a corpus-based system consisting of a database of genreand discipline-specific texts and a companion search engine are developed for an undergraduate L2 writing course. Using digital video technology, this study documents the learners’ interactions with the corpus system over the course of one semester. The findings show that the learners engage in cognitive collaboration with the system and address their lexico-grammatical issues in moment-by-moment development of their linguistic competence rather than simply borrow the text from the corpus. The learners engage in intense hypothesis-testing in order to appropriate the language items from the corpus and in this endeavor, they interact with the system in a highly interactive and multi-layered way. The findings suggest the potential impact of the custom search engine on technology-enhance language learning, i.e., as a teachers’ tool to facilitate the learner's development. This study concludes by discussing implications of custom search engine as a powerful tool for corpus-enhanced language learning.
The zebrafish embryo as a dynamic model of anoxia tolerance

Developing organisms depend upon a delicate balance in the supply and demand of energy to adapt to variable oxygen availability, although the essential mechanisms determining such adaptation remain elusive. In this study, we examine reversible anoxic arrest and dynamic bioenergetic transitions during zebrafish development. Our data reveal that the duration of anoxic viability corresponds to the developmental stage and anaerobic metabolic rate. Diverse chemical inhibitors of mitochondrial oxidative phosphorylation induce a similar arrest in normoxic embryos, suggesting a pathway responsive to perturbations in aerobic energy production rather than molecular oxygen. Consistent with this concept, arrest is accompanied by rapid activation of the energy‐sensing AMP‐activated protein kinase pathway, demonstrating a potential link between the sensing of energy status and adaptation to oxygen availability. These observations permit mechanistic insight into energy homeostasis during development that now enable genetic and small molecule screens in this vertebrate model of anoxia tolerance. Developmental Dynamics 237:1780–1788, 2008. © 2008 Wiley‐Liss, Inc.
Programmed cell death ligand 1 (PD‐L1) expression is not a predominant feature in Ewing sarcomas

Programmed cell death 1 (PD‐1) receptor engagement on T cells by its ligand programmed cell death ligand 1 (PD‐L1) is a key mechanism of immune escape, and antibody blockade of the interaction has emerged as an effective immunotherapeutic strategy in some cancers. The role and relevance of the PD‐1 checkpoint in Ewing sarcoma (EwS) is not yet understood.
Prevalence of Helicobacter pylori in Patients With Brucellosis

Background Helicobacter pylori infection affects approximately 40 million individuals in Turkey. Our prefecture is an endemic area for H. pylori infection and brucellosis. However, there are no data on the H. pylori prevalence among patients with brucellosis. Objectives The primary aim of the current study was to investigate the link between H. pylori infection and brucellosis. The secondary aim was to determine the seroprevalence of H. pylori infection in healthy individuals. Methods Between May 2010 and May 2011, serum was collected from patients with Brucella infection (n = 111) and healthy individuals (n = 120) and analyzed using an enzyme-linked immunosorbent assay kit. Brucella infection was defined as a positive Wright test or blood culture positivity for Brucella in conjunction with disease symptoms and findings. Results Among the 111 patients with brucellosis, 69% (n = 77) had a seropositivity result for H. pylori IgG. The healthy control subjects had an 87% (n = 104) seropositivity for H. pylori IgG. The serum H. pylori IgG antibody seropositivity was significantly lower in the patients with Brucella infection compared with the control subjects (P < 0.001). Conclusion Our results show that the serum prevalence of H. pylori among the patients infected with brucellosis is significantly lower than that in the control population. A negative correlation between H. pylori infection and brucellosis infection might be hypothesized.
A Behavioral and Pharmacological Validation of the Acetone Spray Test in Gerbils with a Chronic Constriction Injury

Cold and mechanical allodynia are important symptoms in patients with neuropathic pain. The study of cold allodynia in animals can help us to understand the underlying pathophysiological mechanisms of neuropathic pain and to validate drugs. The evaluation of cold allodynia in gerbils with a chronic constriction injury of the sciatic nerve on the cold plate is not always stable. We developed a new application method of acetone using a specific spray technique with an Eppendorf® multistepper pipette. The chronic constriction injury of the sciatic nerve in gerbils resulted in a long-lasting mechanical and acetone spray-induced hyperreactivity throughout the testing period, which is clearly different from what was seen in sham-operated animals. The acetone spray test incorporates a multimodal stimulus different from direct cold stimulation. The reactivity to the acetone spray coincides in time and strength with the reactivity observed in mechanical allodynia in gerbils and with mechanical and thermal allodynia in other species. Furthermore, a pharmacological validation of the acetone spray test by different reference compounds was performed. Different compounds effective in neuropathic pain models in rodents influence the hyperreactivity to the acetone spray after acute and chronic administration. This study indicates that the multimodal acetone spray test is a valuable tool in the study of neuropathic pain in rodents.
Peripheral resistance Hypertension Volume expansion Sodium chloride reabsorption Sympathetic activation Leptin Renin-angiotensin activation Obesity

Obesity has become a worldwide epidemic. In Hong Kong, more than a third of the population is overweight. Elevated arterial pressure is a frequent complication of excess body weight, and both obesity and hypertension are components of insulinresistance syndrome. Many obese hypertensive patients will develop type-2 diabetes, which further increases their cardiovascular risk. While lifestyle modification is the key to weight and blood pressure reduction, pharmacological intervention remains essential to lowering blood pressure to target levels in obese patients with hypertension. Antihypertensive drugs such as thiazide diuretics and β-blockers adversely affect glucose metabolism and increase the risk of developing type-2 diabetes. On the other hand, drugs that interfere with the renin-angiotensin system (RAS) improve insulin sensitivity and reduce the incidence of new-onset diabetes. Therefore, the initial selection of antihypertensive therapy for obese patients could have a significant influence on their overall cardiovascular risk.
A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.

OBJECTIVE The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.
Surface Breakdown Characteristics of Composite Insulating Papers in LN2 for a Stop Joint Box of DC HTS Power Cable

One of the key components for dc HTS cable for long-distance line is a stop joint box (SJB). Up to now, the SJB has not been commercialized yet due to some difficulties of dc electrical insulation matters in LN2. Basically, the structure of SJB would be similar to the SJB of oil-filled cable because they adopt liquid insulation and sectionalized cooling separations. The insulation structure of conventional SJB based on ac electric field was no more suitable for dc; hence, there is a need to design suitable insulation structure, which can be applied for dc. In this work, in order to find a solution to reduce dc electric field concentration on the polypropylene laminated paper (PPLP) above epoxy spacer, double layer structure composed of PPLP and Kraft were suggested. To verify the effectiveness of this structure for relieving dc electric field, simulation and experiments were performed. From analytical works, the Kraft layer between PPLP and epoxy has shown noticeable electric field mitigation. Furthermore, surface breakdown tests considering PPLP/Kraft combined layers were conducted to verify the insulation properties of double layer structure. Finally, it was deduced that Kraft layer was effective to enhance surface breakdown voltage. Surface breakdown characteristics of PPLP and Kraft were relevant to the surface roughness of insulating materials.
The Management of Invasive Fungal Infections: What to Consider in Empirical Treatment?

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in immunocompromised patients. Candida and Aspergillus are the most common fungi that lead to IFI. While invasive Candida infections are most commonly seen in patients in intensive care units (ICUs) and very low birth weight infants, aspergillosis is most frequent in immunocompromised patients, especially in patients with hematological malignancies and in those undergoing hematopoietic stem cell transplantation (HSCT). Empirical treatment should be considered in all high-risk patients with hematological malignancies suspected of having IFIs.
Not Quite Normal: Consequences of Violating the Assumption of Normality in Regression Mixture Models

Regression mixture models, which have only recently begun to be used in applied research, are a new approach for finding differential effects. This approach comes at the cost of the assumption that error terms are normally distributed within classes. This study uses Monte Carlo simulations to explore the effects of relatively minor violations of this assumption. The use of an ordered polytomous outcome is then examined as an alternative that makes somewhat weaker assumptions, and finally both approaches are demonstrated with an applied example looking at differences in the effects of family management on the highly skewed outcome of drug use. Results show that violating the assumption of normal errors results in systematic bias in both latent class enumeration and parameter estimates. Additional classes that reflect violations of distributional assumptions are found. Under some conditions it is possible to come to conclusions that are consistent with the effects in the population, but when errors are skewed in both classes the results typically no longer reflect even the pattern of effects in the population. The polytomous regression model performs better under all scenarios examined and comes to reasonable results with the highly skewed outcome in the applied example. We recommend that careful evaluation of model sensitivity to distributional assumptions be the norm when conducting regression mixture models.
Orthogonal Recurrent Neural Networks with Scaled Cayley Transform

Recurrent Neural Networks (RNNs) are designed to handle sequential data but suffer from vanishing or exploding gradients. Recent work on Unitary Recurrent Neural Networks (uRNNs) have been used to address this issue and in some cases, exceed the capabilities of Long Short-Term Memory networks (LSTMs). We propose a simpler and novel update scheme to maintain orthogonal recurrent weight matrices without using complex valued matrices. This is done by parametrizing with a skew-symmetric matrix using the Cayley transform. Such a parametrization is unable to represent matrices with negative one eigenvalues, but this limitation is overcome by scaling the recurrent weight matrix by a diagonal matrix consisting of ones and negative ones. The proposed training scheme involves a straightforward gradient calculation and update step. In several experiments, the proposed scaled Cayley orthogonal recurrent neural network (scoRNN) achieves superior results with fewer trainable parameters than other unitary RNNs.
pyDock: Electrostatics and desolvation for effective scoring of rigid‐body protein–protein docking

The accurate scoring of rigid‐body docking orientations represents one of the major difficulties in protein–protein docking prediction. Other challenges are the development of faster and more efficient sampling methods and the introduction of receptor and ligand flexibility during simulations. Overall, good discrimination of near‐native docking poses from the very early stages of rigid‐body protein docking is essential step before applying more costly interface refinement to the correct docking solutions. Here we explore a simple approach to scoring of rigid‐body docking poses, which has been implemented in a program called pyDock. The scheme is based on Coulombic electrostatics with distance dependent dielectric constant, and implicit desolvation energy with atomic solvation parameters previously adjusted for rigid‐body protein–protein docking. This scoring function is not highly dependent on specific geometry of the docking poses and therefore can be used in rigid‐body docking sets generated by a variety of methods. We have tested the procedure in a large benchmark set of 80 unbound docking cases. The method is able to detect a near‐native solution from 12,000 docking poses and place it within the 100 lowest‐energy docking solutions in 56% of the cases, in a completely unrestricted manner and without any other additional information. More specifically, a near‐native solution will lie within the top 20 solutions in 37% of the cases. The simplicity of the approach allows for a better understanding of the physical principles behind protein–protein association, and provides a fast tool for the evaluation of large sets of rigid‐body docking poses in search of the near‐native orientation. Proteins 2007. © 2007 Wiley‐Liss, Inc.
A functional lagging strand origin does not stabilize plasmid pMV158 inheritance in Escherichia coli.

Plasmid rolling circle replication generates single-stranded DNA intermediates. The intracellular amount of these molecules depends upon the efficiency of the conversion of single-stranded into double-stranded plasmid forms, that is, the functionality of the lagging strand origin (sso). The broad-host-range streptococcal plasmid pMV158 harbors two different ssos, both of which function efficiently in Streptococcus pneumoniae but poorly in Escherichia coli. Plasmid pMV158 is stably inherited in the pneumococcal host, but it is unstable in E. coli. A pMV158 derivative lacking its two ssos is unstable in both strains. We have cloned into this derivative the coliphage f1 lagging strand origin. Whereas the f1 sso was fully functional in E. coli, it did not show any activity in S. pneumoniae, a bacteria closely related to the pMV158 natural host. The presence of the f1 sso did not stabilize pMV158 inheritance in either the gram-positive or the gram-negative host.