Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective series of two hours supine rest after 4fr sheath-based diagnostic cerebral angiography: Outcomes, productivity and cost

There is no standard of care for catheter size or post-procedure supine time in cerebral angiography. Catheter sizes range from 4-Fr to 6-Fr with supine times ranging from two to over six hours. The objective of our study was to establish the efficacy, safety, and cost savings of two-hour supine time after 4-Fr elective cerebral angiography. A prospective, single arm study was performed on 107 patients undergoing elective cerebral angiography. All cerebral angiograms were performed with a 4-Fr sheath-based system without closure devices. Ten minutes of manual compression was applied to the femoral access site, with further compression held as clinically indicated. Patients were then monitored in a nursing unit for two hours supine and subsequently mobilized. Nursing discretion was allowed for earlier mobilization. Patients were called the next day to assess delayed hematoma and bleeding. Estimates of cost savings and productivity increases are provided. All patients ambulated in two hours or less. There were no strokes or vessel dissections. Five patients (4.7%) experienced a palpable hematoma, three patients (2.8%) experienced bleeding immediately following the procedure requiring further compression, and one patient (0.9%) experienced minor groin oozing at home. No patient required transfusion, thrombin injection, or endovascular/surgical management of a groin complication. A two-hour post-procedure supine time resulted in cost savings of $952 per angiogram and a total of $101,864. 4-Fr sheath based cerebral angiography with two-hour post-procedure supine time is safe and effective, and allows for a considerable increase in patient satisfaction, cost savings and productivity.
An attenuated quadruple gene mutant of Mycobacterium tuberculosis imparts protection against tuberculosis in guinea pigs

ABSTRACT Previously we had developed a triple gene mutant of Mycobacterium tuberculosis (MtbΔmms) harboring disruption in three genes, namely mptpA, mptpB and sapM. Though vaccination with MtbΔmms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with MtbΔmms resulted in some pathological damage to the spleens in the early phase of infection. In order to generate a strain that overcomes the pathology caused by MtbΔmms in spleen of guinea pigs and controls dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. MtbΔmmsb mutant strain was highly attenuated for growth and virulence in guinea pigs. Vaccination with MtbΔmmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleen of infected animals. However, the protection imparted by MtbΔmmsb was significantly less in comparison to BCG immunized animals. This study indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis for generating protection against tuberculosis. Summary: In this study, a mutant of M. tuberculosis with the deletion of four important genes has been evaluated in guinea pigs for its attenuation and protective efficacy against tuberculosis.
Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs Ca2+ transients and slow waves in adult mouse small intestine.

Myenteric plexus interstitial cells of Cajal (ICC-MY) in the small intestine are Kit+ electrical pacemakers that express the Ano1/TMEM16A Ca2+-activated Cl- channel, whose functions in the gastrointestinal tract remain incompletely understood. In this study, an inducible Cre-LoxP-based approach was used to advance the understanding of Ano1 in ICC-MY of adult mouse small intestine. KitCreERT2/+;Ano1Fl/Fl mice were treated with tamoxifen or vehicle, and small intestines (mucosa free) were examined. Quantitative RT-PCR demonstrated ~50% reduction in Ano1 mRNA in intestines of conditional knockouts (cKOs) compared with vehicle-treated controls. Whole mount immunohistochemistry showed a mosaic/patchy pattern loss of Ano1 protein in ICC networks. Ca2+ transients in ICC-MY network of cKOs displayed reduced duration compared with highly synchronized controls and showed synchronized and desynchronized profiles. When matched, the rank order for Ano1 expression in Ca2+ signal imaged fields of view was as follows: vehicle controls>>>cKO(synchronized)>cKO(desynchronized). Maintenance of Ca2+ transients' synchronicity despite high loss of Ano1 indicates a large functional reserve of Ano1 in the ICC-MY network. Slow waves in cKOs displayed reduced duration and increased inter-slow-wave interval and occurred in regular- and irregular-amplitude oscillating patterns. The latter activity suggested ongoing interaction by independent interacting oscillators. Lack of slow waves and depolarization, previously reported for neonatal constitutive knockouts, were also seen. In summary, Ano1 in adults regulates gastrointestinal function by determining Ca2+ transients and electrical activity depending on the level of Ano1 expression. Partial Ano1 loss results in Ca2+ transients and slow waves displaying reduced duration, while complete and widespread absence of Ano1 in ICC-MY causes lack of slow wave and desynchronized Ca2+ transients.NEW & NOTEWORTHY The Ca2+-activated Cl- channel, Ano1, in interstitial cells of Cajal (ICC) is necessary for normal gastrointestinal motility. We knocked out Ano1 to varying degrees in ICC of adult mice. Partial knockout of Ano1 shortened the widths of electrical slow waves and Ca2+ transients in myenteric ICC but Ca2+ transient synchronicity was preserved. Near-complete knockout was necessary for transient desynchronization and loss of slow waves, indicating a large functional reserve of Ano1 in ICC.
The influence of extended posthatch holding time and placement density on broiler performance.

Extended posthatch holding (in the hatcher) has been reported to dehydrate chicks, reduce broiler performance, and depress immune response. Nevertheless, some commercial hatcheries are increasing incubation time in an attempt to minimize possible bacterial contamination of incompletely healed navels. The objectives of this study were to determine the effects of posthatch holding on broiler performance and the effects of bird density and additive stress on performance and immune response. Twelve hundred broiler eggs (58 to 70 g) were incubated. Chicks were removed from the hatcher after 528 h of incubation, banded, and weighed. Half of the chicks were returned to the hatcher for an additional 24 h (HELD). Both hatcher treatments were placed at two densities (.07 and .12 m2 per bird). Individual BW were taken at 21 and 43 d of placement and 43 d of age. The HELD chicks weighed significantly less than controls at time of placement. At 21 d postplacement the HELD broilers were significantly heavier than controls, but were similar by 43 d. Total feed conversion was not affected in the HELD treatment, but birds in the . 07 m2 per bird density were less efficient in terms of total feed conversion. Chick holding time and density seemed to affect antibody titers at 5 wk. Although holding chicks in the hatcher for 24 h did not clinically dehydrate chicks or affect performance, it decreased immune response. In addition to less efficient growth, birds in the more crowded pens had depressed immune response.
Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel &bgr; 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNG&bgr;1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene augmentation using adeno-associated virus vectors robustly sustained the rescue of rod function and preserved retinal structure in the dog model. Together, our results reveal an early loss of rod function in CNGB1-deficient patients and a wide window for therapeutic intervention. Moreover, the identification of potential biomarkers of outcome measures, availability of relevant animal models, and robust functional rescue from gene augmentation therapy support future work to move CNGB1-RP therapies toward clinical trials.
Do Lenders Have Favorite Auditors?

Yes. We construct a novel revealed preference measure of financial statement verification based on matching among lenders, borrowers, and auditors. When borrowers use their lenders’ preferred auditors, they borrow larger amounts and at lower rates and contracts depend more on accounting information. Lender preferences are determined by their historical experience with individual auditors; when borrowers in their loan portfolio default or restate their financials, lenders shift their loan portfolio away from the implicated auditor. These preferences impact borrowers’ post-financing auditor choices as well as subsequent matching between borrowers and lenders. Finally, when borrowers follow their lenders’ preferences, loan terms are more sensitive to financials and borrowers are less likely to default in the future. Our findings suggest that, through financial statement verification, auditors play a significant role in contracting efficiency and matching in the private loan market.
Postmolt performance of laying hens molted by high dietary zinc, low dietary sodium, and fasting: egg production and eggshell quality.

Single Comb White Leghorn (SCWL) hens, 65 weeks of age, were assigned to one of four dietary treatments: fasting to a body weight loss of 34% (FAST), administration of a diet containing less than or equal to 500 ppm sodium for 42 days (Lo Na), administration of a diet containing 20,000 ppm zinc for 10 days (Hi Zn), and a control (CON) diet. The hens were subjected to two photoperiod treatments, those receiving 17 hr (17-hr) of light per day throughout the 32-week experiment and those restricted to 8 hr of light per day for the first 42 days followed by a . 5 hr/day increase until 17 hr was reached. Egg production and mortality were recorded daily. Feed consumption, feed conversion, and livability were determined weekly. Beginning on Day 56, eggs were collected at 28-day intervals for determination of egg weight, egg specific gravity, and shell weight. During the molt phase (1 to 6 weeks), the 17-hr light day significantly increased egg production, feed consumption, and decreased feed conversion (kg/doz) across all groups when compared with the 8-hr light/day treatments, but FAST treatments consumed identical amounts under both light treatments. From 7 to 32 weeks during the postmolt phase, egg production was significantly increased and feed conversion decreased by the FAST and Hi Zn treatments relative to CON, Lo Na treatment was intermediate. Feed consumption was significantly higher for the FAST treatment. Overall, there were not significant effects on egg production, feed consumption, and feed conversion. (ABSTRACT TRUNCATED AT 250 WORDS)
Chronic heat stress and respiratory alkalosis: occurrence and treatment in broiler chicks.

The occurrence of respiratory alkalosis and potential benefit derived from treatment were examined in thermostressed 4-week-old broiler chicks. Blood pH was greater (P less than .05) in heat-stressed (32 C) panting birds (7.395) than either nonpanting (7.28) or birds raised at 24 C (7.28). Acute thermostress, obtained by elevating ambient temperature from 32 to 41 C over a 20-min period further elevated (P less than .05) blood pH to 7.521. Chronic heat-stressed broiler chicks suffer from intermittent respiratory alkalosis during panting; with acute heat stress, chicks pant continuously and suffer from alkalosis. Including . 5% sodium bicarbonate (NaHCO3) in the diet of birds subjected to chronic heat stress enhanced body weight gain by 9% even though it tended (P less than .10) to increase blood pH in nonpanting birds. Adding . 3 or 1% ammonium chloride (NH4Cl) to diets decreased blood pH (P less than .01) to 7.194 and increased (P less than .05) body weight gains by 9.5 and 25%, respectively. Effects appeared linear with NH4Cl dose to 1% NH4Cl, but 3% NH4Cl elevated weight gains by only 8% and precipitated blood acidosis (pH 7.09) in nonpanting birds. Supplementing the 1% NH4Cl diet with . 5% NaHCO3 increased weight gains an additional 9%. Manipulating sodium: chloride ratios by addition of calcium chloride increased body weight gain 8% and slightly reduced severity of alkalosis. Data indicate that blood alkalosis limits growth rate of broiler chicks reared under chronic thermostress and that the respiratory alkalosis and weight gain depressions attributed to thermostress can be partially alleviated dietarily.
Genetics of growth and reproduction in the turkey. 9. Long-term selection for increased 16-week body weight.

Sixteen generations of selection of turkeys for increased 16-week body weight alone resulted in a large increase in body weight at 8, 16, 20, and 24 weeks of age of both males and females and at sexual maturity for females. The realized heritability for 16-week body weight was . 29 +/- . 02 for males and . 24 +/- . 01 for females. There was no significant effect on egg production during the first three generations of selection. However, egg production of the growth strain relative to the corresponding randombred control declined greatly during the next two generations. Eleven further generations of selection did not result in additional declines in egg production. These results suggest that the genetic correlation between 16-week body weight and egg production was zero initially, became strongly negative for Generations 4 and 5, and then ultimately returned to zero. Genetic increases in body weight were associated with decreases in intensity of lay with no effect on broodiness. Based on a subjective rating of deviation of legs and ability to walk, the legs of the growth strain were poorer than those of its corresponding randombred control in the last four generations of selection. This indicates that there is a positive genetic correlation between 16-week body weight and frequency of leg problems. Genetic increases in 16-week body weight were accompanied by increases in egg weight and a decrease in rate of response to stimulatory lighting. The effect on fertility was inconsistent. There was no effect on hatch of fertile eggs.
Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes.
Understanding the Intrinsic Motivations of User Acceptance of Hedonic Information Systems: Towards a Unified Research Model

Although user acceptance of entertainment-oriented information systems (IS), which are called Hedonic IS (HIS), has drawn considerable attention in literature, our understanding of user acceptance of HIS is still limited. This article focuses on exploring the intrinsic motivations of HIS acceptance from a unique perspective. It proposes a hybrid HIS acceptance model that considers the unique characteristics of HIS and the multiple conceptual identities of an HIS user. The model integrates intrinsic motivation factors from Hedonic theory, Flow theory, and the PAD (Pleasure, Arousal, and Dominance) emotion model with the Technology Acceptance Model. The proposed hybrid HIS acceptance model has been empirically tested by a quantitative field survey. The results indicate that emotional responses, imaginal responses, and flow experience are three main predictors of HIS acceptance.
A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism

Progress in systems medicine brings promise to addressing patient heterogeneity and individualized therapies. Recently, genome-scale models of metabolism have been shown to provide insight into the mechanistic link between drug therapies and systems-level off-target effects while being expanded to explicitly include the three-dimensional structure of proteins. The integration of these molecular-level details, such as the physical, structural, and dynamical properties of proteins, notably expands the computational description of biochemical network-level properties and the possibility of understanding and predicting whole cell phenotypes. In this study, we present a multi-scale modeling framework that describes biological processes which range in scale from atomistic details to an entire metabolic network. Using this approach, we can understand how genetic variation, which impacts the structure and reactivity of a protein, influences both native and drug-induced metabolic states. As a proof-of-concept, we study three enzymes (catechol-O-methyltransferase, glucose-6-phosphate dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase) and their respective genetic variants which have clinically relevant associations. Using all-atom molecular dynamic simulations enables the sampling of long timescale conformational dynamics of the proteins (and their mutant variants) in complex with their respective native metabolites or drug molecules. We find that changes in a protein’s structure due to a mutation influences protein binding affinity to metabolites and/or drug molecules, and inflicts large-scale changes in metabolism.
A circadian rhythm in photosensitivity as the basis for the testicular response of Japanese quail to intermittent light.

In order to examine the relationship between the circadian rhythm in photosensitivity and intermittent light in stimulating testicular development, Japanese quail were exposed to intermittent light providing a single dark period interruption varying from . 5 to 10 hr in duration. The treatment lasted for 3 weeks. Changes in the cloacal gland size were monitored throughout the test and testis weights were taken at the end of the test (7 and 11 weeks of age). The results indicated that quail have a circadian rhythm in photosensitivity occurring approximately 12 hr after the onset of light (dark-light interface) which lasts for 4 to 6 hr. Testicular stimulation occurred only when light was given within the photosensitive phase. However, this rhythm is subject to phase shifting by night interrupting light flashes. This resulted in variable testicular responses depending upon the relationship between the position of the new photosensitive phase and the available light. Photostimulation of the testes was proportional to the duration of light within the photosensitive phase up to a maximum of 4 hr of light. Intermittent light may be as effective as a single, long photoperiod in stimulating testes development providing that an adequate amount of light is given during the photosensitive phase.
Profiling model T-cell metagenomes with short reads

MOTIVATION T-cell receptor (TCR) diversity in peripheral blood has not yet been fully profiled with sequence level resolution. Each T-cell clonotype expresses a unique receptor, generated by somatic recombination of TCR genes and the enormous potential for T-cell diversity makes repertoire analysis challenging. We developed a sequencing approach and assembly software (immuno-SSAKE or iSSAKE) for profiling T-cell metagenomes using short reads from the massively parallel sequencing platforms. RESULTS Models of sequence diversity for the TCR beta-chain CDR3 region were built using empirical data and used to simulate, at random, distinct TCR clonotypes at 1-20 p.p.m. Using simulated TCRbeta (sTCRbeta) sequences, we randomly created 20 million 36 nt reads having 1-2% random error, 20 million 42 or 50 nt reads having 1% random error and 20 million 36 nt reads with 1% error modeled on real short read data. Reads aligning to the end of known TCR variable (V) genes and having consecutive unmatched bases in the adjacent CDR3 were used to seed iSSAKE de novo assemblies of CDR3. With assembled 36 nt reads, we detect over 51% and 63% of rare (1 p.p.m.) clonotypes using a random or modeled error distribution, respectively. We detect over 99% of more abundant clonotypes (6 p.p.m. or higher) using either error distribution. Longer reads improve sensitivity, with assembled 42 and 50 nt reads identifying 82.0% and 94.7% of rare 1 p.p.m. clonotypes, respectively. Our approach illustrates the feasibility of complete profiling of the TCR repertoire using new massively parallel short read sequencing technology. AVAILABILITY ftp://ftp.bcgsc. ca/supplementary/iSSAKE.