Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic and Pharmacologic Evidence That mTOR Targeting Outweighs mTORC1 Inhibition as an Antimyeloma Strategy

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, proliferation, metabolism, and cell survival, and plays those roles by forming two functionally distinct multiprotein complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Deregulation of the mTOR pathway has been found in different cancers, including multiple myeloma. Agents acting on mTORC1, such as rapamycin and derivatives, are being explored as antitumoral strategies. However, whether targeting mTOR would be a more effective antimyeloma strategy than exclusively acting on the mTORC1 branch remains to be established. In this report, we explored the activation status of mTOR routes in malignant plasma cells, and analyzed the contribution of mTOR and its two signaling branches to the proliferation of myeloma cells. Gene expression profiling demonstrated deregulation of mTOR pathway–related genes in myeloma plasma cells from patients. Activation of the mTOR pathway in myelomatous plasma cells was corroborated by flow cytometric analyses. RNA interference (RNAi) experiments indicated that mTORC1 predominated over mTORC2 in the control of myeloma cell proliferation. However, mTOR knockdown had a superior antiproliferative effect than acting only on mTORC1 or mTORC2. Pharmacologic studies corroborated that the neutralization of mTOR has a stronger antimyeloma effect than the individual inhibition of mTORC1 or mTORC2. Together, our data support the clinical development of agents that widely target mTOR, instead of agents, such as rapamycin or its derivatives, that solely act on mTORC1. Mol Cancer Ther; 13(2); 504–16. ©2014 AACR.
Spatial distribution of high-frequency electromagnetic energy in human head during MRI: numerical results and measurements

Finite Element Method (FEM) using 26-node isoparametric finite elements was applied for modeling saddleshaped head coils used in Magnetic Resonance Imaging (MM) generating linearly polarized radiofrequency (RF) pulses at 64 MHz. The human head was modeled from MR sciplls of a volunteer and additional information were taken from Atlas of Sectional Human Anatomy. The physical dimensions of the head coil and the head permit a calculation of the outside magnetic field by a quasistatic approach. Of course, a full-wave approach was applied within the head. Values of specific energy—specific absorption (SA)— as well as of specific power—specific absorption rate (SAR)—were calculated by the method, simulating the real exposure conditions during MRI. Although the results of the used numerical method were compared previously to the results of the analytical solution with homogeneous sphere and to the results of RF measurements on heterogeneous phantom, a comparison between the numerical results of the modeled~human head and in vivo measurements performed on the human head of the volunteer was made once more. Since the results are in excellent agreement, they argue for the correctness of the numerical method. The "worst-case" temperature elevations δθ of the "hot-spots" were calculated, as well. Finally, the results of SA, SAR, and δθ are compared to the existing recommendations.
Differential bone‐forming capacity of osteogenic cells from either embryonic stem cells or bone marrow‐derived mesenchymal stem cells

For more than a decade, human mesenchymal stem cells (hMSCs) have been used in bone tissue‐engineering research. More recently some of the focus in this field has shifted towards the use of embryonic stem cells. While it is well known that hMSCs are able to form bone when implanted subcutaneously in immune‐deficient mice, the osteogenic potential of embryonic stem cells has been mainly assessed in vitro. Therefore, we performed a series of studies to compare the in vitro and in vivo osteogenic capacities of human and mouse embryonic stem cells to those of hMSCs. Embryonic and mesenchymal stem cells showed all characteristic signs of osteogenic differentiation in vitro when cultured in osteogenic medium, including the deposition of a mineralized matrix and expression of genes involved in osteogenic differentiation. As such, based on the in vitro results, osteogenic ES cells could not be discriminated from osteogenic hMSCs. Nevertheless, although osteogenic hMSCs formed bone upon implantation, osteogenic cells derived from both human and mouse embryonic stem cells did not form functional bone, indicated by absence of osteocytes, bone marrow and lamellar bone. Although embryonic stem cells show all signs of osteogenic differentiation in vitro, it appears that, in contrast to mesenchymal stem cells, they do not possess the ability to form bone in vivo when a similar culture method and osteogenic differentiation protocol was applied. Copyright © 2010 John Wiley & Sons, Ltd.
PERFORMANCE OF LAYING CHICKENS FED DIETARY LEVELS OF RED SORGHUM VARIETY (Sorghum bicolor (L.))

A four week experiment was conducted to evaluate the performance and economics of egg production using red sorghum variety in the diets of Isa Brown layers. The experiment was conducted at the Teaching and Research Farm of Abubakar Tafawa Balewa University, Bauch, between June and August 2014. Three hundred (300) layer birds were allotted to five dietary treatments in a completely randomized design (CRD), the birds were randomly distributed into the five dietary treatments replicated three times of twenty (20) hens per replicate and sixty (60) per diet. In the experimental diets, red sorghum variety replaced maize at 0, 25, 50, 75 and 100% respectively coded as diets 1,2,3,4, and 5 respectively. The results showed that daily feed intake-DFI (121.22 - 148.92g), hen day-HD (59.80 - 70.25%), hen housed -HHP (57.50 - 67.83%), feed conversion ratio-FCR (2.29 - 2.70), egg grading: grade 1 eggs (37.78 - 61.11%), and grade 2 eggs (38.89 - 62.22%) were not affected by the dietary treatments. The cost benefit analysis showed that feed cost in ₦/Kg egg weight was lowest in treatment 3 (50% red sorghum) with a cost saving of N 39.04 per kg of feed. It is therefore concluded that red sorghum can completely replace maize (in the diets of Isa Brown layers with no adverse effects on performance and cost of egg production, however, 50% replacement level was most economical.
Initiation of Human DNA Replication in Vitro Using Nuclei from Cells Arrested at an Initiation-competent State*

Initiation of human DNA replication is investigated in vitro, using initiation-competent nuclei isolated from cells arrested in late G1 phase by a 24-h treatment with 0.5 mm mimosine (Krude, T. (1999) Exp. Cell Res. 247, 148–159). Nuclei isolated from mimosine-arrested HeLa cells initiate semiconservative DNA replication upon incubation in cytosolic extracts from proliferating human cells. Initiation occurs in the absence and presence of a nuclear membrane. The cyclin-dependent kinase (Cdk) inhibitors roscovitine and olomoucine inhibit initiation of DNA replication, indicating a dependence of initiation on Cdk activity. Cell fractionation shows that cyclins A, E, and Cdk2 are bound to nuclei from mimosine-arrested cells. Exogenously added human cyclin A·Cdk2 and cyclin E·Cdk2 complexes, but not cyclin B1/Cdk1 or cyclin D2/Cdk6, can overcome inhibition of initiation by roscovitine in vitro. Depleting Cdk2 from cytosolic extract does not prevent initiation, demonstrating that cyclin·Cdk2 complexes are not required in the soluble extract, but are provided by the nuclei. Initiation depends further on an essential and soluble activity present in cytosolic extracts from proliferating cells, but not from mimosine-arrested cells, acting together with nuclear cyclin/Cdk2 activity.
Mapping the Field: Examining the Recertification of Internationally Educated Teachers

In this article I examine the structural barriers in the recerti cation trajectory of inter nationally educated teachers (IETs) in British Columbia (BC). By applying the Bour dieuian concept of field, I extend from IETs’ experiences in the recertification process to institutional and political factors that affect these experiences. I demonstrate how policies and regulations that govern the field as well as the interplay between its main institutional players, namely, the Teacher Regulation Branch, teacher education programs, and school districts, result in unequal opportunities for IETs to be certified and hired as teachers. As a result, IETs’ potential contribution to diversifying the teacher force in BC is diminished.
Adaptive Neural Tracking Control for Switched High-Order Stochastic Nonlinear Systems

This paper deals with adaptive neural tracking control design for a class of switched high-order stochastic nonlinear systems with unknown uncertainties and arbitrary deterministic switching. The considered issues are: 1) completely unknown uncertainties; 2) stochastic disturbances; and 3) high-order nonstrict-feedback system structure. The considered mathematical models can represent many practical systems in the actual engineering. By adopting the approximation ability of neural networks, common stochastic Lyapunov function method together with adding an improved power integrator technique, an adaptive state feedback controller with multiple adaptive laws is systematically designed for the systems. Subsequently, a controller with only two adaptive laws is proposed to solve the problem of over parameterization. Under the designed controllers, all the signals in the closed-loop system are bounded-input bounded-output stable in probability, and the system output can almost surely track the target trajectory within a specified bounded error. Finally, simulation results are presented to show the effectiveness of the proposed approaches.
Percutaneous Drilling of Symptomatic Accessory Navicular in Young Athletes

Background Results of percutaneous drilling for symptomatic type II accessory tarsal navicular bone are not determined. Hypothesis Percutaneous drilling of accessory navicular synchondrosis will induce or accelerate bone union between the accessory and primary navicular bones. Bone union of the synchondrosis leads to symptomatic relief. Study Design Case series; Level of evidence, 4. Methods Thirty-one feet of 29 patients with type II accessory tarsal navicular treated by percutaneous drilling were reviewed. Results Twenty-four feet (77.4%) were assessed as excellent, 6 (19.4%) as good, and 1 (3.2%) as fair. No feet were assessed as poor. Bone union was obtained in 16 (80%) of the 20 feet when the proximal phalanx of the great toe was immature and in 2 of the 11 feet when it was mature. Conclusion Percutaneous drilling of the synchondrosis was effective for a symptomatic type II accessory navicular, especially in patients with immature proximal phalanx of the great toe.
Risk factors for clinical metastasis in men undergoing radical prostatectomy and immediate adjuvant androgen deprivation therapy.

BACKGROUND Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post- prostatectomy patients who received immediate adjuvant ADT. MATERIALS AND METHODS We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. RESULTS Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS ≥9 and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS ≥9 was an independent predictor of cancer-specific death. CONCLUSIONS Pathologic GS ≥9 and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS ≥9 was an indispensable condition for bone metastasis, which may imply that patients with GS ≤8 on adjuvant ADT are unlikely to develop bone metastasis.
Gene therapy: targeting the myocardium

Effective clinical delivery of gene therapy to the heart requires understanding and design of complex biological systems to deliver therapeutic gene expression. The development of vectors that specifically target the myocardium, in particular bioengineered recombinant viruses, has improved the efficiency of gene delivery to the heart. These tools, coupled with advances in selection and design of the genetic payload, have led to effective cardiac gene therapy in preclinical models. This technology is currently translating to the clinic with a new wave of gene therapy trials for myocardial disease.
Computational Field Shaping for Deep Brain Stimulation With Thousands of Contacts in a Novel Electrode Geometry

Deep brain stimulation (DBS) alleviates symptoms associated with some neurological disorders by stimulating specific deep brain targets. However, incomplete stimulation of the target region can provide suboptimal therapy, and spread of stimulation to tissue outside the target can generate side‐effects. Existing DBS electrodes generate stimulation profiles that are roughly spherical, neither matching nor enabling the mapping of therapeutic targets. We present a novel electrode design and will perform computational modeling of the new design to investigate its use as a next generation DBS electrode.
Association of polymorphism in the transforming growth factor β1 gene with disease outcome and mortality in rheumatoid arthritis

Objective: To investigate whether polymorphism in the transforming growth factor β1 (TGFβ1) gene is associated with disease outcome in rheumatoid arthritis. Methods: 208 patients with established rheumatoid arthritis were genotyped for the TGFβ1 T869C polymorphism using an amplification refractory mutation system–polymerase chain reaction (ARMS-PCR) method. Disease severity was assessed by measuring radiographic damage by Larsen score and functional outcome by the health assessment questionnaire (HAQ). Patients were tracked on the NHS central register for notification of death, and the relation between TGFβ1 polymorphism and mortality was analysed using Cox proportional hazards regression. Results: Patients carrying a TGFβ1 T allele had a higher mean HAQ score than those without this allele (1.60 v 1.22, p = 0.04). The T allele was also associated with higher five year mean area under the curve (MAUC) erythrocyte sedimentation rate (ESR), and nodular disease. Larsen score was higher in patients with the TT genotype compared with CC + CT genotypes, although this was not significant after correction for disease duration. There was a trend of increasing mortality risk with T allele dose after adjustment for age, sex, and disease duration (hazard ratio = 1.6 (95% confidence interval, 1.1 to 2.4), p = 0.01). Conclusions: TGFβ1 T869C gene polymorphism is associated with disease outcome in rheumatoid arthritis. Carriage of the T allele (putatively associated with decreased TGFβ1 production) was associated with increased inflammatory activity and poor functional outcome, while increasing T allele dose was associated with worse survival.
Cost-effectiveness of Respiratory Syncytial Virus Prophylaxis Among Preterm Infants

Objectives. To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies—RSVIG, palivizumab, and no prophylaxis—among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente–Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%. Results. Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was ≤32 weeks, who required ≥28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12 000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33 000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39 000 to $420 000 per hospitalization averted or $110 000 to $1 200 000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization. Conclusion. In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.
Understanding fragile X syndrome: insights from animal models

The fragile X mental retardation syndrome is caused by large methylated expansions of a CGG repeat in the FMR1 gene leading to the loss of expression of FMRP, an RNA-binding protein. FMRP is proposed to act as a regulator of mRNA transport or translation that plays a role in synaptic maturation and function. To study the physiological function of the FMR1 protein, mouse and Drosophila models have been developed. The loss-of-function mouse model shows slightly enlarged testes, a subtle behavioral phenotype, and discrete anomalies of dendrite spines similar to those observed in brains of patients. Studies in Drosophila indicate that FXMR plays an important role in synaptogenesis and axonal arborization, which may underlie the observed deficits in flight ability and circadian behavior of fxr mutant flies. The relevance of these studies to our understanding of fragile X syndrome is discussed.
Evaluation of Bias in Diagnostic-Test Sensitivity and Specificity Estimates Computed by Discrepant Analysis

ABSTRACT When a new diagnostic test is potentially more sensitive than the reference test used to classify persons as infected or uninfected, a substantial number of specimens from infected persons may be reference-test negative but new-test positive. Discrepant analysis involves the performance of one or more additional tests with these specimens, reclassification as infected those persons for whom the new-test-positive results are confirmed, and recalculation of the estimates of new-test sensitivity and specificity by using the revised classification. This approach has been criticized because of the bias introduced by the selective use of confirmation testing. Under conditions appropriate for evaluating a nucleic acid amplification (NAA) test for Chlamydia trachomatis infection with cell culture as the reference test, we compared the bias in estimates based on the discrepant-analysis classification of persons as infected or uninfected with that in estimates based on the culture classification. We concluded that the bias in estimates of NAA-test specificity based on discrepant analysis is small and generally less than that in estimates based on culture. However, the accuracy of discrepant-analysis-based estimates of NAA-test sensitivity depends critically on whether culture specificity is equal to or is slightly less than 100%, and it is affected by competing biases that are not fully taken into account by discrepant analysis.
Risk factors for hydrocephalus and neurological deficit in children born with an encephalocele.

OBJECT There is a known association of hydrocephalus with encephaloceles. Risk factors for hydrocephalus and neurological deficit were ascertained in a series of patients born with an encephalocele. METHODS A retrospective analysis was undertaken of patients treated for encephaloceles at Children's Hospital Los Angeles between 1994 and 2012. The following factors were evaluated for their prognostic value: age at presentation, sex, location of encephalocele, size, contents, microcephaly, presence of hydrocephalus, CSF leak, associated cranial anomalies, and neurological outcome. RESULTS Seventy children were identified, including 38 girls and 32 boys. The median age at presentation was 2 months. The mean follow-up duration was 3.7 years. Encephalocele location was classified as anterior (n = 14) or posterior (n = 56) to the coronal suture. The average maximum encephalocele diameter was 4 cm (range 0.5-23 cm). Forty-seven encephaloceles contained neural tissue. Eight infants presented at birth with CSF leaking from the encephalocele, with 1 being infected. Six patients presented with hydrocephalus, while 11 developed progressive hydrocephalus postoperatively. On univariate analysis, the presence of neural tissue, cranial anomalies, encephalocele size of at least 2 cm, seizure disorder, and microcephaly were each positively associated with hydrocephalus. On multivariate logistic regression modeling, the single prognostic factor for hydrocephalus of borderline statistical significance was the presence of neural tissue (odds ratio [OR] = 5.8, 95% confidence interval [CI] = 0.8-74.0). Fourteen patients had severe developmental delay, 28 had mild/moderate delay, and 28 were neurologically normal. On univariate analysis, the presence of cranial anomalies, larger size of encephalocele, hydrocephalus, and microcephaly were positively associated with neurological deficit. In the multivariable model, the only statistically significant prognostic factor for neurological deficit was presence of hydrocephalus (OR 17.2, 95% CI 1.7-infinity). CONCLUSIONS In multivariate models, the presence of neural tissue was borderline significantly associated with hydrocephalus and the presence of hydrocephalus was significantly associated with neurological deficit. The location of the encephalocele did not have a statistically significant association with incidence of hydrocephalus or neurological deficit. In contrast to modestly good/fair neurological outcome in children with an encephalocele without hydrocephalus, the presence of hydrocephalus resulted in a far worse neurological outcome.