Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrathecal Morphine Analgesia in Idiopathic Scoliosis Surgery: Does Sex or Racial Group Affect Optimal Dosing?

Background We previously determined the intrathecal morphine optimal dose to maximize analgesia in patients undergoing idiopathic scoliosis surgery while minimizing adverse effects. Our purpose was to determine if this protocol was equally effective across sex and racial groups. Methods We studied 287 patients given a moderate dose of intrathecal morphine of 9 to 19 &mgr;g/kg (mean 14 &mgr;g/kg): 240 female and 47 male patients and 224 White (W) and 63 African-American (AA) patients. Factors analyzed included postoperative visual analog pain scores (VAS), time to first opioid dose, total morphine over the first 48 hours, and postoperative complications of respiratory depression requiring pediatric intensive care unit (PICU) admission, nausea/vomiting and pruritis. Results For female and male patients, mean VAS pain scores in postanesthesia care unit (PACU) were 0.48±1.14 and 0.56±1.16, mean times to first opioid dose were 16.65±4.38 and 16.72±4.97 hours, and total morphine over the first 48 hours were 1.49±0.53 and 1.49±0.58 mg/kg, respectively. Respiratory depression and PICU admission occurred in 10 of 240 female (4.1%) and 3 of 47 male (6.4%) patients. Minor complications of nausea/vomiting and pruritis occurred in 78 of 240 female (31.7%) and 12 of 47 male (25.5%) patients. For W and AA patients, mean VAS pain scores in PACU were 0.48±1.10 and 0.46±1.13, mean times to first opioid dose were 16.53±3.77 and 17.12±6.05 hours, and total morphine over the first 48 hours were 1.54±0.53 and 1.30±0.53 mg/kg, respectively. Respiratory depression and PICU admission occurred in 9 of 224 W (4.0%) and 4 of 63 AA (6.3%) patients. Nausea/vomiting and pruritis occurred in 77 of 224 W (34.4%) and 11 of 63 AA (17.5%) patients, respectively. Conclusions Intrathecal morphine results in safe and effective for postoperative pain relief in patients undergoing surgery for idiopathic scoliosis irregardless of sex or race. Level of Evidence III, retrospective comparative study.
An Information Structural Approach to Spoken Language Generation

This paper presents an architecture for the generation of spoken monologues with contextually appropriate intonation. A two-tiered information structure representation is used in the high-level content planning and sentence planning stages of generation to produce efficient, coherent speech that makes certain discourse relationships, such as explicit contrasts, appropriately salient. The system is able to produce appropriate intonational patterns that cannot be generated by other systems which rely solely on word class and given/new distinctions.
Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.
Inference of seasonal and pandemic influenza transmission dynamics

Significance Infectious disease surveillance systems are powerful tools for monitoring and understanding infectious disease dynamics; however, underreporting (due to both unreported and asymptomatic infections) and observation errors in these systems create challenges for delineating a complete picture of infectious disease epidemiology. This issue is true for influenza, an infectious disease of pandemic potential. Here we develop and present influenza inference systems capable of compensating for observational biases and underreporting. Using both Google Flu Trends and Centers for Disease Control and Prevention data in conjunction with Bayesian model inference methods, we are able to infer the evolving epidemiological features of influenza and its impacts among the large population during 2003−2013, including the 2009 pandemic. In addition, differences among regions within the United States are identified. The inference of key infectious disease epidemiological parameters is critical for characterizing disease spread and devising prevention and containment measures. The recent emergence of surveillance records mined from big data such as health-related online queries and social media, as well as model inference methods, permits the development of new methodologies for more comprehensive estimation of these parameters. We use such data in conjunction with Bayesian inference methods to study the transmission dynamics of influenza. We simultaneously estimate key epidemiological parameters, including population susceptibility, the basic reproductive number, attack rate, and infectious period, for 115 cities during the 2003–2004 through 2012–2013 seasons, including the 2009 pandemic. These estimates discriminate key differences in the epidemiological characteristics of these outbreaks across 10 y, as well as spatial variations of influenza transmission dynamics among subpopulations in the United States. In addition, the inference methods appear to compensate for observational biases and underreporting inherent in the surveillance data.
Young Adults' Drug Use: A 17-Year Longitudinal Inquiry of Antecedents

This longitudinal study examined the interrelation of personality and peer factors on young adults' drug use and also the influence of the interaction of personality and peer factors on drug use. The sample of 756 males and females were interviewed four times between the M ages of 6 and 22. Personality attributes in childhood were related to peer factors in early adolescence which, in turn, were related to personality traits in later adolescence. These traits were linked with selection of peers and, ultimately, drug use in young adulthood. Additionally, the adolescent and young adult domains had direct effects on young adults' drug use. Significant interactions indicated that a few protective childhood personality traits buffer the risk of deviant peers in adolescence on young adults' drug use. More earlier protective characteristics from one domain enhanced the effect of later protective traits from the other domain.
Variations in pill appearance of antiepileptic drugs and the risk of nonadherence.

BACKGROUND Generic prescription drugs are bioequivalent to brand-name versions but may not have consistent color or shape, which can cause confusion and lead to interruptions in medication use. We sought to determine whether switching among different-appearing antiepileptic drugs (AEDs) is associated with increased rates of medication nonpersistence, which can have serious medical, financial, and social consequences. METHODS We designed a nested case-control study of commercially insured patients in the United States who initiated an AED. Cases were patients who became nonpersistent, defined as failure to fill a prescription within 5 days of the elapsed days supplied. Controls had no delay in refilling and were matched by sex, age, number of refills, and the presence of a seizure disorder diagnosis. We evaluated the 2 refills preceding nonpersistence and determined whether pill color and/or shape matched ("concordant") or did not match ("discordant"). We compared the odds of discordance among cases and controls using multivariate conditional logistic regression, adjusting for baseline characteristics, and drug type. We repeated our analysis among patients with a seizure diagnosis. RESULTS The AEDs dispensed had 37 colors and 4 shapes. A total of 11,472 patients with nonpersistence were linked to 50,050 controls. Color discordance preceded 136 cases (1.20%) but only 480 controls (0.97%) (adjusted odds ratio [OR], 1.27 [95% CI, 1.04-1.55]). Shape discordance preceded 18 cases (0.16%) and 54 controls (0.11%) (OR, 1.47 [95% CI, 0.85-2.54]). Within the seizure disorder diagnosis subgroup, the risk of nonpersistence after changes in pill color was also significantly elevated (OR, 1.53 [95%, CI 1.07-2.18]). CONCLUSIONS Changes in pill color significantly increase the odds of nonpersistence; this may have important clinical implications. Our study supports a reconsideration of current regulatory policy that permits wide variation in the appearance of bioequivalent drugs.
Midlife and Late‐Life Vascular Risk Factors and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study

Background Diffusion tensor imaging measures of white matter (WM) microstructural integrity appear to provide earlier indication of WM injury than WM hyperintensities; however, risk factors for poor WM microstructural integrity have not been established. Our study quantifies the association between vascular risk factors in midlife and late life with measures of late‐life WM microstructural integrity. Methods and Results We used data from 1851 participants in ARIC (Atherosclerosis Risk in Communities Study) who completed 3‐T magnetic resonance imaging, including diffusion tensor imaging, as part of the ARIC Neurocognitive Study (ARIC‐NCS). We quantified the association among lipids, glucose, and blood pressure from the baseline ARIC visit (1987–1989, ages 44–65, midlife) and visit 5 of ARIC (2011–2013, ages 67–90, late life, concurrent with ARIC‐NCS) with regional and overall WM mean diffusivity and fractional anisotropy obtained at ARIC visit 5 for ARIC participants. We also considered whether these associations were independent of or modified by WM hyperintensity volumes. We found that elevated blood pressure in midlife and late life and elevated glucose in midlife, but not late life, were associated with worse late‐life WM microstructural integrity. These associations were independent of the degree of WM hyperintensity, and the association between glucose and WM microstructural integrity appeared stronger for those with the least WM hyperintensity. There was little support for an adverse association between lipids and WM microstructural integrity. Conclusions Hypertension in both midlife and late life and elevated glucose in midlife are related to worse WM microstructural integrity in late life.
Vector Competence in West African Aedes aegypti Is Flavivirus Species and Genotype Dependent

Background Vector competence of Aedes aegypti mosquitoes is a quantitative genetic trait that varies among geographic locations and among different flavivirus species and genotypes within species. The subspecies Ae. aegypti formosus, found mostly in sub-Saharan Africa, is considered to be refractory to both dengue (DENV) and yellow fever viruses (YFV) compared to the more globally distributed Ae. aegypti aegypti. Within Senegal, vector competence varies with collection site and DENV-2 viral isolate, but knowledge about the interaction of West African Ae. aegypti with different flaviviruses is lacking. The current study utilizes low passage isolates of dengue-2 (DENV-2-75505 sylvatic genotype) and yellow fever (YFV BA-55 -West African Genotype I, or YFV DAK 1279-West African Genotype II) from West Africa and field derived Ae. aegypti collected throughout Senegal to determine whether vector competence is flavivirus or virus genotype dependent. Methodology/Principal Findings Eight collections of 20–30 mosquitoes from different sites were fed a bloodmeal containing either DENV-2 or either isolate of YFV. Midgut and disseminated infection phenotypes were determined 14 days post infection. Collections varied significantly in the rate and intensity of midgut and disseminated infection among the three viruses. Conclusions/Significance Overall, vector competence was dependent upon both viral and vector strains. Importantly, contrary to previous studies, sylvatic collections of Ae. aegypti showed high levels of disseminated infection for local isolates of both DENV-2 and YFV.
Altered follicular helper T cell impaired antibody production in a murine model of myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic diseases which have a high risk of progressing to acute myeloid leukemia. MDS patients have immunologic deficiency, including T and B cells dysfunction. Follicular T helper cells (Tfh, CD4+CXCR5+) are an important subset of helper T cells which help to the formation of germinal centers and B cells differentiation. In this study, we investigated the proportion and function of Tfh using NUP98-HOXD13 transgenic (NHD13) mice model with MDS phenotype. The proportion of Tfh from bone marrow and spleen of NHD13 mice decreased compared with wild type (WT) mice tested by flow cytometry. In NHD13 mice spleens, there were decreased CXCR5+ cells and increased PD-1+ cells using immunohistochemistry. The active markers (ICOS, CD40L and OX40) expressed on Tfh of NHD13 mice were decreased. In contrast, PD-1 expression on Tfh of NHD13 mice was higher than that of WT mice. After coculture with Tfh from NHD13 mice, IgG and IgM production of B cells were decreased. In conclusion, the proportion and function of Tfh in the MDS mice model were altered. The dysfunction and reduction of Tfh may inhibit B cells differentiation and antibody production. Abnormal Tfh might contribute to the immune tolerance promoting the progression of MDS.
A therapeutically targetable mechanism of BCR-ABL–independent imatinib resistance in chronic myeloid leukemia

A large-scale RNA interference screen reveals a new mechanism of imatinib resistance in chronic myeloid leukemia that can be therapeutically targeted. An Irresistible Combination Unlike most cancers, which have variable mutation patterns, chronic myeloid leukemia is normally associated with a specific genetic alteration, which produces a fusion protein called BCR-ABL. Famously, this protein was targeted with the first cancer-specific drug, known as imatinib (Gleevec), which is still the standard therapy for this cancer. Unfortunately, leukemia cells can develop resistance to imatinib, which does not always require mutations in BCR-ABL. Now, Ma et al. have identified a mechanism for imatinib resistance in chronic myeloid leukemia cells that lack mutations in BCR-ABL. The authors also demonstrated that a U.S. Food and Drug Administration–approved drug called trametinib can overcome this resistance and kill leukemia stem cells without harming the nonmalignant precursors that give rise to normal blood cells. Resistance to the BCR-ABL inhibitor imatinib mesylate (IM) poses a major problem for the treatment of chronic myeloid leukemia (CML). IM resistance often results from a secondary mutation in BCR-ABL that interferes with drug binding. However, in many instances, there is no mutation in BCR-ABL, and the basis of such BCR-ABL–independent IM resistance remains to be elucidated. To gain insight into BCR-ABL–independent IM resistance mechanisms, we performed a large-scale RNA interference screen and identified IM-sensitizing genes (IMSGs) whose knockdown renders BCR-ABL+ cells IM-resistant. In these IMSG knockdown cells, RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal–regulated kinase (ERK) signaling is sustained after IM treatment because of up-regulation of PRKCH, which encodes the protein kinase C (PKC) family member PKCη, an activator of CRAF. PRKCH is also up-regulated in samples from CML patients with BCR-ABL–independent IM resistance. Combined treatment with IM and trametinib, a U.S. Food and Drug Administration–approved MEK inhibitor, synergistically kills BCR-ABL+ IMSG knockdown cells and prolongs survival in mouse models of BCR-ABL–independent IM-resistant CML. Finally, we showed that CML stem cells contain high levels of PRKCH, and this contributes to their intrinsic IM resistance. Combined treatment with IM and trametinib synergistically kills CML stem cells with negligible effect on normal hematopoietic stem cells. Collectively, our results identify a therapeutically targetable mechanism of BCR-ABL–independent IM resistance in CML and CML stem cells.
Inference in components of variance models with low replication

In components of variance models the data are viewed as arising through a sum of two random variables, representing between- and within-group variation, respectively. The former is generally interpreted as a group effect, and the latter as error. It is assumed that these variables are stochastically independent and that the distributions of the group effect and the error do not vary from one instance to another. If each group effect can be replicated a large number of times, then standard methods can be used to estimate the distributions of both the group effect and the error. This cannot be achieved without replication, however. How feasible is distribution estimation if it is not possible to replicate prolifically? Can the distributions of random effects and errors be estimated consistently from a small number of replications of each of a large number of noisy group effects, for example, in a nonparametric setting? Often extensive replication is practically infeasible, in particular, if inherently small numbers of individuals exhibit any given group effect. Yet it is quite unclear how to conduct inference in this case. We show that inference is possible, even if the number of replications is as small as 2. Two methods are proposed, both based on Fourier inversion. One, which is substantially more computer intensive than the other, exhibits better performance in numerical experiments.
Resident and infiltrating immune cells in the uveal tract in the early and late stages of experimental autoimmune uveoretinitis.

PURPOSE To investigate the dynamics of resident and infiltrating immune cells in the choroid and iris during the early and late stages of experimental autoimmune uveitis (EAU) in Lewis rats. METHODS Uveoretinitis was induced by footpad injection of crude retinal extract and complete Freund's adjuvant with concurrent intraperitoneal injection of Bordetella pertussis. Five experimental (EAU) and five control animals (adjuvant alone) were studied at days 5, 7, 9, 11 (prodromal stage) and 42 (late stage) after immunization. Five normal animals and five animals injected with B. pertussis alone served as further controls. Immunohistochemical localization of resident macrophages, major histocompatibility complex class II (Ia)+ dendritic cells (DC), infiltrating mononuclear cells, and T cells was performed on wholemounts of isolated choroidal and iris tissue. RESULTS Double immunolabeling confirmed the presence of distinct networks of macrophages (591 +/- 52 cells/mm2) and DC (746 +/- 38 cells/mm2) in the rat choroid. No marked qualitative and quantitative changes were observed in the density or morphologic appearance of ED2+ resident tissue macrophages in the choroid and iris before clinical onset of ocular disease. On day 11, infiltration of ED1+ monocytes had occurred in the iris but not in the choroid; however, marked infiltration of T cells was evident in both choroid (286 +/- 161 cells/mm2) and iris (196 +/- 72 cells/mm2). The total density of Ia+ cells was significantly elevated in the choroid (1152 +/- 192 cells/mm2) at day 11, and small, round Ia+ cells were two to three times more frequent than normal at both sites. The density of T cells and Ia+ cells remained significantly elevated in the choroid and iris in the late stages of EAU. CONCLUSIONS These data suggest resident uveal tract macrophages undergo no significant alteration in density in the early stages of EAU and that the earliest site of mononuclear cellular infiltrate in EAU occurs in the iris. The increased total density of Ia+ cells in the choroid on day 11 and the presence of significantly increased numbers of small, round Ia+ cells in the iris and choroid may represent increased trafficking of DC in the eye during uveoretinitis. Furthermore, the raised numbers of Ia+ cells, concurrent with the influx of T cells, suggests Ia+ DC and macrophages may act as local antigen-presenting cells in the induction of uveoretinitis.
Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors

Goblet cell carcinoid is a relatively rare neuroendocrine tumor of the vermiform appendix with poorly understood molecular pathogenesis. We studied the clinicopathologic features and genetic alterations, including allelic loss of chromosomes 11q, 16q, and 18q; sequencing of the K-ras, β-catenin, and DPC4 (SMAD4) genes; and p53 overexpression and loss of DPC4 by immunohistochemistry; in 16 goblet cell carcinoids. We compared the allelic loss in goblet cell carcinoids to those in 18 gastrointestinal carcinoid tumors. For goblet cell carcinoids, appendiceal perforation was the most common (70%, 7/10) clinical presentation. The mean tumor size was 2.0 ± 1.5 cm (range, 0.4 to 4.5 cm). The tumor invaded to appendiceal serosa in 50% (8/16) of patients, and two patients had metastasis in lymph nodes or adjoining viscera. With mean follow-up of 24 ± 14 months (median, 23 mo), 1 of 10 patients had died of disease, and 2 others had tumor recurrence. All four patients with metastases, recurrences, and/or death from disease had serosal involvement at presentation (P = .02). Loss of heterozygosity of chromosome 11q was present in 25% of goblet cell carcinoids, 14% of ileal carcinoid tumors, and 9% of nonileal carcinoid tumors; of chromosome 16q in 38%, 29%, and 0 (P = .02); and of chromosome 18q in 56%, 86%, and 9% (P = .002), respectively. No mutations of K-ras, β-catenin, or DPC4 genes; p53 overexpression; or loss of staining for DPC4 was present in any tumors. These findings suggest that allelic loss of chromosomes 11q, 16q, and 18q in goblet cell carcinoids and ileal carcinoids may have an important role in the pathogenesis of these tumors.
Real Threats to Your Data Bills – Security Loopholes and Defenses in Mobile Data Charging

Secure mobile data charging (MDC) is critical to cellular network operations. It must charge the right user for the right volume that (s)he authorizes to consume ( i.e. , requirements of authentication, authorization, and accounting (AAA)). In this work, we conduct security analysis of the MDC system in cellular networks. We ﬁnd that all three can be breached in both design and practice, and identify three concrete vulnerabilities: authentication bypass , authorization fraud and accounting volume inaccuracy . The root causes lie in technology fundamentals of cellular networks and the Internet IP design, as well as imprudent implementations. We devise three showcase attacks to demonstrate that, even simple attacks can easily penetrate the operational 3G/4G cellular networks. We further propose and evaluate defense solutions.