Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

Objectives: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites and toxic substances, including chemotherapeutic agents. The aim of this study was to investigate the role of a single‐nucleotide polymorphism (CYP3A5*3 6986A>G), which renders low enzyme activity, in the risk of developing ALL and in the outcome for children with ALL.
Tracking the emergence of pandemic Influenza A/H1N1/2009 and its interaction with seasonal influenza viruses in Singapore.

INTRODUCTION Since the emergence of the pandemic influenza A/H1N1/2009 virus in April 2009, diagnostic testing in many countries has revealed the rapid displacement and then replacement of circulating seasonal influenza viruses by this novel virus. MATERIALS AND METHODS In-house seasonal and pandemic influenza-specific polymerase chain reaction assays were introduced and/or developed at the Molecular Diagnosis Centre (MDC) at the National University Hospital (NUH), Singapore. These assays have been used to test all samples received from in-patients, out-patients, staff and visitors for suspected pandemic influenza A/H1N1/2009 infection. RESULTS Prior to the arrival of the pandemic A/H1N1/2009 virus in Singapore at the end of May 2009, seasonal influenza A/H3N2 predominated in this population, with very little seasonal influenza A/H1N1 and B viruses detected. Within about 1 month of its arrival in Singapore (mainly during June to July 2009), this pandemic virus rapidly displaced seasonal influenza A/H3N2 to become the predominant strain in the Singaporean population served by MDC/NUH. CONCLUSIONS Realtime molecular techniques have allowed the prompt detection of different influenza subtypes during this current pandemic, which has revealed the displacement/replacement of previously circulating seasonal subtypes with A/H1N1/2009. Although some of this may be explained by immunological cross-reactivity between influenza subtypes, more studies are required.
Two Kinetic Patterns of Epitope-Specific CD8 T-Cell Responses following Murine Gammaherpesvirus 68 Infection

ABSTRACT Murine gammaherpesvirus 68 (γHV68) provides an important experimental model for understanding mechanisms of immune control of the latent human gammaherpesviruses. Antiviral CD8 T cells play a key role throughout three separate phases of the infection: clearance of lytic virus, control of the latency amplification stage, and prevention of reactivation of latently infected cells. Previous analyses have shown that T-cell responses to two well-characterized epitopes derived from ORF6 and ORF61 progress with distinct kinetics. ORF6487-specific cells predominate early in infection and then decline rapidly, whereas ORF61524-specific cells continue to expand through early latency, due to sustained epitope expression. However, the paucity of identified epitopes to this virus has limited our understanding of the overall complexities of CD8 T-cell immune control throughout infection. Here we screened 1,383 predicted H-2b-restricted peptides and identified 33 responses, of which 21 have not previously been reported. Kinetic analysis revealed a spectrum of T-cell responses based on the rapidity of their decline after the peak acute response that generally corresponded to the expression patterns of the two previously characterized epitopes. The slowly declining responses that were maintained during latency amplification proliferated more rapidly and underwent maturation of functional avidity over time. Furthermore, the kinetics of decline was accelerated following infection with a latency-null mutant virus. Overall, the data show that γHV68 infection elicits a highly heterogeneous CD8 T-cell response that segregates into two distinctive kinetic patterns controlled by differential epitope expression during the lytic and latency amplification stages of infection.
Association between a history of mycobacterial infection and the risk of newly diagnosed Sjögren’s syndrome: A nationwide, population-based case-control study

Objective To address the association between a history of tuberculosis (TB) or nontuberculous mycobacterial (NTM) infection and the risk of newly diagnosed Sjögren’s syndrome (SS). Methods Using a nationwide, population-based, claims dataset, and after excluding those who had rheumatoid arthritis or systemic lupus erythematosus, we identified 5,751 newly diagnosed SS cases during 2007–2012, and compared them to 86,265 non-SS controls matched (1:15) for age, sex, and the year of first SS diagnosis date. The association between the risk of incident SS and a history of mycobacterial infection, including TB and NTM, was quantified by calculating odds ratios (ORs) with 95% confidence intervals (CIs) using conditional logistic regression analysis after adjustment for Charlson comorbidity index (CCI) and bronchiectasis. Results The mean age was 55±14 years, and the proportion of female gender was 87.8% in both newly diagnosed SS cases andnon-SS controls. An association was observed between NTM infection (OR, 11.24; 95% CI, 2.37–53.24) and incident SS, but not between TB infection and incident SS (OR, 1.29; 95% CI, 0.97–1.71) after adjustment for CCI and bronchiectasis. The association between NTM and SS risk was remarkably strong among those aged between 45 and 65 years (OR, 39.24; 95% CI, 3.97–387.75) and those without bronchiectasis (OR, 39.98; 95% CI, 3.83–376.92). Conclusion The study reveals a significant association of newly diagnosed SS with a history NTM infection, especially among individuals aged 40–65 years or those without bronchiectasis.
Antibodies to the glutamate receptor in mania

Dickerson F, Stallings C, Vaughan C, Origoni A, Khushalani S, Yolken R. Antibodies to the glutamate receptor in mania. Bipolar Disord 2012: 14: 547–553. © 2012 The Authors.Journal compilation © 2012 John Wiley & Sons A/S.
Improving diagnostic precision, care and syndrome definitions using comprehensive next-generation sequencing for the inherited bone marrow failure syndromes

Background Phenotypic overlap among the inherited bone marrow failure syndromes (IBMFSs) frequently limits the ability to establish a diagnosis based solely on clinical features. >70 IBMFS genes have been identified, which often renders genetic testing prolonged and costly. Since correct diagnosis, treatment and cancer surveillance often depend on identifying the mutated gene, strategies that enable timely genotyping are essential. Methods To overcome these challenges, we developed a next-generation sequencing assay to analyse a panel of 72 known IBMFS genes. Cases fulfilling the clinical diagnostic criteria of an IBMFS but without identified causal genotypes were included. Results The assay was validated by detecting 52 variants previously found by Sanger sequencing. A total of 158 patients with unknown mutations were studied. Of 75 patients with known IBMFS categories (eg, Fanconi anaemia), 59% had causal mutations. Among 83 patients with unclassified IBMFSs, we found causal mutations and established the diagnosis in 18% of the patients. The assay detected mutant genes that had not previously been reported to be associated with the patient phenotypes. In other cases, the assay led to amendments of diagnoses. In 20% of genotype cases, the results indicated a cancer surveillance programme. Conclusions The novel assay is efficient, accurate and has a major impact on patient care.
Etude de la dynamique vibrationelle des verres

Le travail actuel de these est consacre a l'etude de la dynamique vibrationnelle du verre et en particulier a la recherche sur l'anomalie de basse frequence: le « Boson Peak » (BP). Dans le premier chapitre, les aspects generaux de l'etat vitreux sont presentes. Ici nous discutons comment le comportement thermodynamique anormal des verres peut etre associe a la presence du Boson Peak dans la densite vibrationnelle (DOS) du verre. Dans le deuxieme chapitre, nous discutons les techniques spectroscopiques principales utilisees dans cette etude: Diffusion non elastique nucleaire et la diffusion non elastique de rayons X. Dans le troisieme chapitre, nous presentons l'etude du verre « hyperquenched ». Les effets de l'histoire thermique sur les proprietes dynamique et structurales des verres sont etudies. Le quatrieme chapitre est consacree a l'etude de l'effet de la pression et de la densite sur le DOS d'un verre. Les changements de la DOS sont correlees une fois de plus avec les changements macroscopiques a moins qu'une transformation structurale ait lieu. En conclusion, nous presentons une etude sur la dynamique a haute frequence (dans la region de frequence de THz) d'ortho-terphenyl vitreux, et l'effet de la pression sur cette dynamique est discute. En comparant nos resultats a d'autres donnees disponibles dans la litterature, il a ete possible de deduire quelques conclusions sur la nature des modes acoustique aux energies identiques a celle du BP.
Comparative study of subthreshold characteristics of different antimonide-based and nitride-based dual material gate (DMG) HEMTs

As MOSFET technology reaching its limits, new devices like HEMTs (high electron mobility transistors) are gradually gaining more interests. HEMTs have high mobility due to reduce scattering for the spatially separated doped region. But as their dimensions reach the nano-scale region, different SCEs (short channel effects) and carrier transport inefficiency creep in. To solve these problems a new structure, DMG (dual material gate) HEMT has been proposed. In this paper we have shown comparison of subthreshold characteristics among different antimonide-based DMG HEMTs and between antimonide-based and nitride-based DMG HEMTs. We have found that as the band-offsets in the heterojunction become deeper, the effect of using DMG over SMG (single material gate) reduces in case of antimonide-based HEMTs. Our work also shows that DMG structure is more effective in reducing SCEs for antimonide-based HEMTs than nitride-based HEMTs, while nitride-based DMG HEMTs give more efficient carrier transport than its antimonide-based counterpart.
Climate change in Peruvian newspapers: The role of foreign voices in a context of vulnerability

Media coverage of climate change has been an area of continued research during the last years, mostly with a focus on developed countries. This study attempts to contribute to this body of work by analyzing the coverage in a developing country. The study presents a content analysis of newspaper coverage of climate change in Peru through the study of frames, geographical focus, and climate change strategies (mitigation/adaptation). Additionally, the role of foreign voices is assessed by comparing the coverage by Peruvian reporters with the coverage by wire services, and by determining the types of sources present in the articles. Results show a prevalence of an effects frame, followed by a politics frame. Also, the study found a significant amount of stories originating from wire services. In general, coverage prioritizes mitigation strategies and policies while providing limited attention to adaptation, which can be insufficient for a highly vulnerable country.
Un-met supportive care needs of Iranian breast cancer patients.

BACKGROUND Assessment of supportive needs is the requirement to plan any supportive care program for cancer patients. There is no evidence about supportive care needs of Iranian breast cancer patients. So, the aims of present study were to investigate this question and s predictive factors. MATERIALS AND METHODS A descriptive- correlational study was conducted, followed by logistic regression analyses. The Supportive Care Needs Survey was completed by 136 breast cancer patients residing in Iran following their initial treatment. This assessed needs in five domains: psychological, health system and information, physical and daily living, patient care and support, and sexuality. RESULTS Patient perceived needs were highest in the health systems and information (71%), and physical and daily living (68%) domains. Logistic regression modeling revealed that younger participants have more un-met needs in all domains and those with more children reported fewer un-met needs in patient care and support domains. In addition, married women had more un-met supportive care needs related to sexuality. CONCLUSIONS The high rate of un-met supportive care needs in all domains suggests that supportive care services are desperately required for breast cancer patients in Iran. Moreover, services that address informational needs and physical and daily living needs ought to be the priority, with particular attention paid to younger women. Further research is clearly needed to fully understand supportive care needs in this cultural context.
Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma.

PURPOSE Reports suggest that a subset of uveal melanoma is familial. The association of uveal melanoma with breast and ovarian cancer and the increased risk in BRCA2-linked families implicates germline BRCA2 mutations as the cause of a subset of uveal melanomas. Similarly, the association between cutaneous and uveal melanomas in some families, coupled with the high frequency of somatic deletions of the INK4A-ARF locus in uveal melanomas, strongly suggests that mutations in P16(INK4A) and P15 account for a proportion of uveal melanomas. METHODS To examine this proposition, a systematically ascertained series of 385 patients with uveal melanoma were screened for germline mutations in BRCA2, P16(INK4A), P14(ARF), and P15. RESULTS One patient was found to harbor a Gly35Ala substitution in exon 1alpha of P16(INK4A), which has previously been reported to be pathogenic. No mutations were detected in P14(ARF) or P15. None of the patients harbored germline nucleotide changes that lead to truncation or that create or disrupt consensus splice sites of BRCA2 or missense variants with clear pathogenic potential. CONCLUSIONS These findings suggest that less than 2% of cases of uveal melanoma can be ascribed to germline mutations in BRCA2, P16(INK4A), P14(ARF), or P15. It is likely that mutations in other genes contribute to an inherited predisposition to uveal melanoma.
Polyclonal activation of rat splenic lymphocytes after in vivo administration of Mycoplasma pulmonis and its relation to in vitro response

The plaque-forming cell (PFC) assay with sheep erythrocytes (SRBC) sensitized with different antigens and a 4-h tritiated thymidine pulse assay were used to determine whether polyclonal activation occurs in rats following in vivo administration of Mycoplasma pulmonis. Injection of M. pulmonis into F344 rats resulted in an increase in the number of splenic immunoglobulin M-secreting PFC that produced antibodies reactive with the trinitrophenyl hapten and with SRBC. This polyclonal response reached a peak by 72 h after injection and returned to normal levels by 96 h, at which time the specific response to M. pulmonis reached its peak. Heat treatment and preopsonization of M. pulmonis with antiserum before injection resulted in reduced numbers of PFC against M. pulmonis-sensitized SRBC, trinitrophenyl hapten-sensitized SRBC, and SRBC. The number of PFC against the three types of target cells also increased in LEW rats after immunization with M. pulmonis. The number of PFC against SRBC and staphylococcal protein A-sensitized SRBC was higher in immunized LEW rats than in immunized F344 rats. Examination of unimmunized animals also revealed that LEW rats had higher initial numbers of PFC than did F344 rats. These results showed that polyclonal activation occurs in rats following in vivo administration of M. pulmonis and that LEW rats have an inherent propensity to develop higher nonspecific responses in vivo than F344 rats.
Evalution of Serum Lipid Profiles in Turkish Children Aged Two to Eighteen Years.

OBJECTIVE The purpose of this study was to evaluate dyslipidaemia in children according to age, gender, percentiles, mother's education level, breastfeeding duration and areas of residence. METHODS A total of 285 children (137 girls; 148 boys), aged between two and 18 years, were enrolled in this cross-sectional, epidemiologic study. Lipid profiles were assessed and its relation with sociodemographic features was evaluated. RESULTS Dyslipidaemia prevalence was 37.4% (n = 107). High very low-density lipoprotein cholesterol (VLDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels are related with percentiles of the children (p = 0.006, p = 0.03, respectively). Gender was a significant factor for VLDL-C, which was higher in girls than boys (p = 0.04). Total cholesterol levels were high in 14 children (4.9%); 72 of the study group (25.3%) had high triglyceride levels; HDL-C levels were low in 52 children (18.2%). CONCLUSION All the parameters of dyslipidaemia are not so high in our region. However, as early detection of dyslipidaemia should begin in childhood, we should perform periodic checks to prevent cardiovascular risks.
Impact of Implementing Developmental Screening at 12 and 24 Months in a Pediatric Practice

OBJECTIVES. The purpose of this study was to investigate the effectiveness and costs of incorporating a parent-completed developmental screening tool, the Ages and Stages Questionnaire, into the 12- and 24-month well-child visits under “real-world” conditions, using a combined in-office and mail-back data collection protocol. METHODS. A convenience sample of 1428 caregivers and children presenting for their 12- or 24-month well-child visit between April 2005 and March 2006 participated. Children with identified delays or disorders were excluded. Board-certified pediatricians (n = 18) and nurse practitioners (n = 2) acted as secondary participants. Pediatricians were blinded to Ages and Stages Questionnaire results when completing the Pediatric Developmental Impression. Patients with delayed Ages and Stages Questionnaire or Pediatric Developmental Impression results were referred for additional evaluation. RESULTS. Referral rates increased by 224%. Pediatrician referral on the basis of the Pediatric Developmental Impression was predicted significantly by suspected communication delay and gross motor delay. The Ages and Stages Questionnaire and Pediatric Developmental Impression results differed significantly, with overall agreement of 81.8%. Of Ages and Stages Questionnaire–delayed cases, 67.5% were not detected by pediatricians. Of the 78 patients referred on the basis of combined Ages and Stages Questionnaire and Pediatric Developmental Impression results, 53 would not have been referred on the basis of Pediatric Developmental Impression results alone; 37 patients qualified for special services, and 44 were scheduled for additional developmental monitoring. The rate of Ages and Stages Questionnaire return by caregivers/parents was 54%. CONCLUSIONS. Referral rates increased dramatically, with the greatest increase at 12 months. Although patients with pediatrician referrals were likely to qualify for services (96%), physician referrals accounted for only 42% of total referrals, which highlights the need for pediatric developmental screening. The 54% Ages and Stages Questionnaire return rate, although acceptable under study conditions, calls for alternative implementation strategies.
The Two-Dimensional Gabor Function Adapted to Natural Image Statistics: A Model of Simple-Cell Receptive Fields and Sparse Structure in Images

The two-dimensional Gabor function is adapted to natural image statistics, leading to a tractable probabilistic generative model that can be used to model simple cell receptive field profiles, or generate basis functions for sparse coding applications. Learning is found to be most pronounced in three Gabor function parameters representing the size and spatial frequency of the two-dimensional Gabor function and characterized by a nonuniform probability distribution with heavy tails. All three parameters are found to be strongly correlated, resulting in a basis of multiscale Gabor functions with similar aspect ratios and size-dependent spatial frequencies. A key finding is that the distribution of receptive-field sizes is scale invariant over a wide range of values, so there is no characteristic receptive field size selected by natural image statistics. The Gabor function aspect ratio is found to be approximately conserved by the learning rules and is therefore not well determined by natural image statistics. This allows for three distinct solutions: a basis of Gabor functions with sharp orientation resolution at the expense of spatial-frequency resolution, a basis of Gabor functions with sharp spatial-frequency resolution at the expense of orientation resolution, or a basis with unit aspect ratio. Arbitrary mixtures of all three cases are also possible. Two parameters controlling the shape of the marginal distributions in a probabilistic generative model fully account for all three solutions. The best-performing probabilistic generative model for sparse coding applications is found to be a gaussian copula with Pareto marginal probability density functions.
Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide release

Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti‐inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg−1, i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO−2 plus NO−3). Pretreatment with ethanol extract of E. rutaecarpa (25,50 and 100 mg kg−1, i.v.), 1 h before LPS, dose‐dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over‐production in plasma in endotoxaemic rats. A selective inducible NO‐synthase (iNOS) inhibitor, aminoguanidine (15 mg kg−1, i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia.