Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactive, Computer-Based Pediatric Chest Atlas

Objectives The authors created a computer-based, interactive atlas of pediatric chest radiographs to facilitate (1) understanding of normal variants and (2) interpretation of pediatric chest radiographs in the acute setting. Methods Seventy-three normal pediatric chest radiographs were selected for inclusion in the atlas by consensus after review by 3 pediatric radiologists. Sixteen abnormal pediatric chest radiographs showing a variety of abnormalities (infection, malignancy, congenital abnormalities, foreign body, and acquired disease), as well as 4 normal adult chest radiographs, were also included in the atlas. Images for the atlas were derived from Digital Imaging and Communications in Medicine-compliant data. The atlas software was written in C# and offers features of a picture archiving and communication system viewer. In addition, the atlas offers annotated series that describe particular radiographic features of normal variants and disease. Results The digital, interactive pediatric chest atlas displays normal chest radiographs of children aged 7 days to 17.8 years, as well as 4 normal adult chest radiographs and 16 abnormal pediatric chest radiographs. The digital interactive format of the atlas allows for (1) easy manipulation of atlas cases and (2) direct comparison between normal atlas cases and provided abnormal cases, as well as (3) the potential for direct comparison with images displayed on an institution’s picture archiving and communication system. The atlas is available for free download at http://www.seattlechildrens. org/radiologyeducation/pediatric-chest. Conclusions Improved interpretation of pediatric chest radiographs in the acute setting may be facilitated by a comprehensive, computer-based, pediatric chest atlas.
Internal duplications in α‐helical membrane protein topologies are common but the nonduplicated forms are rare

Many α‐helical membrane proteins contain internal symmetries, indicating that they might have evolved through a gene duplication and fusion event. Here, we have characterized internal duplications among membrane proteins of known structure and in three complete genomes. We found that the majority of large transmembrane (TM) proteins contain an internal duplication. The duplications found showed a large variability both in the number of TM‐segments included and in their orientation. Surprisingly, an approximately equal number of antiparallel duplications and parallel duplications were found. However, of all 11 superfamilies with an internal duplication, only for one, the AcrB Multidrug Efflux Pump, the duplicated unit could be found in its nonduplicated form. An evolutionary analysis of the AcrB homologs indicates that several independent fusions have occurred, including the fusion of the SecD and SecF proteins into the 12‐TM‐protein SecDF in Brucella and Staphylococcus aureus. In one additional case, the Vitamin B12 transporter‐like ABC transporters, the protein had undergone an additional fusion to form protein with 20 TM‐helices in several bacterial genomes. Finally, homologs to all human membrane proteins were used to detect the presence of duplicated and nonduplicated proteins. This confirmed that only in rare cases can homologs with different duplication status be found, although internal symmetry is frequent among these proteins. One possible explanation is that it is frequent that duplication and fusion events happen simultaneously and that there is almost always a strong selective advantage for the fused form.
Qualitative Research in a Cross-Cultural Context: Fijian Experiences

In this article, the authors discuss the experiences of conducting qualitative research in traditional Fijian communities. This provided the setting for the cross-cultural exchange between the researcher and research participants and from which the authors draw important considerations for the design of future qualitative studies. In particular, the authors discuss the need to adapt essentially Western research designs to accommodate different cross-cultural styles of facilitation, group dynamics, spatial arrangements, gender issues, protocol, patterns of participation, and perception of time. They propose a model that clarifies the types of roles and styles of facilitation observed in a Fijian workshop setting and comment on how different cross-cultural dynamics between the researcher and participants can influence the success of qualitative research.
Sensitization to Cow's Milk Proteins during Refeeding of Guinea Pigs Recovering from Polydeficient Malnutrition

We have previously shown that milk sensitization aggravates intestinal dysfunction in the malnourished guinea pigs, suggesting that it may also impair the recovery from malnutrition. To test this hypothesis, the growing guinea pigs were malnourished by feeding only maize for 7 d and then were refed for 21 d with a balanced diet containing either intact or hydrolyzed cow's milk proteins. The control animals received the hydrolyzed milk protein diet for 28 d. After an initial period of total inhibition of growth owing to maize, guinea pigs gained weight regularly, with both balanced diets, and there was no evidence of mucosal damage at the end of the refeeding period. However, refeeding with intact milk proteins induced milk sensitization, which was demonstrated on the systemic level by the presence of anti-β-lactoglubulin IgG1 antibodies, and on the local level by the intestinal anaphylaxis measured by the increase in short circuit current induced by β-lactoglobulin (16.4 ± 2.6 µA/cm2) in jejunal segments mounted in Ussing chambers. Such an immune sensitization was associated with impaired intestinal permeability, as both the ionic conductance (21.0 ± 1.6 versus 14.6 ± 0.7 mS/cm2) and the transepithelial fluxes of horseradish peroxidase (537 ± 203 versus 152 ± 28 ng/h·cm2) were significantly increased in guinea pigs refed with the intact milk proteins compared with controls. In contrast, there was no difference in intestinal permeability between controls and guinea pigs refed with the hydrolyzed milk protein diet. These data show that sensitization to cow's milk proteins can develop in guinea pigs recovering from severe malnutrition and may impair full intestinal repair.
In the Wake of the MTA: Charting a New Course for the Study and Treatment of Children with Attention-Deficit Hyperactivity Disorder

This paper considers 3 questions addressed by the National Institute of Mental Health's Collaborative Multimodal Treatment Study of Children With Attention-Deficit Hyperactivity Disorder (ADHD), the MTA study, of pharmacological and behavioural interventions for 7- to 9-year-old ADHD children. First, do behavioural interventions represent a viable treatment option for families of children with ADHD? Second, what are the relative benefits of behavioural and pharmacological interventions? Finally, are there advantages to combining behavioural and pharmacological interventions for children with ADHD? In the absence of secondary analyses, the MTA's primary intent-to-treat analyses released to date are difficult to interpret. While behavioural interventions represented a viable option for many families, the doses achieved via systematic titration and follow-up medication-management protocols yielded larger effect sizes on unblinded primary symptom reports than did behavioural treatments or the medication management used by most families in the community control conditions. Finally, while combined medication and behavioural management demonstrates some benefits, a more definitive conclusion awaits a detailed presentation of secondary analyses and follow-up data.
The Effect of Silver, Zinc Oxide, and Titanium Dioxide Nanoparticles Used as Final Irrigation Solutions on the Fracture Resistance of Root-Filled Teeth

Aim This study was conducted to evaluate the effect of three nanoparticle solutions used as final root canal irrigants on the fracture resistance of endodontically treated roots. Materials and Methods Sixty intact single-rooted premolar teeth were used after removing the crowns below the cementum–enamel junction to standardize the length of the remaining roots to 13 mm. After instrumenting the roots using ProTaper Universal rotary instruments up to size F4, the roots were randomly divided into six groups (n=10) according to the final irrigating solutions: Group 1: normal saline; Group 2: 2% chlorhexidine (CHX); Group 3: 17% EDTA+2.5% NaOCl; Group 4: 17% EDTA+0.1% silver nanoparticle (SNP) solution; Group 5: 17% EDTA+0.1% titanium dioxide nanoparticle (TNP) solution; Group 6: 17% EDTA+0.1% zinc oxide nanoparticle (ZNP) solution. After filling the root canals with gutta-percha and AH Plus sealer, the fracture resistance (FR) values were measured. The data were subjected to the one-way analysis of variance and the Tamhane post hoc test (p=0.05). Results EDTA + NaOCl had the lowest FR value, followed by normal saline and CHX (p values < 0.05). No significant difference was found between the FR of roots irrigated with CHX and normal saline (p > 0.05). The application of nanoparticles (SNP, TNP, and ZNP) was associated with a significantly greater FR than that of other irrigation solutions (p values < 0.05). Conclusion The final irrigation of root canals with nanoparticles enhanced the fracture resistance of the endodontically treated roots. The lowest FR value was observed for NaOCl.
Phenylalanine Kinetics in Sick Preterm Neonates with Respiratory Distress Syndrome

ABSTRACT: The cause of hyperphenylalaninemia in sick preterm infants has yet to be determined; one reason may be reduced tolerance to phenylalanine as a consequence of immaturity of phenylalanine hydroxylase. Phenylalanine metabolism was studied in vivo in 23 ventilated preterm infants of gestational age 23 to 36 wk within the first 6 d of life using a continuous i.v. infusion of the stable isotopelabeled amino acids [2H5]phenylalanine, [2H4] tyrosine, and [2H2]tyrosine. Phenylalanine hydroxylation was calculated from two different methods. In the first method, used in all 23 infants receiving glucose and in seven of these infants who subsequently received parenteral nutrition, phenylalanine hydroxylation was calculated from the plasma enrichments of [2H5]phenylalanine and [2H4]tyrosine and from the molar ratio of tyrosine to phenylalanine in mammalian tissue protein. In this instance, the mean hydroxylation was 16.0 (SD 10.9) and 48.4 (SD 14.9) µmol/kg/h, which was 17.3% (SD 8.4%) and 33.2% (SD 9.8%) of the total phenylalanine flux for infants receiving glucose and parenteral nutrition, respectively. Additionally, in six infants receiving glucose, hydroxylation was calculated from the measured phenylalanine (2H5), independent tyrosine (2H2) fluxes, and the plasma enrichments of (2H5) phenylalanine and its hydroxylation product [2H4]tyrosine. In this case, hydroxylation was 20.5 (SD 13.0) (µmol/kg/h, which represented 22.3% (SD 9.8%) of the phenylalanine flux. In the same six infants, phenylalanine hydroxylation derived using the first method was 22.2 (SD 13.1) µmol/kg/h, 23.6% (SD 9.9%) of the total phenylalanine flux. The close agreement between phenylalanine hydroxylation calculated from the enrichment of plasma with [2H2]tyrosine and estimated from the proportion of phenylalanine to tyrosine in body protein confirms that the independent measurement of tyrosine flux by a constant infusion of [2H2]tyrosine is not routinely required in the measurement of phenylalanine hydroxylation in preterm infants. These results do not support the hypothesis that phenylalanine hydroxylase activity is low in preterm infants.
Measurement of the surface free energy of bacterial cell surfaces and its relevance for adhesion

An experimental technique is described to determine contact angles on bacterial layers deposited on cellulose triacetate filters. Measurements with water, water-n-propanol mixtures, and alpha-bromonaphthalene were employed to calculate surface free energies of various oral bacteria. Differences of 30 to 40 erg cm-2 were obtained for four different bacterial species isolated from the human oral cavity, if the concept of dispersion and polar surface free energies is applied. The free energies obtained were used to calculate interfacial free energies of adhesion of these bacteria from saliva onto tooth surfaces. Bacterial adhesion is energetically unfavorable, if the enamel surface free energy is less than 50 erg cm-2.
EARLY CHIMERISM OF MACROPHAGES AND LYMPHOCYTES IN LUNG TRANSPLANT RECIPIENTS IS PREDICTIVE OF GRAFT TOLERANCE1

Background. The persistence of donor cells derived from the graft (chimerism) has been documented in various tissues after organ transplantation. It was suggested that stable chimerism might reflect a state of donor-specific tolerance. Chimerism of macrophages and lymphocytes were studied over time after lung transplantation as well as its impact on graft tolerance. Material and Methods. Macrophages and lymphocytes were purified from bronchoalveolar lavage sequentially obtained from 24 patients between 1 and 41 months posttransplantation (20, 22, 24, and 17 patients at, respectively, 1, 3, 6, and 12 months). DNA was extracted from these cells and their recipient-donor origin was evaluated by PCR amplification of highly polymorphic DNA regions (minisatellites). Results. We show that the remaining donor cells over the first month vary from 10 up to 50% and 5 up to 55% for lymphocytes and macrophages respectively (±2 SD). All patients presented some chimerism up to the 6th postoperative month. Good correlation was observed between the residual amount of donor lymphocytes and macrophages during the first 3 months (P <0.001). Patients with at least 30% donor lymphocytes at 1 month after transplantation had less rejections (≥stage II) in the follow up (P =0.0007). The same observation is true for donor macrophages although to lower extend (P =0.02). The chimerism lost its predictive value beyond 3 months. Conclusions. These data demonstrate that a level of chimerism above 30% of either donor lymphocytes or macrophages at 1 month is related to a better state of graft tolerance. However, chimerism decreases markedly beyond 3 months and has then no predictive value.
Relating Watershed Characteristics to Non-point Source Pollution in Miyun Reservoir Watershed Using Principal Components Analysis (PCA)

The watershed Landscape characteristics are important variables that influence surface water quality. Freshwater research and management efforts could be greatly enhanced by a better understanding the relationship between these variables and surface water quality. The major focus of this paper involved modeling relationships between watershed characteristics variables and water quality indicators. The Miyun reservoir watershed was the selected study site. Statistical analyses were performed to quantify the relationship between landscape metrics, hydrologic and surface water quality. PCA eliminated cross-correlations between variates and reduced the 13 input variables to 5 components that accounted for >92% of variance. TN, NO3-N, NO2-N and NH4+-N coefficient of variation were predicted with PCA regression. Results showed that landscape characteristics in the study watershed could account for as much as 60% of the variation of water quality indicators
CD4 T Cells Are Not Required for the Induction of Dengue Virus-Specific CD8 T Cell or Antibody Responses but Contribute to Protection after Vaccination

The contribution of T cells to the host response to dengue virus (DENV) infection is not well understood. We previously demonstrated a protective role for CD8 + T cells during primary DENV infection using a mouse-passaged DENV strain and IFN-a/bR 2/2 C57BL/6 mice, which are susceptible to DENV infection. In this study, we examine the role of CD4 + T cells during primary DENV infection. Four I-A b –restricted epitopes derived from three of the nonstructural DENV proteins were identified. CD4 + T cells expanded and were activated after DENV infection, with peak activation occurring on day 7. The DENV-specific CD4 + T cells expressed intracellular IFN-g, TNF, IL-2, and CD40L, and killed peptide-pulsed target cells in vivo. Surprisingly, depletion of CD4 + T cells before DENV infection had no effect on viral loads. Consistent with this observation, CD4 + T cell depletion did not affect the DENV-specific IgG or IgM Ab titers or their neutralizing activity, or the DENV-specific CD8 + T cell response. However, immunization with the CD4 + T cell epitopes before infection resulted in significantly lower viral loads. Thus, we conclude that whereas CD4 + T cells are not required for controlling primary DENV infection, their induction by immunization can contribute to viral clearance. These findings suggest inducing anti-DENV CD4 + T cell responses by vaccination may be beneficial. D engue virus (DENV) is a mosquito-borne RNA virus in the Flaviviridae family, which also includes West Nile virus (WNV), yellow fever virus, and Japanese encepha-litis virus. The four serotypes of DENV (DENV1–4) share ∼65– 75% homology at the amino acid level (1). Infections with DENV can be asymptomatic, or cause disease ranging from dengue fever (DF) to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (2). DF is a self-limiting illness with symptoms that include fever, headache, myalgia, retro-orbital pain, nausea, and vomiting. DHF and DSS are characterized by increased vascular permeability, thrombocytopenia, hemorrhagic manifestations, and, in the case of DSS, shock, which can be fatal. The incidence of DENV infections has increased 30-fold in the past 50 y, and DF and DHF/DSS are a significant cause of morbidity and mortality worldwide (2). However, vaccine development has been challenging, as a vaccine should protect against all four DENV serotypes (3). Severe dengue disease (DHF/DSS) most often occurs in individuals experiencing a secondary infection with a heterologous DENV serotype, suggesting the immune response contributes to the …
Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent'sJapan disease.

BACKGROUND The annual urinary screening of Japanese children above three years of age has identified a progressive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrocalcinosis, and this represents a variant of Dent's disease. Hitherto, 12 mutations of the X-linked renal specific chloride channel, CLCN5, have been reported in the Dent'sJapan variant. To further identify such CLCN5 mutations and to define the structure-function relationships of this channel, we have investigated five unrelated, non-consanguinous Japanese families with this disorder. METHODS Leukocyte DNA from probands was used with CLCN5 primers for PCR amplification of the coding region, and the DNA sequences of the products determined. Functional studies were performed by expressing the mutants in Xenopus oocytes. RESULTS Five CLCN5 mutations consisting of two nonsense (R648X and R704X), two missense (S270R and L278F) and one acceptor splice site mutation (ag-->cg) in intron 4 were identified. The missense and splice site mutations represent novel abnormalities. Heterologous expression in Xenopus oocytes of wild-type and the missense mutants demonstrated that the mutations, which were translated, either abolished or markedly reduced chloride conductance. CONCLUSIONS These results expand the spectrum of CLCN5 mutations associated with this renal disorder and provide insight into possible structure-function relationships. For example, both the missense mutations are located within a short putative loop between two transmembrane domains, and our results suggest that this region may have an important functional role in the regulation of channel activity.
Cancer cells preferentially lose small chromosomes

Genetic and genomic aberrations are the primary cause of cancer. Chromosome missegregation leads to aneuploidy and provides cancer cells with a mechanism to lose tumor suppressor loci and gain extra copies of oncogenes. Using cytogenetic and array‐based comparative genomic hybridization data, we analyzed numerical chromosome aneuploidy in 43,205 human tumors and found that 68% of solid tumors are aneuploid. In solid tumors, almost all chromosomes are more frequently lost than gained with chromosomes 7, 12 and 20 being the only exceptions with more frequent gains. Strikingly, small chromosomes are lost more readily than large ones, but no such inverse size correlation is observed with chromosome gains. Because of increasing levels of proteotoxic stress, chromosome gains have been shown to slow cell proliferation in a manner proportional to the number of extra gene copies gained. However, we find that the extra chromosome in trisomic tumors does not preferentially have a low gene copy number, suggesting that a proteotoxicity‐mediated proliferation barrier is not sustained during tumor progression. Paradoxically, despite a bias toward chromosome loss, gains of chromosomes are a poor prognostic marker in ovarian adenocarcinomas. In addition, we find that solid and non‐solid cancers have markedly distinct whole‐chromosome aneuploidy signatures, which may underlie their fundamentally different etiologies. Finally, preferential chromosome loss is observed in both early and late stages of astrocytoma. Our results open up new avenues of enquiry into the role and nature of whole‐chromosome aneuploidy in human tumors and will redirect modeling and genetic targeting efforts in patients.
Class switch recombination in selective IgA‐deficient subjects

Selective IgA deficiency is a common immunodeficiency in Caucasians, but the molecular basis of the disorder remains elusive. To address this issue we examined the molecular events leading to IgA production. Naive IgD positive B cells were purified from four donors with IgA deficiency and four control donors, all Caucasians. Stimulation of B cells from IgA‐deficient donors with the cytokines transforming growth factor (TGF)‐β, interferon (IFN)‐γ or interleukin (IL)‐10 in the presence of anti‐CD40 antibodies showed reduced expression of both activation‐induced cytidine deaminase (AID) and α germline transcripts (GLT) compared to controls. It was possible, however, to induce AID and α GLT when stimulating the cells with anti‐CD40 antibody and TGF‐β in the combination with IL‐10. Moreover, in anti‐CD40 antibody‐stimulated cultures, addition of IL‐10 or IL‐10 + TGF‐β in combination, induced IgA production, albeit lower than found in B cells from controls. The B cells from the IgA‐deficient subjects were less effective in differentiating into CD138+ X‐box binding protein 1 (XBP‐1)+ plasma cells when stimulated with TGF‐β, IFN‐γ or IL‐10. Interestingly, when adding IL‐4 to TGF‐β alone or in combination with IL‐10, the immunoglobulin production in B cells from IgA‐deficient donors was comparable with those of normal controls. These data show that in healthy subjects in vitro IgA production can be up‐regulated by addition of IL‐10 to CD40‐stimulated B cells, whereas a similar B cell differentiation does not occur in IgA‐deficient subjects. Addition of IL‐4, however, reverts this abnormality.