Miracle-dz/UniFAR-FTUs huggingface dataset:
Spontaneous T cell mediated keratoconjunctivitis in Aire-deficient mice

Background/aims: Patients with autoimmune polyendocrinopathy-candiasis-ectodermal dystrophy (APECED) develop severe keratoconjunctivitis, corneal scarring and visual loss, but the precise pathogenesis is unknown. This study evaluated the ocular surface immune cell environment, conjunctival goblet cell density and response to desiccating environmental stress of the autoimmune regulatory (Aire) gene knockout murine model of APECED. Methods: Aire-deficient and wild type (WT) mice were subjected to desiccating stress from a drafty, low-humidity environment and pharmacological inhibition of tear secretion for 5 days. Immune cell populations (CD4+, CD8+, CD11b+, CD45+) and goblet cell density were measured in ocular surface tissues and meibomian glands, and compared with baseline values. Results: Greater CD4+ T cell populations were observed in the conjunctival epithelium of Aire-deficient mice (p<0.001) compared with WT. Aire-deficient mice also had greater numbers of CD4+, CD8+, and CD11b+ cells in the peripheral cornea at baseline and following desiccating stress. The meibomian glands of Aire-deficient mice demonstrated greater CD4+, CD8+, CD45+ and CD11b+ cells at baseline (p<0.001) and following desiccating stress. Conjunctival goblet cell density was lower at baseline and following desiccating stress in Aire-deficient compared with WT mice (p<0.001). Conclusion: Aire-deficiency leads to infiltration of CD4+ and CD8+ T cells on the ocular surface and meibomian glands, which is accompanied by goblet cell loss. Desiccating stress promotes this proinflammatory milieu. Immune-mediated mechanisms play a role in the severe blepharitis and keratoconjunctivitis in the murine model of APECED.
Extending TP-monitors for intra-transaction parallelism

Inter-transaction parallelism, the concurrent execution of independent client transactions, is currently well supported by database systems. Intra-transaction parallelism, the parallel execution of operations within the same transaction, is generally not supported, even though often necessary especially in non-standard applications. The authors show how database operations within the same transaction can be executed concurrently by executing them as independent sub-transactions. This is possible because they employ a two-level transaction approach where the lower level is provided by virtually any of today's databases. The higher level is realised by a transaction processing monitor that is extended with an additional transaction manager for the scheduling of application service calls. They present results of a prototype implementation using Tuxedo and a relational database system using a document management application as an example.
In vivo proton observed carbon edited (POCE) 13C magnetic resonance spectroscopy of the rat brain using a volumetric transmitter and receive‐only surface coil on the proton channel

In vivo carbon‐13 (13C) MR spectroscopy (MRS) is capable of measuring energy metabolism and neuroenergetics, noninvasively in the brain. Indirect (1H‐[13C]) MRS provides sensitivity benefits compared with direct 13C methods, and normally includes a 1H surface coil for both localization and signal reception. The aim was to develop a coil platform with homogenous B1+ and use short conventional pulses for short echo time proton observed carbon edited (POCE) MRS.
A Novel Potassium Channel in Lymphocyte Mitochondria*

The margatoxin-sensitive Kv1.3 is the major potassium channel in the plasma membrane of T lymphocytes. Electron microscopy, patch clamp, and immunological studies identified the potassium channel Kv1.3, thought to be localized exclusively in the cell membrane, in the inner mitochondrial membrane of T lymphocytes. Patch clamp of mitoplasts and mitochondrial membrane potential measurements disclose the functional expression of a mitochondrial margatoxin-sensitive potassium channel. To identify unambiguously the mitochondrial localization of Kv1.3, we employed a genetic model and stably transfected CTLL-2 cells, which are genetically deficient for this channel, with Kv1.3. Mitochondria isolated from Kv1.3-reconstituted CTLL-2 expressed the channel protein and displayed an activity, which was identical to that observed in Jurkat mitochondria, whereas mitochondria of mock-transfected cells lacked a channel with the characteristics of Kv1.3. Our data provide the first molecular identification of a mitochondrial potassium conductance.
Spatial Scale and the Spread of a Fungal Pathogen of Gypsy Moth

cies forms a wavefront that moves across the landscape at For reasons of logistics, most ecological studies focus on a constant speed (fig. 1), and for an interspecific interacsmall spatial scales, in study plots that typically range in tion the speed of the wavefront depends on the densities size from 0.1 m to 1 ha (Kareiva and Andersen 1990), of both interacting species. This means that small inyet many interesting ecological phenomena occur at creases in the density of the host or the pathogen can scales that range from square kilometers to the size of the lead to large increases in the speed of the wavefront of globe (Mooney and Drake 1986; Vitousek 1994). If disease, and the long-term rate of spread of the disease small-scale studies are to have relevance for large-scale will be higher than the initial rate of spread. We therephenomena, the ability to extrapolate between scales is fore use the model to ask whether the higher rate of critical. One way of extrapolating between spatial scales is spread of the disease at the larger scale may have been through the use of mathematical models that incorporate due to a combination of higher densities of both host explicit spatial structure. In this note, we use data from a and pathogen at the larger scale. The density of the host field experiment on the spatial spread of an insect pathoin the region in which large-scale spread occurred was gen (Hajek et al. 1996) to try to understand the spread of higher than it was where the pathogen was experimenthe pathogen over a large area of central New York and tally introduced, and pathogen densities were higher in Pennsylvania (Elkinton et al. 1991). the region of large-scale spread because the disease had The disease in our study is the fungal pathogen Entobuilt up to high levels in the previous season’s epidemic. mophaga maimaiga that infects larvae of the gypsy moth Our question is then, What fraction of the higher rate at Lymantria dispar. This pathogen was first introduced into the regional scale can be explained by the wavefront of North America between 1910 and 1911 as a biological disease reaching its long-term spread rate in a higher control agent to be used against gypsy moth (Hajek et al. density population? In other words, to what extent is the 1995). For unknown reasons, it then apparently disaphigher rate at the larger scale due simply to density efpeared until it caused a massive epidemic among northfects, rather than to a different mechanism of spread at eastern gypsy moth populations in 1989 (Hajek et al. the larger scale? 1990a). The large-scale data that we use track the spread
Effects of supplemental soybean oil level on in vitro digestion and performance of prepubertal beef heifers.

In vitro digestion and growth studies were conducted to evaluate the effects of level of soybean oil inclusion in forage-based diets. In Exp. 1, diets were bromegrass hay (H), bromegrass hay and corn-soybean meal supplement (C), C with 3% added soybean oil (O3), and C with 6% added soybean (O6). Diets containing supplements were formulated to be isonitrogenous and isocaloric. Treatment means were compared using a single-degree-of-freedom contrast (H vs C, O3, and O6) and orthogonal polynomial contrasts within diets C, O3, and O6. Diet H had the lowest (P = .0003) IVDMD and a linear decline (P = .0001) in IVDMD was observed from C to O6, but 24-h IVDMD disappearance was greatest (P = .001; quadratic) for O3. Total VFA increased from C to O3 and then decreased from O3 to O6 (quadratic; P = .001), and acetate:propionate ratio decreased linearly (P = .0001) from C to O6. Changes in long-chain fatty acids reflected biohydrogenation by ruminal microbes; however, only 18:3 was hydrogenated to the same extent across all diets. In Exp. 2, 36 Angus x Gelbvieh heifers (260.0 +/- 6.0 kg initial BW) were individually fed C, O3, or O6 as mixed rations for 104 d. Diets were formulated to be isonitrogenous and provide ADG of . 91 kg. Feed efficiency and ADG was greatest (P < .02; quadratic) for O3 heifers. Serum NEFA increased linearly (P = .02) and serum glucose (P = .02), cholesterol (P = .002), and GH (P = .04) showed a quadratic response to level of dietary soybean oil. Plasma proportions of 16:0, 16:1, 18:0, and 18:1 increased quadratically (P < .03), and 18:2 increased linearly (P < .001) from C to O6. In Exp. 3, 42 Angus x Gelbvieh heifers (288.7 +/- 6.6 kg initial BW) were divided into six pens (two pens/treatment) in a randomized complete block designed experiment. Rations were delivered as hay plus a top-dressed supplement (C, O3, or O6). Heifers fed O3 conceived 10 d earlier (quadratic; P = .06) than heifers fed C and O6. Other production estimates did not differ (P > or = .10) among dietary treatments. Inclusion of soybean oil at 3% of a forage-based diet increased total VFA, many blood metabolites, ADG, and feed efficiency, and it decreased time to conception. Adding soybean oil as 3% of a forage-based diet is an acceptable feeding strategy for developing beef heifers.
PIK3CA mutations in advanced ovarian carcinomas

PIK3CA belongs to the phosphatidylinositol 3‐kinases (PI3Ks) family, which play an important role in proliferation, adherence, transformation and cell survival through the PI3K/AKT signaling pathway. Somatic activating mutations of this gene have recently been detected in several types of cancers. In the present study, 109 advanced ovarian carcinomas were analyzed for PIK3CA mutations in exon 9 and exon 20 by direct sequencing. Activating missense mutations were observed in 4 of the 109 tumors in addition to one variant leading no change of the PIK3CA protein. Two of the cases with mutations were mucinous and clear cell tumors, suggesting that PIK3CA mutations are more common in these rare histological types. © 2005 Wiley‐Liss, Inc.
Are "Progressive" Mutations Produced by X-Rays?

PAGE 495 1. The physical background of the problem. 11. Evidence concerning the duality of the X-ray effect on chro 111. A partial separation of the Werent genetic effects of X-rays. IV. The production of multiple allelomorphs. 507 V. An induced mutation visibly d8erent from a known lass of VI. First attempts to induce mutations in both of two oppqsite VII. Reverse mutations a t the locus of scute. VIII. A reverse mutation a t the locus of forked. IX. Proof of the induction of reverse mutations of forked
Idiopathic orbital inflammation: a new dimension with the discovery of immunoglobulin G4-related disease

Purpose of review To review idiopathic orbital inflammation, with particular reference to the evolving entity of ocular adnexal immunoglobulin G4 (IgG4) disease. Recent findings Emerging evidence suggests that sclerosing idiopathic orbital inflammation can be an IgG4-related disease and discovery of this link has further reduced the subset of ‘idiopathic orbital inflammation’. Ocular adnexal IgG4 disease should especially be considered if the orbital disease is bilateral or where there is systemic involvement. New reports are linking the possibility of lymphoma arising from a background of IgG4-positive inflammation in both the orbit and in other organs, and both the physician and the patient should be aware of this long-term risk. Summary Although the diagnosis of IgG4-related orbital disease continues to be challenging, there is a growing understanding of the pathophysiology and this is likely to be key to developing a clinical strategy for the diagnosis and effective treatment of this condition.
Different subtypes of epithelioid sarcoma and their clinical implication: long‐term multi‐institutional experience with a rare sarcoma

Epithelioid sarcoma (ES) is a very rare soft‐tissue sarcoma with a high tendency of recurrence and metastasis. We analyzed clinical features of ES and aimed to identify the potential role of radio‐ and chemotherapy in ES. Fifty‐five patients diagnosed with ES between 1997 and 2014 were enrolled from seven tertiary hospitals in Korean Cancer Research Group. The clinical variables were retrospectively reviewed and analyzed. Forty‐six (84%) patients underwent surgical resection of ES, and among them, 27 experienced recurrence. In these patients, resection margin status and adjuvant radiotherapy were independent prognostic factors for longer recurrence‐free survival (RFS), while adjuvant chemotherapy did not influence RFS. Twenty‐two (40%) patients received palliative chemotherapy for metastatic or recurrent ES, and in these patients, palliative chemotherapy was the only independent prognostic factor for longer overall survival. Intriguingly, the clinical benefit of radio‐ and chemotherapy was observable only in proximal ES, but not in extremity ES, indicating that subtypes of ES might respond to radio‐ or chemotherapy differently. Proximal ES seems to benefits more from active anticancer treatment than conventional extremity ES. The aggressive characteristics of proximal ES could be overcome with an optimal multimodal treatment.
Feasibility of Nonanatomical Liver Resection in Diligently Selected Patients with Hepatoblastoma and Comparison of Outcomes with Anatomic Resection

Abstract Introduction Treatment guidelines for hepatoblastoma discourage nonanatomic liver resections. However, the evidence for this is inadequate and comes from a study performed almost two decades ago which additionally contained inherent limitations. This study aimed to assess the feasibility and oncologic outcomes of nonanatomic resections (NAR) performed in diligently selected patients and compare the results with anatomic resections (AR). Materials and Methods A total of 120 patients who underwent liver resections for hepatoblastoma between January 2008 and July 2019 were reviewed. Feasibility of NAR was based on postchemotherapy relations to vessels, site of the lesion, and possibility of achieving negative resection margins. Results AR was performed in 95 patients and 25 had NAR. The NAR cohort had similar International Childhood Liver Tumors Strategy Group (SIOPEL) risk group distribution. Blood loss and operative times were lower in patients undergoing NAR. No differences were noted between the two groups concerning postoperative morbidity and hospitalization. There were no pathologic positive margins or local recurrences in the NAR patients. Relapse free (RFS) and overall survival (OS) was similar in the two groups (p = 0.54 and 0.96, respectively). Subgroup analysis of only posttreatment extent of tumor (POSTTEXT) I and II patients also showed no difference in RFS or OS for the two groups with a persistent significant difference in operative times and blood loss. Conclusion NAR is feasible with clear margins in carefully selected patients. It is not associated with more complications and outcomes are not inferior to AR. NAR is associated with lesser blood loss and operative time.
Partition Model–Based 99mTc-MAA SPECT/CT Predictive Dosimetry Compared with 90Y TOF PET/CT Posttreatment Dosimetry in Radioembolization of Hepatocellular Carcinoma: A Quantitative Agreement Comparison

90Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment 99mTc-macroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of 99mTc-MAA SPECT/CT and posttreatment dosimetry based on 90Y time-of-flight (TOF) PET/CT. Methods: We compared the 99mTc-MAA SPECT/CT results for 27 treatment sessions (25 HCC patients, 41 tumors) with 90Y SIRT (7 glass spheres, 20 resin spheres) and the posttreatment 90Y TOF PET/CT results. Three-dimensional voxelized dose maps were computed from the 99mTc-MAA SPECT/CT and 90Y TOF PET/CT data. Mean absorbed dose (Dmean) was evaluated to compute the predicted-to-actual dose ratio (DRmean=DmeanMAA/Dmean90Y) in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance (ρc) was used to measure accuracy (Cb) and precision (ρ). Results: Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose Dmean90Y was 240 Gy for glass and 122 Gy for resin in TVs and 72 Gy for glass and 47 Gy for resin in NTVs. DRmeanTV was 1.46 ± 0.58 (0.65–2.53) for glass and 1.16 ± 0.41 (0.54–2.54) for resin, and the respective values for DRmeanNTV were 0.88 ± 0.15 (0.56–1.00) and 0.86 ± 0.2 (0.58–1.35). DR variability was substantially lower in NTVs than in TVs. The Lin concordance between DmeanMAA and Dmean90Y (resin) was significantly better for tumors larger than 150 mL than for tumors 150 mL or smaller (ρc = 0.93 and Cb = 0.95 vs. ρc = 0.57 and Cb = 0.93; P < 0.05). Conclusion: In 90Y radioembolization of HCC, predictive dosimetry based on 99mTc-MAA SPECT/CT provided good estimates of absorbed doses calculated from posttreatment 90Y TOF PET/CT for tumor and nontumor tissues. The low variability of DRNTV demonstrates that pretreatment dosimetry is particularly suitable for minimizing radiation-induced hepatotoxicity.
Diffusion‐collision model for the folding kinetics of myoglobin

The diffusion‐collision model has been used to analyze the folding kinetics of myoglobins. The microdomains, which are the basic units that coalesce during the folding, are identified with the helices and the stabilizing contacts between helices are determined form the native structure. Both association and disassociation reactions are included and a range of stabilization parameters is investigated to determine the variations in overall rate and the relative contributions made by the different intermediates during the folding process. In a comparison of folding to the native state and to the midpoint of the folding transitions. (i.e., 50% native protein at the completion of the reaction) significant differences in the contributing intermediates are found.
Wt 1 controls retinoic acid signalling in embryonic epicardium through transcriptional activation of Raldh 2

Epicardial-derived signals are key regulators of cardiac embryonic development. An important part of these signals is known to relate to a retinoic acid (RA) receptor-dependent mechanism. RA is a potent morphogen synthesised by Raldh enzymes, Raldh2 being the predominant one in mesodermal tissues. Despite the importance of epicardial retinoid signalling in the heart, the molecular mechanisms controlling cardiac Raldh2 transcription remain unknown. In the current study, we show that Wt1-null epicardial cells display decreased expression of Raldh2 both in vivo and in vitro. Using a RA-responsive reporter, we have confirmed that Wt1-null epicardial cells actually show reduced synthesis of RA. We also demonstrate that Raldh2 is a direct transcriptional target of Wt1 in epicardial cells. A secondary objective of this study was to identify the status of RA-related receptors previously reported to be critical to epicardial biology (PDGFRα,β; RXRα). PDGFRα and PDGFRβ mRNA and protein levels are downregulated in the absence of Wt1, but only Pdgfra expression is rescued by the addition of RA to Wt1-null epicardial cells. RXRα mRNA levels are not affected in Wt1-null epicardial cells. Taken together, our results indicate that Wt1 critically regulates epicardial RA signalling via direct activation of the Raldh2 gene, and identify a role for Wt1 in the regulation of morphogen receptors involved in the proliferation, migration, and differentiation of epicardial and epicardially-derived cells (EPDC).
The Children's Depression Inventory (CDI) as measure of depression in Swedish adolescents. A normative study

Self-rating scales are an economical and practical aid in the diagnostic work-up. However, normative data from the general population are needed to interpret scores. Four hundred and five adolescents selected to be fairly representative of the general population (both ethnical Swedes and born abroad) filled in a questionnaire containing the Children's Depression Inventory (CDI), the Multidimensional Anxiety Scale for Children (MASC) and background data (including socio-economic status (SES). The CDI was reliable in terms of internal consistency (0.86) with a mean inter-item correlation of 0.18 and item-total score correlations ranging from 0.26 to 0.57. The CDI sub-scales (Negative Mood, Ineffectiveness, Anhedonia and Negative Self-esteem had good internal consistency values slightly above 0.60, except for sub-scale Interpersonal Problems with poor internal consistency (0.36). The 90th and 95th percentiles respectively were defined by scores 15 and 18 and above for boys and by scores 20 and 23 and above for girls. Common correlates of high scores were female gender, broken family but not SES, nor ethnicity. Also, some estimates of the convergent validity of the CDI were found in a Pearson correlation of 0.40 with the MASC total score and in the capacity of the CDI (predictive validity); OR = 1.1 in predicting suicidal ideation. The CDI has some, but as of yet not sufficient indications of being a valid and reliable measure of depression in adolescence and scores can be used to indicate, though not prove the absence or presence of, depression.
The Majority of Currently Circulating Human Immunodeficiency Virus Type 1 Clade B Viruses Fail To Prime Cytotoxic T-Lymphocyte Responses against an Otherwise Immunodominant HLA-A2-Restricted Epitope: Implications for Vaccine Design

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) mutates to escape immune selection pressure, but there is little evidence of selection mediated through HLA-A2, the dominant class I allele in persons infected with clade B virus. Moreover, HLA-A2-restricted responses are largely absent in the acute phase of infection as the viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2. Here we demonstrate an A2-restricted epitope within Vpr (Vpr59-67) that is targeted by acute-phase HIV-1-specific CD8+ T cells, but only in a subset of persons expressing HLA-A2. Individuals in the acute stage of infection with viruses containing the most common current sequence within this epitope (consensus sequence) were unable to mount epitope-specific T-cell responses, whereas subjects infected with the less frequent I60L variant all developed these responses. The I60L variant epitope was a stronger binder to HLA-A2 and was recognized by epitope-specific T cells at lower peptide concentrations than the consensus sequence epitope. These data demonstrate that HLA-A2 is capable of contributing to the acute-phase cytotoxic T-lymphocyte response in infected subjects, but that most currently circulating viruses lack a dominant immunogenic epitope presented by this allele, and suggest that immunodominant epitopes restricted by common HLA alleles may be lost as the epidemic matures.