Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclosporine and long-term kidney graft survival.

BACKGROUND Previous analysis of kidney transplant data from the Collaborative Transplant Study database showed that patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 7 years posttransplantation. Longer-term and additional analyses have now been performed. METHODS Data from cadaver kidney transplants performed between 1985 and 1998 were analyzed retrospectively. Patients were included if they had a functioning graft 1 year posttransplantation, and the daily cyclosporine dose administered 1 year posttransplantation was reported. Data on cyclosporine dose, serum creatinine concentration, and systolic blood pressure were recorded 1 and 5 years after transplantation; information on graft survival was documented at yearly intervals. RESULTS Patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 10 years posttransplantation. Cyclosporine <2 mg/kg/day was least beneficial overall and in subanalyses based on age, risk level, and 1-year serum creatinine concentration. The microemulsion cyclosporine formulation (Neoral) was associated with a significantly higher 4-year graft survival rate than the conventional formulation (Sandimmune; P=0.0001). Median systolic blood pressure 5 years posttransplantation was similar in each 1-year cyclosporine dose category (range of medians 139.0-140.0 mmHg). The percentages of patients with serum creatinine concentrations of <130, 130-260, 260-400, or >400 micromol/L 1 and 5 years posttransplantation were similar across 1-year cyclosporine dose categories, with the exception of >6 mg/kg/day, where there was a shift toward a less favorable serum creatinine concentration over time. CONCLUSIONS The 1-year cyclosporine dose was significantly associated with long-term graft survival, with evidence of underimmunosuppression at doses <3 mg/kg/day and overimmunosuppression at doses >6 mg/kg/day, but had little influence on systolic blood pressure or serum creatinine concentration at doses up to 6 mg/kg/day.
The emergence of present perfect verb forms: semantic influences on selective imitation

ABSTRACT This study investigates forms and functions of the perfect in 22 preschool children. Children retold and re-enacted two-sentence stories which modelled the perfect. Although the perfect appeared to be emerging in imitative speech, including certain ungrammatical forms, children varied in the extent to which they used it and appreciated its meaning of current relevance. Three factors were found to influence children's selective imitation and paraphrasing of the perfect: form of the verb (present perfect versus perfect progressive), semantic sense of the perfect, and duration of the lexical verb. Children's performance demonstrates the need to consider not only the developmental frequency of advanced, optional verb forms but the generality of their use and their relation to the child's lexicon.
Islet Transplantation in Type 1 Diabetic Patients Using Calcineurin Inhibitor-Free Immunosuppressive Protocols Based on T-Cell Adhesion or Costimulation Blockade

Background. The applicability of islet transplantation as treatment for type 1 diabetes is limited by long-term graft dysfunction, immunosuppressive drug toxicity, need for multiple donors, and increased risk of allosensitization. We describe two immunosuppressive regimens based on the costimulation blocker belatacept (BELA) or the antileukocyte functional antigen-1 antibody efalizumab (EFA), which permit long-term islet allograft survival and address some of these concerns. Methods. Ten patients with type 1 diabetes with hypoglycemic unawareness received intraportal allogeneic islet transplants. Immunosuppression consisted of antithymocyte globulin induction and maintenance with sirolimus or mycophenolate and BELA (n=5) or EFA (n=5). Results. All five BELA-treated patients achieved independence after single transplants; one resumed partial insulin use 305 days after transplant but is now independent after a second transplant. All five patients treated with EFA achieved independence after one (3/5) or two (2/5) islet transplants and remained independent while on EFA (392–804 days). After EFA was discontinued because of withdrawal of the drug from the market, two patients resumed intermittent insulin use; the others remain independent. No patient in either group developed significant side effects related to the study drugs, and none have been sensitized to alloantigens. All have stable renal function. Conclusions. These two novel immunosuppressive regimens are effective, well tolerated, and the first calcineurin inhibitor/steroid-sparing islet protocols resulting in long-term insulin independence. Although EFA is no longer available for clinical use, these early results demonstrate that a regimen using BELA may be an effective alternative to improve graft function and longevity while minimizing renal and &bgr;-cell toxicity.
Robust Online i-Vectors for Unsupervised Adaptation of DNN Acoustic Models: A Study in the Context of Digital Voice Assistants

Supplementing log filter-bank energies with i-vectors is a popular method for adaptive training of deep neural network acoustic models. While offline i-vectors (the target utterance or other relevant adaptation material is available for i-vector extraction prior to decoding) have been well studied, there is little analysis of online i-vectors and their robustness in multi-user scenarios where speaker changes can be frequent and unpredictable. The authors of [1] showed that online adaptation could be achieved through segmental i-vectors computed using the hidden Markov model (HMM) state alignments of utterances decoded in the recent past. While this approach works well in general, it could be rendered ineffective by speaker changes. In this paper, we study robust extensions of the ideas proposed in [1] by: (a) updating ivectors on a per-frame basis based on the incoming target utterance, and (b) using lattice posteriors instead of one-best HMM state alignments. Experiments with different i-vector implementations show that: (a) when speaker changes occur, lattice-based frame-level i-vectors provide up to 6% word error rate reduction relative to the baseline [1], and (b) online i-vectors are more effective, in general, when the microphone characteristics of test utterances are not seen in training.
Antigenic relatedness of two strains of hepatitis A virus determined by cross-neutralization

Cell culture-adapted HM-175 (Australia) and PA-21 (Panama) strains of hepatitis A virus were compared in a cross-neutralization radioimmunofocus inhibition assay. The ratio of antibody titers achieved with two sera against the two viruses differed by less than twofold, indicating a high degree of antigenic relatedness between epidemiologically disparate strains of virus.
Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice

We previously showed that activation of G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) signaling modulates descending inhibition of pain. In this study, we investigated the involvement of fatty acid-GPR40/FFAR1 signaling in the transition from acute to chronic pain. We used GPR40/FFAR1-knockout (GPR40KO) mice and wild-type (WT) mice. A plantar incision was performed, and mechanical allodynia and thermal hyperalgesia were evaluated with a von Frey filament test and plantar test, respectively. Immunohistochemistry was used to localize GPR40/FFAR1, and the levels of free fatty acids in the hypothalamus were analyzed with liquid chromatography-tandem mass spectrometry. The repeated administration of GW1100, a GPR40/FFAR1 antagonist, exacerbated the incision-induced mechanical allodynia and significantly increased the levels of phosphorylated extracellular signal-regulated kinase in the spinal cord after low-threshold touch stimulation in the mice compared to vehicle-treated mice. The levels of long-chain free fatty acids, such as docosahexaenoic acid, oleic acid, and palmitate, which are GPR40/FFAR1 agonists, were significantly increased in the hypothalamus two days after the surgery compared to levels in the sham group. Furthermore, the incision-induced mechanical allodynia was exacerbated in the GPR40KO mice compared to the WT mice, while the response in the plantar test was not changed. These findings suggested that dysfunction of the GPR40/FFAR1 signaling pathway altered the endogenous pain control system and that this dysfunction might be associated with the development of chronic pain.
The “L-shaped Tunneling Technique”: A Modified Technique Facilitating a more Discreet Implantable Port Positioning

Purpose Venous port catheters, also known as “totally implantable venous access devices” (TIVADs), are now the standard of care in patients requiring long-term intermittent intravenous drug administration. We describe a modification of the implantation technique that we use in our department in order to improve the cosmetic result of a TIVAD. Methods After ultrasound-guided venous access in the internal jugular vein (IJV) or another appropriate vein has been obtained, we create a port pocket in the deltopectoral groove, in the upper-lateral chest wall, in a “far-lateral-oblique” orientation, respecting the individual patient's relaxed skin tension lines. Then we create a subcutaneous tunnel using a straight metal tunneler in two steps: first tunneling cranially and perpendicular to the port incision for a small distance, and then, after turning the tunneler at a right angle continuing in a straight line until we exit at the venous access site. Results This configuration not only prevents catheter kinking, to ensure uninhibited flow, but also allows us to place the port pocket in a more discreet position, in order to offer a better cosmetic result to our patients. Conclusions Adoption of a “far-lateral-oblique” port implantation site along with the “L-shaped tunneling technique” will offer doctors who are implanting TIVADs a useful alternative for a better cosmetic result.
Pluripotent Lineage Definition in Bovine Embryos by Oct4 Transcript Localization1

Abstract The POU-domain transcription factor Pou5f1 (Oct4) is restricted to pluripotent embryonic cells and the germ line of the mouse and is required for the maintenance of pluripotency of cells within the inner cell mass of the mouse blastocyst. Despite highly conserved genomic organization and regulatory regions between the mouse Oct4 gene and its bovine orthologue, bovine Oct4 protein is not restricted to the inner cell mass of blastocyst-stage embryos, suggesting that Oct4 may not be a key regulator of pluripotency in the bovine. We analyze the temporal and spatial distribution of Oct4 transcript in bovine oocytes and preimplantation-stage embryos, and in contrast to protein distribution, we find strong conservation between bovine and mouse. Oct4 transcript is present at low levels in the bovine oocyte. Similar to mouse, bovine Oct4 transcription begins one to two cell cycles after zygotic genome activation, followed by a sharp increase in transcription subsequent to compaction. Oct4 transcript is ubiquitously present in all cells of embryos at the morula stage; however, in Day 7 bovine blastocysts, Oct4 signal is not visible in the trophectoderm by in situ hybridization, indicating that transcriptional downregulation of Oct4 on differentiation is similar to that observed in mouse and other mammals. These results indicate that in contrast to protein distribution, regulation of Oct4 transcription is conserved between mammalian species.
THE NEEDLE IN THE 100 deg2 HAYSTACK: UNCOVERING AFTERGLOWS OF FERMI GRBs WITH THE PALOMAR TRANSIENT FACTORY

The Fermi Gamma-ray Space Telescope has greatly expanded the number and energy window of observations of gamma-ray bursts (GRBs). However, the coarse localizations of tens to a hundred square degrees provided by the Fermi GRB Monitor instrument have posed a formidable obstacle to locating the bursts’ host galaxies, measuring their redshifts, and tracking their panchromatic afterglows. We have built a target-of-opportunity mode for the intermediate Palomar Transient Factory in order to perform targeted searches for Fermi afterglows. Here, we present the results of one year of this program: 8 afterglow discoveries out of 35 searches. Two of the bursts with detected afterglows (GRBs 130702A and 140606B) were at low redshift (z = 0.145 and 0.384, respectively) and had spectroscopically confirmed broad-line Type Ic supernovae. We present our broadband follow-up including spectroscopy as well as X-ray, UV, optical, millimeter, and radio observations. We study possible selection effects in the context of the total Fermi and Swift GRB samples. We identify one new outlier on the Amati relation. We find that two bursts are consistent with a mildly relativistic shock breaking out from the progenitor star rather than the ultra-relativistic internal shock mechanism that powers standard cosmological bursts. Finally, in the context of the Zwicky Transient Facility, we discuss how we will continue to expand this effort to find optical counterparts of binary neutron star mergers that may soon be detected by Advanced LIGO and Virgo.
Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic options

Central nervous system (CNS) dissemination is a rare (4–5%) but usually fatal complication of aggressive lymphomas. Prophylaxis modalities to prevent CNS dissemination in aggressive lymphomas cannot be widely applied to every lymphoma patient since it is associated with increased risk of neurotoxicity. Therefore, identification of high‐risk patients as the best candidates to receive CNS prophylaxis constitutes a major endpoint in the management of these malignancies. Various risk factors and models for CNS recurrence have been described. Parameters reflecting the extent and proliferation of the disease, like elevated serum lactate dehydrogenase levels, involvement of multiple extranodal sites, advanced stage and high age‐adjusted International Prognostic Index (IPI) score, as well as the involvement of specific anatomic sites, like testes, orbit, paranasal sinuses, have been identified and confirmed as important to predict CNS dissemination. Management of this complication in aggressive lymphomas with conventional‐dose chemotherapy is associated with disappointing results, while some preliminary but encouraging experiences suggest a potential role of high‐dose chemotherapy and stem cell transplantation. The analysis of recent clinical studies could lead to advancement in the prognosis of aggressive lymphomas, but several questions regarding the optimum chemotherapy combination, the best conditioning regimen and the role of radiation therapy and intrathecal chemotherapy remain still unanswered. The purposes of the present review are to critically analyse current data on the risk of CNS dissemination in aggressive lymphomas, the clinical presentation of secondary CNS lymphomas and the efficacy of CNS prophylaxis as well as to discuss the available therapeutic options for this devastating event. Copyright © 2009 John Wiley & Sons, Ltd.
(20S*,24S*)-25-Hydroxy-20,24-epoxy-A-homo-4-oxadammaran-3-one (Chrysura) isolated from the leaves of Walsura chrysogyne

The title dammarane triterpenoid, C30H50O4, assigned the name chrysura, was isolated from an ethyl acetate extract of Walsura chrysogyne leaves (Meliaceae). It has 20S*,24S* relative stereochemistry and an oxepanone ring with two methyl groups at position 4. The two cyclohexane rings adopt chair conformations. The cyclopentane and tetrahydrofuran rings have envelope conformations; their mean planes make a dihedral angle of 13.1 (3)°, indicating that the rings are only slightly tilted with respect to each other. There is an intramolecular C—H⋯O hydrogen bond in the molecule, which forms S(6) and S(7) ring motifs. In the crystal, molecules are linked via O—H⋯O and C—H⋯O hydrogen bonds, forming chains propagating along [001] which stack along the b-axis direction.
Towards the 13-valent pneumococcal conjugate universal vaccination

Pneumococcal disease epidemiology has changed after introduction of pneumococcal conjugate vaccines. Seven-valent vaccine (PCV7) has been effective in reducing invasive pneumococcal disease (IPD). In Europe, PCV13 effectiveness was estimated at 78% (95% CI: −18–96%) for 2-priming doses. In Italy, PCV7 was introduced in 2006 in the childhood immunization schedule and replaced with PCV13 in 2010. In Apulia, vaccination coverage has reached 95.1% (birth-cohort 2010). We estimated PCV program effectiveness and its impact on S. pneumoniae diseases. PCV Effectiveness: We used the screening method. We calculated the Proportion of Population Vaccinated from immunization registries and detected cases through a laboratory-confirmed surveillance among hospitalized children ≤60 months. A confirmed IPD case was a child with PCR positive for S. pneumoniae. Differences among children were assessed with the Chi-square or the Fisher exact test (P value < 0.05). PCV Impact: We constructed time series using outcome-specific Poisson regression models: hospitalization rate in pre-PCV era and hospitalization risk ratios (RRs) with 95% CIs for both PCV7 and PCV7/PCV13 shifting era. We calculated hospitalization RR with 95% CIs comparing pre-PCV years with vaccination period. The PCV effectiveness was 84.3% (95% CI: 84.0–84.6%). In May 2010-January 2013, we enrolled 159 suspected IPD of whom 4 were confirmed. Two (fully vaccinated) were caused by serotype 9V, 1 (not vaccinated) by serotype 3, 1 (vaccinated with 2 PCV13 doses) by 15B/C. The most important reduction was for pneumococcal pneumonia (RR: 0.43, 95% CI: 0.21–0.90). The PCV program show promising results in terms of both PCV13 effectiveness and its impact in reducing IPD in children <5 years.
Unifying the two different classes of plant non-specific lipid-transfer proteins allergens classified in the WHO/IUIS allergen database through a motif with conserved sequence, structural and electrostatic features

The ubiquitously occuring non-specific lipid-transfer proteins (nsLTPs) in plants are implicated in key processes like biotic and abiotic stress, seed development and lipid transport. Additionally, they constitute a panallergen multigene family present in both food and pollen. Presently there are 49 nsLTP entries in the WHO/IUIS allergen database (http://allergen.org/). Analysis of full-length allergens identified only two major classes (nsLTP1,n=32 and nsLTP2,n=2), although nsLTPs are classified into many other groups. nsLTP1 and nsLTP2 are differentiated by their sequences, molecular weights, pattern of the conserved disulphide bonds and volume of the hydrophobic cavity. The conserved R44 is present in all full length nsLTP1 allergens (only Par j 2 from Parietaria judaica has K44), while D43 is present in all but Par j 1/2 from P. judaica (residue numbering based on PDBid:2ALGA). Although, the importance of these residues is well-established in nsLTP1, the corresponding residues in nsLTP2 remain unknown. A structural motif comprising of two cysteines with a disulphide bond (C3-C50), R44 and D43 identified a congruent motif (C3/C35/R47/D42) in a nsLTP2 protein from rice (PDBid:1L6HA), using the CLASP methodology. This also provides a quantitative method to assess the cross-reactivity potential of different proteins through congruence of an epitope and its neighbouring residues. Future work will involve obtaining the PDB structure of an nsLTP2 allergen and Par j 1/2 nsLTP1 sequences with a missing D43, determine whether nsLTP from other groups beside nsLTP1/2 are allergens, and determine nsLTP allergens from other plants commonly responsible for causing allergic reactions (chickpea, walnut, etc.) based on a genome wide identification of genes with conserved allergen features and their in vitro characterization.
Safety and Tolerability of the Rivastigmine Patch: Results of a 28-week Open-label Extension

The primary objective of the open-label extension was to evaluate the long-term safety and tolerability of a transdermal rivastigmine patch up to 1 year, as a novel approach to treatment in Alzheimer disease. This was a 28-week extension to a 24-week, double-blind, double-dummy, placebo-controlled, and active-controlled study evaluating rivastigmine patches [9.5 mg/24 h (10 cm2) and 17.4 mg/24 h (20 cm2)] and oral capsules (3 to 6 mg twice-daily). Patients entering the extension were switched directly to 9.5 mg/24 h rivastigmine patch and increased to 17.4 mg/24 h patch, irrespective of their double-blind study treatment. Primary measures included safety and tolerability assessments, including adverse events and serious adverse events. Of 1195 patients randomized to treatment, 870 (72.8%) completed the double-blind study and entered the open-label extension. During weeks 1 to 4 of the extension, 9.5 mg/24 h rivastigmine patch was well tolerated overall by patients formerly randomized to rivastigmine capsule or patch groups: ≤2.5% reported nausea and ≤1.9% reported vomiting. No unexpected safety issues arose, and skin tolerability was good; similar to the double-blind study. During the 28-week, open-label extension phase, the patch seemed to be well tolerated with a favorable safety profile.
Encouragement is Nothing Without Control: Factors Influencing the Development of Reaching and Face Preference

Four parent-guided training procedures aimed at facilitating independent reaching were compared in 36 threemonth-old infants recruited for this study and 36 infants taken from previously published reports. Training procedures systematically varied whether parental encouragement to act on external objects was provided, and whether self-produced experiences of moving an object were present. Reaching behavior was assessed before and after training, and face preference was measured after training by recording infants’ eye gaze in a visual-preference task. Results showed that simultaneous experiences of parental encouragement and selfproduced object motion encouraged successful reaching and face preference. Neither experience in isolation was effective, indicating that both external encouragement and self-produced action experiences are necessary to facilitate successful reaching. However, experiences with self-produced object motion increased infants’ face preference. This result provides evidence for a developmental link between self-produced motor experiences and the emergence of face preference in three-month-old infants.