Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver Transplantation with Grafts from Controlled Donors after Cardiac Death: A 20‐Year Follow‐up at a Single Center

The first liver transplantation (LTx) in Sweden was performed in 1984, but brain death as a legal death criterion was not accepted until 1988. Between November 1984 and May 1988, we performed 40 consecutive LTxs in 32 patients. Twenty‐four grafts were from donors after cardiac death (DCD) and 16 grafts from heart‐beating donors (HBD). Significantly, more hepatic artery thrombosis and biliary complications occurred in the DCD group (p < 0.01 and p < 0.05, respectively). Graft and patient survival did not differ between the groups. In the total group, there was a significant difference in graft survival between first‐time LTx grafts and grafts used for retransplantation. There was better graft survival in nonmalignant than malignant patients, although this did not reach statistical significance. Multivariate analysis revealed cold ischemia time and post‐LTx peak ALT to be independent predictive factors for graft survival in the DCD group. In the 11 livers surviving 20 years or more, follow‐up biopsies were performed 18–20 years post‐LTx (n = 10) and 6 years post‐LTx (n = 1). Signs of chronic rejection were seen in three cases, with no difference between DCD and HBD. Our analysis with a 20‐year follow‐up suggests that controlled DCD liver grafts might be a feasible option to increase the donor pool.
Off-pump coronary artery bypass grafting for patients with three-vessel disease.

BACKGROUND Off-pump coronary artery bypass grafting (CABG) has been performed since 1996 in our institute, and its application has recently been expanded to patients with three-vessel disease. A study was performed to clarify the benefit of off-pump CABG for patients with three-vessel disease. METHODS Between June 1, 1991 and September 30, 2001, a total of 1089 patients with three-vessel disease (832 men and 257 women; mean age, 64.0 +/- 9.1 years) underwent on-pump CABG. After 1997, a total of 310 patients with three-vessel disease (223 men and 87 women; mean age, 68.8 +/- 8.6 years) underwent off-pump CABG. Data of the historical cohort of on-pump CABG and the concurrent cohort of off-pump CABG were analyzed retrospectively. RESULTS The 2 groups were age and gender matched. Significant comorbidities were more often observed in the off-pump group than in the on-pump group. The mean number of bypass grafts in the off-pump versus on-pump CABG was 3.3 vs 3.7, P <. 0001. The mean intubation period, intensive care unit stay, and postoperative hospital stay were 7.9 vs 11.7 hours, 2.2 vs 3.0 days, and 14.5 vs 17.5 days, respectively (P <.0001). In-hospital mortality rate (0.6% vs 1.2%, respectively) and morbidity rates (10.3% vs 12.9%, respectively) were not significantly different. After surgery, calculated event-free rates at 2 years were 93.3% vs 91.9%, respectively; P = not significant. CONCLUSIONS In patients with multivessel disease, off-pump CABG provided early recovery, and its complication rates and early follow-up results were equivalent to on-pump CABG.
The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies.

OBJECTIVE Serum thyroglobulin (Tg) is the marker of differentiated thyroid carcinoma (DTC) after total thyroidectomy, but its value is limited by the interference of anti-Tg antibodies (TgAb). Detection of Tg in fine-needle aspiration biopsy (Tg-FNAB) washout fluid is used to identify neck DTC recurrences/metastases, but the interference of serum TgAb in this procedure is unknown. PATIENTS AND METHODS Seventy-three patients (41 after surgery for thyroid cancer and 32 with thyroid nodules) evaluated for suspicious cervical lymph nodes were retrospectively reviewed. Tg was assayed by immunoradiometric assay or chemiluminescent assay in ultrasound-guided FNAB used for cytology. Serum TgAb were detected by passive agglutination or chemiluminescent assay. On the basis of preliminary data obtained in lymphadenitis, Tg-FNAB more than 36 ng/ml and more than 1.7 ng/ml (in the presence or absence of thyroid gland, respectively) was considered as indicative of metastasis. RESULTS In 51 TgAb-negative patients, Tg-FNAB was positive in 15 (12 with malignant and three with nondiagnostic cytology), all with histologically confirmed DTC metastases. Of the remaining 36 patients with negative Tg-FNAB, 30 had nonsuspicious and six had suspicious cytology. Histology of the latter showed four undifferentiated thyroid cancer metastases and two lymphadenitis. In 22 TgAb-positive patients, Tg-FNAB was positive in 14 (12 with malignant and two with nondiagnostic cytology), all with histologically confirmed DTC metastases. CONCLUSIONS Clinical performance of Tg-FNAB appears to be not substantially affected by TgAb, and this procedure remains superior to cytology in the identification of DTC neck metastases. However, cytology should always be performed because, irrespective of TgAb, Tg is undetectable in FNAB from undifferentiated metastases.
Downregulation of GSTπ expression by tryptanthrin contributing to sensitization of doxorubicin-resistant MCF-7 cells through c-jun NH2-terminal kinase-mediated apoptosis

Overexpression of GSTπ and underexpression of Topo II expression are associated with multidrug resistance (MDR) phenotype through nontransporter pathway. Tryptanthrin, a quinazoline derivative, was reported to sensitize resistant cells to doxorubicin by downregulation of MDR1 expression. This study aims to extendedly investigate the effect of tryptanthrin on the role of nontransporter-based genes in determining the MDR response in doxorubicin-resistant MCF-7 cells (MCF-7/adr). Results show that tryptanthrin downregulates GSTπ expression and reduces glutathione S-transferase (GST) activity, but has no effect on Topo II expression. Less production of GSTπ decomposes the protein–protein interactions of GSTπ and c-jun NH2-terminal kinase (JNK). The resulting free-form JNK undergoes phosphorylation upon elevated intracellular doxorubicin accumulation and subsequently activates JNK-mediated apoptosis. In conclusion, in addition to transporter pathway, tryptanthrin reverses MDR partly by modulating GSTπ-related pathway, a nontransporter pathway, in MCF-7/adr cells. It indicates that tryptanthrin may act as a potential chemoadjuvant agent through multiple targets.
Pharmacokinetics and Pharmacodynamics of CHF5074 After Short-term Administration in Healthy Subjects

CHF5074 has been shown to inhibit brain &bgr;-amyloid deposition and attenuate memory deficits in different transgenic mice models of Alzheimer disease. We evaluated the safety, pharmacokinetics, and pharmacodynamics of 3 ascending dose regimens of CHF5074 (200, 400, and 600 mg/d for 14 d) in a double-blind, placebo-controlled, parallel group study involving 48 healthy subjects. Plasma, urine, and cerebrospinal fluid (CSF) samples were collected for measuring drug and main metabolite concentrations and potential biomarkers of pharmacodynamic activity (&bgr;-amyloid1-40, &bgr;-amyloid1-42, soluble CD40 ligand, and tumor necrosis factor-&agr;). All subjects completed the study, and no serious or severe adverse events were reported. The maximum tolerated dose was close to 600 mg/d with mild diarrhea being the most frequent adverse event at this dose. CHF5074 reached peak plasma levels 2 to 3 hours after drug administration and then was slowly eliminated (t1/2z=30 h) in the urine as glucoronide. Systemic exposure to the drug appeared to be dose-proportional with a 2-fold accumulation ratio at steady state. Metabolite plasma levels peaked at 4 to 5 hours and accounted for about 25% of the parent compound. Drug levels in the CSF were dose-proportional. The drug dose-dependently lowered the levels of the soluble CD40 ligand, a marker of microglia activation, in both plasma and CSF samples.
Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection

Alveolar bone loss is a result of an aggressive form of periodontal disease (PD) associated with Aggregatibacter actinomycetemcomitans (Aa) infection. PD is often observed with other systemic inflammatory conditions, including arthritis. Melanocortin peptides activate specific receptors to exert antiarthritic properties, avoiding excessing inflammation and modulating macrophage function. Recent work has indicated that melanocortin can control osteoclast development and function, butwhether such protection takes place in infection‐induced alveolar bone loss has not been investigated. The purpose of this study was to evaluate the role of melanocortin in Aainduced PD. Mice were orally infected with Aa and treated with the melanocortin analog DTrp8‐γMSH or vehicle daily for 30 d. Then, periodontal tissue was collected and analyzed. Aα‐infected mice treated with DTrp8‐γMSH presented decreased alveolar bone loss and a lower degree of neutrophil infiltration in the periodontium than vehicle‐treated animals; these actions were associated with reduced periodontal levels of TNF‐α, IFN‐γ, and IL‐17A. In vitro experiments with cells differentiated into osteoclasts showed that osteoclast formation and resorptive activity were attenuated after treatment with DTrp8‐γMSH. Thus, melanocortin agonism could represent an innovative way to tame over exuberant inflammation and, at the same time, preserve bone physiology, as seen after Aa infection. —Madeira, M. F. M. , Queiroz‐Junior, C. M. , Montero‐Melendez, T. , Werneck, S. M. C. , Corrêa, J. D. , Soriani, F.M. , Garlet, G. P., Souza, D.G. , Teixeira, M.M. , Silva, T.A. , Perretti, M.Melanocortin agonismas a viable strategy to control alveolar bone loss induced by oral infection. FASEB J. 30, 4033–4041 (2016). www.fasebj. org
Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation

Regulation between protein kinases is critical for the establishment of signaling pathways/networks to 'orchestrate' cellular processes. Besides posttranslational phosphorylation, alternative pre-mRNA splicing is another way to control kinase properties, but splicing regulation between two kinases and the effect of resulting variants on cells has barely been explored. Here we examined the effect of the protein kinase A (PKA) pathway on the alternative splicing and variant properties of the Ca++/calmodulin-dependent protein kinase kinase 2 (CaMKK2) gene in B35 neuroblastoma cells. Inclusion of the exon 16 of CaMKK2 was significantly reduced by H89, a PKA selective inhibitor. Consistently, overexpressed PKA strongly promoted the exon inclusion in a CaMKK2 sequence-dependent way in splicing reporter assays. In vitro, purified CaMKKβ1 variant proteins were found to be kinase-active. In cells, they were differentially phosphorylated by PKA. In RNA interference assays, CaMKKβ1 was found to be essential for forskolin-induced neurite growth. Interestingly, overexpression of the variant without exon 16 (-E16) promoted neurite elongation while the other one (+E16) promoted neurite branching; in contrast, reduction of the latter one enhanced neurite elongation. Moreover, the variants are differentially expressed and the exon 16-containing transcripts highly enriched in the brain, particularly the cerebellum and hippocampus. Thus, PKA regulates the alternative splicing of CaMKK2 to produce variants that differentially modulate neuronal differentiation. Taken together with the many distinct variants of kinases, alternative splicing regulation likely adds another layer of modulation between protein kinases in cellular signaling networks.
Impact of Chronic HIV/SIV Infection on T Follicular Helper Cell Subsets and Germinal Center Homeostasis

The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has renewed optimism for developing an effective vaccine against HIV-1. The generation of most bNAbs requires multiple rounds of B cell receptor affinity maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their production. However, less than 1% of HIV-infected patients develop bNAbs that arise late in the course of infection, indicating probable Tfh and B cell dysfunctions in this context. Since the last few years, many studies have characterized Tfh cells from lymph nodes and spleen of HIV-infected individuals and SIV-infected macaques. Various lymphoid Tfh cell subsets have been identified, including precursor Tfh (pTfh), germinal center Tfh (GC Tfh), and the regulatory counterpart of Tfh cells, the follicular regulatory T cells. The latter have been reported to play a crucial role in the control of T and B cell crosstalk and GC reactions. More recently, circulating Tfh-like cells (cTfh) have been identified. Meanwhile, advances in single-cell technologies have made possible to analyze the transcriptional profiles of low abundant cells, such as Tfh populations. Using transcriptional signatures, we review here the impact of chronic SIV/HIV infection on Tfh, GC Tfh, pTfh, and cTfh differentiation and helper T cell functions with regard to their capacity to induce efficient B cell maturation. We will explore some hypothesis to explain the increased proportion of Tfh cells reported in chronically infected individuals and the impact on HIV pathogenesis.
Specific changes in human brain after hypoglycemic injury.

BACKGROUND AND PURPOSE Very few reports are available on serial changes in the human brain after severe hypoglycemic injury. The aim of this study was to investigate sequential neuroradiological changes in brains of patients after hypoglycemic coma compared with those after cardiac arrest previously studied with the same methods. METHODS We repeatedly studied CT scans and MR images obtained at 1.5 T in four vegetative patients after profound hypoglycemia associated with diabetes mellitus. RESULTS In all patients, consecutive CT scans showed symmetrical, persistent low-density lesions with transient enhancement in the caudate and lenticular nuclei and transient enhancement in the cerebral cortex 7 to 14 days after onset. Serial MR images consistently revealed symmetrical lesions of persistent hyperintensity and hypointensity on T1- and T2-weighted images, respectively, in the caudate and lenticular nuclei, cerebral cortex, substantia nigra, and/or hippocampus from 8 days to 12 months after onset. CONCLUSIONS Repeated MR images revealed specific lesions in the bilateral basal ganglia, cerebral cortex, substantia nigra, and hippocampus, which suggests the particular vulnerability of these areas to hypoglycemia in the human brain. We speculate that the localized lesions represent tissue degeneration, including some combination of selective neuronal death, proliferation of astrocytic glial cells, paramagnetic substance deposition, and/or lipid accumulation. The absence of localized hemorrhages on MR images in hypoglycemic encephalopathy is in marked contrast to the presence of regional minor hemorrhages in postischemic-anoxic encephalopathy.
Asymmetric Driving Current Modification of CMOS LTPS-TFTs With ${\rm HfO}_{2}$ Gate Dielectric

In this paper, the asymmetric driving current Idrv modification of CMOS low-temperature poly-Si thin-film transistors (LTPS-TFTs) with HfO<sub>2</sub> gate dielectric is demonstrated by the interfacial layer (IL) engineering of HfO<sub>2</sub>/poly-Si interface. P-channel LTPS-TFT has much higher Idrv ~ 0.789 mA than the n-channel LTPS-TFT ~ 0.274 mA under the same overdrive gate voltage. This asymmetric I<sub>drv</sub> is due to the characteristics of field effect mobility μ<sub>FE</sub> that p-channel LTPS-TFT has much higher hole μ<sub>FE</sub> ~ 80.16 cm<sup>2</sup>/Vs than the electron μ<sub>FE</sub> ~ 38.26 cm<sup>2</sup>/V s of n-channel LTPS-TFT. The modification of HfO<sub>2</sub>/poly-Si interface by O<sub>2</sub> plasma can enhance the electron μFE ~ 34% and reduce the hole μ<sub>FE</sub> ~ 22.4%, resulting in balanced I<sub>drv</sub> of CMOS LTPS-TFTs that n-channel device shows I<sub>drv</sub> ~ 0.553 mA and p-channel device shows I<sub>drv</sub> ~ 0.590 mA. In addition, the phonon scattering would also be improved by the IL growth and recovered to initial condition after IL removal. Consequently, the IL engineering of CMOS LTPS-TFTs with HfO<sub>2</sub> gate dielectric would be a good candidate for the application of system-on-panel or 3-D integrated circuits.
Carisma y liderazgo carismático: una aproximación empírica desde las perspectivas de Bass y Friedman

SE PARTE DE LA BASE QUE EL LIDERAZGO CARISMATICO ES UN FENOMENO IMPORTANTE, QUE PUEDE Y DEBE SER ESTUDIADO EMPIRICAMENTE. EN LA LITERATURA SE LOCALIZAN DOS INSTRUMENTOS CAPACES DE MEDIRLO: EL A.C. T. (FRIEDMAN, 1980) QUE CONCIBE EL CARISMA COMO EXPRESIVIDAD NO VERBAL Y EL M.L. Q. (BASS, AVOLIO, 1990) QUE CONCIBE EL CARISMA COMO EL FACTOR MAS IMPORTANTE DEL LIDERAZGO TRANSFORMACIONAL. SE DEMUESTRA EMPIRICAMENTE EN DOS ORGANIZACIONES SANITARIAS ESPANOLAS (N=161) QUE EL CARISMA DEL LIDER, MEDIDO POR EL MLQ, ESTA FUERTEMENTE RELACIONADO CON LA SATISFACCION, EFICACIA Y ESFUERZO-EXTRA DE LOS SUBORDINADOS. ESTA RELACION SE MANTIENE CUANDO SE UTILIZAN INDICES OBJETIVOS DE EFICACIA. ASIMISMO, CUANDO SE PONEN EN RELACION LAS DOS ESCALAS QUE MIDEN EL CARISMA (A.C.T. Y M.L.Q.) Y UNA TERCERA RELACIONADA (S.M.S. DE SNYDER) SE DEMUESTRA QUE LOS LIDERES CARISMATICOS, EN CONTRA DE LO QUE MANTIENEN ALGUNAS TEORIAS CLASICAS DEL CARISMA, SON ALTAMENTE SENSIBLES A LAS DEMANDAS DE SU ENTORNO Y A LAS NECESIDADES DE SUS SEGUIDORES. SE SOSTIENE QUE, GRACIAS A ESTA SENSIBILIDAD SON CAPACES DE FORMULAR PROYECTOS O VISIONES ATRACTIVAS PARA SUS SEGUIDORES. ES EN ESTA VISION DONDE RADICA, Y NO EN UNAS SUPUESTAS CUALIDADES MAGICAS, EL MOTOR DEL LIDERAZGO CARISMATICO.
Natural variation underlies alterations in Nramp aluminum transporter (NRAT1) expression and function that play a key role in rice aluminum tolerance

Significance Acidic soils compose significant land areas in the tropics and subtropics. On acid soils, aluminum (Al) toxicity inhibits root growth, leading to reduced crop yields. Rice is the most Al-tolerant cereal crop. We examined the natural variation in rice Nramp aluminum transporter (OsNRAT1), which encodes a transporter mediating Al uptake from the root tip cell wall into the cell, where it is sequestered in the vacuole. We identified tolerant and sensitive NRAT1 alleles that exhibited lower NRAT1 expression and reduced Al uptake in the sensitive allele, resulting in a significant reduction in rice Al tolerance. These findings indicate that the NRAT1 transporter plays a major role in rice Al tolerance and open the door for using NRAT1 to improve Al tolerance in other cereal species. Aluminum (Al) toxicity is a major constraint for crop production on acid soils which compose ∼40% of arable land in the tropics and subtropics. Rice is the most Al-tolerant cereal crop and offers a good model for identifying Al tolerance genes and mechanisms. Here we investigated natural variation in the rice Nramp aluminum transporter (NRAT1) gene encoding a root plasma membrane Al uptake transporter previously hypothesized to underlie a unique Al tolerance mechanism. DNA sequence variation in the NRAT1 coding and regulatory regions was associated with changes in NRAT1 expression and NRAT1 Al transport properties. These sequence changes resulted in significant differences in Al tolerance that were found to be associated with changes in the Al content of root cell wall and cell sap in 24 representative rice lines from a rice association panel. Expression of the tolerant OsNRAT1 allele in yeast resulted in higher Al uptake than did the sensitive allele and conferred greater Al tolerance when expressed in transgenic Arabidopsis. These findings indicate that NRAT1 plays an important role in rice Al tolerance by reducing the level of toxic Al in the root cell wall and transporting Al into the root cell, where it is ultimately sequestered in the vacuole. Given its ability to enhance Al tolerance in rice and Arabidopsis, this work suggests that the NRAT1 gene or its orthologs may be useful tools for enhancing Al tolerance in a wide range of plant species.
Mitotic rate maturation in the Peyer's patches of fetal sheep and in the bursa of Fabricius of the chick embryo

The metaphase arrest technique was used to quantitate the mitotic rate in sheep Peyer's patches (PP) and in the chicken bursa of Fabricius. It was shown that the mitotic rate in these tissues was the same whether or not the animal had been exposed to extrinsic antigen. The mitotic rate was calculated from the rate of accumulation of metaphase cells in tissue sections taken up to 4 h after i.v. vincristine. The follicular B cells in PP of fetal sheep at 3–5 days before birth, and in the bursas of chick embryos 2–3 days before hatching, none of which had experienced extrinsic antigen, entered mitosis at a rate of 5.2%/h and 7.5%/h, respectively. A similar analysis was done on animals at approximately 6 weeks of age, at which stage the PP and bursa had received chronic exposure to antigen from the gut. The mitotic rates were not significantly different from those in fetuses, i.e., 5.4%/h for PP and 6.0%/h for the bursa. In the follicles of both young lambs and juvenile chickens, the mitotic rate was 2–3 times greater in the outer, or cortical zone, than in the inner, or medullary zone. In a similar study of the thymus, no significant differences were found between the mitotic rates in fetal sheep and young lambs. The mitotic rate for the thymus was 15–20‐fold less than for the PP. It is proposed that sheep PP, the chicken bursa and the thymus have in common the important characteristic of establishing a maximal rate of lymphocyte division prior to being exposed to antigen.
Using a medium-fill simulation to evaluate the microbial contamination rate for USP medium-risk-level compounding.

PURPOSE The estimated microbial contamination rate for complex, multiple-step, medium-risk-level compounding was studied. METHODS The results of evaluations of the aseptic technique of pharmacists and technicians in compounding complex USP medium-risk-level sterile preparations were compiled to estimate the microbial contamination rate. The testing took place in 2002 and 2003 at a single institution and involved reconstitution of sterile dry growth medium and a series of complicated transfers of the medium from vials and ampuls to intravenous bags. The bags were incubated at 25-35 degrees C for 14 days and observed for microbial growth. RESULTS Of 539 evaluations, 28 (5.2%) resulted in preparations that yielded microbial growth. Pharmacists' compounding resulted in a slightly lower contamination rate (4.4%) than that of technicians (6.2%). Inadvertent touch contamination may have been the principal source of the contamination. CONCLUSION . A two-year series of 539 evaluations of the aseptic technique of pharmacists and technicians conducted with sterile growth medium and designed to simulate the compounding of USP medium-risk-level sterile preparations yielded an overall contamination rate of 5.2%.