Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy activation by rapamycin eliminates mouse Mallory‐Denk bodies and blocks their proteasome inhibitor‐mediated formation

The proteasomal and lysosomal/autophagy pathways in the liver and other tissues are involved in several biological processes including the degradation of misfolded proteins. Exposure of hepatocyte cell lines to proteasome inhibitors (PIs) results in the formation of inclusions that resemble Mallory‐Denk bodies (MDBs). Keratins are essential for MDB formation and keratin 8 (K8)‐overexpressing transgenic mice are predisposed to MDB formation. We tested the hypothesis that PIs induce MDBs in vivo and that autophagy participates in MDB turnover. The effect of the PI bortezomib (which is used to treat some malignancies) on MDB formation was tested in K8‐overexpressing mice and in cultured cells. Inclusion formation was examined using immune and conventional electron microscopy (EM). Bortezomib induced MDB‐like inclusions composed of keratins, ubiquitin, and p62 in cultured cells. Short‐term exposure to bortezomib induced similar inclusions in K8‐overexpressing but not in nontransgenic mice, without causing liver injury. In bortezomib‐treated mice, autophagy was activated in hepatocytes as determined by EM and biochemical analysis. Further activation of autophagy by rapamycin (Rap) decreased the number of inclusions in bortezomib‐treated K8 transgenic mice significantly. Rap also led to resorption of spontaneously formed MDBs in aging K8‐overexpressing mice. Immune EM demonstrated K8‐positive and ubiquitin‐positive structures in autophagic vacuoles in the mouse liver. Conclusion: PIs alone are sufficient to induce MDBs in susceptible animals, while Rap‐mediated activation of autophagy prevents MDB formation and causes MDB resorption. These findings suggest that some patients treated with PIs may become predisposed to MDB formation. Autophagy provides a potential cellular mechanism for the resorption of cytoplasmic inclusions. (HEPATOLOGY 2008.)
16S rRNA-Based Analysis of Microbiota from the Cecum of Broiler Chickens

ABSTRACT The microbiota of the intestinal tract of chickens plays an important role in inhibiting the establishment of intestinal pathogens. Earlier culturing and microscopic examinations indicated that only a fraction of the bacteria in the cecum of chickens could be grown in the laboratory. Therefore, a survey of cecal bacteria was done by retrieval of 16S rRNA gene sequences from DNA isolated from the cecal content and the cecal mucosa. The ribosomal gene sequences were amplified with universal primers and cloned or subjected to temporal temperature gradient gel electrophoresis (TTGE). Partial 16S rRNA gene sequences were determined from the clones and from the major bands in TTGE gels. A total of 1,656 partial 16S rRNA gene sequences were obtained and compared to sequences in the GenBank. The comparison indicated that 243 different sequences were present in the samples. Overall, sequences representing 50 phylogenetic groups or subgroups of bacteria were found, but approximately 89% of the sequences represented just four phylogenetic groups (Clostridium leptum, Sporomusa sp., Clostridium coccoides, and enterics). Sequences of members of the Bacteroides group, the Bifidobacterium infantis subgroup, and of Pseudomonas sp. each accounted for less than 2% of the total. Sequences related to those from the Escherichia sp. subgroup and from Lactobacillus, Pseudomonas, and Bifidobacterium spp. were generally between 98 and 100% identical to sequences already deposited in the GenBank. Sequences most closely related to those of the other bacteria were generally 97% or less identical to those in the databases and therefore might be from currently unknown species. TTGE and random cloning indicated that certain phylogenetic subgroups were common to all birds analyzed, but sequence data from random cloning also provided evidence for qualitative and quantitative differences among the cecal microbiota of individual birds reared under very similar conditions.
[lymphatic Mapping and Sentinel Lymph Node Biopsy in patients with Breast Cancer ].

UNLABELLED Axillary lymphadenectomy is the standard of care in breast cancer patients. Lymphatic mapping has arisen as an alternative offering less morbidity. OBJECTIVE To determine the success rate of subareolar blue dye injection (SM) in sentinel node (SN) biopsy and its value in axillary staging. METHODS 62 stages I and II breast cancer patients without palpable axillary nodes received subareolar injection of blue dye; an intraoperative study of the SN was carried out. Axillary lymphadenectomy was carried out in all patients. Sensitivity, specificity, positive predictive value, and negative predictive value were measured. RESULTS In 58/62 patients (93.5%), SN was identified; 19/58(32%) patients had nodal metastases, 18 were identified in intraoperative study, and only one false negative; 12/18 patients showed metastasis in other axillary nodes (66%), in 6 (27%) the only metastasis site was SN. Sensitivity/specificity of the SN was 92.8 and 88.6%, respectively. Positive predictive value is 72.2% and negative predictive value is 97.5% CONCLUSION SAI of blue dye allows identification of SN in 93.5%; with high sensitivity. SN negative predictive value is 97.5% in this study.
Perceived communication between physicians and breast cancer patients as a predicting factor of patients' health‐related quality of life: a longitudinal analysis

Communication between cancer patients and healthcare providers is recognized as an important aspect of these patients' health‐related quality of life (HRQOL). Nevertheless, no study has examined whether perceived communication between physicians and breast cancer patients is a determining factor in their HRQOL along the disease's trajectory. This longitudinal study aimed to ascertain whether such communication influenced the HRQOL of such women at three points in time.
Iterative solvers for Tikhonov regularization of dense inverse problems

According to the special demands arising from the development of science and technology, in the last decades appeared a special class of problems that are inverse to the classical direct ones. Such an inverse problem is concerned with the opposite way, usually followed by a direct one: finding the cause of a given effect or finding the law of evolution given the cause and effect. Very frequently, such inverse problems are modelled by Fredholm first-kind integral equations that give rise after discretization to (very) ill-conditioned linear systems, in classical or least squares formulation. Then, an efficient numerical solution can be obtained by using the Tikhonov regularization technique. In this respect, in the present paper, we propose three Kovarik-like algorithms for numerical solution of the regularized problem. We prove convergence for all three methods and present numerical experiments on a mathematical model of an inverse problem concerned with the determination of charge distribution generating a given electric field.
Relationship between the methylation status of dietary flavonoids and their growth‐inhibitory and apoptosis‐inducing activities in human cancer cells

Flavonoids are polyphenolic compounds widely distributed in the plant kingdom. Compelling research indicates that flavonoids have important roles in cancer chemoprevention and chemotherapy possibly due to biological activities that include action through anti‐inflammation, free radical scavenging, modulation of survival/proliferation pathways, and inhibition of the ubiquitin–proteasome pathway. Plant polyphenols including the green tea polyphenol (‐)‐epigallocatechin gallate or (‐)‐EGCG, and the flavonoids apigenin, luteolin, quercetin, and chrysin have been shown to inhibit proteasome activity and induce apoptosis in human leukemia cells. However, biotransformation reactions to the reactive hydroxyl groups on polyphenols could reduce their biological activities. Although methylated polyphenols have been suggested to be metabolically more stable than unmethylated polyphenols, the practical use of methylated polyphenols as cancer preventative agents warrants further investigation. In the current study, methylated and unmethylated flavonoids were studied for their proteasome‐inhibitory and apoptosis‐inducing abilities in human leukemia HL60 cells. Methylated flavonoids displayed sustained bioavailability and inhibited cellular proliferation by arresting cells in the G1 phase. However, they did not act as proteasome inhibitors in either an in vitro system or an in silico model and only weakly induced apoptosis. In contrast, unmethylated flavonoids exhibited inhibition of the proteasomal activity in intact HL60 cells, accumulating proteasome target proteins and inducing caspase activation and poly(ADP‐ribose) polymerase cleavage. We conclude that methylated flavonoids lack potent cytotoxicity against human leukemia cells and most likely have limited ability as chemopreventive agents. J. Cell. Biochem. 105: 514–523, 2008. © 2008 Wiley‐Liss, Inc.
Extracorporeal Membrane Oxygenation for Newborn Respiratory Failure: Forty‐five Cases

Abstracts Respiratory failure is a common cause of death in newborn infants. The standard treatment for this condition (oxygen and airway pressure) can cause lung damage and is itself a major contributor to morbidity and death among the newborn. Extracorporeal membrane oxygenation involves the use of a modified heart-lung machine to support gas exchange for a period of days or weeks until the lung has recovered. In the past 8 years, the present authors have used the method in the treatment of 45 newborn infants with respiratory failure. This report describes their total experience and updates previous publications on the subject. The patients were selected and referred by neonatologists, who pronounced them unresponsive to maximum therapy. They were said to have less than a 10 per cent chance to survive before entering the study. In all cases, venoarterial cardiopulmonary bypass was established by cannulating the right atrium via the right jugular vein and the aortic arch via the right common carotid artery. The extracorporeal circuit included polyvinylchloride tubing, a membrane lung, a pump with a 10-ml venous reservoir bladder, and a heat exchange to maintain temperature (Fig. 1). The priming volume of the circuit was approximately 450 ml. During priming, care was taken to ever, the patients were returned to maximal ventilatory support without extracorporeal membrane oxygenation. Four such patients suffered cardiac arrest, brain damage, or intracranial hemorrhage in the process. Of 25 survivors, 20 are apparently normal, healthy children with normal growth and development. Two patients had mild spasticity of the lower extremities, which has since improved almost to the normal state. One child developed hydrocephalus in the newborn period and has a functioning ventriculoarterial shunt. One child has a large right encephalic cyst with severe neurological impairment at 2 years of age. Another child, treated for right-sided diaphragmatic hernia, regained sufficient pulmonary function to permit discontinuation of extracorporeal membrane oxygenation. This child was discharged briefly from the hospital but died of chronic respiratory failure at the age of 1 year and 6 months.
Genetic resistance to Trypanosoma congolense infections in mice

The mechanisms of genetic resistance or "trypanotolerance" to infection with Trypanosoma congolense were investigated in two strains of mice. One strain C57BL, is outstandingly resistant to most stabilates of T. congolense and can survive for over 80 days, whereas CFLP, in common with most other strains, generally succumbs in less than 20 days. Evaluation of several pathophysiological and immunological parameters showed that after infection both strains initially developed similar levels of parasitemia, anemia, biochemical derangement, and immunosuppression. The most outstanding difference was after day 8 postinfection, when the susceptible strain (CFLP) sustained high levels of parasitemia (10(9) trypanosomes per ml) until death 2 to 4 days later, whereas the resistant strain (C57BL) showed a marked decrease to less than 10(6) trypanosomes per ml by day 10 postinfection. Clear evidence that this was associated with the presence of trypanocidal antibody in the resistant mice was provided by the results of an infectivity neutralization test on serum collected from each strain at 10 days postinfection. Chronically infected C57BL mice showed declining waves of parasitemia and a slow restoration of most hematological and biochemical indexes to near normal levels by 80 days postinfection, although at this stage they remained immunosuppressed.
Simultaneous 99mtc/111in spect reconstruction using accelerated convolution-based forced detection monte carlo

Simultaneous multi-isotope Single Photon Emission Computed Tomography (SPECT) imaging has a number of applications in cardiac, brain, and cancer imaging. The major concern however, is the significant crosstalk contamination due to photon scatter between the different isotopes. The current study focuses on a method of crosstalk compensation between two isotopes in simultaneous dual isotope SPECT acquisition applied to cancer imaging using 99mTc and 111In. We have developed an iterative image reconstruction technique that simulates the photon down-scatter from one isotope into the acquisition window of a second isotope. Our approach uses an accelerated Monte Carlo (MC) technique for the forward projection step in an iterative reconstruction algorithm. The MC estimated scatter contamination of a radionuclide contained in a given projection view is then used to compensate for the photon contamination in the acquisition window of other nuclide. We use a modified ordered subset-expectation maximization (OS-EM) algorithm named simultaneous ordered subset-expectation maximization (Sim-OSEM), to perform this step. We have undertaken a number of simulation tests and phantom studies to verify this approach. The proposed reconstruction technique was also evaluated by reconstruction of experimentally acquired phantom data. Reconstruction using Sim-OSEM showed very promising results in terms of contrast recovery and uniformity of object background compared to alternative reconstruction methods implementing alternative scatter correction schemes (i.e., triple energy window or separately acquired projection data). In this study the evaluation is based on the quality of reconstructed images and activity estimated using Sim-OSEM. In order to quantitate the possible improvement in spatial resolution and signal to noise ratio (SNR) observed in this study, further simulation and experimental studies are required.
Evaluation of BCG vaccination among Puerto Rican children.

In 1949-51 a clinical trial of BCG vaccine was conducted among 191827 children in Puerto Rico 1-18 years of age. The trial was designed to simulate a mass vaccination campaign. Follow-up was continued until 1969. Among the 1976 tuberculosis cases estimated to have occurred without vaccination 29% were nonreactors to 10 TU of tuberculin and thus were eligible for vaccination. The average annual tuberculosis rate was 27.6/100000 among controls and 19.7/100000 among vaccinees a reduction of 28.7%. However the overall reduction in tuberculosis that would have resulted from a complete vaccination program was less than 9%. Vaccination did not reduce the severity of cases that occurred among nonreactors. The reduction in tuberculosis attributable to vaccination showed only minor variations by age race and urban versus rural residence; however BCG effectiveness was significantly greater among males than females. Screening with 100 TU of tuberculin would not have resulted in a significantly different estimate of the effectiveness of BCG. It is noted that high tuberculosis case rates and low risks of acquiring new infections can coexist in the same population. In such circumstances BCG vaccination can do little good and can actually do harm by interfering with the identification of infected persons. The Puerto Rican experience demonstrates the need to estimate as carefully as possible the actual risk of infection before a vaccination campaign is commenced.
Comparative Study of the Polyvinyl Siloxane Technique With Resin-Splinted Transfer Copings Used for Multiple Implant Abutment Impressions

Statements of Problem: The lack of passivity in implant dentistry may result in failures. Therefore, impression is the first procedure in the fabrication of a passive prosthesis. The aim of this study is to compare the polyvinyl siloxane technique with a resin-splinted transfer copings used for multiple implant abutment impression. Methods: A master cast was obtained from an edentate ridge. From the master cast, 30 casts were obtained using 3 different impression techniques. Control technique was made with polyvinyl siloxane. Resin-splinted transfer copings in condensation siloxane or irreversible hydrocolloid were used as test. The distances between analogs were obtained using a profile projector. Statistical analysis was carried out using 1-way analysis of variance. Results: No significant difference among the 3 impression techniques (P > 0.05) was observed. Conclusion: Resin-splinted transfer copings in condensation siloxane or irreversible hydrocolloid produced impressions as accurately as polyvinyl siloxane.
Reduction Mammaplasty: Criteria for Insurance Coverage

The guidelines by which insurers determine eligibility for coverage of reduction mammaplasty must rely largely on only subjective materials, yet they often apply strict criteria ranging from minimum resection weights to outright refusal to compensate. I have reviewed the data from 100 consecutive reduction mammaplasties performed by me over the last 2 years. Body weight, combined specimen weight, and height relationships were studied. Patientidentifiable questionnaires regarding the presence or absence of preoperative regional discomforts were sent to the same group. It was not possible to construct a useful formula that would verify either subject complaints of discomfort or the prospect for their relief based on body dimension or specimen weight. This study suggests that a graded, three-level minimum specimen weight standard for body weights less than 70 kg, 70 to 79 kg, and over 80 kg would be more equitable. (Plast. Reconstr. Surg. 95: 1029, 1995.)
3D periodic multiscale TiO2 architecture: a platform decorated with graphene quantum dots for enhanced photoelectrochemical water splitting

Micropatterned TiO2 nanorods (TiO2NRs) via three-dimensional (3D) geometry engineering in both microscale and nanoscale decorated with graphene quantum dots (GQDs) have been demonstrated successfully. First, micropillar (MP) and microcave (MC) arrays of anatase TiO2 films are obtained through the sol–gel based thermal nanoimprinting method. Then they are employed as seed layers in hydrothermal growth to fabricate the 3D micropillar/microcave arrays of rutile TiO2NRs (NR), which show much-improved photoelectrochemical water-splitting performance than the TiO2NRs grown on flat seed layer. The zero-dimensional GQDs are sequentially deposited onto the surfaces of the microscale patterned nanorods. Owing to the fast charge separation that resulted from the favorable band alignment of the GQDs and rutile TiO2, the MP-NR-GQDs electrode achieves a photocurrent density up to 2.92 mA cm−2 under simulated one-sun illumination. The incident-photon-to-current-conversion efficiency (IPCE) value up to 72% at 370 nm was achieved on the MP-NR-GQDs electrode, which outperforms the flat-NR counterpart by 69%. The IPCE results also imply that the improved photocurrent mainly benefits from the distinctly enhanced ultraviolet response. The work provides a cost-effective and flexible pathway to develop periodic 3D micropatterned photoelectrodes and is promising for the future deployment of high performance optoelectronic devices.
Inhibition of P-glycoprotein-mediated docetaxel efflux sensitizes ovarian cancer cells to concomitant docetaxel and SN-38 exposure

The first-line treatment of ovarian cancer is based on cytoreductive surgery and the use of anticancer drugs. The main disadvantage in the usage of anticancer drugs is the wide capacity of cancer cells to acquire a resistance to chemotherapeutic agents and therefore new treatment strategies have to be developed and tested. In this study, the responses of seven ovarian carcinoma cell lines to docetaxel and a camptothecin derivative, SN-38, were evaluated. We further studied the expression of P-glycoprotein (P-gp), the best described mechanism of drug resistance, in these cells and the effect of treatment with a specific P-gp inhibitor (PGP-4008). Simultaneous treatment with docetaxel and SN-38 (docetaxel+SN-38) had an antagonistic growth effect that was not dependent on the administration schedule. Both drugs alone or in combination induced G2M cell cycle arrest. Docetaxel was a more potent inducer of apoptosis than SN-38, but simultaneous treatment with docetaxel+SN-38 decreased the proportion of apoptotic cells to the same level observed after exposure to SN-38 alone. SN-38 increased P-gp expression in all cell lines. PGP-4008 enhanced docetaxel-mediated growth inhibition and apoptosis, but it did not have an effect when used simultaneously with SN-38. When cells were treated with docetaxel, SN-38, and PGP-4008 simultaneously, the growth was inhibited more efficiently and the proportion of apoptotic cells was higher than that without PGP-4008. Thus, treatment of ovarian cancer cells with docetaxel+SN-38 may have antagonistic effects. The simultaneous administration of a P-gp inhibitor may prevent docetaxel efflux, thereby sensitizing cells to docetaxel and other chemotherapeutic agents.
Regulatory T Cell Suppression and Anergy Are Differentially Regulated by Proinflammatory Cytokines Produced by TLR-Activated Dendritic Cells1

CD25+CD4+ regulatory T cells (Tregs) are required for the maintenance of peripheral tolerance to certain self Ags. In this study, the requirements for murine Treg-suppressive activity and proliferation were examined in the context of the maturation of myeloid dendritic cells (DCs). We find that the suppressive function of Tregs is critically dependent on immature DCs and is readily reversed by the maturation of DCs induced by GM-CSF, but does not require TLR activation of either DCs or Tregs. In contrast, reversal of Treg anergy is dependent on TLR activation of DCs, and involves the potentiation of Treg responsiveness to IL-2 by cooperative effects of IL-6 and IL-1, both of which are produced by TLR-activated, mature DCs. Thus, proinflammatory cytokines produced by TLR-activated, mature DCs are required for reversal of Treg anergy, but are not required to overcome Treg suppression.