Miracle-dz/UniFAR-FTUs huggingface dataset:
Concepts in the use of TRAIL/Apo2L: an emerging biotherapy for myeloma and other neoplasias

TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) is a member of the TNF superfamily of death ligands that selectively induces apoptosis in tumour cells of diverse origins. In this report, we have reviewed recent studies examining TRAIL/Apo2L-induced apoptosis in multiple myeloma (MM), a B-cell malignancy which, in spite of its initial sensitivity to steroids, cytotoxic and high-dose chemotherapy, remains incurable. Recently, we demonstrated that TRAIL/Apo2L induces apoptosis of steroid- and chemotherapy-sensitive and resistant MM cell lines. Moreover, TRAIL/Apo2L selectively induced apoptosis of patient MM tumour cells while sparing non-malignant bone marrow and peripheral blood mononuclear cells. In addition, TRAIL/Apo2L inhibited the growth of human plasmacytomas xenografted into mice. Importantly, TRAIL/Apo2L-induced apoptosis was unaffected by IL-6, a potent growth and survival factor for MM cells which, as we and others have previously shown, blocks various pro-apoptotic signals including Fas ligand, which like TRAIL/Apo2L is also a member of the TNF family of ligands. In view of the potential clinical application of TRAIL/Apo2L to the treatment of MM, we have attempted to discern intracellular mechanisms of action and resistance for TRAIL/Apo2L in MM, along with strategies to increase sensitivity and overcome resistance of MM cells to TRAIL/Apo2L. These studies demonstrated that doxorubicin, an agent which is commonly used to treat MM patients, upregulated the expression of the DR5 death-signalling TRAIL receptor and synergistically enhanced the pro-apoptotic effect of TRAIL on MM cells. Moreover, NF-κB inhibitors such as SN50 (a cell permeable inhibitor of NF-κB nuclear translocation) as well as the proteasome inhibitor PS-341, which is currently in Phase II clinical trials, also enhanced the pro-apoptotic activity of TRAIL/Apo2L in MM cells. Lastly, TRAIL/Apo2L-induced apoptosis in MM cells was dependent on caspase-8 activation and inhibited by the caspase regulatory proteins FLIP and cIAP2. These studies provide a framework for the use of TRAIL/Apo2L as a single agent or as part of combination therapy for the treatment of MM.
The Bethesda Terminology for Reporting Thyroid Cytopathology: From Theory to Practice in Europe

Objectives: A 2007 conference held at the National Cancer Institute, Bethesda, Md. , USA, proposed a new terminology for classifying the results of thyroid fine-needle aspiration (FNA) – The Bethesda System for Reporting Thyroid Cytology (TBSRTC). The need to standardize thyroid FNA terminology was emphasized during the 35th European Congress of Cytology in 2009. An interobserver review study to assess the new terminology for analyzing the results of thyroid FNA was organized by the scientific committee of the European Federation of Cytology Societies. Study Design: Four experts in thyroid FNA examined and classified 116 FNAs according to the 6 levels of TBSRTC which are: nondiagnostic (ND); benign; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), with those of Hürthle cell type reported as follicular neoplasm, Hürthle cell type/suspicious for a follicular neoplasm, Hürthle cell type (FNHCT/SFNHCT); suspicious (SUS), and malignant. Results: The total consensus was 62.1%; the cytopathologists disagreed on 44 cases, including 8 cases of AUS/FLUS and 18 of FN/SFN; 59% of the cases had no consensus. They agreed on 73 and 80% of the cases classified as benign and malignant, respectively, and on 58.3% of the SUS cases. The percentage of no consensus for each expert was between 32 and 39%. Conclusions: Disagreement regarding the use of TBSRTC terminology for classifying the results of thyroid FNA mainly occurred in the most-often criticized categories of AUS/FLUS and FN/SFN.
Allergic fungal sinusitis in the pediatric population.

OBJECTIVE To determine the optimal treatment in pediatric patients with allergic fungal sinusitis (AFS). DESIGN A retrospective review of 10 patients diagnosed as having AFS. SETTING Academic tertiary medical center. PATIENTS Pediatric patients who fulfilled 5 criteria necessary for diagnosis of AFS: (1) type 1 hypersensitivity; (2) nasal polyposis; (3) characteristic computed tomographic scan; (4) histological evidence of eosinophilic mucus without evidence of fungal invasion into sinus tissue; and (5) a positive fungal stain or culture of sinus contents. TREATMENT All patients were treated with functional endoscopic sinus surgery with removal of fungal debris. Adjuvant therapy included nasal irrigations, postoperative endoscopic cleanings, and systemic corticosteroids in 9 of 10 patients. MEAN OUTCOME MEASURE Clinical disease monitored endoscopically by means of an objective staging system. RESULTS Five patients were without disease (stage 0), 1 had allergic mucin and mucosal edema (stage I), 1 had allergic mucin and polypoid edema (stage II), and 3 had polyps and/or fungal debris (stage III). CONCLUSIONS The treatment and prognosis of pediatric AFS are similar to those of adult AFS. However, systemic corticosteroids should be weaned aggressively in children to minimize complications, particularly long-term growth retardation.
Spontaneous Perforation Of Bile Duct, Clinical Presentation, Laboratory Work Up, Treatment And Outcome.

BACKGROUND Spontaneous perforation of bile duct (SPBD) is a rare and often misdiagnosed entity. Though rare, it is the second most common surgical cause of jaundice in infants, after biliary atresia. This study was planned to determine the clinical presentation, study different diagnostic modalities, treatment and outcome of patients with spontaneous perforation of bile duct. METHODS This descriptive case series, comprising 22 patients with spontaneous perforation of bile duct over a period of 24 months. Clinical presentation, biochemical abnormalities, imaging details, treatment options and outcome were studied. RESULTS Total 22 patients (12 Males and 10 Females) between ages of 1.5-36 months were studied. Associated anatomical defects included choledochal cyst in 7 (31.8%) while acquired biliary atresia in 1 (4.5%). Elevated liver enzymes (ALT and AST) were present in 16 patients (72.7%) and 5 (22.7%) had bilirubin above 3 mg/dl. Coagulopathy was seen in 8 (36.6%) patients. Abdominal USG showed presence of ascites in all 22 (100%), hydrocele in 2 (9.0%), inguinal hernia in 1 (4.5%), choledochal cyst in 7 (31.8%) and atretic gall bladder suggestive of acquired biliary atresia in one (4.5%) patient. HIDA scan was diagnostic in all 17 (77.27%) in which it was performed. MRCP was done in 3 (13.6%) patients. Mortality frequency was 3/22 (13.6%); one died of post-surgical sepsis second one was cirrhotic at time of presentation and didn't make It. Two were lost to follow up one which died at home while we lost contact with fourth patient. CONCLUSIONS Spontaneous perforation of bile duct can present and should be suspected as an important cause of neonatal biliary ascites or peritonitis. Most patients can be managed with intravenous antibiotics, percutaneous drainage and ttube insertion while patients with choledochal cysts required cholecystectomy with roux en y choledochjejunostomy. Timely recognition and intervention is associated with favourable outcome.
Impact of repeated methamphetamine pretreatment on intravenous self-administration of the drug in males and estrogenized or non- estrogenized ovariectomized female rats.

OBJECTIVE The female animals were already recorded to respond differently to methamphetamine (MET) abuse than males. This gender dissimilarity may be caused by the influence of estral cycles and different susceptibility to behavioural sensitization. METHODS Influences of gender and pre-exposure to MET were studied in the rat model of MET intravenous self-administration (IVSA). The fixed ratio (FR) paradigm was employed in male rats (M) and estrogenized (F-ESTR) and non-estrogenized ovariectomized female rats (F-OVX) either pre-exposed or not-exposed to MET pretreatment. RESULTS In rats that were not pre-exposed to MET, F-ESTR self-administered more MET infusions than each of the other groups, but F-OVX self-administered less than each of the other groups; the same trend was apparent in the MET pretreated groups. MET pre-exposure decreased subsequent MET IVSA in all groups except F-OVX. CONCLUSION Thus, pre-exposure to MET and the loss of inherent estrogen in females notably decreased the intake of MET by rats, suggesting that abuse liability was reduced. Estrogen's effects on MET self-administration here correspond with accumulating evidence of stronger behavioural responses of females to drugs of abuse.
IL-25 Downregulates Th1/Th17 Immune Response in an IL-10–Dependent Manner in Inflammatory Bowel Disease

Background:Interleukin 25 (IL-25) is involved in the initiation of T helper cell (Th)2–mediated immunopathologies. In this study, we investigated the expression of IL-25 in inflammatory bowel disease (IBD) and its role in the induction of CD4+ T-cell differentiation. Methods:Expression of IL-25 in inflamed mucosa of patients with IBD was determined by quantitative real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. The correlation of IL-25 expression with endoscopic disease activities and C-reactive protein was evaluated. Peripheral blood and lamina propria CD4+ T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies in the presence of IL-25. Transcription factors and cytokines were determined with real-time polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. Results:IL-25 was significantly decreased in the sera and inflamed mucosa of patients with active IBD compared with controls. It was upregulated in the sera of patients with Crohn's disease after treatment with infliximab. The levels of IL-25 in inflamed mucosa and sera were inversely correlated with endoscopic disease activities and C-reactive protein, respectively, in IBD. IL-25 could markedly inhibit IBD CD4+ T cells to produce tumor necrosis factor, interferon &ggr;, and IL-17A but promote IL-10 secretion. It suppressed the differentiation of IBD CD4+ T cells into Th1 and Th17 cells but did not interfere with Th2 cell differentiation. Importantly, blockade of IL-10 secretion by IBD CD4+ T cells markedly attenuated the inhibitory role of IL-25 in modulating both Th1 and Th17 immune responses. Conclusions:IL-25 is markedly decreased in IBD and inhibits IBD CD4+ T-cell activation and differentiation into Th1/Th17 cells in an IL-10–dependent manner, suggesting that it may be a potential therapeutic agent for IBD.
Heterohemoantibodies in inbred strains of mice. II. Immune agglutinins and hemolysins for sheep and chicken red cells.

Summary 1.Titers of immune hemoantibodies in mice of 10 inbred strains revealed characteristic patterns for each strain, with considerable variations between strains. 2.The possible role of genetic, metabolic, and hormonal factors in relation to this difference in response of mice to immunization with hemoantigens was discussed. 3.Among 11 strains tested, all five low-tumor strains showed a high immune response, whereas of six high-tumor or high-leukemia strains, five exhibited a low immune response. A possible interpretation of these findings was presented.
Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis

Trisomy 13, trisomy 18, and triploidy belong to the chromosomal abnormalities which are compatible with life, but which are also associated with a high rate of spontaneous abortion, intrauterine death, and a short life span. This study was conducted to analyze natural outcome after prenatal diagnosis of these disorders. Between January 1, 1999 and December 31, 2009, we investigated all amniocenteses and chorionic villus biopsies carried out at our department. All cases with fetal diagnosis of triploidy, trisomy 13, and 18 were analyzed, with a focus on cases with natural outcome. Overall, 83 (78%) cases of pregnancy termination and 24 (22%) patients with natural outcome (NO) were identified. The NO group included 15 cases of trisomy 18, six cases of triploidy, and three cases of trisomy 13. No case of triploidy was born alive. The live birth rate was 13% for trisomy 18 and 33% for trisomy 13. The three live‐born infants with trisomy 13 and 18 died early after a maximum of 87 hr postpartum. Our data are consistent with the literature concerning outcome of triploidy, with none or only a few live births. Analyzes of trisomy 13 and 18 indicate a very short postnatal life span. Different study designs and diverse treatment strategies greatly affect the fetal and neonatal outcome of fetuses with triploidy, trisomy 13, and 18. More studies analyzing natural outcome after prenatal diagnosis of these chromosomal abnormalities are needed. Non‐termination of these pregnancies remains an option, and specialists advising parents need accurate data for counseling. © 2011 Wiley Periodicals, Inc.
Autophagy and CD4+ T lymphocyte destruction by HIV-1

The first step of HIV-1 infection is mediated by the binding of envelope glycoproteins (Env) to CD4 and two major coreceptors, CCR5 or CXCR4. The HIV-1 strains that use CCR5 are involved in primo-infection (i.e., the early stages following a new infection), whereas those HIV-1 strains that use CXCR4 play a major role in the demise of CD4+ T lymphocytes and a rapid progression toward AIDS. Notably, binding of X4 Env expressed on cells to CXCR4 triggers apoptosis of uninfected CD4+ T cells. We now have just demonstrated that, independently of HIV-1 replication, transfected or HIV-1-infected cells that express X4 Env induce autophagy and accumulation of Beclin 1 in uninfected CD4+ T lymphocytes via CXCR4. Moreover, autophagy is a prerequisite to Env-induced apoptosis in uninfected bystander T cells, and CD4+ T cells still undergo an Env-mediated cell death with autophagic features when apoptosis is inhibited. To the best of our knowledge, these findings represent the first example of autophagy triggered through binding of virus envelope proteins to a cellular receptor, without viral replication, leading to apoptosis. Here, we proposed hypotheses about the significance of Env-induced Beclin 1 accumulation in CD4+ T cell death and about the role of autophagy in HIV-1 infected cells depending on the coreceptor involved. Addendum to: Autophagy is Involved in T Cell Death After Binding of HIV-1 Envelope Proteins to CXCR4 L. Espert, M. Denizot, M. Grimaldi, V. Robert-Hebmann, B. Gay, M. Varbanov, P. Codogno and M. Biard-Piechaczyk J Clin Invest 2006; In press
Melamine residues in eggs of quails fed on diets containing different levels of melamine

1. An experiment was conducted to determine residual melamine concentrations in eggs of quail given diets containing different concentrations of melamine, and to estimate the time at which withdrawing melamine from the diet would result in undetectable concentrations in eggs. A total of 600 Japanese quails (Coturnix coturnix japonica) were randomly divided into 5 treatments, and given melamine at concentrations of 0, 2, 10, 50, and 100 mg/kg diet respectively for 30 d. From d 31 to 41, all quails were given a diet without melamine. Each diet was offered to 4 replicates (cages) of 30 quails each. On d 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, and 41, eggs were collected for the determination of melamine and cyanuric acid levels. 2. Throughout the 41 d experimental period, inclusion levels of melamine in the diets of quails had no significant effect on daily feed intake, egg production percentage, and feed efficiency. No detectable amount of cyanuric acid was found in all eggs. When the diets contained melamine at 2 mg/kg, the amounts of melamine in eggs were below the detection limit. During the entire 30 d exposure, the maximum melamine concentrations in eggs were 0·162, 0·998 and 1·784 mg/kg for the 10, 50 and 100 mg/kg treatment groups, respectively, which demonstrated a linear dose-response relationship. 3. Upon feeding a diet without melamine, the melamine concentration in eggs decreased rapidly. The time taken for the amounts of melamine to decline below the detection limit were 1, 5, and 5 d for quails fed on the diets containing melamine at 10, 50, and 100 mg/kg respectively. 4. Melamine is not metabolised into cyanuric acid in quails, and a positive relationship exists between the concentrations in feed and in eggs.
Chemoprevention of lung cancer by lycopene.

An investigation was conducted to assess the chemopreventive potential of lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and their products, administered during the post-initiation stage in a multiorgan carcinogenesis model. One hundred eighteen B6C3F1 mice of both sexes were subjected to combined treatment with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH) from day 11 after birth to week 9 (DMD treatment) (groups 1 and 2) or given their vehicles (group 3). Then group 1 received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32. Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or 50 ppm). The incidences and multiplicities of lung adenomas plus carcinomas combined in male mice in group 1 receiving LP 50 ppm were significantly decreased as compared to the DMD alone or DMD and LP 25 ppm group values (75.0 vs 18.8%, P < 0.02; 0.94+/-0.17 v.s 0.25+/-0.14, P < 0.001). While hepatocellular carcinomas were lacking in the DMD and LP groups, two cases were found in the DMD alone group (not statistically significant). The values for aberrant crypt foci (ACF) and tumors in the colon and kidney did not show any significant variation among the carcinogen-treated subgroups. The results of this study provide evidence that the tomato carotenoid, lycopene, may have potential as a chemopreventive agent against carcinogenesis in the male lung.
D ec 2 02 1 A Flaw in IIT ’ s Treatment of Neuronal Noise

Gulio Tononi’s Integrated Information Theory (IIT) is an audacious attempt to pin down the abstract, phenomenological experiences of consciousness into a rigorous,mathematical framework. We show that IIT’s stance in regards to neuronal noise is inconsistent with experimental data demonstrating neuronal noise in the brain plays a critical role in learning, visual recognition, and even categorical representation. IIT predicts that entropy due to noise will reduce information produced by a physical system, which is inconsistent with Engel et. al. and Grossman et. al.’s data demonstrating that decision-related noise is a necessary condition for learning and visual recognition task. IIT must therefore be reformulated to accommodate experimental evidence showing both the successes and failures of noise.
Leadership Training, Inter-ethnic Conflict Management, and the Youth: A Case Study of One Non-Governmental Organization (NGO) in Nairobi, Kenya

Leadership Training, Inter-ethnic Conflict Management, and the Youth: A Case St udy of One Non-Governmental Organization (NGO) in Nairobi, Kenya. (August 2012) Paul Mutinda Mbutu, B.A., Messiah College; M.A., Wheaton College Chair of Advisory Committee: Dr. J. Kevin Barge While many non-governmental organizations provide leadership training in interethnic conflict management to Kenyan youth, relatively little is known about what go es into such training. This dissertation is a case study illustrating how the trai ning structure operates. The purpose of this dissertation is to address the challenges associ ated with youth leadership training in inter-ethnic conflict management, how these chal l nges are managed, what differences the training makes, and how it is transferred back int o the real-life of the youth. To better understand these issues, a two-month qualitative study was conducted divided in two phases involving trainers, youth participants, program designers, and community leaders. Twenty two interviews and 2 focus groups were completed. Re sults demonstrated four communicative challenges involved in the design of youth leadership training were: (1) audience analysis, (2) material resources, (3) pa rtici nt challenges, and (4) diversity. Results showed that trainers addressed the communicative chal lenges by using the following management strategies: needs assessment, financ ial management,
Cancer risk among Danish women with cosmetic breast implants

The available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10–15 years after breast implantation. We extended follow‐up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow‐up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973–95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0–1.4), during a mean follow‐up period of 14.4 years (range = 0–30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5–1.0), and an increased risk of non‐melanoma skin cancer (SIR = 2.1; 95% CI = 1.5–2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non‐melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8–1.2). With respect to other site‐specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non‐melanoma skin cancer of 1.1 (95% CI = 0.8–1.6), 0.7 (95% CI = 0.4–1.3) and 1.5 (95% CI = 0.8–2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non‐melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants. © 2005 Wiley‐Liss, Inc.