Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of HA14‐1 on Apoptosis‐Regulating Proteins in HeLa Cells

Overexpression of Bcl‐2 has been recognized in various malignancies. Recently, HA14‐1, a Bcl‐2 antagonist, has been identified for its anti‐apoptotic effect. However, mode of action of HA14‐1 still remains to be elucidated. In this study, we examined HA14‐1 binding efficiency with receptor proteins through molecular docking. Cell viability using HeLa cells was evaluated through MTT assay after exposure to different concentration of HA14‐1. Moreover, after HA14‐1 exposure, expressions of tumor suppressor protein (p53), BH3‐only protein (Puma) and apoptosis‐associated proteins were analyzed by Western blotting. From the results, it was found that HA14‐1 occupied all three domains; BH1, BH2, and BH3 within the hydrophobic pocket of Bcl‐2. However, HA14‐1 occupied only BH1 and BH3 of Bcl‐xl, conversely, no such stable bond was observed for Bax and Bak. ARG107 and TYR101 were the amino acids involved in the binding of HA14‐1 to Bcl‐2 and Bcl‐xl, respectively. Additionally, decrease in Bcl‐2 and Bcl‐xl expression along with increase in p53 and Puma expression after exposure to HA14‐1 was observed. The results suggested p53 pathway to be the probable mechanism of action for the induction of apoptosis in HeLa cell by downregulating the effect of anti‐apoptotic proteins suggesting that HA14‐1 may provide therapeutic potential for the treatment of human cervical cancer.
Long-term Follow-up of a Randomized Trial Comparing the Beger and Frey Procedures for Patients Suffering From Chronic Pancreatitis

Objective:To report on the long-term follow-up of a randomized clinical trial comparing pancreatic head resection according to Beger and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy according to Frey for surgical treatment of chronic pancreatitis. Summary Background Data:Resection and drainage are the 2 basic surgical principles in surgical treatment of chronic pancreatitis. They are combined to various degrees by the classic duodenum preserving pancreatic head resection (Beger) and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy (Frey). These procedures have been evaluated in a randomized controlled trial by our group. Long-term follow up has not been reported so far. Methods:Seventy-four patients suffering from chronic pancreatitis were initially allocated to DPHR (n = 38) or LE (n = 36). This postoperative follow-up included the following parameters: mortality, quality of life (QL), pain (validated pain score), and exocrine and endocrine function. Results:Median follow-up was 104 months (72-144). Seven patients were not available for follow-up (Beger = 4; Frey = 3). There was no significant difference in late mortality (31% [8/26] versus 32% [8/25]). No significant differences were found regarding QL (global QL 66.7 [0–100] versus 58.35 [0–100]), pain score (11.25 [0–75] versus 11.25 [0–99.75]), exocrine (88% versus 78%) or endocrine insufficiency (56% versus 60%). Conclusions:After almost 9 years’ long-term follow-up, there was no difference regarding mortality, quality of life, pain, or exocrine or endocrine insufficiency within the 2 groups. The decision which procedure to choose should be based on the surgeon's experience.
Prevalence and Correlates of Hepatitis C among Injection Drug Users: The Significance of Duration of Use, Incarceration, and Race/Ethnicity

The study examined associations between hepatitis C (HCV) seropositivity and a lifetime history of jail or correctional facility incarceration among injection drug users. The sample consisted of 351 injection drug users recruited in inner-city neighborhoods of Baltimore. Multiple logistic regressions were fit to assess associations between HCV seropositivity and a lifetime history of incarceration for the total sample and stratified by race. Analyses demonstrated HCV nearly two times greater for whites than African Americans. In addition, HCV was 2.6 times greater in participants incarcerated in correctional facilities and HCV was 7.4 times greater in participants reporting more than 5 years of injection drug use compared to participants reporting less than 1 year of injection drug use. The study findings suggest that incorporating systematic HCV screening, prevention, and treatment programs within correctional systems represents a vital yet under-utilized strategy to reduce HCV transmission in society as a whole.
Demonstration of developing myelodysplasia/acute myeloid leukaemia in haematologically normal patients after high‐dose chemotherapy and autologous bone marrow transplantation using X‐chromosome inactivation patterns

Autologous bone marrow or peripheral blood stem cell transplantation may carry an increased risk of secondary myelodysplasia (MDS) and acute myeloid leukaemia (AML), which are already recognized as complications of conventional treatment for lymphoid malignancies. In order to ascertain whether it is possible to detect the evolution of such a clone at an early stage in its development we have studied X‐chromosome inactivation patterns (XCIPs) in three informative females who developed abnormal myelopoiesis after high‐dose chemotherapy and ABMT. In one patient transplanted for relapsed Hodgkin's disease a leukaemic clone comprising approximately 50% of the patient's myeloid cells was detectable by comparison of peripheral blood granulocyte and T‐cell XCIPs when the full blood count and morphology were normal. She presented with AML 7 months later. In two patients transplanted for AML, XCIP analysis was complicated by constitutively skewed Lyonization patterns, nevertheless a progressive alteration could be demonstrated by serial analyses. In one patient a difference was detectable 28 months before presentation with MDS. In the other patient, despite evident mild pancytopenia and alterations in her XCIPs over the past 4 years, she has developed no definitive myelodysplastic features and oligoclonality due to stem cell failure cannot be excluded. These studies show that XCIPs can be used to predict development of MDS/AML in some patients, but the technique is limited by technical variability and frequent constitutional skewing in the haemopoietic system.
Obesity in adults in Turkey: age and regional effects.

BACKGROUND In this study, the body mass index (BMI) of Turkish population is calculated using a sample of 4205 persons consisting of 2263 male and 1942 female individuals in 2007. The study contains data from all seven geographical regions (Aegean, Black Sea, Central Anatolia, Eastern Anatolia, Marmara, Mediterranean and Southeast Anatolia) of Turkey and from all age groups from 20 to 85 years. METHOD In this study, height and weight data were measured and used for calculating the BMI of Turkish population accounting for age and regional effects. RESULTS This study's analysis found that age, region and gender are significant determinants on obesity of Turkish population. Also, Turkish population has higher obesity prevalence than most of the European countries. Overall, it was found that 56% of Turkish Population is overweight while 41% is in the normal range. CONCLUSIONS This is the first study related to obesity in Turkey covering all seven regions and all age groups. Analyzing the differences of obesity prevalence between genders, geographical regions and age groups will be beneficial for better understanding the reasons behind obesity in Turkey.
Tobacco carcinogen metabolites and DNA adducts as biomarkers in Head and Neck cancer: Potential screening tools and prognostic indicators

Head and neck squamous cell carcinoma (HNSCC) is one of many cancers that are strongly associated with tobacco use. Whereas HNSCC is often seen in tobacco users, many tobacco users do not develop carcinoma; and the differences between smokers with and without HNSCC are poorly studied to date. Some smokers may be inherently more susceptible to developing carcinoma due to patterns of tobacco use, innate metabolism of carcinogens, or altered excretion. Identifying those smokers at greatest risk for HNSCC would have great benefit through targeted smoking cessation efforts and enhanced surveillance. One approach to better understand the extent of exposure to, and metabolism of, tobacco carcinogens is through the use of tobacco‐specific metabolites. Tobacco‐specific metabolites can identify patterns of dose, exposure, and metabolism, and perhaps ultimately characterize the important differences between smokers who develop HNSCC and smokers who do not. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Metabolism of the macrolide immunosuppressant, tacrolimus, by the pig gut mucosa in the Ussing chamber

1 The macrolide tacrolimus (FK506), used as an immunosuppressant, is a cytochrome P450 (CYP) 3A substrate in the liver. The metabolism of tacrolimus and the transport of its metabolites in the pig gut was studied in the Ussing chamber. Tacrolimus and its metabolites were quantified by h.p.l.c. /mass spectrometry. 2 In the Ussing chamber, demethyl, didemethyl, hydroxy and hydroxy‐demethyl tacrolimus were generated. Their formation was concentration‐ and time‐dependent. The metabolite pattern was not different from that after incubation of tacrolimus with human small intestinal microsomes. 3 The metabolite formation was highest in the duodenum and declined in the order duodenum > 4 Since tacrolimus metabolism was inhibited by the specific CYP3A inhibitors, troleandomycin and ketoconazole, we concluded that these enzymes are involved in intestinal metabolism of tacrolimus. 5 Tacrolimus metabolites re‐entered the mucosa chamber (>90%) and passed through the small intestinal preparation into the serosa chamber. 6 It is concluded that tacrolimus is metabolized in the intestine, that the metabolites are able to re‐enter the gut lumen and also enter into the portal vein and that small intestinal metabolism and transport is at least in part responsible for the low oral bioavailability of tacrolimus
Can the “Golden Hour of Shock” Safely Be Extended in Blunt Polytrauma Patients? Prospective Cohort Study at a Level I Hospital in Eastern Switzerland

Abstract Background: The objective was to test, in this trauma system, the North American hypothesis that exceeding the 60-minute limit for the entire prehospital time (“golden hour of shock”) increases mortality of blunt polytrauma patients. Methods: In a prospective, observational, cohort study conducted between 1990 and 1996, a severity characterization of trauma (ASCOT) score was used to compare the actual mortality with the predicted mortality in 107 blunt polytrauma patients (Group 1) with prehospital rescue periods ≤60 minutes (time from accident until arrival at the emergency department). The same comparison was performed for 147 blunt polytrauma patients (Group 2) with rescue periods >60 minutes. Inclusion criteria were blunt trauma of at least two body sites, an Injury Severity Score (ISS) of ≥8, and direct admission to the trauma centre. Multivariate regression analysis was performed to test for bias and confounding, and to identify factors that might influence mortality. Odd ratio (OR) and 95% confidence interval (CI) were calculated. Results: The mortality in Group 1 was 14%, and was not statisticvally significantly higher than the 10.2% observed for Group 2. 4.8 patients, or 47% more than predicted, died in Group 1 (p = 0.057). The corresponding figures in Group 2 were 4.2 patients or 22% fewer than predicted (p = 0.19). Multivariate logistic regression confirmed this trend with a significant mortality odds ratio of 8 (95% CI 1.7 to 38.5) for Group 1 compared to Group 2. Significantly more patients in Group 2 were treated by emergency physicians. Conclusions: It appears in this trauma system, in which emergency physicians often are deployed, that the ‘golden hour of shock’ can be extended safely in many blunt polytrauma patients, since this was associated with better survival figures than in those patients for whom the time was <1 hour.
Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response

Toll-like receptors recognising self-derived nucleic acids may participate in the pathogenesis of autoimmune diseases. Following the description of an enhanced population of toll-like receptor-9 (TLR-9) expressing auto-antibody producing B lymphocytes in active lupus, we explored the expression of TLR-9 in the renal tissue of patients with lupus. TLR-9 expression was studied in the kidneys of 12 lupus and 10 control samples from macroscopically unaffected areas of patients with renal adenocarcinoma by immunohistochemistry. A semiquantitative score was assigned separately for tubular, interstitial and glomerular expression. TLR-9 was expressed in the renal tubules and interstitial tissue in both patients with lupus and controls. Six of 12 patients with lupus with proliferative or membranous nephritis – as compared to none of the controls – exhibited both tubulointerstitial and glomerular TLR-9 expression. Biopsies with glomerular TLR-9 expression had a higher activity index (mean ± SD, 6.3 ± 3.5 in the presence of TLR-9 glomerular expression as compared to 1.3 ± 1.8 in its absence, P = 0.015, t-test). This study documents for the first time the up-regulation of TLR-9 within the glomerulus of patients with lupus nephritis. Activation of TLR-9 expressing glomerular cells by endogenous nucleic acids (nucleosomes) may amplify the inflammatory response.
Insulin and glucagon regulation of gluconeogenesis in preruminating and ruminating bovine.

Hepatocyte monolayers were established from young preruminating (7 to 14 d of age) or older ruminating (11 to 12 wk of age) calves and used to evaluate the effects of insulin and glucagon on incorporation of carbon from 2.5 mM [2-14C]propionate and 2.0 mM [U-14C]lactate into glucose and glycogen. Developmental state (young preruminating vs older ruminating) of the donor calf did not affect the rate of gluconeogenesis from propionate in the absence of hormones. Insulin decreased (P < .05) gluconeogenesis and increased (P < .05) glycogenesis from propionate and lactate in hepatocytes from preruminating calves but had no effect on hepatocytes from ruminating calves. Lactate was poorly metabolized to glucose and was not responsive to glucagon in hepatocytes from ruminating calves compared with hepatocytes from preruminating calves. Hepatocytes responded to glucagon by increasing (P < .05) gluconeogenesis from propionate. Maximal responsiveness to glucagon did not differ between ruminating and preruminating calves, but hepatocytes from preruminating calves responded at lower glucagon concentrations (P < .05). These data demonstrate a similar capacity of hepatocytes from preruminating and ruminating calves to metabolize propionate to glucose, but there was a seven- to eightfold decrease in gluconeogenesis from lactate in ruminating calves that was accompanied by a decreased response to acute changes in insulin and glucagon.
Mirror Therapy with Neuromuscular Electrical Stimulation for improving motor function of stroke survivors: A pilot randomized clinical study.

OBJECTIVE This study was to investigate the effects of Mirror Therapy (MT) combined with Neuromuscular Electrical Stimulation (NMES) on muscle strength and tone, motor function, balance, and gait ability in stroke survivors with hemiplegia. METHODS This study was a randomized controlled trial. Twenty-seven hemiplegic stroke survivors from a rehabilitation center participated in the study. The participants were randomly assigned to either an experimental or a control group. The experimental group (n = 14) underwent MT combined with NMES and conventional physical therapy, and the control group (n = 13) underwent conventional physical therapy alone. Muscle strength and tone, balance, and gait ability were examined at baseline and after 4 weeks of intervention. A hand-held dynamometer was used to assess muscle strength, the Modified Ashworth Scale (MAS) was used to assess muscle tone, the Berg Balance Scale (BBS) and Timed Up and Go test (TUG) were used to ascertain balance, and the 6-m Walk Test (6mWT) was used to examine gait ability. RESULTS After the intervention, compared to baseline values, there were significant improvements in muscle strength and MAS, BBS, TUG, and 6mWT values in the experimental group (P< 0.05). In addition, at post-intervention, there were significant differences between the two groups in muscle strength and BBS (P< 0.05). CONCLUSION MT combined with NMES may effectively improve muscle strength and balance in hemiplegic stroke survivors. However, further studies are necessary to demonstrate brain reorganization after MT combined with NMES.
Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma.

Five unrelated mouse tumours have been shown to carry activated transforming genes using the NIH/3T3 transfection assay. Three of these tumours, a T‐cell lymphoma, a fibrosarcoma and a macrophage tumour, were found to carry an activated c‐Ki‐ras gene. A c‐Ha‐ras gene was shown to be activated in a myeloid leukaemia and a recently identified member of the ‘ras’ gene family, N‐ras, was found to be activated in a lung carcinoma. The T‐cell lymphoma, L5178Y‐ES, is a more aggressively growing metastatic variant which arose spontaneously from the parental tumour, L5178Y‐E. Although DNA from both parental and variant tumours was shown to transfer a genetic marker to recipient cells equally well, only the metastatic variant carried an activated c‐Ki‐ras gene detectable by transfection. The altered growth behaviour of the L5178Y‐ES cells may therefore be the result of the spontaneous activation of the c‐Ki‐ras gene after the lymphoma cells had already become tumorigenic.
Mesobuthus gibbosus (Scorpiones: Buthidae) on the island of Rhodes — hybridization between Ulysses’ stowaways and native scorpions?

Allozyme data suggest that the Rhodes population of Mesobuthus gibbosus is a hybrid population of recent origin. Namely, it is a mixture between an autochthonous population and an artificially introduced population probably from the Greek mainland. All samples were mainly composed of F1 hybrid genotypes and genotypes either fixed for autochthonous or introduced alleles. Back‐cross hybrid genotypes were very rare. Mitochondrial DNA analysis, in contrast, revealed only one group of closely related haplotypes that are unique for the Rhodes populations, thus suggesting asymmetric introgression of the two marker classes.
Clinical implications of MR imaging findings in the white matter in very preterm infants: a 2-year follow-up study.

PURPOSE To explore the association between diffuse excessive high signal intensity (DEHSI), punctate white matter (WM) lesions, and ventricular dilatation around term-equivalent age (TEA) and at clinical follow-up at 2 years in very preterm infants and the effect on neurodevelopment. MATERIALS AND METHODS Ethical approval for this prospective study was given by the institutional review board, and informed parental consent was obtained. An unselected cohort of 110 preterm infants (gestational age, < 32 weeks) was imaged around or after TEA. Clinical follow-up was performed at a corrected age of 2 years and consisted of a neurologic examination and a mental and developmental assessment (Bayley Scales of Infant Development). Univariate analyses and logistic and linear regression were performed to examine the relationships between variables. RESULTS DEHSI was found in 58 of 65 (89%) infants imaged around TEA. DEHSI was never detected in infants imaged after postmenstrual age of 50 weeks and showed no association with neurodevelopmental outcome. Punctate WM lesions and ventricular dilatation were significantly associated with mental (P = .02 for punctate WM lesions) and psychomotor developmental delay (P < .001 and P = .03, respectively), motor delay (P = .002 and P = .02, respectively), and cerebral palsy (P = .01 and P = .03, respectively). CONCLUSION Because of its high incidence in preterm infants around TEA, its absence after a postmenstrual age of 50 weeks, and its association with normal neurologic outcome at a corrected age of 2 years, DEHSI should not be considered part of the spectrum of WM injury, but rather a prematurity-related developmental phenomenon.
Interrelationship of blood transfusion, non‐A, non‐B hepatitis and hepatocellular carcinoma: Analysis by detection of antibody to hepatitis C virus

To clarify the relationship between hepatitis C virus infection and the development of hepatocellular carcinoma as sequelae of non‐A, non‐B posttransfusion hepatitis, 231 patients with chronic non‐A, non‐B hepatitis (96 with chronic hepatitis, 81 with cirrhosis and 54 with hepatocellular carcinoma) were analyzed for antibody to hepatitis C virus and were compared with 125 patients with chronic hepatitis B (50 with chronic hepatitis, 46 with cirrhosis and 29 with hepatocellular carcinoma). Antibody to hepatitis C virus was detected in 89.6%, 86.4% and 94.4% of patients with non‐A, non‐B hepatitis‐related chronic hepatitis, cirrhosis and hepatocellular carcinoma, respectively, compared with 6%, 17.4% and 34.5% with similar diseases related to hepatitis B. A history of transfusion was documented in 52%, 33% and 42% of anti‐hepatitis C virus‐positive cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma. The mean intervals between the date of transfusion and the date of diagnosis of anti‐hepatitis C virus—positive chronic hepatitis, cirrhosis and hepatocellular carcinoma were 10, 21.2 and 29 yr, respectively. In 21 patients with transfusion‐associated hepatocellular carcinoma, anti‐hepatitis C virus was present in each serial sample available for testing, including samples obtained up to 14 yr before the diagnosis of hepatocellular carcinoma. These data suggest the slow, sequential progression from acute hepatitis C virus—related non‐A, non‐B hepatitis through chronic hepatitis and cirrhosis to hepatocellular carcinoma and support a causal association between hepatitis C virus and hepatocellular carcinoma. (HEPATOLOGY 1990; 12:671–675).
The structure and stability of common mental disorders: the NEMESIS study.

BACKGROUND We analyzed the underlying latent structure of 12-month DSM-III-R diagnoses of 9 common disorders for the general population in the Netherlands. In addition, we sought to establish (1) the stability of the latent structure underlying mental disorders across a 1-year period (structural stability) and (2) the stability of individual differences in mental disorders at the level of the latent dimensions (differential stability). METHODS Data were obtained from the first and second measurement of the Netherlands Mental Health Survey and Incidence Study (NEMESIS) (response rate at baseline: 69.7%, n = 7076; 1 year later, 79.4%, n = 5618). Nine common DSM-III-R diagnoses were assessed twice with the Composite International Diagnostic Interview with a time lapse of 1 year. Using structural equation modeling, the number of latent dimensions underlying these diagnoses was determined, and the structural and differential stability were assessed. RESULTS A 3-dimensional model was established as having the best fit: a first dimension underlying substance use disorders (alcohol dependence, drug dependence); a second dimension for mood disorders (major depression, dysthymia), including generalized anxiety disorder; and a third dimension underlying anxiety disorders (simple phobia, social phobia, agoraphobia, and panic disorder). The structural stability of this model during a 1-year period was substantial, and the differential stability of the 3 latent dimensions was considerable. CONCLUSIONS Our results confirm the 3-dimensional model for 12-month prevalence of mental disorders. Results underline the argument for focusing on core psychopathological processes rather than on their manifestation as distinguished disorders in future population studies on common mental disorders.