Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered gene expression in phenotypically normal renal cells from carriers of tumor suppressor gene mutations

BACKGROUND: The inherently complex signaling networks of tumors result from genetic and epigenetic alterations that occur during cancer initiation and progression. METHODS: In an attempt to identify early molecular changes associated with dominantly inherited predisposition to “two-hit” renal tumors, the expression profiles of primary cultures of phenotypically normal renal epithelial cells from individuals bearing a germline mutation in either the von Hippel- Lindau (VHL) or the tuberous sclerosis complex (TSC) gene were compared to that of renal epithelial cells from control nonmutation carriers by microarray analysis. RESULTS: Reliability of the microarray data from pooled samples was confirmed by real-time RT-PCR. Principal Component Analysis revealed substantial differences in the gene expression profiles of the renal epithelial cells from VHL and TSC mutation carriers. In several instances, the microarray data confirm our present knowledge of the cellular pathways affected by biallelic VHL and TSC mutations. CONCLUSIONS: These findings demonstrate that heterozygosity for a mutant tumor suppressor gene may alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner. Detectable effects of “one-hit” represent early molecular changes in tumorigenesis that may serve as targets for chemopreventive intervention. Running Title: Gene Expression in Heterozygous TSC and VHL Renal Cells
Endoscopic Third Ventriculostomy Vs Cerebrospinal Fluid Shunt in the Treatment of Hydrocephalus in Children: A Propensity Score–Adjusted Analysis

BACKGROUNDEndoscopic third ventriculostomy (ETV) has preferentially been offered to patients with more favorable prognostic features compared with shunt. OBJECTIVETo use advanced statistical methods to adjust for treatment selection bias to determine whether ETV survival is superior to shunt survival once the bias of patient-related prognostic factors is removed. METHODSAn international cohort of children (≤ 19 years of age) with newly diagnosed hydrocephalus treated with ETV (n = 489) or shunt (n = 720) was analyzed. We used propensity score adjustment techniques to account for 2 important patient prognostic factors: age and cause of hydrocephalus. Cox regression survival analysis was performed to compare time-to-treatment failure in an unadjusted model and 3 propensity score—adjusted models, each of which would adjust for the imbalance in prognostic factors. RESULTSIn the unadjusted Cox model, the ETV failure rate was lower than the shunt failure rate from the immediate postoperative phase and became even more favorable with longer duration from surgery. Once patient prognostic factors were corrected for in the 3 adjusted models, however, the early failure rate for ETV was higher than that for shunt. It was only after about 3 months after surgery did the ETV failure rate become lower than the shunt failure rate. CONCLUSIONSThe relative risk of ETV failure is initially higher than that for shunt, but after about 3 months, the relative risk becomes progressively lower for ETV. Therefore, after the early high-risk period of ETV failure, a patient could experience a long-term treatment survival advantage compared with shunt. It might take several years, however, to realize this benefit.
REPETITIVE ELECTRICAL ACTIVITY OF THE MUSCLE MEMBRANE INDUCED IN CHLORIDE‐FREE MEDIUM

1. Superficial fibres of frog skeletal muscle were electrically stimulated in Ringer solution where the chloride content had been replaced by various weakly permeant anions. Changes of the membrane potential were recorded at three different time scales. The complex response was initiated by a volley of fast repetitive action potentials (10–20 ms cycle length) superimposed on the ascending phase of a transient depolarization to ‐ 35 mV. The transient depolarization was followed by a membrane potential oscillation (0.3–0.6 s cycle length). The parameters of the volley and membrane potential oscillation were not greatly affected by the substituent anion.
The Five-Step Lower Blepharoplasty: Blending the Eyelid-Cheek Junction

Background: Lower lid blepharoplasty has potential for significant long-lasting complications and marginal aesthetic outcomes if not performed correctly, or if one disregards the anatomical aspects of the orbicularis oculi muscle. This has detracted surgeons from performing the technical maneuvers necessary for optimal periorbital rejuvenation. A simplified, “five-step” clinical approach based on sound anatomical principles is presented. Methods: A review of 50 lower lid blepharoplasty patients (each bilateral) using the five-step technique was conducted to delineate the efficacy in improving lower eyelid aesthetics. Digital images from 50 consecutive primary lower blepharoplasty patients (100 lower lids: 37 women and 13 men) were measured using a computer program with standardized data points that were later converted to ratios. Results: Of the 100 lower eyelid five-step blepharoplasties analyzed, complication rates were low and data points measured demonstrated improvements in all aesthetic parameters. The width and position of the tear trough, position of the lower lid relative to the pupil, and the intercanthal angle were all improved. There were no cases of lower lid malposition. Conclusions: Aesthetic outcomes in lower lid blepharoplasty can be improved using a five-step technical sequence that addresses all of the anatomical findings. Lower lid blepharoplasty results are improved when (1) the supportive deep malar fat compartment is augmented; (2) lower lid orbicularis oculi muscle is preserved with minimal fat removal (if at all); (3) the main retaining structure (orbicularis retaining ligament) is selectively released; (4) lateral canthal support is established or strengthened (lateral retinacular suspension); and (5) minimal skin is removed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Screening for family members of patients with nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is well known for its peculiarly skewed distribution with highest incidence in Southern Chinese population. Familial aggregation is evident, hence screening for early detection is offered by oncology centers in Hong Kong to first‐degree relatives of patients with NPC. During the period 1994–2001, 929 family members were screened in our center. The screenees were advised to attend an annual examination that includes serological test against Epstein Barr Virus (EBV), physical examination to exclude cervical lymphadenopathy and cranial nerve palsy, and endoscopic examination of the nasopharyngeal region. Two different methods were used for the serology test: indirect immuno‐fluorescent (IF) test for IgA against viral capsid antigen; and starting in 1997 enzyme‐linked immunosorbent assay (ELIZA) against nuclear antigen and viral capsid antigen. Twelve cases of nasopharyngeal carcinoma were diagnosed, giving a detection rate of 5/1,155 (433/100,000) person‐year for male and 7/1,404 (499/100,000) person‐year for female participants observed. The corresponding average annual incidence in Hong Kong during this period was 24.1 and 9.6 per 100,000, respectively. Forty‐one percent of these detected cases had Stage I disease, whereas only 2% of patients referred to the department for primary treatment presented with such early disease. Six cases were detected at first visit, and all were EBV‐positive. Another 78 screenees with positive serology at first visit were followed up for 204 person years, and thus far NPC was detected in 3 after an interval of 6–32 months. Of the 845 initially EBV‐negative screenees followed up for 2,337 person‐years, NPC was detected in 3 after an interval of 12–45 months. One showed sero‐conversion at the time of diagnosis. We conclude that family members of known patients do show a substantially higher risk of developing NPC, and regular screening by current method improves the chance of early detection. © 2004 Wiley‐Liss, Inc.
Fitting the distributions of length of stay by parametric models.

OBJECTIVES The purpose of this study was to assess the adequacy of three widely used models--Lognormal, Weibull, and Gamma--for describing the distribution of length of stay. This is a fundamental step in the development of outliers resistant (robust) methods for the statistical analysis of this kind of data, where the main objective is to determine measures of average and total resource consumption of groups of patients. Current practice uses several types of trimming rules, many of which are based on the Lognormal model, although theoretical and experimental bases are still insufficient. METHODS The three models were adjusted using robust procedures based on M-estimators to approximately 5 million stays grouped by Diagnosis-Related Groups (DRGs). The resulting 3,279 samples were collected in five European countries during 3 years. RESULTS Most of the distributions observed could be fitted with one of these models. The descriptions provided by the Gamma and the Weibull models were similar, and the Gamma model could be omitted. The casemix description provided by the Log-normal-Weibull family was, for certain countries, significantly better than the one provided by the single Lognormal model. Often, for a given DRG and a given country, length of stay distributions could be described with the same model during several years. A given DRG, however, usually had to be described by means of different models for different countries. CONCLUSIONS Practical and conceptual consequences of the results are discussed. They can be extended to the analyses of other consumption variables used in health services. Statistical procedures for casemix description, including current rules of trimming, should be improved by means of more flexible families of models.
Effect of the alcohol extract of the seeds of Mucuna pruriens on free radicals and oxidative stress in albino rats

In vitro and in vivo studies were made with an alcohol extract of the seeds of Mucuna pruriens (Fabaceae) to investigate its antioxidant property. In vitro studies were carried out in rat liver homogenate to investigate the chemical interaction of various phytochemicals with different species of free radicals. The effect was also checked on iron‐induced lipid peroxidation, oxidation of GSH content, and its interaction with hydroxyl and superoxide radicals. There was no change on the rate of aerial oxidation of GSH content but it significantly inhibited FeSO4 induced lipid peroxidation. It also inhibited the specific chemical reactions induced by superoxides and hydroxyl radicals. The removal of these species was through direct chemical interaction. An in vivo study on albino rats for 30 days showed no toxic effect up to a dose of 600 mg/kg body weight, on oral administration. There was no change in the level of TBA‐reactive substances, reduced glutathione content and SOD activity in the liver. The activity of serum GOT, GPT and alkaline phosphatase was also unchanged. Thus it could be concluded that the alcohol extract of the seeds of M. pruriens has an antilipid peroxidation property, which is mediated through the removal of superoxides and hydroxyl radicals. Copyright © 2002 John Wiley & Sons, Ltd.
An Enemy Old and New: The Dönme, Anti-Semitism, and Conspiracy Theories in the Ottoman Empire and Turkish Republic

The main focal point in Ottoman and Turkish antisemitism is the figure of the Dönme—the descendants of Jews who converted to Islam along with their messiah Shabbatai Tzevi. The focus on the Dönme arises from the perception of the Salonikan-based Young Turks as a cabal of Dönme, or secret Jews. It was immediately in the wake of the 1908 constitutional revolution—which culminated in the dethronement of Abdülhamid II, and ultimately led to the construction of the secular Turkish republic—that antisemitic conspiracy theories centering on the Dönme were first voiced. These arguments were expanded after 1923 to claim that the man who abolished the caliphate and established the secular state, the Salonikan Atatürk, was a Dönme. Turkish antisemitism was fed by Nazism and Turkish anti-Zionism from the mid 1920s to 1945, and was more openly articulated after the creation of Israel, but it remained a retelling of the events of 1908.From 1908 to today, the Dönme character—a secret Jew hiding in the guise of the nation’s leader who surreptitiously aims to destroy Turkey on behalf of world Jewry—has been the stock figure in anti-government conspiracy theories promoted by Islamists dispossessed of their authority, extreme rightists, and secularists divested of their power. Antisemitic conspiracy theories gain traction among all elements of Turkish society based on the racist assumption that only a Turkish Muslim can have Turkey’s interests at heart, while a Jew—here the false convert, the secret Jew Dönme—can only serve foreign interests at odds with those of the Turks.
The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many biological and pharmacological activities including antioxidation and tumor cell cytotoxicity. We examined the type of cell death in human leukemic HL-60 cells after CAPE treatment in order to elucidate the relationship between CAPE-induced alterations of the redox state and apoptosis. CAPE treatment (6 μg/ml) resulted in marked growth inhibition up to 70.3±4.0% at day 2. This inhibition was partially blocked by pretreatment with N-acetyl-L-cycteine (NAC). Agarose gel electrophoresis showed evident DNA fragmentation after CAPE treatment. CAPE induced a significant decrease in mitochondrial transmembrane potential to about half of the untreated level after 6 h and a rapid depletion of intracellular glutathione (GSH) down to 41.7±6.0% after 1 h. Pretreatment of HL-60 cells with NAC reversed the GSH depletion and partially rescued cells from CAPE-induced apoptosis. With regard to intracellular reactive oxygen species, CAPE caused a fast and profound scavenging of H2O2 (19% of untreated cells after a 2-h treatment) but not of superoxide anion. These results suggest that apoptosis induced by CAPE is associated with mitochondrial dysfunction, GSH depletion and selective scavenging of H2O2 in human leukemic HL-60 cells.
Loss of viability and induction of apoptosis in human keratinocytes exposed to Staphylococcus aureus biofilms in vitro

Bacteria colonizing chronic wounds are believed to exist as polymicrobial, biofilm communities; however, there are few studies demonstrating the role of biofilms in chronic wound pathogenesis. This study establishes a novel method for studying the effect of biofilms on the cell types involved in wound healing. Cocultures of Staphylococcus aureus biofilms and human keratinocytes (HK) were created by initially growing S. aureus biofilms on tissue culture inserts then transferring the inserts to existing HK cultures. Biofilm‐conditioned medium (BCM) was prepared by culturing the insert‐supported biofilm in cell culture medium. As a control planktonic‐conditioned medium (PCM) was also prepared. Biofilm, BCM, and PCM were used in migration, cell viability, and apoptosis assays. Changes in HK morphology were followed by brightfield and confocal microscopy. After only 3 hours exposure to BCM, but not PCM, HK formed dendrite‐like extensions and displayed reduced viability. After 9 hours, there was an increase in apoptosis (p≤0.0004). At 24 hours, biofilm‐, BCM‐, and PCM‐exposed HK all exhibited reduced scratch closure (p≤0.0001). The results demonstrated that soluble products of both S. aureus planktonic cells and biofilms inhibit scratch closure. Furthermore, S. aureus biofilms significantly reduced HK viability and significantly increased HK apoptosis compared with planktonic S. aureus.
Dynamics of Acutely Irradiated Skin Epidermal Epithelium in Swine: Modeling Studies

AbstractA mathematical model, which describes the dynamics of acutely irradiated skin epidermal epithelium in swine, is developed. This model embodies the key mechanisms of regulation of skin epidermal epithelium and the principal stages of development of its cells (basal, prickle, and corneal). The model is implemented as a system of nonlinear ordinary differential equations, whose variables and parameters have clear biological meaning. The modeling results for the dose- and time-dependent changes in basal and prickle cell populations are in a good agreement with relevant experimental data. The correlation between the experimental data on the dynamics of moist reaction in acutely irradiated swine skin epidermal epithelium and the corresponding modeling results on the dynamics of corneal cells is revealed. Proceeding from this, the threshold level of corneal cells, which indicates the appearance of the moist reaction, is found. All this bears witness to the validity of employment of the developed model, after appropriate identification, in the investigation and prediction of radiation effects on skin epidermal epithelium in humans.
Interobserver agreement in mr enterography for diagnostic assessment in patients with Crohn's disease.

PURPOSE To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MATERIALS AND METHODS MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendall's W-test was used for the statistical comparison of concordance. RESULTS In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendall's W 0.527 – 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendall's W value of 0.402 – 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendall's W 0.497 – 0.581). CONCLUSION MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine.
Effects of Rivastigmine on Sustained Attention in Schizophrenia: An fMRI Study

Abstract: This study assessed the neural correlates of the effects of rivastigmine, a CNS-selective cholinesterase inhibitor, given as an add-on therapy to antipsychotics-treated patients with schizophrenia who displayed moderate cognitive impairments, using functional magnetic resonance imaging (fMRI) during a sustained attention task. The study used a placebo-controlled, randomized, double-blind longitudinal design. Twenty patients stable on antipsychotics, 11 assigned to receive rivastigmine and 9 to receive placebo, underwent fMRI and clinical assessments at baseline and after 12 weeks. The fMRI task used a periodic block design and involved 3 conditions: rest, detecting a nonzero number ("nonzero" condition), and detecting a specific number ("specific number" condition) among a series of 6-digit numbers. Online data (via button presses) were acquired on both occasions. Behavioral results showed a trend (P = 0.075) for the rivastigmine-treated patients to have more correct responses and the placebo group to have fewer correct responses at 12 weeks compared with baseline in the "nonzero" condition. There was also an increase in regional brain activity in the cerebellum in the rivastigmine group at 12 weeks in both conditions, which was only partially explained by change in behavioral measures; no change was observed in the placebo group. Our results showed that rivastigmine treatment increased cerebellar activity and influenced attentional processes.
Comparison of distributions of survivin among tissues from urinary bladders of dogs with cystitis, transitional cell carcinoma, or histologically normal urinary bladders.

OBJECTIVE To compare distributions of survivin among tissues from urinary bladders of dogs with cystitis, transitional cell carcinoma (TCC), or histologically normal urinary bladders. SAMPLE POPULATION 24 archived and 7 fresh-frozen specimens of urinary bladders from dogs with cystitis. PROCEDURES Immunohistochemical analysis of archived tissue specimens was performed to identify survivin protein in the nucleus and cytoplasm of cells by use of polyclonal rabbit anti-survivin antibody. Tissues that contained > or = 5% immunoreactive cells were considered positive for survivin protein. Reverse-transcription PCR analysis was performed on fresh-frozen tissues to identify survivin mRNA. Data on tissues from dogs with TCC or histologically normal urinary bladders that were obtained during another study were used for statistical comparisons. RESULTS Twelve of 24 (50%) cystitic tissues were positive for nuclear survivin, compared with 28 of 41 (68%) TCC tissues and 0 of 46 (0%) normal tissues. Two of 24 (8%) cystitic tissues were positive for cytoplasmic survivin, compared with 7 of 41 (17%) TCC tissues and 17 of 46 (37%) normal tissues. Proportions of specimens that contained nuclear or cytoplasmic survivin were significantly different between cystitic and normal tissues but not between cystitic and TCC tissues. Four of 7 cystitic tissues were positive for survivin mRNA, which was comparable with results for TCC and normal tissues. CONCLUSIONS AND CLINICAL RELEVANCE Nuclear survivin was detected in TCC and cystitic tissues but not in normal urinary bladder tissues. Additional studies are needed to determine whether nuclear survivin contributes to the development or progression of TCC.
Conserved structure and spatiotemporal function of the compact rhodopsin kinase (GRK1) enhancer/promoter.

PURPOSE To demonstrate that the crucial elements responsible for the spatial and temporal expression patterns of rhodopsin kinase (Rk) are contained within a narrow conserved segment immediately flanking the Rk transcription start sites. METHODS Sequences upstream of the mouse Rk gene were compared to the human sequence to identify areas of conservation. Transgenic mice carrying a segment of the conserved human DNA sequence linked upstream of the green fluorescent protein (GFP) gene were examined by fluorescence microscopy and RT-PCR to localize GFP expression in retina and pineal gland. Rk and GFP temporal expression patterns were further compared by immunostaining and real-time RT-PCR in transgenic eyes during development. RESULTS Comparison of the mouse and human 5' flanking sequence revealed only a small island of conserved sequence upstream of the respective Rk start sites. Uniform GFP expression was supported by a 0.2 kb fragment of the conserved human sequence in the transgenic mouse rods, cones, and pinealocytes. Developmental studies revealed an exponential rise in Rk and GFP transcripts in the first ten day postnatal period followed by a plateau later extending to adulthood. Rk and GFP proteins were first detected after postnatal day 10 and rose in parallel afterwards, overlapping in time with the maturation of photoreceptor outer segments and eye opening. CONCLUSIONS The conserved short enhancer/promoter immediately upstream of the Rk gene contains the key elements required for appropriate response to spatial and temporal cues during photoreceptor cell differentiation and fate determination. The above studies narrow the core sequences that govern gene expression in photoreceptors in vivo.