Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental changes in the number, size, and orientation of GFAP‐positive cells in the CA1 region of rat hippocampus

Changes in extracellular potassium concentration as measured with ion‐selective microelectrodes revealed abnormally large accumulations in the hippocampus during postnatal development. While rises in [K+]o during stimulation of the Schaffer collaterals were limited to about 12 mM in adult animals, identical stimulations elicited rises to levels as large as 18 mM in juveniles. Since astrocytes are believed to play an important role in K+ homeostasis, we studied the postnatal development of astrocytes in the CA1 region of rat hippocampus in four age groups using a polyclonal antibody against glial fibrillary acidic protein (GFAP). The main proliferation of GFAP‐positive cells (GFAPpc) occurred in all laminae between postnatal days 8 and 16. The number of GFAP‐positive astrocytes per unit area was reached in stratum lacunosum‐moleculare and stratum oriens at about 2 weeks and in stratum radiatum at about 3 weeks of age. During further development—at the age of 24 days—the orientation of individual astrocytes in stratum radiatum became polar with an orientation almost perpendicular to stratum pyramidale. This was revealed by an analysis based on determination of the quotients between the angular orientation of the processes of single individual GFAP‐positive cells. When the crossing points of all glial processes over vertical and horizontal grid lines were determined and respective quotients evaluated, the same development towards a perpendicular orientation of astrocytes was noted in stratum radiatum. The same approach revealed a transient orientation parallel to the fissure in stratum lacunosum‐moleculare around day 24. Camera lucida drawings of GFAPpc in stratum radiatum revealed that astrocytes became larger during the first three postnatal weeks, followed by a reduction of various parameters (e.g., cell extension, branching pattern) until adulthood. The observed developmental changes of astroglial cells may contribute to the known delayed maturation of potassium regulation in rat hippocampus.
Use of Buccal Mucosal Grafts in Hypospadia-Crippled Adult Patients

The buccal mucosa has begun to be used as a free graft in complex hypospadias repair gradually and successfully in recent years. However, there are limited experiences regarding use of the buccal mucosa in adult patients. In this study, the authors describe their experience using buccal mucosal grafts in hypospadias-crippled adult patients. Between March 1996 and February 2001, the buccal mucosa was used in 26 cases of complex hypospadias in which local penile skin was not present or it was insufficient for urethral repair. All patients were adults (age range, 17–24 y; average, 21 y). In these patients in whom penile skin was insufficient, urethral repair by buccal mucosa was planned, with the stipulation that at least 6 months had passed from the previous operation. The buccal mucosa has been applied to 23 patients alone and in combination with penile skin in three patients. After surgery, the patients were followed-up for 3 to 18 months (average, 12 mo). During the follow-up, fistula in the line of the proximal anastomosis, meatal stenosis, and the fistula together with meatal stenosis developed in nine (35%), four (15%), and two patients (7%), respectively. It is concluded that buccal mucosa is the free graft material that should be the first choice in complex hypospadias cases that are circumcised or undergo operation more than once and when the penile skin is not available.
Colorectal Cancer Screening: How Health Gains and Cost-Effectiveness Vary by Ethnic Group, the Impact on Health Inequalities, and the Optimal Age Range to Screen

Background: Screening programs consistently underserve indigenous populations despite a higher overall burden of cancer. In this study, we explore the likely health gains and cost-effectiveness of a national colorectal cancer screening program for the indigenous Māori population of New Zealand (NZ). Methods: A Markov model estimated: health benefits (quality-adjusted life-year; QALY), costs, and cost-effectiveness of biennial immunochemical fecal occult blood testing (FOBTi) of 50- to 74-year-olds from 2011. Input parameters came from literature reviews, the NZ Bowel Screening Programme Pilot, and NZ linked health datasets. Equity analyses substituted non-Māori values for Māori values of background (noncolorectal cancer) morbidity and mortality, colorectal cancer survival and incidence, screening coverage, and stage-specific survival. We measured the change in “quality-adjusted life expectancy” (QALE) as a result of the intervention. Results: Based upon a threshold of GDP per capita (NZ$45,000), colorectal cancer screening in NZ using FOBTi is cost-effective: NZ$2,930 (US$1,970) per QALY gained [95% uncertainty interval: cost saving to $6,850 (US$4,610)]. Modeled health gains per capita for Māori were less than for non-Māori: half for 50- to 54-year-olds (0.031 QALYs per person for Māori vs. 0.058 for non-Māori), and a fifth (0.003 c.f. 0.016) for 70- to 74-year-olds and ethnic inequalities in QALE increased with colorectal cancer screening. Conclusions: Colorectal cancer screening in NZ using FOBTi is likely to be cost-effective but risks increasing inequalities in health for Māori. Impact: To avoid or mitigate the generation of further health inequalities, attention should be given to underserved population groups when planning and implementing screening programs. Cancer Epidemiol Biomarkers Prev; 26(9); 1391–400. ©2017 AACR.
Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro.

BACKGROUND Antiestrogens inhibit the stimulative effects of estrogens on breast cancer growth, but the mechanism(s) by which they trigger tumor regression are not completely understood. Growth retardation and tumor regression can be achieved by enhanced cell death and/or arrested cell proliferation. PURPOSE Our aim was to investigate the effect of a new antiestrogen, toremifene, on human breast cancer cells grown either in culture or as tumors in nude mice. METHODS The growth and morphology of in vitro cultured cells of the human breast cancer cell line MCF-7 were monitored by time-lapse video. MCF-7 cells and ZR-75-1 human breast cancer cells were grown as tumors in nude mice and subsequently examined by electron microscopy. The integrity of DNA isolated from these cells was determined by standard gel electrophoretic techniques. Northern blot hybridization analysis was used to determine the steady-state levels of the mRNAs for testosterone-repressed prostatic message-2 (TRPM-2), tumor growth factor beta-1 (TGF beta 1), and pS2 (a small, cysteine-rich protein of unknown function). RESULTS Time-lapse video microscopy of the cell cultures indicated that treatment with 7.5 microM toremifene for 3 days caused approximately 60% of the cells to exhibit morphologic characteristics typical of cells undergoing programmed death, or apoptosis. The number of mitoses gradually decreased to zero over a 3- to 4-day period. Estrogen withdrawal for the same length of time resulted in an approximately equal number of apoptoses and mitoses. These changes were not associated with the pattern of DNA fragmentation, detectable as ladders in agarose gels, that is characteristic of the DNA of cells undergoing apoptosis. Elevated levels of TRPM-2 and TGF beta 1 mRNAs were observed in in vitro or in vivo grown tumor cells treated with 5-10 microM toremifene. Elevated levels of TRPM-2, but not TGF beta 1, mRNA were observed in the tumor cells after estrogen withdrawal. The steady-state level of pS2 mRNA in the tumor cells dropped in response to either toremifene treatment or estrogen withdrawal. CONCLUSION Toremifene causes growth inhibition of estrogen-sensitive breast cancer cells by inducing some cells to undergo apoptosis and by inhibiting other cells from entering mitosis. The higher than normal amounts of TRPM-2 and TGF beta 1 protein that would likely result from the elevated levels of TRPM-2 and TGF beta 1 mRNAs measured in these cells after toremifene treatment may have an important role in the growth inhibition process. IMPLICATION Apoptosis as an active, targeted process provides a potential new therapeutic approach for treating breast cancer.
Delayed Full‐Thickness Skin Grafts Revisited

BACKGROUND There are many options for the management of surgical defects after Mohs micrographic surgery (MMS). For patients with complex defects who are not candidates for immediate grafting or who lack appropriate donor skin for a flap or who do not desire to undergo a major flap procedure, delayed full-thickness skin grafting (FTSG) may be an option. OBJECTIVE To determine the role and usefulness of delayed FTSG in the management of Mohs surgical defects. METHODS The records of 70 patients, seen over a 5-year period, who had their Mohs surgical defects repaired with a FTSG or who were scheduled for a delayed FTSG, were reviewed, along with their accompanying photographs (when available). The outcome of immediate and delayed FTSG was compared in terms of (1) graft loss, (2) epidermal sloughing, (3) thickening and/or irregularity, (4) contour correction, (5) hypopigmentation/hyperpigmentation, (6) persistent erythema, and (7) need for surgical revision. RESULTS Twenty-seven patients underwent immediate FTSG, and 20 patients underwent delayed FTSG on an average 3.6 weeks after Mohs surgery. Twenty patients, originally scheduled for a delayed FTSG, were allowed to heal by second intention, with a very satisfactory cosmetic result in most instances. When patients undergoing immediate FTSG were compared with those undergoing delayed FTSG, there was essentially no difference in the two groups, as judged by the parameters cited previously here. CONCLUSION Delayed skin grafting is often a viable option for patients undergoing Mohs surgery who are not candidates for immediate FTSG or who lack appropriate donor skin for a flap or who do not desire a major flap repair. It also has the added advantage in that as these patients are monitored in preparation for delayed grafting, it quite often becomes obvious that a significant proportion (more than 50%) can be allowed to heal by second intention with a satisfactory cosmetic result.
Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses.

BACKGROUND The angiogenesis inhibitor, sorafenib, remains the only available therapy of hepatocellular carcinoma (HCC). Only recently patents of VEGF receptors-3 inhibitors are developed. Thus, a novel approach against HCC is essential for a better therapeutic outcome. OBJECTIVE The aims of this study were to examine the chemopreventive action of saffron's main biomolecule, crocin, against chemically-induced liver cancer in rats, and to explore the mechanisms by which crocin employs its anti-tumor effects. METHOD We investigated the anti-cancer effect of crocin on an experimental carcinogenesis model of liver cancer by studying the anti-oxidant, anti-inflammatory, anti-proliferation, pro-apoptotic activities of crocin in vivo. In addition, we provided a network analysis of differentially expressed genes in tissues of animals pre-treated with crocin in comparison to induced-HCC animals' tissues. To further support our results, in vitro analysis was carried out. We assessed the effects of crocin on HepG2 cells viability by treating them with various concentrations of crocin; in addition, effects of crocin on cell cycle distribution of HepG2 cells were investigated. RESULTS Findings reported herein demonstrated the anti-proliferative and pro-apoptotic properties of crocin when administrated in induced- HCC model. Crocin exhibited anti-inflammatory properties where NF-κB, among other inflammatory markers, was inhibited. In vitro analysis confirmed crocin's effect in HepG2 by arresting the cell cycle at S and G2/M phases, inducing apoptosis and down regulating inflammation. Network analysis identified NF-κB as a potential regulatory hub, and therefore, a candidate therapeutic drug target. CONCLUSION Taken together, our findings introduce crocin as a candidate chemopreventive agent against HCC.
Cytomegalovirus Infection in Steroid-refractory Ulcerative Colitis: A Case-Control Study

Cytomegalovirus (CMV) infection is reported to be a cause of steroid-refractory ulcerative colitis (UC), but the strength of this association has not been tested in a case control study. Controlled studies have also not been performed to determine the sensitivity of available immunohistochemical techniques to detect CMV in this setting. The pathology database at Stanford Hospital was searched for UC patients with a diagnosis of “severe colitis” between the years 1992 and 2002 and medical records were reviewed. Forty patients were identified with refractory UC, defined as poor response to high-dose systemic steroids for >2 weeks. Another group of 40 patients with severe, but nonrefractory, UC was case-matched for age and year of biopsy. A series of 40 patients who underwent colectomy for reasons other than inflammatory bowel disease with representative sections of “normal” colon were selected as noncolitis controls. CMV inclusions were detected on hematoxylin and eosin (H&E) in 2 of 40 patients with refractory UC, but not in other patients. Immunohistochemistry (IHC) detected CMV in 10 of 40 (25%) patients with refractory UC and 1 of 40 (2.5%) patients with nonrefractory UC (P = 0.007). The CMV-positive cases initially identified on IHC but not on H&E were re-reviewed for viral inclusions on H&E: 3 had rare, but typical, inclusions; 3 had atypical inclusions; and 3 had no inclusions. CMV was not detected by H&E or IHC in 40 noncolitis controls. Of 10 steroid-refractory UC patients with CMV detected, 7 were refractory to cyclosporin or 6-mercaptopurine/azathioprine (70%) and 6 had undergone proctocolectomy (60%) prior to detection of the CMV. Two patients with recognized CMV infection were treated with gancyclovir, improved, and were able to taper off steroids and avoid proctocolectomy. This study provides evidence that unrecognized and therefore untreated CMV infection is significantly associated with steroid-refractory UC. Moreover, IHC is more sensitive than H&E for detection of CMV and should be considered as part of the routine evaluation of steroid-refractory UC patients, before proceeding with other medical or surgical therapy that may be unnecessary once the CMV is treated.
DHPLC‐based mutation analysis of ENG and ALK‐1 genes in HHT Italian population

Hereditary haemorrhagic telangiectasia (HHT or Rendu‐Osler‐Weber syndrome) is an autosomal dominant disorder characterized by localized angiodysplasia due to mutations in endoglin, ALK‐1 gene, and a still unidentified locus. The lack of highly recurrent mutations, locus heterogeneity, and the presence of mutations in almost all coding exons of the two genes makes the screening for mutations time‐consuming and costly. In the present study, we developed a DHPLC‐based protocol for mutation detection in ALK1 and ENG genes through retrospective analysis of known sequence variants, 20 causative mutations and 11 polymorphisms, and a prospective analysis on 47 probands with unknown mutation. Overall DHPLC analysis identified the causative mutation in 61 out 66 DNA samples (92.4%). We found 31 different mutations in the ALK1 gene, of which 15 are novel, and 20, of which 12 are novel, in the ENG gene, thus providing for the first time the mutational spectrum in a cohort of Italian HHT patients. In addition, we characterized the splicing pattern of ALK1 gene in lymphoblastoid cells, both in normal controls and in two individuals carrying a mutation in the non‐invariant –3 position of the acceptor splice site upstream exon 6 (c.626‐3C>G). Functional essay demonstrated the existence, also in normal individuals, of a small proportion of ALK1 alternative splicing, due to exon 5 skipping, and the presence of further aberrant splicing isoforms in the individuals carrying the c.626‐3C>G mutation. © 2006 Wiley‐Liss, Inc.
Unplanned Pregnancies Among HIV-Infected Women in Care—United States

Objective:To examine the prevalence of unplanned pregnancies among HIV-infected women in care in the United States. Methods:We used the 2007–2008 cycles of the Medical Monitoring Project, which collected data on HIV-infected adults in care. Women were included if they had an HIV diagnosis before 45 years of age and responded to questions about pregnancies and pregnancy planning after HIV diagnosis. Logistic regression was used to calculate unadjusted and adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for correlates of unplanned pregnancies among women with ≥1 pregnancy at or after an HIV diagnosis. Results:Of 1492 women, 382 (25.6%) reported ≥1 pregnancy after HIV diagnosis (median diagnosis age = 25.0 years; interquartile range = 21.0–30.0); 58% were non-Hispanic black, 22% Hispanic, and 15% non-Hispanic white. Of those, 326 (85.3%) reported ≥1 unplanned pregnancy; 124 (32.5%) reported recent unprotected vaginal and/or anal sex with a male partner with either negative or unknown HIV status. Unplanned pregnancies were more likely among women who reported nadir CD4 cell counts <200 cells/&mgr;L (AOR = 2.3; 95% CI: 1.2 to 4.8) or did not report nadir CD4 cell counts (AOR = 4.3; 95% CI: 1.9 to 10.5) compared with women who reported nadir CD4 cell counts ≥200 cells/&mgr;L; and who received public assistance in the most recent year before Medical Monitoring Project interview (AOR = 2.1; 95% CI: 1.1 to 3.8) compared with women who did not receive assistance. Conclusions:Unplanned pregnancies were prevalent among our sample. To avoid unplanned pregnancies, HIV-infected women need access to effective family planning services and risk reduction discussions during routine care visits.
Regulation of Switching Frequency and Bias of the Bacterial Flagellar Motor by CheY and Fumarate

ABSTRACT The effect of CheY and fumarate on switching frequency and rotational bias of the bacterial flagellar motor was analyzed by computer-aided tracking of tethered Escherichia coli. Plots of cells overexpressing CheY in a gutted background showed a bell-shaped correlation curve of switching frequency and bias centering at about 50% clockwise rotation. Gutted cells (i.e., withcheA to cheZ deleted) with a low CheY level but a high cytoplasmic fumarate concentration displayed the same correlation of switching frequency and bias as cells overexpressing CheY at the wild-type fumarate level. Hence, a high fumarate level can phenotypically mimic CheY overexpression by simultaneously changing the switching frequency and the bias. A linear correlation of cytoplasmic fumarate concentration and clockwise rotation bias was found and predicts exclusively counterclockwise rotation without switching when fumarate is absent. This suggests that (i) fumarate is essential for clockwise rotation in vivo and (ii) any metabolically induced fluctuation of its cytoplasmic concentration will result in a transient change in bias and switching probability. A high fumarate level resulted in a dose-response curve linking bias and cytoplasmic CheY concentration that was offset but with a slope similar to that for a low fumarate level. It is concluded that fumarate and CheY act additively presumably at different reaction steps in the conformational transition of the switch complex from counterclockwise to clockwise motor rotation.
DESIGN AND CONSTRUCTION OF A WIND TUNNEL FOR ENVIRONMENTAL FLOW STUDIES

speed-open loop and driven by a 2 kW, 4 m 3 /s, axial flow fan. The main core of the designed wind tunnel is the long sectio n (3.5 m length) devoted to produce and simulate the atmospheric boundary la yer (ABL) for various environmental flow studies. The simulation of the A BL can be achieved for different earth surface conditions by inserting of well designed spires arrangement and arrays of roughness elements. The dprocedure and the construction steps for the main components of t he wind tunnel are summarized. The experimental results of the mean ax ial velocity profiles for different fan speeds are presented and discusse d for the preliminary characterization of the wind tunnel. The results sh ow that the present wind tunnel is capable to maintain long run steady flow characteristics and reproducible flow patterns. The use of designed tri angular spires and cube roughness elements is successful in simulating real ABL of thickness up to 600 m corresponding to urban area.
Full-scan mass spectral evidence for 3-epi-25-hydroxyvitamin D3 in serum of infants and adults

Abstract Background: Since the introduction of liquid chromatography-mass spectrometry (LC/MS) for assessing vitamin D status, it has been shown that the C-3 epimer can account for a significant proportion of circulating 25-hydroxyvitamin D3 (25OHD3) concentrations in infants. However, some question whether monitoring a single MS transition at a chromatographic retention time typical for 3-epi-25OHD3 sufficiently warrants conclusions about the identity of the substance generating the signal. Therefore, we aimed to substantiate the evidence for 3-epi-25OHD3 in infants by collision induced dissociation (CID)-MS/MS product ion scans. A second objective was mass spectrometric investigation of the presence and prevalence of the 3-epi metabolite in serum from adults. Methods: Serum samples from six infants and 32 adults were studied using an ultra performance LC/tandem MS (UPLC/MS/MS) method designed to separate the 3-epi-25OHD3 from 25OHD3. Samples were submitted to liquid/liquid extraction and Sephadex LH-20 fractionation, prior to column-switching UPLC with MS/MS recording of CID product ion spectra of the [M+H]+ precursor ion. The respective standards were analyzed under identical UPLC/MS/MS conditions for comparison. Results: In the chromatograms of all samples, two peaks eluted with retention characteristics and spectra closely matching those observed for the 25OHD3 and the 3-epi standards. The percentage of the 3-epi metabolite relative to 25OHD3 in infants ranged from 15% to 41%, and in adults from 2.5% to 17%. Conclusions: This preliminary finding suggests that the prevalence of 3-epi-25OHD3 in serum of infants is considerable, and that even in adults the concentrations of this form should not be neglected.
Hedging Labor Income Risk over the Life-Cycle

We show that the decision to participate in the stock market depends on the ability of equities to hedge the individual permanent earnings shocks, consistent with implications of life-cycle models. Those households who refrain from stock investing display positive correlation between their own permanent income innovations and market returns. These results owe to a two-step empirical strategy. First, a minimum distance estimation disentangles the aggregate from the idiosyncratic permanent of labor income risks. The second step reconstructs the individual life-cycle dynamics of persistent shocks through a Kalman filter applied to the estimated labor income process. We are thus able to obtain the full cross-sectional distribution of individual correlations between permanent shock and market returns.