Miracle-dz/UniFAR-FTUs huggingface dataset:
Estrogen receptor-mediated processes in normal and cancer cells.

The role of estrogens in breast and other cancers has been extensively investigated for many years, and historically most of these studies have focused on the hormonal regulation of cell proliferation. The most recent work in this area has focused on the expression of genes likely to mediate proliferation (e.g., growth factors, proto-oncogenes, etc.) and their regulation by the classic nuclear estrogen receptor, ER-alpha. In this chapter, we present a synopsis of several new developments in this area of ER-regulated gene expression. These developments include the following: 1) the selective activation of ER domains by partial estrogen antagonists, such as tamoxifen and other ligands; 2) the effects of ER-alpha overexpression and gene knockout on the development of breast and uterine cancers in experimental animal models; 3) mechanisms by which steroid hormones regulate programmed cell death, cell cycle progression, cell-substratum interactions, and genomic instability in cancer cells; 4) identification of nuclear proteins that interact with the ER in the presence of agonists and antagonists, the effect of ligand binding on the receptor structure, and the interactions of liganded and nonliganded receptors with coactivators, corepressors, and other regulatory proteins; and 5) the biochemical properties, cellular distribution, and potential biologic roles for the newly discovered ER-beta. Although there is an increasing interest in understanding the role of estrogens as endogenous carcinogens, it remains clear that ER-mediated regulation of gene expression plays many significant roles in normal and cancer cells, and increased knowledge of the mechanisms involved will improve our overall understanding of hormonal carcinogenesis.
Intra-abdominal pressure and the morbidly obese patients: the effect of body mass index.

BACKGROUND Abdominal compartment syndrome and intra-abdominal hypertension cause morbidity and mortality. Body mass index (BMI) may affect intra-abdominal pressure (IAP). Knowledge of the baseline IAP in the obese and the effect of BMI are not clearly defined. METHODS IAPs were measured in 37 morbidly obese patients undergoing elective gastric bypass. Measurements were obtained via bladder pressure using a standard technique. IAP was measured after intubation (P1) and postoperatively after extubation (P2). Data collected included age, gender, BMI, previous surgeries, comorbidities, IAP, and laparoscopic versus open procedure. RESULTS Mean BMI was 47.7 kg/m (range, 37-71.8 kg/m), and mean age was 45 years (range, 32-64 years). P1 mean was 9.4 mm Hg +/- 0.6 mm Hg, and P2 mean was 10.0 mm Hg +/- 0.6 mm Hg. Laparoscopic versus open procedure was unrelated to postoperative IAP. Previous surgeries and comorbidities were unrelated to IAP. P1 increased as BMI increased. For each unit increase of BMI, IAP increased by 0.14 mm Hg +/- 0.07 mm Hg (p = 0.05). Higher BMI and age were independent predictors of increased P2, with IAP increased 0.23 mm Hg +/- 0.07 mm Hg for each unit BMI (p = 0.0015) and 0.20 mm Hg +/- 0.06 mm Hg for each year increase in age (p = 0.0014). CONCLUSIONS Baseline IAP in the obese is greater than normal weight population (0-6 mm Hg), but not in range of intra-abdominal hypertension (>12 mm Hg). Postoperative status is unrelated to IAP. Elevated BMI does impact IAP, but the incremental value is small. Markedly increased IAP should not be attributed solely to elevated BMI and should be recognized as a pathologic condition.
Methods for Quality Control of Low-resolution MALDI-ToF Spectra

Protein profiling of human blood serum or plasma using MALDI-ToF mass spectrometry may be used for identification of candidates for disease biomarkers. Due to many biological and technical difficulties emerging during preparation of the sample and spectra measurement quality control step is becoming important. In this study we compared different methods for finding low quality spectra based on the Pearson correlation coefficient and proposed two novel solutions. First one utilizes information about area under the measured spectrum and other incorporates modeling of signal-to-noise ratio of spectra intensity by mixture of Gaussians. Obtained results show that removing of outlying samples increases the similarity of spectra obtained within the same experimental conditions. What is more important it increases reproducibility of peak detection by decreasing the coefficient of variation of peaks intensities within a group and increasing its prevalence. This work shows that appropriate identification and removing of low quality spectra is a necessary step in analysis of mass spectrometry data and proposed tools are appropriate for quality control of MALDI-ToF data.
Septic Arthritis After Arthroscopic Anterior Cruciate Ligament Reconstruction

We performed a retrospective study of knee joint in fections after arthroscopic anterior cruciate ligament reconstruction at our institution. Two thousand five hundred anterior cruciate ligament reconstructions were performed between 1988 and 1993. Seven (0.3%) patients experienced postoperative deep infec tions of the knee. All anterior cruciate ligament recon structions were performed using arthroscopically as sisted techniques. Six (86%) of these patients had concomitant open procedures performed, including meniscal repair, posterolateral corner reconstruction, and medial collateral ligament reconstruction. Four pa tients had acute (<2 weeks), two patients had sub- acute (2 weeks to 2 months), and one patient had late (>2 months) infections. All patients had positive cul tures from knee joint aspirates with the organisms Staphylococcus aureus, Staphylococcus epidermidis, Peptostreptococcus, or a combination thereof. All pa tients underwent immediate arthroscopic irrigation and debridement. All infections were intraarticular; six pa tients also had extraarticular sites of infection. Four patients underwent repeat irrigation and debridement at approximately 1 week. The anterior cruciate liga ment graft was removed from four patients. All patients were treated with intravenous antibiotics for 4 to 6 weeks, protected weightbearing, and physical therapy. At a mean followup of 29 months, mean knee exten sion was 0°, and mean knee flexion was 122° (range, 70° to 135°). Six (86%) patients had minimal to no pain in their operative knee, and they were satisfied with their functional results.
Risk Factors for Recovery of Ampicillin-Sulbactam-Resistant Escherichia coli in Hospitalized Patients

ABSTRACT Ampicillin-sulbactam resistance in Escherichia coli is an emerging problem. This study determined risk factors for the recovery of ampicillin-sulbactam-resistant E. coli in hospitalized patients. A case-control design was used to compare two groups of case patients with control patients. The first group of case patients consisted of patients from whom nosocomially acquired ampicillin-sulbactam-resistant E. coli strains were isolated, and the second group of case patients consisted of patients from whom ampicillin-sulbactam-susceptible E. coli strains were isolated. Control patients were a random selection among 5% of all patients admitted during the same time period. Risk factors analyzed included antimicrobial drug exposure, comorbid conditions, and demographics. Univariate and multivariate analyses were performed. Ampicillin-sulbactam-resistant E. coli strains were isolated from 175 patients, and ampicillin-sulbactam-susceptibleE. coli strains were isolated from 577 patients. Nine hundred thirty-four control patients were selected. Exposure to penicillin antibiotics as a class and to ampicillin and ampicillin-sulbactam individually were the only significant, independent risk factors associated with the isolation of ampicillin-sulbactam-resistant E. coli (odds ratio [OR] = 2.32 [P < 0.001], OR = 3.04 [P = 0.02], and OR = 1.72 [P= 0.04], respectively), but they were not associated with the isolation of ampicillin-sulbactam-susceptible E. coli. Interestingly, exposure to piperacillin-tazobactam tended to protect against the isolation of E. coli strains resistant to ampicillin-sulbactam, but this did not reach statistical significance (OR = 0.13; P = 0.11).
Pedicle Screw Placement in the Thoracic Spine: A Comparison of Image-Guided and Manual Techniques in Cadavers

Study Design. A cadaveric study comparing image guidance technology to fluoroscopic guidance as a means of pedicle screw placement in the thoracic spine, using a unique starting point for screw placement. Objective. To assess accuracy of thoracic pedicle screw placement using image guidance versus fluoroscopic guidance for screw insertion. Summary of Background Data. While use of pedicle screws in the thoracic spine has been increasing, its adoption has been slower than for the lumbar spine, reflecting concern regarding possible vascular or spinal cord injury due to screw malplacement. Given these risks, efforts to improve the accuracy of thoracic pedicle screw placement remain appropriate. Stereotactic guidance has been applied in other aspects of spinal surgery to improve the accuracy of instrumentation placement. Methods. Pedicle screws were placed in the thoracic spines of eight cadavers, using either a stereotactic guidance or a manual, fluoroscopically guided technique. A slightly more superior and lateral starting point from prior descriptions was used. Each cadaver was instrumented with pedicle screws in the upper thoracic (T1–T2), middle thoracic (T4–T7), and lower thoracic (T9–T10) regions. In the upper and middle thoracic regions, screws with a 4.0-mm shank diameter were used while in the lower thoracic region a shank diameter of 4.5 mm was used. Postinstrumentation CT scans, followed by anatomic dissections, were used to evaluate screw exit rates and orientation relative to the pedicle axis. Exit rates for the two techniques and the effect of vertebral level on exit rate were compared using a &khgr;2 analysis. The effect of pedicle diameter was tested using a Pearson correlation coefficient. Results. No significant differences in the overall exit rates or orientation were found between the two techniques. There were significant differences in exit rates between the middle (47%), compared with the upper (9%) and lower (16%) thoracic regions, respectively (P < 0.001). A significant correlation between pedicle diameter and exit rate was also found (P < 0.0001). Conclusion. Our study showed no significant differences in the overall exit rates between the two techniques. Image guidance may increase confidence of surgeons with limited experience in thoracic pedicle screw placement. Successful placement of screws within the pedicle varies with the anatomic diameter of the pedicle itself. Concerns regarding accuracy of screw placement should be greatest in the middle thoracic vertebrae (T4–T7), where pedicle diameters are smallest and proximity of the great vessels is nearest.
Management of low risk prostate cancer: active surveillance and focal therapy

Purpose of review To summarize the current understanding of the natural history and molecular biology of low-risk prostate cancer, and review the indications for surveillance and focal therapy. Recent findings Low-risk prostate cancer, diagnosed in 40–50% of newly diagnosed men in a screened population, represents overdiagnosis in most cases. Gleason pattern 3 cells typically lack the molecular machinery and the genetic abnormalities, which characterize true cancers, with two important caveats. Thirty percent of patients diagnosed with low-risk prostate based on a systematic biopsy cancer harbor higher-grade cancer that is unrepresented on the biopsy. Secondly, a very small minority harbor prehistologic molecular alterations that result in progression to more aggressive disease. Favorable-risk prostate cancer is better viewed as one of multiple risk factors for the presence of higher-grade prostate cancer, and should be managed with close follow-up. Radical intervention should be reserved for clear evidence of more aggressive disease. Focal therapy should be offered to men with higher-risk disease either at baseline, as an alternative to whole gland radiation or surgery or when active surveillance ‘fails’ (the patient transitions from low risk to higher risk). The two strategies should be seen as complimentary elements of care that can be applied in a risk-stratified manner – taking account of patient preference – from the outset or in sequence Summary Active surveillance is appropriate for most men with low-risk prostate cancer, and focal therapy may complement active surveillance for those men wishing to continue a tissue-preserving strategy.
Endoproteolytic Processing of the Ebola Virus Envelope Glycoprotein: Cleavage Is Not Required for Function

ABSTRACT Proteolytic processing is required for the activation of numerous viral glycoproteins. Here we show that the envelope glycoprotein from the Zaire strain of Ebola virus (Ebo-GP) is proteolytically processed into two subunits, GP1 and GP2, that are likely covalently associated through a disulfide linkage. Murine leukemia virions pseudotyped with Ebo-GP contain almost exclusively processed glycoprotein, indicating that this is the mature form of Ebo-GP. Mutational analysis identified a dibasic motif, reminiscent of furin-like protease processing sites, as the Ebo-GP cleavage site. However, analysis of Ebo-GP processing in LoVo cells that lack the proprotein convertase furin demonstrated that furin is not required for processing of Ebo-GP. In sharp contrast to other viral systems, we found that an uncleaved mutant of Ebo-GP was able to mediate infection of various cell lines as efficiently as the wild-type, proteolytically cleaved glycoprotein, indicating that cleavage is not required for the activation of Ebo-GP despite the conservation of a dibasic cleavage site in all filoviral envelope glycoproteins.
Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy

Rationale: The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration. Objective: Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy. Methods and Results: Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit+ cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit− mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit+ population is further enriched by selection for a CD133+ endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry. Conclusions: Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients.
Increased inattentional blindness in severe traumatic brain injury: Evidence for reduced distractibility?

Primary objective: To examine the role of selective attention and visual perception in medicating inattentional blindness in a severe traumatic brain injured sample. Research design: Cross-sectional design with age and education matched control sample. Methods and procedures: Twenty participants with severe traumatic brain injury (n = 10) and matched controls (n = 10) completed a series of tests of focused attention (Stroop test), divided attention (Trail Making Test), visual perception (Visual Object and Space Perception Battery) and two tasks of inattentional blindness. Main outcomes and results: The group with severe TBI were significantly slower on the Stroop test and TMT and displayed significantly elevated Stroop interference and TMT ratio scores. On the inattentional blindness tasks, fewer TBI participants identified a distracting stimulus. Conclusion: The results indicate severe TBI is associated with deficits to focused and divided attention with the finding of a potentially more debilitating impairment arising from reduced distractibility following severe TBI.
Life-Course Socioeconomic Status and Metabolic Syndrome Among Midlife Women.

OBJECTIVES We examine whether women's risks of having metabolic syndrome (MetS) at pre/early-menopausal baseline, and of developing MetS after baseline, are associated with childhood and adult socioeconomic statuses (SESs); and whether the associations are mediated by adult reproductive, economic, behavioral, and psychosocial factors. METHOD Using data on white and black women collected prospectively for 12 years in the Study of Women's Health Across the Nation, we estimated odds of MetS at pre/early-menopausal baseline with logistic regression, and incidence of MetS after baseline with Cox proportional hazards models. RESULTS Women raised in "adverse" childhood SES had marginally greater odds of MetS at baseline than did women raised in "good" SES, and women with a high school credential or less had significantly greater odds than college-educated women, in mutually adjusted models. The elevated odds partly reflected SES-related differences in exercise and alcohol consumption. Incidence after baseline was associated with education, not childhood SES, and partly mediated by health behaviors. Differences in the probability of surviving without MetS between the most and least socioeconomically advantaged women nearly doubled between ages 50 and 60. DISCUSSION Childhood and adult SES predict women's risks of MetS as they approach the menopause transition; adult SES is primarily important afterwards.
Role of phosphodiesterase and protein kinase G on nitric oxide-induced inhibition of prolactin release from the rat anterior pituitary.

OBJECTIVE In order to determine the mechanism by which nitric oxide (NO) inhibits prolactin release, we investigated the participation of cGMP-dependent cAMP-phosphodiesterases (PDEs) and protein kinase G (PKG) in this effect of NO. METHODS Anterior pituitary glands of male rats were incubated with inhibitors of PDE and PKG with or without sodium nitroprusside (NP). Prolactin release, and cAMP and cGMP concentrations were determined by RIA. RESULTS AND CONCLUSIONS The inhibitory effect of NP (0.5 mmol/l) on prolactin release and cAMP concentration was blocked by EHNA (10(-4)mol/l) and HL-725 (10(-4)mol/l), inhibitors of cGMP-stimulated cAMP-PDE (PDE2). 8-Br-cGMP (10(-4) and 10(-3)mol/l), which mimics cGMP as a mediator of NP effects on prolactin release, also decreased cAMP concentration. Zaprinast (10(-4)mol/l), a selective inhibitor of specific cGMP-PDE (PDE5), potentiated the NP effect on cAMP concentration. Rp-8-[(4-chlorophenyl)thio]-cGMP triethylamine (Rp-8-cGMP, 10(-7)-10(-6)mol/l), an inhibitor of PKG, reversed the effect of NP on prolactin release. The present study suggests that several mechanisms are involved in the inhibitory effect of NO on prolactin release. The activation of PDE2 by cGMP may mediate the inhibitory effect of NO on cAMP concentration and therefore on prolactin release. NO-activated PKG may also be participating in the inhibitory effect of NO on prolactin release.
Time‐shifted reproductive behaviours among fall armyworm (Noctuidae: Spodoptera frugiperda) host strains: evidence for differing modes of inheritance

The noctuid moth Spodoptera frugiperda consists of two strains associated with different larval host plants (most notably corn and rice). These strains exhibit differential temporal patterns of female calling and copulation during scotophase, with the corn strain more active earlier in the night. We investigated strain‐specific constraints in reproductive timing, mating interactions between the two strains, and the mode of inheritance of timing of female calling, male calling, copulation and oviposition. We observed an allochronic shift of all reproductive behaviours by approximately 3 h and a parallel shift of nonreproductive locomotor activity, suggesting involvement of the circadian clock. The corn strain was more variable in the timing of calling and copulation than the rice strain. Rice strain females were more restricted in the timing of copulation than rice strain males, while such differences between the sexes were not apparent in the corn strain. There were significant interactions between the strains affecting onset times of copulation and male calling. The four investigated reproductive traits differed in their modes of inheritance: timing of female and male calling exhibited strong maternal effects, timing of copulation was controlled by a combination of maternal effects and corn strain dominant autosomal factors, and timing of oviposition was inherited in a corn strain dominant fashion. We conclude that the allochronic separation of reproduction between fall armyworm strains is asymmetric, less pronounced than previously thought, and under complex genetic control.
Corrigendum: Beyond Purity: Moral Disgust Toward Bad Character

Original article: Giner-Sorolla, R. , & Chapman, H. A. (2017). Beyond purity: Moral disgust toward bad character. Psychological Science, 28, 80–91. doi:10.1177/0956797616673193 In this article, some effect sizes in the Results section for Study 1 were reported incorrectly and are now being corrected. In the section titled Manipulation Checks: Act and Character Ratings, we reported a d value of 0.32 for the one-sample t test comparing participants’ act ratings with the midpoint of the scale; the correct value is 0.30. The sentence should read as follows: Follow-up one-sample t tests using the midpoint of the scale as a test value (because participants compared John with Robert) indicated that the cat beater’s actions were judged to be less wrong than the woman beater’s actions, t(86) = −2.82, p = . 006, d = 0.30. In the section titled Emotion Ratings, we reported a d value of 0.42 for the paired-samples t test comparing relative ratings of facial disgust and facial anger; the correct value is 0.34. In addition, the effect-size statistic is dz rather than d. The sentence should read as follows: As predicted, a paired-samples t test indicated that relative facial-disgust ratings (M = 4.36, SE = 0.21) were significantly different from relative facial-anger ratings (M = 3.63, SE = 0.20), t(86) = −3.12, p = . 002, dz = 0.34; this indicates that the cat-beater and woman-beater scenarios differentially evoked disgust and anger. Later in that section, we reported a d value of 0.21 for the one-sample t test comparing ratings of facial disgust with the midpoint of the scale; the correct value is 0.20. In the same sentence, we reported a d value of 0.21 for the one-sample t test comparing ratings of facial anger with the midpoint of the scale; the correct value is 0.19. The sentence should read as follows: Follow-up one-sample t tests against the midpoint of the scale showed trends in the predicted directions, with higher disgust for the cat beater compared with the woman beater, t(86) = 1.7, p = . 088, d = 0.20, and higher anger for the woman beater compared with the cat beater, t(86) = −1.82, p = . 072, d = 0.19 (see Fig. 1). These errors do not affect the significance of the results or the overall conclusions for Study 1.