Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated levels and distinct patterns of expression of A‐type cyclins and their associated cyclin‐dependent kinases in male germ cell tumors

Aberrant expression of several key regulators controlling the G1/S phase of the cell cycle has been implicated in human male germ cell tumorigenesis. Given the critical role of cyclin A2 at both the G1/S and G2/M transitions and the essential role for cyclin A1 in male germ cell development, our present study focused on the involvement of the A‐type cyclins in the transformation and progression of male germ cell tumors (GCTs). The expression of the A‐type cyclins and their catalytic partners Cdk1 and Cdk2 was examined in all types and stages of human male GCTs, including carcinoma in situ(CIS), seminoma and non‐seminoma GCTs, along with normal testis samples. Elevated levels of cyclin A2, Cdk1 and Cdk2 were detected in the majority of GCTs and were correlated with the invasiveness of the tumors (p < 0.05). Cyclin A1 expression was virtually undetectable in CIS and seminoma, but was aberrantly expressed in all non‐seminomatous GCTs. Cyclin A2 expression was strongly correlated with that of its catalytic partners Cdk1 and Cdk2 in all types of testicular tumors examined (p < 0.05), whereas a strong correlation between cyclin A1 and Cdk1 or Cdk2 was only seen in non‐seminomatous GCTs (p < 0.05). Histone kinase activities of cyclin A1/Cdks and cyclin A2/Cdks were found to be elevated in tumors. Our data suggest that aberrant expression of A‐type cyclins and their Cdks is a significant factor in male germ cell tumorigenesis. The abundant ectopic expression of cyclin A1 in non‐seminomatous GCTs and its absence in CIS and seminomas is likely linked to the tumor transformation and progression and may be relevant to clinical prognosis. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience. wiley.com/jpages/0020‐7136/suppmat/index.html. © 2003 Wiley‐Liss, Inc.
Short-term Effects of Catheter Pressure and Time Control in Vacuum Aspiration Abortion for Early High-risk Pregnancies

Background: We aimed to evaluate an approach to induced abortions during early pregnancies that controls the suction pressure and restricts the duration of the procedure. Methods: Three hundred patients programmed for induced early pregnancy abortions, hospitalized in the Shandong Provincial Maternity & Child-care Hospital from October 2013 to October 2015, were enrolled. Patients were randomly assigned to either research or control group. In the research group, operation pressure was controlled at 400 mmHg and operation time in the uterine cavity was kept at less than 75 s. In the control group, pressure ranged from 400–500 mmHg. Clinical variables were recorded for each patient until the fourth month after surgery, correlation and multivariate analyses were carried. Results: Compared with control group, anesthesia and intervention durations and the suction pressure were significantly lower and the endometrial thickness of the first late follicular phase after operation was significantly larger in the research group (P<0.05). In the first postoperative month, the number of patients who reported menstruation flow decreased by more than 1/3 of its normal volume was significantly lower than that in the control group (P<0.05). In the third postoperative month, the thickness of the late follicular phase endometrium was significantly larger than that in the control group (P<0.001). The mean intraoperative pressure and intrauterine operation duration both influenced the endometrial thickness of follicular phase. Conclusion: Controlling the suction pressure and time for vacuum aspiration abortions during early pregnancies can reduce the incidence of intrauterine adhesions and better protect the endometrium.
Human HDAC7 Histone Deacetylase Activity Is Associated with HDAC3in Vivo *

Histone deacetylases (HDACs) are part of transcriptional corepressor complexes and play key roles in regulating chromatin structure. Three different classes of human HDACs have been defined based on their homology to HDACs found in Saccharomyces cerevisiae: RPD3 (class I), HDA1 (class II), and SIR2 (class III). Here we describe the identification and functional characterization of HDAC7, a new member of the human class II HDAC family. Although HDAC7 is localized mostly to the cell nucleus, it is also found in the cytoplasm, suggesting nucleocytoplasmic shuttling. The HDAC activity of HDAC7 maps to a carboxyl-terminal domain and is dependent on the interaction with the class I HDAC, HDAC3, in the cell nucleus. Cytoplasmic HDAC7 that is not bound to HDAC3 is enzymatically inactive. We provide evidence that the transcriptional corepressors SMRT and N-CoR could serve as critical mediators of HDAC7 activity by binding class II HDACs and HDAC3 by two distinct repressor domains. Different class II HDACs reside in the cell nucleus in stable and autonomous complexes with enzymatic activity, but the enzymatic activities associated with HDAC7 and HDAC4 rely on shared cofactors, including HDAC3 and SMRT/N-CoR.
Ectodermally derived FGF8 defines the maxillomandibular region in the early chick embryo: epithelial-mesenchymal interactions in the specification of the craniofacial ectomesenchyme.

The most rostral cephalic crest cells in the chick embryo first populate ubiquitously in the rostroventral head. Before the influx of crest cells, the ventral head ectoderm expresses Fgf8 in two domains that correspond to the future mandibular arch. Bmp4 is expressed rostral and caudal to these domains. The rostral part of the Bmp4 domain develops into the rostral end of the maxillary process that corresponds to the transition between the maxillomandibular and premandibular regions. Thus, the distribution patterns of FGF8 and BMP4 appear to foreshadow the maxillomandibular region in the head ectoderm. In the ectomesenchyme of the pharyngula embryo, expression patterns of some homeobox genes overlap the distribution of their upstream growth factors. Dlx1 and Barx1, the targets of FGF8, are expressed in the mandibular ectomesenchyme, and Msx1, the target of BMP4, in its distal regions. Ectopic applications of FGF8 lead to shifted expression of the target genes as well as repatterning of the craniofacial primordia and of the trigeminal nerve branches. Focal injection of a lipophilic dye, DiI, showed that this shift was at least in part due to the posterior transformation of the original premandibular ectomesenchyme into the mandible, caused by the changed distribution of FGF8 that defines the mandibular region. We conclude that FGF8 in the early ectoderm defines the maxillomandibular region of the prepharyngula embryo, through epithelial-mesenchymal interactions and subsequent upregulation of homeobox genes in the local mesenchyme. BMP4 in the ventral ectoderm appears to limit the anterior expression of Fgf8. Ectopic application of BMP4 consistently diminished part of the mandibular arch.
The effects of daily intake timing of almond on the body composition and blood lipid profile of healthy adults

BACKGROUND/OBJECTIVES Timing of almond intake during a day may result differently in the perspectives of body composition and changes of lipid profile. The current study was conducted to compare the effects of daily almond intake as a preload versus as a snack on body composition, blood lipid profile, and oxidative and inflammation indicators among young Korean adults aged 20–39 years old. SUBJECTS/METHODS Participants were randomly assigned to one of three groups: a pre-meal almond group (PM), a snack almond group (SN) in which participants were instructed to consume 56 g of almonds either as a preload before meals or as a snack between meals, respectively, and a control group (CL) in which participants were provided high-carbohydrate iso-caloric control food. Measurements were performed at baseline, weeks 8 and 16. RESULTS A total of 169 (M 77/F 92) out of the 227 participants completed the study between June 2014 and June 2015 (n = 58 for PM; 55 for SN; and 56 for CL). A significant decrease in body fat mass was observed in the PM group at both weeks 8 and 16 compared with the CL. There were significant intervention effects on changes of body fat mass (P = 0.025), body fat percentages (P = 0.019), and visceral fat levels (P < 0.001). Consuming almonds as a daily snack reduced the levels of total cholesterol (P = 0.043) and low-density lipoprotein (LDL) cholesterol (P = 0.011) without changing high-density lipoprotein (HDL) cholesterol compared with the CL. CONCLUSION Almond consumption as a preload modified body fat percentages, whereas snacking on almonds between meals improved blood lipid profiles. This trial was registered at ClinicalTrials.gov as NCT03014531.
MGMT promoter methylation as a potential prognostic marker for acute leukemia

Introduction It has been proved that genetic and epigenetic changes play a significant role in the development and progression of acute leukemia. The aim of our study was to evaluate the frequency and prognostic implications of genetic and epigenetic alterations in p15, MGMT, DNMT3A and TP53 genes in acute leukemias. Material and methods We included in the study 59 patients with acute leukemia. Evaluation of TP53 and DNMT3A mutations was performed using sequencing analysis and PCR-RFLP, respectively. Methylation status of MGMT and p15 genes was evaluated using MSP and COBRA, respectively. For assessment of global DNA methylation ELISA-based kit was used. Results We found that overall survival was higher for ALL patients. MGMT promoter methylation was significantly associated with patients age at the time of diagnosis (p = 0.03). TP53 and DNMT3A mutations were observed only in AML patients (16.67% and 8.8%, respectively). Patients with acute leukemia and p15 promoter methylation had significantly more frequently mutated TP53 gene (p = 0.04) and AML patients with p15 promoter methylation had significantly more frequently detected global hypomethylation of DNA (p = 0.009). In the group of ALL patients we noted an opposite trend: only patients negative for p15 promoter methylation were characterized by global DNA hypomethylation. Conclusions Our findings demonstrate that MGMT promoter methylation can have a considerable impact on the development of acute leukemia in older patients. DNMT3A and TP53 mutations may play a significant role in AML development. However, further studies conducted in a larger cohort of patients are needed to determine its clinical utility.
Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic hemodynamics in cirrhosis.

BACKGROUND & AIMS Therapeutic paracentesis may be associated with a circulatory dysfunction, manifested by a marked increase of the plasma renin activity and plasma norepinephrine. The aim of the study was to characterize the systemic and hepatic hemodynamic changes associated with paracentesis-induced circulatory dysfunction. METHODS Changes in plasma renin, aldosterone, and norepinephrine, and in systemic and hepatic hemodynamics were assessed 1 hour and 6 days after complete mobilization of ascites in 37 patients treated by total paracentesis plus intravenous dextran-70 infusion. RESULTS Paracentesis-induced circulatory dysfunction occurred in 10 patients (renin and norepinephrine increased from 9.0 +/- 10.5 to 28.8 +/- 19.0 ng.mL-1.h-1 and from 752.0 +/- 364.0 to 1223.0 +/- 294.0 pg/mL, respectively) and was associated with significant reduction in systemic vascular resistance (-13.0% +/- 2.6%; P < 0.05) and increase in hepatic venous pressure gradient (from 19.5 +/- 1.5 to 22.5 +/- 2.4 mm Hg; P < 0.01). In the remaining 27 patients, mobilization of ascites also induced a significant but smaller reduction in systemic vascular resistance (-5.0% +/- 1.6%; P < 0.05) without significant changes in renin, norepinephrine, and hepatic venous pressure gradient. CONCLUSIONS Paracentesis-induced circulatory dysfunction is predominantly caused by an accentuation of the arteriolar vasodilation already present in untreated cirrhotic patients with ascites. The homeostatic activation of endogenous vasoactive systems may account for the increased intrahepatic vascular resistance associated with this condition.
Evaluation of through-silicon-via process using scanning laser beam induced current (SLBIC) system

The manufacturing process of through-silicon-via (TSV) for 3D integration is complicated, and the high yield for each process is required. The relationship between the depth of the barrier/seed layer and the electroplating copper fill is investigated by using the scanning laser beam induced current (SLBIC) method. After reactive etching of via holes with diameters ranging from 50 μm to 150 μm, copper seed layer is deposited by sputtering, and then the electroplating of copper is performed. From the back surface of the sample, the infrared laser beam with wavelength of 1064nm was scanned, and the induced current between copper layer and silicon back surface is measured in order to obtain the current image. By changing the focus point of laser beam, the location of TSV failure is analyzed in depth direction.
Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group.

BACKGROUND AND METHODS Multiple sclerosis often occurs in young women, and the effect of pregnancy on the disease is poorly understood. We studied 254 women with multiple sclerosis during 269 pregnancies in 12 European countries. The women were followed during their pregnancies and for up to 12 months after delivery to determine the rate of relapse per trimester and the score on the Kurtzke Expanded Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability). The relapse rate in each trimester was compared with the rate during the year before the pregnancy. The effects of epidural analgesia and breast-feeding on the frequency of relapse during the first three months post partum and the disability score at 12 months post partum were also determined. RESULTS The mean (+/-SD) rate of relapse was 0.7+/-0.9 per woman per year in the year before pregnancy; it was 0.5+/-1.3 during the first trimester (P=0.03 for the comparison with the rate before pregnancy), 0.6+/-1.6 during the second trimester (P=0.17), and 0.2+/-1.0 during the third (P<0.001). The rate increased to 1.2+/-2.0 during the first three months post partum (P<0.001) and then returned to the prepregnancy rate. The mean Kurtzke disability score worsened by 0.7 point during 33 months of follow-up, with no apparent acceleration during the post-partum period. Neither breast-feeding nor epidural analgesia had an adverse effect on the rate of relapse or on the progression of disability in multiple sclerosis. CONCLUSIONS In women with multiple sclerosis, the rate of relapse declines during pregnancy, especially in the third trimester, and increases during the first three months post partum before returning to the prepregnancy rate.
Helicobacter pylori–negative duodenal ulcers: prevalence, clinical characteristics, and prognosis—results from a randomized trial with 2-year follow-up

ObjectiveThe proportion of Helicobacter pylori–negative duodenal ulcer disease appears to be increasing. Data on clinical outcome and prognosis in this subgroup are lacking.METHODS:Two hundred seventy-six duodenal ulcer patients randomized, irrespective of H. pylori status, to either eradication therapy or maintenance omeprazole (double-blind, double-dummy design) for 1 yr were studied. Patients were followed up for a total of 2 yr, with visits performed every 2 months the first year and every 6 months the following year. Endoscopies for assessment of ulcer relapse were done at 6 and 12 months or in the event of symptomatic relapse. H. pylori status was assessed by culture, immunohistochemistry, and urea breath test at entry, at 6, 12, and 24 months or at failure. The primary endpoint was discontinuation, irrespective of reason. Patients were considered H. pylori negative if all three tests were negative. Patients were considered H. pylori–positive if any of the three diagnostic tests were positive. Study staff were blinded to H. pylori results.RESULTS:Thirty-two (12%) patients were H. pylori negative at entry. There were no differences according to H. pylori status for a number of clinical and demographic characteristics. However, H. pylori–negative patients had a shorter history of ulcer symptoms and were more likely to be NSAID users (19% vs 1%, p < 0.001). Only 28% of the H. pylori–negative patients completed the study, as compared with 40% of H. pylori–positive patients (p = 0.0005). The main reasons for the poorer prognosis in H. pylori–negative patients were relapse of ulcer/ulcer not healed (35% vs 26%) and relapse of severe dyspepsia symptoms without ulcer relapse (16% vs 7%). H. pylori–negative patients randomized to eradication therapy left the study early compared with H. pylori–negative patients randomized to long-term omeprazole therapy. Outcome in omeprazole-treated patients did not differ according to H. pylori status (p = 0.3). CONCLUSIONS:Clinical characteristics in H. pylori–negative and positive duodenal ulcer patients differ little. Clinical outcome over 2 yr is significantly poorer in H. pylori–negative patients, especially if treated empirically with eradication therapy. These results suggest that H. pylori infection should be assessed in all duodenal ulcer patients before treatment is decided.
Perceived stress and physiological dysregulation in older adults

We use a population-based representative sample of older Taiwanese to investigate links between respondents' perceived levels of stress and a broad set of biological measures. These biomarkers were collected at a single time (2000) and reflect sympathetic nervous system (SNS)-activity, hypothalamo-pituitary-adrenal (HPA)-activity, immune function, cardiovascular function, and metabolic pathways. We model the relationship between perceived stress and (1) extreme values for each of 16 individual biological indicators; and (2) a measure of cumulative physiological dysregulation based on the full set of biomarkers. We consider two measures of perceived stress, one derived from the 2000 interview and the second based on data from three interviews (1996–2000). Age and sex-adjusted models reveal significant associations between measures of perceived stress and extreme values of cortisol, triglycerides, interleukin-6 (IL-6), dehydroepiandrosterone sulphate (DHEAS) and fasting glucose. Examined individually, numerous biomarkers, including those pertaining to blood pressure and obesity, are not significantly related to perceived stress. Jointly, however, the measure of cumulative physiological dysregulation is associated with both the level of perceived stress at a given time and to a longitudinal measure of perceived stress. Some results suggest that the relationship between level of perceived stress and physiological response is stronger for women than men.
Non-stoichiometric inhibition in integrated lead finding – a literature review

ABSTRACT Introduction: Non-stoichiometric inhibition summarizes different mechanisms by which low-molecular weight compounds can reproducibly inhibit high-throughput screening (HTS) and other lead finding assays without binding to a structurally defined site on their molecular target. This disqualifies such molecules from optimization by medicinal chemistry, and therefore their rapid elimination from screening hit lists is essential for productive and effective drug discovery. Areas covered: This review covers recent literature that either investigates the various mechanisms behind non-stoichiometric inhibition or suggests assays and readouts to identify them. In addition, combination of the various methods to distill promising molecules out of raw primary hit lists step-by-step is considered. Emerging technologies to demonstrate target engagement in cells are also discussed. Expert opinion: Over the last few years, awareness of non-stoichiometric inhibitors within screening libraries and HTS hit lists has considerably increased, not only in the pharmaceutical industry but also in the academic drug discovery community. This has resulted in a variety of methods to detect and handle such compounds. These range from in silico approaches to flag suspicious compounds, and counterassays to measure non-stoichiometric inhibition, to biophysical methods that positively demonstrate stoichiometric binding. In addition, novel technologies to verify target engagement within cells are becoming available. While still a time- and resource-consuming nuisance, non-stoichiometric inhibitors therefore do not fundamentally jeopardize the discovery of low molecular weight lead and drug candidates. Rather, they should be viewed as a manageable issue that with appropriate expertise can be overcome through integration of the above-mentioned approaches.
Waist-to-height ratio as a screening tool for children with risk factors for cardiovascular disease

Background: Waist-to-height ratio (WHtR) has been recommended as a tool for predicting cardiovascular risk in children. However, there is little evidence about the accuracy of using WHtR as a predictor of disease risk in pre-school children. Aims: To assess the accuracy of waist-to-height ratio (WHtR), waist circumference (WC) and body mass index (BMI) as well as to determine the optimal cut-off values for each of these measures in order to identify pre-school children with cardiovascular risks. Subjects and methods: This study conducted a cross-sectional analysis of 315 children between 3–4 years of age. Multiple risk factors for cardiovascular disease (MRFCD) were defined as having two or more of the following conditions: HDL-c < 35 mg/dL, LDL-c ≥ 110 mg/dL, triglycerides ≥ 150 mg/dL and systolic and/or diastolic blood pressure ≥ 90th percentile. Results: The accuracy of WHtR in identifying cardiovascular risk in pre-school children was not significantly different compared to BMI or WC, for both sexes. The optimal cut-off measures for predicting cardiovascular risk in boys and girls, respectively, were as follows: 0.51 and 0.49 for WHtR; 0.61 and 0.69 for BMI Z-score; and 51.2 cm and 50.2 cm for WC. Conclusions: The data support the use of a 0.5 cut-off value for WHtR to predict cardiovascular risk factors among pre-school children and suggest that using WHtR is comparable to both BMI and WC.