Miracle-dz/UniFAR-FTUs huggingface dataset:
Adiposity blunts the positive relationship of thyrotropin with proprotein convertase subtilisin-kexin type 9 levels in euthyroid subjects.

BACKGROUND Effects of thyroid function status on lipoprotein metabolism may extend into the euthyroid range. Low-density lipoprotein (LDL) metabolism is governed by proprotein convertase subtilisin-kexin type 9 (PCSK9), which down-regulates LDL receptor expression, resulting in higher LDL cholesterol (LDL-C). Here, we tested whether plasma PCSK9 correlates with thyroid function in nonobese and obese euthyroid subjects. METHODS We assessed the extent to which plasma PCSK9 is determined by thyrotropin (TSH) in 74 euthyroid subjects (31 women; TSH between 0.5 and 4.0 mU/L and free thyroxine [FT4] between 11.0 and 19.5 pM) with varying degrees of obesity (body mass index [BMI] ranging from 20.2 to 40.4 kg/m(2)). RESULTS TSH, FT4, PCSK9, non-high-density lipoprotein cholesterol (non-HDL-C), LDL-C, and apolipoprotein B (apoB) levels were not different between 64 nonobese subjects (BMI<30 kg/m(2)) and 10 obese subjects (BMI≥30 kg/m(2); p>0.20 for each). PCSK9 correlated positively with TSH in nonobese subjects (r=0.285, p=0.023). In contrast, PCSK9 was not associated positively with TSH in obese subjects (r=-0.249, p=0.49). The relationship of PCSK9 with TSH was different between nonobese and obese subjects when taking age, sex, FT4, and the presence of anti-thyroid antibodies into account (multiple linear regression analysis: β=-0.320, p=0.012 for the interaction term between the presence of obesity and TSH on PCSK9), and was also modified by BMI as a continuous trait (β=-0.241, p=0.062 for the interaction term between BMI and TSH on PCSK9). Non-HDL-C, LDL-C, and apoB levels were dependent on PCSK9 in nonobese subjects (p≤0.01 for each), but not in obese subjects (p>0.50), Accordingly, BMI interacted negatively with PCSK9 on non-HDL-C (p=0.028) and apoB (p=0.071). CONCLUSIONS This study suggests that circulating PCSK9 levels correlate with thyroid function even in the normal range. This relationship appears to be blunted by obesity. Thyroid functional status may influence cholesterol metabolism through the PCSK9 pathway.
The Significance of the Expression of FBXO31 in Gastric Cancer

Loss of Heterozygosity (LOH) is commonly considered to be one of a reason when some genes lose their function. Numbers of tumor suppressor genes are existing on the LOH lesion and chromosome 16q24 had been reported as a LOH region in gastric cancer. Little is known about what kind of tumor suppressor genes locates around the position. F-box protein, (FBXO31) is a candidate tumor suppressor gene encoded in chromosome 16q24.3 and LOH of the gene was reported in breast cancer, hepatocellular carcinoma and ovarian cancer but the status of FBXO31 was not analyzed in gastric cancer so far. One hundred twenty-seven pairs of tumor and corresponding normal tissue specimens collected from gastric cancer patients who underwent gastrectomy. Total RNAs were extracted from those samples and the expression of FBXO31 was investigated using real time quantitative RT-PCR analysis. Patients were classified into FBXO31 high expression group and low expression group. Clinicopahological factors were compared between the two groups and importance of FBXO31 was investigated. The standardized expression of FBXO31 was not significantly different between tumor (0.43 ± 0.46) and the corresponding 0.49 ± 0.55 in normal tissue (p = 0.39). Two years survival rate was 77% in FBXO31 high expression group and 54% in low expression group however the chance of survival rate of high expression group was dropped in 5 years (Wilcoxon p = 0.01). Clinicopathological factors were compared between the two groups and peritoneal dissemination was observed significantly higher in FBXO31 low expression group than did in high expression group (p = 0.0398). In order to predict existence of peritoneal dissemination of gastric cancer before surgery, FBXO31 may become a favorite marker for the low risk of peritoneal dissemination.
Dynamic properties of imidazolium orthoborate ionic liquids mixed with polyethylene glycol studied by NMR diffusometry and impedance spectroscopy

We used 1H pulsed field gradient nuclear magnetic resonance to study the self‐diffusion of polyethylene glycol (PEG) with average molecular mass of 200 and ions in mixtures of PEG with imidazolium bis(mandelato)borate (BMB) and imidazolium bis(oxalato)borate ionic liquids (ILs). The IL was mixed with PEG in the concentration range of 0–100 wt%. Within the temperature range of 295 to 353 K, the diffusion coefficient of BMB is slower than that of the imidazolium cation. The diffusion coefficients of PEG, as well as the imidazolium cation and BMB anions, differ under all experimental conditions tested. This demonstrates that the IL in the mixture is present in at least a partially dissociated state. Generally, increasing the concentration of PEG leads to an increase in the diffusion coefficients of PEG and both the ions and decreases their activation energy for diffusion. Nuclear magnetic resonance chemical shift alteration analysis showed that the presence of PEG changes the chemical shifts of both ions but in different directions. Impedance spectroscopy was used to measure the ionic conductivity of the ILs mixed with PEG. Copyright © 2017 John Wiley & Sons, Ltd.
Current Practices in Professional Training and Technical Assistance of HIV Care Providers

This issue of the Journal of HIV/AIDS & Social Services is devoted to a rarely documented aspect of the HIV/AIDS epidemic: the training of the diverse cadre of professionals who care for HIV-infected individuals and the development of organizational capacity so that medical care and social service agencies can support the work of these care providers. The importance of professional training and technical assistance for the current state of HIV/AIDS care is best appreciated when we consider how far we have come from the dark days, nearly a quarter of a
Reduction of Ischemia-reperfusion Injury to Skin Flap by Treatment with Monoclonal Antibody to Endothelial Leukocyte Adhesion Molecule-1

The selectin family, which mediates adhesion of activated leukocytes to the vascular endothelium, plays an important role in inflammation. Endothelial leukocyte adhesion molecule-1 (SLAM-1) is expressed on activated vascular endothelium and mediates the special leukocyte rolling phenomenon seen when leukocytes adhere to vascular endothelium. We investigated changes in skin flap survival / necrosis due to treatment with the monoclonal antibody (Mab) to ELAM-1. Twenty-five male Sprague-Dawley rats (225-250 g) were used in the experiment. A 45 •~ 30 mm pedicled skin flap with superficial epigastric vessels was designed in the right inguinal region and prepared. Animals in the treated group received anti-ELAM-1 Mab intravenously 15 minutes prior to reperfusion ; those in the control group received normal saline. By tracing the outline of viable and nonviable areas skin flap viability was assessed. Data were collected for the subsequent 7 days. These data corroborated with histological evidence on comparable areas of the flap. Tracing analysis revealed an average flap survival area of 91.7% in the treated group and 18.3% in the control group (P < 0.005). Histopathologically, few inflammatory changes were observed in the treated group, while marked damage was observed in the control group. We conclude that treating skin flaps with anti-ELAM-1 was effective in reducing ischemia-reperfusion (I-R) injury after 9 hours of warm ischemia.
Screening for Cushings Syndrome in obese patients

We reviewed the medical records of morbidly obese patients referred to our clinic prior to bariatric surgery between January 2001 and December 2011. All patients had a complete medical history including physical examination, and 387 (300 female; mean age 46,5 ± 11,2 yr; mean BMI 52,8 ± 27,1 kg/m2) underwent screening for CS as part or our pre-surgical protocol. As screening for autonomous cortisol secretion, we performed an overnight 1 mg Dexamethasone Suppression Test (DST). Serum cortisol < 1,8 μg/dl was the cut-off point for normal suppression.
Spinal metastases due to thyroid carcinoma: an analysis of 202 patients.

BACKGROUND Spinal metastases (SMs) due to thyroid cancer (TC) are associated with significantly reduced quality of life. The goal of this study is to analyze the clinical manifestations, presentation, and treatments of TC SMs, and to describe specific features of SMs associated with different TC types. PATIENTS AND METHODS A retrospective analysis of 202 TC SM patients treated at Medstar Washington Hospital Center (37) and collected from the literature (165) was performed. RESULTS The mean age of patients with SMs was 56.9±14.7 years, and the female-to-male ratio was 2.1:1. Of all patients, 29% (28% of follicular thyroid cancer [FTC] and 37% of papillary thyroid cancer [PTC]) had SMs only. Twenty-nine percent of all patients and 54% of patients with single-site SMs had neither bone non-SMs nor solid organ metastases at the time of presentation. Thirty-five percent of patients had SMs as an initial presentation of TC. TC patients presenting with SMs had a lower rate of other bone and visceral involvement compared with patients whose SMs were diagnosed at the time of thyroid surgery or during follow-up (p<0.05). SMs were more often the initial manifestation of FTC (41% vs. 24%), while PTC SMs were more commonly diagnosed after TC diagnosis (76% vs. 59%; p<0.05). PTC SMs were more frequently diagnosed as synchronous (63% vs. 36% in FTC) versus FTC SMs that developed as metachronous metastases (64% vs. 37% in PTC; p<0.01). All FTC SMs developed within 82 (0-372) months and all PTC SMs within 35 (0-144) months (p<0.01). In FTC SMs as TC manifestation, solid organ metastases involvement was less common than in FTC SMs that were found after TC diagnosis (34% vs. 67%; p<0.01); multisite FTC SMs compared to solitary FTC SMs were associated with the development of other bone nonspinal metastases (82% vs. 30%; p<0.01) and solitary organ metastases (65% vs. 41%; p<0.01). These correlations were not observed in PTC SMs. FTC patients often had neural structure compression (myelopathy/radiculopathy; 72% vs. 36% in PTC), while PTC patients frequently were asymptomatic (38% vs. 5% in FTC; p<0.01). FTC SMs more commonly were (131)I-avid (p<0.01). FTC patients required surgery more frequently (72% vs. 55% in PTC; p<0.05). CONCLUSIONS Our study reveals that a significant part of TC SMs patients have solitary spinal involvement at the time of presentation and may be considered for aggressive treatment with the intention to improve quality of life and survival. FTC SMs and PTC SMs appear to have distinct presentations, behavior, and treatment modalities, and should be categorized separately for treatment and follow-up planning.
Characterisation of histone variant distribution in human embryonic stem cells by transfection of in vitro transcribed mRNA

Recent studies, primarily in mouse embryonic stem cells, have highlighted the unique chromatin state of pluripotent stem cells, including the incorporation of histone variants into specific genomic locations, and its role in facilitating faithful expression of genes during development. However, there is little information available on the expression and subcellular localisation of histone variants in human embryonic stem cells (hESCs). In this study, we confirmed the expression of a panel of histone variant genes in several hESC lines and demonstrated the utility of transfection of in vitro transcribed, epitope‐tagged mRNAs to characterise the subcellular localisation of these proteins. The subcellular localisations of variant histone H3 (CENP‐A, H3.3), H2A (MACROH2A, H2AX, H2AZ, H2ABBD) and H1 (H1A, HB, H1C, H1D) were examined, revealing distinct nuclear localisation profiles for each protein. These data highlight the differences between murine (m) ESCs and hESCs, including the presence of a MACROH2A‐enriched inactive X chromosome in undifferentiated XX hESC lines. We also provide the first evidence for MACROH2A accumulation on the Y‐chromosome in XY hESCs. Mol. Reprod. Dev. 76: 1128–1142, 2009. © 2009 Wiley‐Liss, Inc.
Developmental timing of mRNA translation—integration of distinct regulatory elements

Targeted mRNA translation is emerging as a critical mechanism to control gene expression during developmental processes. Exciting new findings have revealed a critical role for regulatory elements within the mRNA untranslated regions to direct the timing of mRNA translation. Regulatory elements can be targeted by sequence‐specific binding proteins to direct either repression or activation of mRNA translation in response to developmental signals. As new regulatory elements continue to be identified it has become clear that targeted mRNAs can contain multiple regulatory elements, directing apparently contradictory translational patterns. How is this complex regulatory input integrated? In this review, we focus on a new challenge area—how sequence‐specific RNA binding proteins respond to developmental signals and functionally integrate to regulate the extent and timing of target mRNA translation. We discuss current understanding with a particular emphasis on the control of cell cycle progression that is mediated through a complex interplay of distinct mRNA regulatory elements during Xenopus oocyte maturation. Mol. Reprod. Dev. 77: 662–669, 2010. © 2010 Wiley‐Liss, Inc.
High temperature causes masculinization of genetically female medaka by elevation of cortisol

In poikilothermic vertebrates, sex determination is sometimes influenced by environmental factors such as temperature. However, little is known about the molecular mechanisms underlying environmental sex determination. The medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. Recently, it was reported that XX medaka can be sex‐reversed into phenotypic males by high water temperature (HT; 32–34°C) treatment during the sex differentiation period. Here we report that cortisol caused female‐to‐male sex reversal and that metyrapone (an inhibitor of cortisol synthesis) inhibited HT‐induced masculinization of XX medaka. HT treatment caused elevation of whole‐body levels of cortisol, while metyrapone suppressed the elevation by HT treatment during sexual differentiation. Moreover, cortisol and 33°C treatments inhibited female‐type proliferation of germ cells as well as expression of follicle‐stimulating hormone receptor (fshr) mRNA in XX medaka during sexual differentiation. These results strongly suggest that HT induces masculinization of XX medaka by elevation of cortisol level, which, in turn, causes suppression of germ cell proliferation and of fshr mRNA expression. Mol. Reprod. Dev. 77: 679–686, 2010. © 2010 Wiley‐Liss, Inc.
Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases

A new classification of adenocarcinoma (ADC) was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) in 2011. The present study evaluates its prognostic value in stage I disease of Japanese cases. One‐hundred‐and‐seventy‐nine cases with pathological stage I ADC were classified according to the new classification system and their association with disease recurrence was analyzed. Eighteen (10.1%) and 24 (13.4%) cases were adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), respectively. One‐hundred‐and‐thirty‐seven cases (76.5%) were invasive adenocarcinoma (IVA), in which 43 (24.0%) were lepidic (LEP), 59 (33.0%) were acinar (ACN), 16 (8.9%) were papillary (PAP), 1 (0.6%) was micropapillary (MPAP), 12 (6.7%) were solid predominant subtypes (SOL), and 6 (3.4%) were invasive mucinous adenocarcinoma (MUC). The5‐year disease‐free survivals (DFS) of patients with AIS and MIA were 100%. Those of LEP, ACN, PAP, SOL and MUC were 93.5%, 83.7%, 75.0%, 44.4% and 62.5%, respectively. Multivariate analysis showed that high‐histological grade (SOL, MPAP, MUC) had an independent prognostic value to predict post‐operative recurrence (HR 3.661, 95% CI 1.421–9.437, P = 0.007). In conclusion, the present study demonstrates a prognostic value of the 2011 IASLC/ATS/ERS classification of ADC in Japanese cases.
Sperm status and DNA dose play key roles in sperm/ICSI‐mediated gene transfer in caprine

In relation to the growing recent interest in the establishment of sperm‐mediated gene transfer (SMGT) technology as a convenient and effective method for the simple production of transgenic animals, in this study the possibility of using SMGT to produce transgenic caprine embryos was investigated for the first time. Buck sperm were directly incubated with different concentrations (0–500 ng) of pcDNA/his/Lac‐Z plasmid and used for IVF or ICSI. Sperm used for ICSI were categorized into motile or live‐immotile group before being injected into oocytes. In a separate experiment, dead sperm prepared by repeated freezing/thawing were used for DNA‐incubation before ICSI. Sham injection was carried out by intracytoplasmic injection of approximately the same volume of media containing different doses of DNA using an ICSI needle. Transgene expression and transmission were detected by X‐Gal staining and PCR analysis of developed embryos, respectively. A reasonable blastocyst rate was observed in all the groups. Only embryos in the sham group were negative for transgene transmission. Transgene expression was completely dependent on the delivery technique and status of sperm, and was only observed in the live‐immotile and dead ICSI groups. The results of this study showed that the technique (IVF vs. ICSI vs. sham injection), sperm status (motile vs. live‐immotile vs. dead) and to some extent DNA concentration affect embryo development, transgene transmission and expression. Mol. Reprod. Dev. 77:868–875, 2010. © 2010 Wiley‐Liss, Inc.
Validity and reproducibility of Ki‐67 assessment in gastrointestinal stromal tumors and leiomyosarcomas

With the aim of standardizing Ki‐67 immunohistochemistry, we assessed interobserver and interlaboratory variability of the Ki‐67 labeling index and Ki‐67 score among eight general pathologists for 24 gastrointestinal stromal tumors (GISTs) and 12 leiomyosarcomas, which were predominantly of the gastrointestinal (GI) tract, mesentery and retroperitoneum, based on a review of a tissue microarrays subjected to immunohistochemistry with antibodies for Ki‐67. For Ki‐67 immunostaining of mesenchymal tumors of the GI tract, including GISTs, differences were seen in the scores given by regional hospitals. Conversely, for two categories of the Ki‐67 labeling index, namely <10% and ≥10%, concordance of the Ki‐67 score between microscopic observation and image analysis, and between the observers, was good, but it was not good for the other four categories of the index for <5%, 5–9%, 10–29%, and ≥30%. The concordance of the Ki‐67 scores between the observers in two categories was higher using the Ki‐67 pre‐stained tissue microarrays (TMAs) within each participating institute than that using the Ki‐67 stained TMAs between the participating institutes. The reproducibility of a 10% cut‐off value for the Ki‐67 labeling index to predict the prognosis of GISTs was relatively high, but there is an urgent need to standardize the staining technique.
Cancer‐initiating cell marker‐positive cells generate metastatic tumors that recapitulate the histology of the primary tumors

Cancer‐initiating cell (CIC) hypothesis suggests that CICs may be responsible for the generation of tumors that recapitulate the histology of the primary tumor at distant sites. We investigated the distribution of CIC markers (podoplanin (PDPN), CD44, and p63) positive cells of lung squamous cell carcinoma (SqCC) within primary and matched lymph node (LN) metastatic tumors to confirm this hypothesis (n = 113). In 61 cases, the PDPN‐positive cells were localized in more peripheral areas of the tumor nests than the CD44‐ and p63‐positive cells. This distribution pattern corresponded to a ‘hierarchical distribution (HD)’ reported previously. Among the cases with HD‐(+) primary tumors (n = 61), the number showing HD‐(+) LN metastatic tumors was 31 (51%), while among the cases with HD‐(−) primary tumors (n = 52), the number showing HD‐(+) LN metastatic tumors was 7 (13%) (p < 0.01). Primary and matched pulmonary metastatic (PM) tumors were also analyzed (n = 31), and a significant relationship of the HD pattern between them was also detected (p = 0.01). These results indicate that PDPN‐positive cells might reflect the most immature cells in the differentiation process of metastatic SqCC and might generate metastatic tumors that recapitulate the histologic heterogeneity of the primary tumor.
Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis.

BACKGROUND Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)--compounds formed by the transformation of proteins--were evaluated as potential new markers of oxidative stress in this disease. METHODS This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; M age = 38 ± 13 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. RESULTS Serum d-ROMs were elevated, and BAP decreased in HT patients compared with controls (p < 0.001), and the two parameters were inversely correlated (r = -0.211; p = 0.027), clearly indicating an enhanced oxidative stress. Furthermore, AGE levels were higher in HT patients (M = 223.18 AU/g prot) than in controls (M = 189.636 AU/g prot; p = 0.020) and inversely correlated with BAP levels (r = -0.196; p = 0.037). In uni- and multivariate analysis, serum antithyroperoxidase antibodies were the main predictors for d-ROMs (p = 0.006), BAP (p < 0.001), and AGEs (p = 0.014), irrespective of thyrotropin and/or free thyroxine values. No differences in AOPPs levels were found between patients and controls (p = 0.923). CONCLUSIONS Oxidants are increased and antioxidants decreased in euthyroid HT patients. As a result, the oxidative/antioxidative balance is shifted toward the oxidative side. Moreover, this study reports on a possible significant involvement of AGEs in HT, thus contributing to a better definition of the redox homoeostasis dysregulation in HT.
Arterial Steal Phenomena

Our report on the reversal of blood flow in the left carotid artery in this month's issue of theArchives of Surgery(110:399-401, 1975) is the latest description of a wide variety of physiologic steal phenomena due to obstructive lesions in major thoracic-cervical arterial branches. Although the clinical case of "subclavian steal" was recognized and described by Contorni1only in 1960, it is now well known that this and additional steal phenomena in other parts of the body are not rare. Obstruction in any of the major thoracic aortic arch stems or their branches may result in a clinical steal syndrome. This phenomenon may occur in any situation in which a hemodynamically significant obstructive lesion is present in a proximal segment of a vessel, resulting in decreased pressure and flow in its distal patent segment. Perfusion of the distal patent segment is then maintained by siphoning off, in a