Miracle-dz/UniFAR-FTUs huggingface dataset:
Recovery of cellular E‐cadherin precedes replenishment of estrogen receptor and estrogen‐dependent proliferation of breast cancer cells rescued from a death stimulus

Loss of estrogen‐responsiveness and impaired E‐cadherin expression/function has been linked to increased metastatic potential of breast cancer cells. In this study, we report that proliferation of breast cancer cells can resume following removal of a toxic stimulus causing severe impairment of cell adhesion and estrogen responsiveness. This type of response was induced by okadaic acid (OA) in MCF‐7 cells, and was accompanied by an almost complete block of DNA synthesis, loss of cell–cell contact and cell detachment from culture dishes, loss of estrogen receptor (ER), progesterone receptor (PR) and E‐cadherin, whereas only a weak, if any, inhibition of protein synthesis could be observed. These responses were detected in MCF‐7 cells after a 1‐day treatment with 50 nM OA, and could be reversed if OA‐treated cells were recovered in a culture medium devoid of the toxin, so that rescued cells resumed growth 8–12 days after replating. By pulse‐chase experiments, we found that protein synthesis was not significantly affected in rescued cells, whose DNA synthesis, instead, was almost completely blocked during the first days of MCF‐7 cell rescue from OA treatment. We also analyzed E‐cadherin, mitogen activated protein kinase isoforms ERK1 and ERK2, Bcl‐2 and BAX proteins during the rescue of MCF‐7 cells from OA‐induced cell death, and found that their expression followed temporally defined patterns. Cellular levels of E‐cadherin returned to control levels within the first days of the rescue, followed by ER, ERK1, and ERK2, and finally by Bcl‐2 and BAX proteins. Under our experimental conditions, restoration of cell adhesion did not require a functional ER system, but recovery of a normal ER pool accompanied resumption of estrogen‐dependent proliferation of OA‐treated MCF‐7 cells. © 2002 Wiley‐Liss, Inc.
Cross-border Buyout Performance

Using a novel dataset of 2,639 cross-border buyout investments during 1998-2007 in 38 countries, we find that the institutional quality of the portfolio company country, as measured by the ranking in the composite index of political, economic and financial risk, is an important determinant of cross-border buyout performance in terms of exit success. The higher the institutional quality of the portfolio company country, the higher the probability of a successful exit via IPO or M&A. PE firms’ international experience, industrial experience, and reputation based on deal experience help to improve buyout exit success and their industrial experience could mitigate the adverse influence of institutional distance between the portfolio company and the PE firm countries.
Clinical presentation, burden of disease and treatment in young-onset and late-onset rheumatoid arthritis: a matched-pairs analysis taking age and disease duration into account.

OBJECTIVES The aim of this study is to compare clinical features and treatment of young onset rheumatoid arthritis with late-onset rheumatoid arthritis. METHODS Nine thousand five hundred forty-one patients with rheumatoid arthritis (RA) enrolled in the national database of the German Collaborative Arthritis Centres in 2007-2009 were stratified by age at disease onset: up to 65 years (YORA), >65 years (LORA). To enable unbiased comparisons between the two groups despite their systematic differences in age and disease duration, we performed two separate matched-pairs analyses: the impact of current age was assessed by matching YORA and LORA patients for disease duration and sex (n=1,550 pairs). To identify the influence of disease duration, a second sample matched for age and sex (n=1,158 pairs) was drawn. RESULTS At identical age, YORA patients had higher disease activity (DAS28), worse functional capacity and were less frequently in remission when compared with LORA patients. YORA patients also suffered more frequently from RA-related co-morbidities such as cardiovascular disease, chronic renal disease and osteoporosis. Matched for disease duration, there were no differences between the two groups concerning disease severity and remission rates, global health or pain intensity. Independent of age or disease duration, YORA patients reported more sleep disorders and fatigue. LORA patients received significantly fewer synthetic or biologic DMARDs than YORA patients. CONCLUSIONS Duration of RA, rather than age, explains differences in disease burden between YORA and LORA patients. The lower prescription rates of synthetic and in particular biologic DMARDs, despite lower remission rates, indicate a potential treatment deficit in older patients.
Promoter polymorphisms of IL2, IL4, and risk of gastric cancer in a high‐risk Chinese population

Interleukin 2 (IL2) is a typical Th1 cytokine, and interleukin 4 (IL4) is an inducible Th2 cytokine. These cytokines are critical mediators of the Th1/Th2 balance and apoptosis potential and involved in the process of inflammation‐mediated carcinogenesis in human organs, including the gastrointestinal tract. Therefore, we tested the hypothesis that functional variants in IL2 and IL4 were associated with risk of gastric cancer by genotyping two promoter polymorphisms in IL2 G‐330T (rs2069762) and IL4 T‐168C (rs2070874) in a case‐control study of 1045 patients with incident gastric cancer and 1100 cancer‐free controls in a high‐risk Han Chinese population. We found that, compared with the IL4 ‐168TT genotype, heterozygous ‐168TC and combined ‐168TC/CC genotypes were associated with a significantly decreased gastric cancer risk [adjusted odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.67–0.98 for ‐168TC; OR = 0.83, 95% CI = 0.69–1.00 for ‐168TC/CC, respectively]. Furthermore, this significant protective effect was more evident for gastric cardia cancer patients (adjusted OR = 0.73, 95% CI = 0.56–0.95 for ‐168TC/CC vs. ‐168TT). For IL2 G‐330T, subjects carrying GT/TT genotypes also had a significantly reduced risk of gastric cardia cancer (adjusted OR = 0.68, 95% CI = 0.46–0.99), compared with those carrying the GG genotype. Our results indicate that IL4 T‐168C and IL2 G‐330T promoter polymorphisms may contribute to the etiology of gastric cardia cancer in Chinese populations. © 2008 Wiley‐Liss, Inc.
Opposite Effects of Enalapril and Nitrendipine on Natriuretic Response to Atrial Natriuretic Factor: Renal Function Evaluated With Clearance Studies in Humans

In clearance studies, we analyzed the effect of Ca2+ entry blockade with nitrendipine treatment (20 mg b.i.d. for 4 days) and of converting enzyme inhibition with enalapril treatment (20 mg b.i.d. for 4 days) on renal response to atrial natriuretic factor (ANF) (25 μg bolus followed by an infusion of 0.03 /μg/kg/min for 90 minutes) in six healthy volunteers who were taking 300 mmol sodium daily. In a control study ANF was administered without Ca2+ entry blockade or converting enzyme inhibition. Natriuresis rose from 239±38 to 605±137 /imol/min in the control study (p < 0.05), from 330±53 to 943±152 /unol/min with Ca2+ entry blockade (p < 0.05), and from 236±22 to 344±39 /μmol/min with converting enzyme inhibition (NS). ANF induced a rise in mairinial free water clearance, inulin clearance, and in the excretion of multiple electrolytes except potassium. Fractional lithium reabsorption fell. In general, these effects were stronger during Ca2+ entry blockade and blunted during converting enzyme inhibition. p-Aminohippurate clearance tended to decrease during the control study (NS), remained constant during Ca2+ entry blockade, and decreased significantly when ANF was infused during converting enzyme inhibition (p < 0.05 vs. control and vs. Ca2+ entry blockade study). Blood pressure was lowered by Ca2+ entry blockade and, to a somewhat greater extent, by converting enzyme inhibition, but ANF administration induced no additional fall except for a short-term drop during Ca2+ entry blockade. From these data we conclude that, in healthy humans, the effects of ANF on natriuresis and renal sodium handling are enhanced by Ca2+ entry blockade and blunted by converting enzyme inhibition. These effects might be explained by amplification of (preglomerular? ) ANF-induced vasodilation during Ca2+ entry blockade and amplification of (postglomerular? ) ANF-induced vasoconstriction during converting enzyme inhibition.
Management of Contralateral N0 Neck in Pyriform Sinus Carcinoma

Objective: The hypopharynx has a rich lymphatic network that places patients with tumors of the hypopharynx at high risk for early dissemination of the disease into the cervical lymphatics. Therefore, ipsilateral elective neck dissection of clinically N0 neck in lateralized lesions of hypopharyngeal squamous cell carcinomas (SCCs) is widely accepted as a standard treatment. However, the management of the contralateral N0 neck is still controversial. The aim of this study was to evaluate the incidence and predictive factors of contralateral occult lymph node metastasis in pyriform sinus SCC.
The role of forward‐ and backward‐looking information for inflation expectations formation

Assuming that private forecasters learn inflation dynamics to form their inflation expectations and that they believe a hybrid New Keynesian Phillips curve (NKPC) to capture the true data‐generating process of inflation, we aim at establishing the role of backward‐ and forward‐looking information in the inflation expectation formation process. We find that longer term expectations are crucial in shaping shorter horizon expectations. While the influence of backward‐looking information seems to diminish over time, we do not find evidence of a structural break in the expectation formation process of professional forecasters. Our results further suggest that the weight put on longer term expectations does not solely reflect a mean‐reverting process to trend inflation. Rather, it might also capture beliefs about the central bank's long‐run inflation target and its credibility to achieve inflation stabilization.
Pattern of interictal hypometabolism in PET scans with fludeoxyglucose F 18 reflects prior seizure types in patients with mesial temporal lobe seizures.

BACKGROUND Interictal hypometabolism is routinely used as an indicator of the epileptogenic zone in patients with complex partial seizures (CPSs). However, the regional pattern of hypometabolism varies without obvious reasons, even among patients with identical epileptogenic zones and causes. OBJECTIVE To investigate whether this pattern may be related to the electroencephalographic and clinical features of the seizure that precedes the positron emission tomographic (PET) scan with fludeoxyglucose F 18. PATIENTS AND METHODS Fifty-three patients with CPSs were first classified into 4 groups, depending on the features of the seizure that preceded the PET scan (determined from findings from electroencephalography and videotelemetry). In 14 patients, this seizure was focal limbic (characterized by aurae or staring spells); in 18, the CPS was widespread limbic (including automatisms). Ten patients had a CPS with posturing, and 11 had a secondarily generalized CPS. Regions with a hemisphere-normalized concentration of fludeoxyglucose F 18 below the 95% confidence interval of values from 8 control subjects were defined as hypometabolic. The location of these regions was then compared among the 4 groups, and the degree of hypometabolism was related to the time from the seizure to the PET scan with fludeoxyglucose F 18. RESULTS The hypometabolic area was limited to the epileptogenic zone if the preceding seizure was focal limbic, whereas in patients with widespread limbic seizures, it included one or several additional areas of the limbic cortex (P = .03). Patients with posturing differed from both previous groups by having hypometabolism in the extralimbic frontal lobe (P < .001), and subjects with secondarily generalized seizures differed from all others because of cerebellar (P < .001) and parietal lobe (P < .05) reductions. The time between the seizure and the performance of the PET scan did not correlate with the degree or extent of hypometabolism. CONCLUSIONS Mechanisms involved in the generation of a seizure that precedes a PET scan with fludeoxyglucose F 18 seem to influence the "interictal" hypometabolic pattern. Therefore, caution should be used when interpreting scans that are preceded by a nonhabitual seizure.
Morphological characterisation of Crohn’s disease fistulae

Background: Fistulae are a common complication in up to 35% of all patients with Crohn’s disease. Their therapy is difficult and frequently unsatisfactory. To date, no histological comparison of Crohn’s disease fistulae with non-inflammatory bowel disease fistulae has been performed. In addition, Crohn’s disease fistulae have not been well characterised morphologically. Methods: Eighty four fistulae from Crohn’s disease patients were compared with 13 fistulae from controls. Haematoxylin-eosin staining, electron microscopy, and immunohistochemistry for panCytokeratin (epithelial cells), CD20 (B cells), CD45R0 (T cells), and CD68 (macrophages) were performed according to standard techniques. In addition, histopathological findings were compared with clinical and laboratory data. Results: In 31.0% of controls and 27.4% of Crohn’s disease specimens, fistulae had a lining of flattened intestinal epithelium without goblet cells or, in the case of cutaneous/perianal disease, narrow squamous epithelium. Non-epithelialised fistulae were covered by a thin layer of (myo)fibroblasts, focally forming a new basement membrane, as demonstrated by electron microscopy. All fistulae were surrounded by granulation tissue. Crohn’s disease fistulae presented with central infiltration by CD45R0+ T cells, followed by a small band of CD68+ macrophages and dense accumulation of CD20+ B cells. In contrast, in controls, there was dense infiltration by CD68+ macrophages with only few CD20+ B cells and CD45R0+ T lymphocytes. Conclusions: Fistulae in Crohn’s disease differ markedly from non-Crohn’s disease fistulae with regard to their cellular composition. The presence of an epithelial lining in a subgroup of fistulae may be important for the therapeutic approach and healing process.
Chronic kidney disease in the BCR-ABL1-negative myeloproliferative neoplasm: a single-center retrospective study

Background/Aims Renal complications related to BCR-ABL1-negative myeloproliferative neoplasms (MPNs) have not been examined fully in Asian populations. Methods We analyzed estimated glomerular filtration rate (eGFR) and its changes with time retrospectively in patients with BCR-ABL1-negative MPN from 2005 to 2015. Results The prevalence of chronic kidney disease (CKD) was 11% (6.6% having stage 3 and 4.4% having stage 4). In a linear regression analysis of eGFR versus time (years), overall, patients showed increased eGFR (mL/min/1.73 m2) by 0.51 (95% confidence interval [CI], –0.30 to 1.33; p = 0.22). Patients with polycythemia vera (PV), and those treated with hydroxyurea, showed statistically significant increases in eGFR (1.59; 95% CI, 0.28 to 2.90; p = 0.22 in PV; and 1.55; 95% CI, 0.56 to 2.54; p = 0.22 in treatment with hydroxyurea). In total, 17 patients (20.5%) showed rapid loss of eGFR (<–3 mL/min/1.73 m2per year). This rapid loss in eGFR was associated with a higher incidence of kidney disease (23.5% vs. 6.1%, p= 0.05) and a higher percentage of patients with high neutrophil (>7.0 × 109 /L) and high monocyte (> 0.7 × 109 /L) counts (76.5% vs. 50%, p=0.05; 52.9% vs. 28.8%, p= 0.06, respectively). More patients had high serum lactate dehydrogenase (> 500 U/L) levels (52.9% vs. 25.8%, p = 0.03) at diagnosis. Conclusions CKD is prevalent in patients with BCR-ABL1-negative MPN. Active cytoreductive therapy has the potential to improve kidney function in BCR-ABL1-negative MPN.
Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister–Killian syndrome

Identification of the isochromosome 12p (i(12p)) associated with Pallister–Killian syndrome is complicated by the low frequency of this supernumerary chromosome in PHA stimulated peripheral blood lymphocytes, and frequently requires cytogenetic analysis of fibroblast cells. Recently, it has been shown that array CGH techniques are able to detect tetrasomy 12p in peripheral blood, even when not identified by traditional cytogenetic techniques. We studied 15 patients with a previous cytogenetic and clinical diagnosis of Pallister–Killian syndrome using genome‐wide SNP arrays to investigate the ability of this platform to identify the i(12p) in blood and tissue. Array analysis verified tetrasomy 12p in all samples from fibroblasts, but was only able to detect it in 46% of blood samples. The genotyping information available from the SNP arrays allowed for the detection of as low as 5% mosaicism, as well as suggesting a Meiosis II origin for the isochromosome in the majority of patients. Analysis of the percentage of abnormal cells with patient age at time of study suggests that the frequency of the i(12p) decreased with age in blood, but not in fibroblasts. These highlight the power of SNP arrays in detecting and characterizing the isochromosome 12p in Pallister–Killian syndrome as well as underscoring the important utility of traditional cytogenetic techniques. © 2012 Wiley Periodicals, Inc.
Harvesting the middle hepatic vein with a right hepatectomy does not increase the risk for the donor

The harvesting of the middle hepatic vein (MHV) with a right hepatectomy for living‐donor liver transplantation allows an optimal venous drainage for the recipient but can also have adverse effects for the donor. This study compares morbidity, early liver function, and volume regeneration in 2 groups of donors who underwent right hepatectomy with (MHV+, n = 21) or without (MHV−, n = 20) MHV harvesting during 2 successive periods. The operative time was 401 ± 60 minutes in the MHV+ group compared with 392 ± 63 minutes in the MHV− group, and the transection time was 152 ± 53 minutes in the MHV+ group compared with 131 ± 30 minutes in the MHV− group (not significant). Blood loss in the MHV+ group was 773 ± 343 mL compared with 613 ± 361 mL in the MHV− group (not significant). The graft weight and remnant liver volume ratio were similar in the MHV+ and MHV− groups (763 ± 200 gm vs. 832 ± 156 gm and 42% ± 9.5% vs. 43% ± 8.3%, respectively). Postoperative biologic liver function tests showed that prothrombin time (PT) ratio on postoperative days 1 and 3 were significantly lower in the MHV+ group compared with the MHV− group (53% vs. 65% and 63% vs. 72%, respectively, P < .05). There were no differences in postoperative alanine aminotransferase and aspartate aminotransferase peak levels between the MHV+ and MHV− groups (319 ± 198 IU /L vs. 310 ± 110 IU /L and 317 ± 226 IU /L vs. 296 ± 125 IU /L, respectively). Bilirubin maximal blood level was similar in the 2 groups (32 ± 17 μmol/L in the MHV+ group vs. 43 ± 16 μmol/L in the MHV− group, P < .05). No donor died. The overall morbidity was lower in the MHV+ group compared with the MHV− group (36% vs. 55%; P > .05, not significant). The donor's remnant liver volume regeneration, evaluated by computed tomography (CT) volumetric study on day 7, was similar in the 2 groups (97% ± 29% in the MHV+ group and 103% ± 39% in the MHV− group, P > .05). The results of this comparative study show that right hepatectomy with the MHV neither affects morbidity nor impairs early liver function and regeneration in donors. (Liver Transpl 2004;10:71–76.)
Gene-expression profiling in vaccine therapy and immunotherapy for cancer

The identification of tumor antigens recognized by T cells led to the design of therapeutic strategies aimed at eliciting adaptive immune responses. The last decade of experience has shown that, although active immunization can induce enhancement of anticancer T-cell precursors (easily detectable in standard assays), most often they are unable to induce tumor regression and, consequently, have scarcely any impact on overall survival. Moreover, in the few occasions when tumor rejection occurs, the mechanisms determining this phenomenon remain poorly understood, and data derived from in vivo human observations are rare. The advent of high-throughput gene-expression analysis (microarrays) has cast new light on unrecognized mechanisms that are now deemed to be central for the development of efficient immune-mediated tumor rejection. The aim of this article is to review the data on the molecular signature associated with this process. We believe that the description of how the mechanism of immune-mediated tissue destruction occurs would contribute to our understanding of why it happens, thereby allowing us to develop more effective immune therapeutic strategies.
Bond Strength and Bioactivity of Zn-Doped Dental Adhesives Promoted by Load Cycling

Abstract The purpose of this study was to evaluate if mechanical loading influences bioactivity and bond strength at the resin–dentin interface after bonding with Zn-doped etch-and-rinse adhesives. Dentin surfaces were subjected to demineralization by 37% phosphoric acid (PA) or 0.5 M ethylenediaminetetraacetic acid (EDTA). Single bond (SB) adhesive—3M ESPE—SB+ZnO particles 20 wt% and SB+ZnCl2 2 wt% were applied on treated dentin to create the groups PA+SB, SB+ZnO, SB+ZnCl2, EDTA+SB, EDTA+ZnO, and EDTA+ZnCl2. Bonded interfaces were stored in simulated body fluid for 24 h and tested or submitted to mechanical loading. Microtensile bond strength (MTBS) was assessed. Debonded dentin surfaces were studied by high-resolution scanning electron microscopy. Remineralization of the bonded interfaces was assessed by atomic force microscope imaging/nanoindentation, Raman spectroscopy/cluster analysis, and Masson’s trichrome staining. Load cycling (LC) produced reduction in MTBS in all PA+SB, and no change was encountered in EDTA+SB specimens, regardless of zinc doping. LC increased the mineralization and crystallographic maturity at the interface; a higher effect was noticed when using ZnO. Trichrome staining reflected a narrow demineralized dentin matrix after loading of dentin surfaces that were treated with SB-doped adhesives. This correlates with an increase in mineral platforms or plate-like multilayered crystals in PA or EDTA-treated dentin surfaces, respectively.