Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer Stem Cell Gene Variants in CD44 Predict Outcome in Stage II and Stage III Colon Cancer Patients.

BACKGROUND/AIM Growing evidence suggests that human cancers are stem cell diseases and recent data support the existence of cancer stem cells (CSCs) in a variety of malignancies, including colon cancer. These CSCs were shown to be capable of initiating tumor development and progression. Several studies have suggested CD133, CD26 and CD44 as markers of tumor-initiating cells of colon cancer. The purpose of the present study was to assess the impact of single-nucleotide polymorphisms (SNPs) in stem cell-related genes on clinical outcome in a large cohort of colon cancer patients with clinical stage II and III. PATIENTS AND METHODS Data from 599 consecutive patients with colon cancer stage II and III, treated between 1995 and 2011 at a single centre, were retrospectively evaluated. Genomic DNA was extracted from paraffin-embedded normal tissue distant from the tumor to obtain germline DNA. Allelic distribution of polymorphisms was tested for deviation from Hardy-Weinberg equilibrium using χ2-test. The association of polymorphisms with time to recurrence (TTR) and overall survival (OS) was analyzed using Kaplan-Meier curves and compared by the log-rank test. Case-wise deletion for missing polymorphisms was used in univariable and multivariable analyses. RESULTS CD44 rs187115 showed a statistically significant association with TTR; patients carrying at least one G allele had a significant reduced risk of recurrence compared to patients with the homozygous A/A variant (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.48-0.94, p=0.019). CD44 rs13347 showed a statistically significant association with OS. Patients carrying at least one T allele in rs13347 had a significantly reduced risk of death compared to patients with the homozygous C/C variant (HR=0.61, 95% CI=0.41-0.92, p=0.019). None of the other investigated polymorphisms (CD44 rs187116, CD44 rs7116432, CD44 rs353639, DPP4 rs2268889, DPP4 rs3788979, DPP4 rs7608798 and CD133 rs2240688) were associated with either TTR or OS. CONCLUSION Germline variants rs13347 and rs187115 in the stem cell gene CD44 are prognostically relevant in stage II and III colon cancer patients.
Dental Habits, Knowledge, and Attitudes of Young Drug Addicts

The aim of the present study was to obtain information about a group of young drug addicts' dental habits, knowledge, and attitudes. Semistructured interviews with openended questions based on well-defined hypotheses were obtained with 20 intravenous drug addicts attending a Danish addiction clinic. All the interviews were taped and typed out verbatim. The analysis of the interviews was primarily carried out qualitatively. Almost all the addicts had been enrolled in the Public Child Dental Care system and the majority vividly remembered this as an unpleasant experience. None of the addicts attended a dentist regularly after having finished school, when the drug abuse usually started. Only a need for acute relief could generally motivate the addicts to visit a dentist, and in the few instances they were questioned about any drug abuse or viral hepatitis infection they usually concealed this. They evidenced very limited knowledge concerning the causes and prevention of dental decay and periodontal disease, and the high prevalence of dental caries was often believed to be caused solely or partly by the ascorbic acid or citric acid that is mixed and injected together with the drugs. A distinct behaviour with a neglected oral hygiene and an excessive intake of candy, soft drinks, and other food with a high sugar content was common. The dietary habits were related to the injection of the drugs in a ritual manner. The drug addicts only realized how deplorable their dental health had become during periods of abstinence, and then they were often embarrassed or ashamed of their esthetic appearance, although this was not perceived to have a negative influence on attempts at resocialization. Any improvement in the dental behaviour in this group and a decrease in their dental disease is undoubtedly closely connected with stopping drug abuse, or at least reducing it, together with an improvement in these individuals' entire situation.
Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis

Objective To evaluate the relationship between subclinical hypothyroidism (SCH) and the risk of miscarriage before 20 weeks of pregnancy. Methods Literature databases were searched, including the PubMed, Web of Science, Embase and Cochrane databases, from January 1, 1980, to December 31, 2015. The following search terms were used: subclinical hypothyroidism, hypothyroidism, thyroid dysfunction, thyroid hypofunction, subclinical thyroid disease, thyroid dysfunction, pregnancy loss, abortion and miscarriage. Studies comparing the prevalence of miscarriage in pregnant women with SCH with those who were euthyroid were selected. From the studies matched, the relative risk (RR) and corresponding 95% confidence interval (95% CI) were calculated to yield outcomes. All the statistical analyses were performed using Review Manager (Revman) Version 5.3 and Stata Version 12.0 software. The publication bias of the studies was assessed by forest plot and Begg’s test, while the stability of the results was evaluated by sensitivity analysis. Results Nine articles satisfying the inclusion criteria were analysed. Compared to euthyroid pregnant women, patients with non-treated SCH had a higher prevalence of miscarriage (RR = 1.90, 95% CI1.59–2.27, P<0.01). Additionally, SCH patients in the international diagnostic criteria group were more likely to suffer miscarriages than those in the ATA diagnostic criteria group (χ2 = 11.493, P<0.01). Moreover, there was no difference between patients with treated SCH and euthyroid women (RR = 1.14, 95% CI0.82–1.58, P = 0.43). Compared to isolated SCH women, the miscarriage risk of SCH patients with thyroid autoimmunity (TAI) was obviously higher (RR = 2.47, 95% CI1.77–3.45, P<0.01), and isolated SCH patients also had a higher prevalence of miscarriages than euthyroid women (RR = 1.45, 95% CI1.07–1.96, P = 0.02). A heterogeneity test, forest plot and Begg’s test suggested that there was no significant heterogeneity or publication bias among the included articles, while the result of sensitivity analysis showed that our study exhibited high stability. Conclusion SCH is a risk factor for miscarriage in women before 20 weeks of pregnancy, and early treatments can reduce the miscarriage rate. Regardless of the diagnostic criteria used, the miscarriage rate increased as long as a pregnant woman was confirmed to have SCH. The results show that the omission diagnostic rate may increase when the ATA diagnostic criteria are used. In addition, SCH patients with TAI have a higher prevalence of miscarriage, while isolated SCH patients also have a higher miscarriage rate than euthyroid women. Thus, we recommend early treatments to avoid adverse pregnancy outcomes and complications.
A synthetic lethal screen identifies ATR-inhibition as a novel therapeutic approach for POLD1-deficient cancers

The phosphoinositide 3-kinase-related kinase ATR represents a central checkpoint regulator and mediator of DNA-repair. Its inhibition selectively eliminates certain subsets of cancer cells in various tumor types, but the underlying genetic determinants remain enigmatic. Here, we applied a synthetic lethal screen directed against 288 DNA-repair genes using the well-defined ATR knock-in model of DLD1 colorectal cancer cells to identify potential DNA-repair defects mediating these effects. We identified a set of DNA-repair proteins, whose knockdown selectively killed ATR-deficient cancer cells. From this set, we further investigated the profound synthetic lethal interaction between ATR and POLD1. ATR-dependent POLD1 knockdown-induced cell killing was reproducible pharmacologically in POLD1-depleted DLD1 cells and a panel of other colorectal cancer cell lines by using chemical inhibitors of ATR or its major effector kinase CHK1. Mechanistically, POLD1 depletion in ATR-deficient cells caused caspase-dependent apoptosis without preceding cell cycle arrest and increased DNA-damage along with impaired DNA-repair. Our data could have clinical implications regarding tumor genotype-based cancer therapy, as inactivating POLD1 mutations have recently been identified in small subsets of colorectal and endometrial cancers. POLD1 deficiency might thus represent a predictive marker for treatment response towards ATR- or CHK1-inhibitors that are currently tested in clinical trials.
A regret theory-based route choice model

ABSTRACT In this paper, a regret-theory-based stochastic user equilibrium model of route choice is proposed by introducing a regret aversion parameter to reflect the regret degree of travelers. Route choice is governed by a logit formula in which the disutility of a route is codetermined by its performance and the anticipated regret experienced by comparing with other competitive routes. The proposed model is formulated as a variational inequality problem and solved by the path-based algorithm using the method of successive averages. Numerical results obtained from three example networks show that the attitude of regret aversion indeed affects the travelers’ route choice behavior and that the proposed model can more flexibly depict the choice behavior than existing models.
Assessment of Use of the COBAS AMPLICOR System with BACTEC 12B Cultures for Rapid Detection of Frequently Identified Mycobacteria

ABSTRACT The use of the COBAS AMPLICOR System (Roche Molecular Diagnostics, Basel, Switzerland), the only automated system for PCR testing, was evaluated for a rapid identification of mycobacteria with positive BACTEC 12B cultures. Two hundred ninety-six specimens with a growth index of ≥30 were analyzed for the presence of Mycobacterium tuberculosis complex, Mycobacterium avium, andMycobacterium intracellulare. Compared to traditional methods and provided that samples with PCR inhibition are retested at a 1:10 dilution, the sensitivity and specificity of the COBAS AMPLICOR System with BACTEC 12B cultures were 100 and 98%, respectively. The COBAS AMPLICOR method is rapid and reliable for identifying the most common mycobacteria in cultures.
Asymmetries in import-retail cost pass-through: Analysis of the seafood value chain in Germany

ABSTRACT This study examines the degree of price transmission in the German Alaska pollock, cod and salmon value chains. Moreover, in addition to aggregated market prices used in most studies, access to prices by retailer type allows investigation of different adjustment patterns by value chain. Using monthly average prices, the Johansen and consistent threshold cointegration models are estimated. The results indicate the presence of price transmission relationship and equilibrium adjustment asymmetries, such that agents only react to shocks when the deviation from equilibrium is above or below a certain nonzero threshold value. In most cases, retail outlets exercise market leadership in the Alaska pollock and cod chains while some bidirectional adjustments are observed in the salmon value chains. Overall, import prices adjust to deviations above the threshold value following a shock to the retail prices for Alaska pollock and cod. For salmon, deviations above the threshold value are generally not transmitted.
Predictable Surprise: The Spatial and Social Morphology of Aging Suburbs in the U.S. Metropolitan Areas

Elderburbs, defined as old suburban neighborhoods in terms of their ‘built environments’ and ‘demographic structures’, have emerged prominently in academic discussion due to the social vulnerability and outdated built environments of senior dominant neighborhoods that barely meet the needs of their aging populations. Even though previous literature has revealed concerns about suburban decline and the growing number of seniors, these two points of interest have largely been examined in isolation from one another. Thus, this paper attempts to unveil the spatial and social morphology of Elderburbs in 20 U.S. metropolitan areas from 1990 to 2010. Elderburbs were identified by two major criteria; built year (first-generation suburbs built between 1950 and 1970) and demographic aging (based on elderly, elderly-child, and elderly dependency ratios). The findings of this study indicate that Elderburbs have increased and expanded out to suburban areas, especially in the Northeast and Midwest. On the contrary, Elderburbs in the South have decreased and moved closer to core cities. Differing from our assumptions, both Elderburbs and Elderurbans were found to be less socially vulnerable than ordinary suburban and urban neighborhoods.
Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyrene

Benzo[a]pyrene (BaP) is an agonistic ligand for the aryl hydrocarbon receptor (AhR) and a major environmental carcinogen implicated in the aetiology of lung cancer through the induction of benzo[a]pyrene diol epoxidation (BPDE) and BPDE–DNA adducts. Because BaP metabolization requires cytochrome P‐450 1A1 (CYP1A1) induction through activation of the AhR, we hypothesized that resveratrol, a natural competitive inhibitor of AhR, could prevent these adverse effects of BaP on the lung. Balb‐C mice were injected for 5 weeks with corn oil, BaP (5 mg kg−1 week−1), resveratrol (50 mg kg−1 week−1) or BaP + resveratrol. Immunohistochemistry was performed on lung sections for the determination of CYP1A1 protein, BPDE–DNA adducts and apoptosis. A semi‐quantitative immunohistochemistry score (H score) was used for data analysis. Mice exposed to BaP had a signiﬁcant induction of lung BPDE–DNA adducts when compared with controls (H scores: control, 26, interquartile range 18–33; BaP, 276, interquartile range 269–288; P < 0.01). The BPDE–DNA adduct induction by BaP was abrogated signiﬁcantly by resveratrol (H score: BaP + resveratrol, 103, interquartile range 96–113). A similar pattern was found by immunohistochemistry for apoptosis (H scores: control, 121, interquartile range 102–137; BaP, 288, interquartile range 282–292, P < 0.05; BaP + resveratrol, 132, interquartile range 121–141, P = NS) and CYP1A1 (H scores: control, 170.3, interquartile range 164–175; BaP, 302.3, interquartile range 291–315, P < 0.05; BaP + resveratrol, 200.7, interquartile range 174–215, P = NS). Western blotting conﬁrmed that resveratrol prevented BaP‐induced CYP1A1 expression. This increase in CYP1A1 expression in response to BaP administration most likely causes BaP metabolism, BPDE–DNA adduct formation and subsequent apoptosis. All BaP‐induced effects could be prevented by resveratrol, suggesting a possible chemopreventive role for this natural phytoalexin against the development of lung cancer. Copyright © 2003 John Wiley & Sons, Ltd.
İdeal Emeklilik Yaşının Belirlenmesi ve Yaşlanmadaki Gelişmeler: Türkiye Üzerine Bir İnceleme

Nufusun yaslanmasi, sosyal guvenlik planlarinin surdurulebilirligi acisindan onemli etkiye sahiptir. Tartisma, demografik egilimlerin ideal emeklilik yasinin belirlenmesine yansitilip yansitilmamasi veya nasil yansitilacagi uzerinedir. Calismada, nufus yapisi ve olumlulukte meydana gelen gelismeler temel alinarak, nufusun yaslanmasi olculerinden geleneksel ve ileriye donuk olanlar kullanilarak ve farkli karar kriterleri karsilastirilarak emeklilik yasi belirlenmektedir. Sabit beklenen omru ve nesiller arasi adaleti temel alan kritere gore emeklilik yasi, sabit destek oranina nazaran daha yuksektir, zaman icinde dalgalanma gosterir ve kadinlarda erkeklere gore daha yuksektir. Onerilen yaslar, 2010 yili icin daha az farkli olmakla birlikte genelde resmi emeklilik yasindan oldukca farklidir. Yaslanmayi farkli olcme yontemleri, yaslilik tanimlari ve farkli karar kriterleri her bir paydasin ragbet edecegi degisen ideal emeklilik yasini beraberinde getirmektedir. Yastaki cinsiyetler arasi farklar ile hali hazirdaki nufus ve olumluluk egilimleri ise daha esnek olarak degerlendirilmelidir
Meta-analysis of associations between telomere length and colorectal cancer survival from observational studies

Background Telomere length (TL) has been reported to be associated with the risk and survival of several cancers. But it is unclear for the prognostic role of TL in colorectal cancer (CRC). Materials and Methods Relevant citations were searched and identified using several major online databases through April 2017 which investigated associations between TL and CRC prognosis. We combined summary estimates using hazard ratios (HRs) with 95% confidence interval (CI), which were pooled using a random-effects model. Overall survival (OS) was set as the primary outcome of interest. Results There are 8 cohort studies encompassing 1622 patients included in the meta-analysis. Pooled estimate indicated that long TL was not significantly associated with patient OS (HR 1.26, 95% CI, 0.76 to 2.08). When we conducted subgroup analyses based on baseline charcteristics, we found that long TL (versus short TL) was significantly associated with poor OS in studies conducted in Europe (n = 4, HR 2.73, 95% CI, 1.65 to 4.52, I2 = 0), using Southern blot to measure TL (n = 3, HR 2.93, 95% CI, 1.69 to 5.10, I2 = 0) and patients’ age more than 60 years (n = 3, HR 2.65, 95% CI, 1.22 to 5.76, I2 = 0). We found no significant associations between TL and patient disease-free, recurrence-free or progression-free survival (HR 1.19, 95% CI, 0.45 to 3.15). Conclusions Current evidence did not provide solid indication that long TL is significantly associated with improved or poor survival for patients with CRC. Further large sample size prospective cohort studies are warranted to determine the true relationship for specific patients.
Diagnosis of thrombotic thrombocytopenic purpura based on modulation by patient plasma of normal platelet adhesion under flow condition

Summary. We have designed a simple test for the early diagnosis and treatment monitoring of thrombotic thrombocytopenic purpura (TTP). We examined plasma from 24 TTP patients and normal plasma using a cone and plate(let) analyser (CPA). Test plasma was mixed with citrated normal whole blood (group O) and subjected to flow at a shear rate of 1800/s. Mixing normal plasma (12·5, 25, 50 or 75 µl) with heterologous normal whole blood (final volume of 200 µl) resulted in a decrease of surface coverage (SC, maximally by 63%) and, to a lesser extent, of average size (AS, maximally by 37%) due to dilution of the blood sample. In contrast, mixing the same quantities of acute TTP plasma with normal blood yielded an increase in both SC (up to 125%) and AS (up to 130%). Increased SC and/or AS were detected in all 15 patients in acute phase and in three out of 14 patients in remission. Following repeated plasmapheresis, the enhanced platelet deposition in five patients with acute TTP returned to almost normal patterns. Mixing plasma from patients with other thrombocytopenic conditions in this way resulted in a decrease in both SC and AS, and did not differ from control subjects. In conclusion, the CPA is a simple and specific laboratory test that can be used for the diagnosis and monitoring of plasma exchange therapy in TTP.
Protoporphyrin IX Fluorescence Photobleaching during ALA‐Mediated Photodynamic Therapy of UVB‐Induced Tumors in Hairless Mouse Skin

Abstract— Fluorescence photobleaching of protoporphyrin IX (PpIX) during superficial photodynamic therapy (PDT), using 514 nm excitation, was studied in UVB‐induced tumor tissue in the SKH‐HR1 hairless mouse. The effects of different irradiance and light fractionation regimes upon the kinetics of photobleaching and the PDT‐induced damage were examined. Results show that the rate of PpIX photobleaching (i.e. fluorescence intensity vs fluence) and the PDT damage both increase with decreasing irradiance. We have also detected the formation of fluorescent PpIX photoproducts in the tumor during PDT, although the quantity recorded is not significantly greater than generated in normal mouse skin, using the same light regime. The subsequent photobleaching of the photoproducts also occurs at a rate (vs fluence) that increases with decreasing irradiance. In the case of light fractionation, the rate of photobleaching increases upon renewed exposure after the dark period, and there is a corresponding increase in PDT damage although this increase is smaller than that observed with decreasing irradiance. The effect of fractionation is greater in UVB‐induced tumor tissue than in normal tissue and the damage is enhanced when fractionation occurs at earlier time points. We observed a variation in the distribution of PDT damage over the irradiated area of the tumor: at high irradiance a ring of damage was observed around the periphery. The distribution of PDT damage became more homogeneous with both lower irradiance and the use of light fractionation. The therapeutic dose delivered during PDT, calculated from an analysis of the fluorescence photobleaching rate, shows a strong correlation with the damage induced in normal skin, with and without fractionation. The same correlation could be made with the data obtained from UVB‐induced tumor tissue using a single light exposure. However, there was no such correlation when fractionation schemes were employed upon the tumor tissue.
Characterization of fibronectin assembly by platelets adherent to adsorbed laminin‐111

Summary. Background: Various types of laminin (LN) are ubiquitous components of basement membrane and exposed to blood upon localized damage of vascular endothelial cells. Fibronectin is a plasma protein that is insolubilized into fibrils in a regulated fashion by, for example, lysophosphatidic acid (LPA)‐stimulated fibroblasts or platelets spread on supportive adhesive ligands. Objective: To study assembly of plasma fibronectin by LPA‐activated platelets adherent to LN‐111 via α6β1 integrin. Results: Platelets adherent to LN‐111‐bound plasma fibronectin or its N‐terminal 70 kD fragment in fibrillar arrays at the periphery of spread platelets under static but not shear conditions. Formation of fibronectin arrays under static conditions was inhibited by co‐incubation with the N‐terminal 70 kD fragment or with a 49‐amino acid peptide that binds to the N‐terminal region of fibronectin. Approximately 7000 fibronectin dimers bound per adherent platelet with a Kd of 50 nm. Bound 70 kD fragment was readily solubilized with deoxycholate (DOC), whereas bound fibronectin became progressively insoluble. Bound 70 kD fragment became resistant to DOC extraction after treatment with a cell‐impermeable, reducible crosslinker. Crosslinked 70 kD fragment was found in a high molecular weight complex. As with fibroblasts, signaling molecules modulating actin cytoskeletal organization controlled expression of binding sites for the N‐terminal 70 kD region of fibronectin on adherent platelets. Conclusions: These results indicate that platelets adherent to LN‐111 via α6β1 support subsequent assembly of fibronectin, but possibly only under conditions of intermittent or stagnant blood flow.