bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells
Authors: Paquet-Fifield Sophie , Koh Shir Lin , Cheng Lesley , Beyit Laura M. , Shembrey Carolyn , Mølck Christina , Behrenbruch Corina , Papin Marina , Gironella Meritxell , Guelfi Sophie , Nasr Ramona , Grillet Fanny , Prudhomme Michel , Bourgaux Jean-Francois , Castells Antoni , Pascussi Jean-Marc , Heriot Alexander G. , Puisieux Alain , Davis Melissa J. , Pannequin Julie , Hill Andrew F. , Sloan Erica K. , Hollande Frédéric 
Published: March 2018

Abstract
Posttreatment recurrence of colorectal cancer, the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSC). The tight junction (TJ) protein claudin-2 is overexpressed in human colorectal cancer, where it enhances cell proliferation, colony formation, and chemoresistance in vitro. While several of these biological processes are features of the CSC phenotype, a role for claudin-2 in the regulation of these has not been identified. Here, we report that elevated claudin-2 expression in stage II/III colorectal tumors is associated with poor recurrence-free survival following 5-fluorouracil–based chemotherapy, an outcome in which CSCs play an instrumental role. In patient-derived organoids, primary cells, and cell lines, claudin-2 promoted colorectal cancer self-renewal in vitro and in multiple mouse xenograft models. Claudin-2 enhanced self-renewal of ALDHHigh CSCs and increased their proportion in colorectal cancer cell populations, limiting their differentiation and promoting the phenotypic transition of non-CSCs toward the ALDHHigh phenotype. Next-generation sequencing in ALDHHigh cells revealed that claudin-2 regulated expression of nine miRNAs known to control stem cell signaling. Among these, miR-222-3p was instrumental for the regulation of self-renewal by claudin-2, and enhancement of this self-renewal required activation of YAP, most likely upstream from miR-222-3p. Taken together, our results indicate that overexpression of claudin-2 promotes self-renewal within colorectal cancer stem-like cells, suggesting a potential role for this protein as a therapeutic target in colorectal cancer.
Significance: Claudin-2-mediated regulation of YAP activity and miR-222-3p expression drives CSC renewal in colorectal cancer, making it a potential target for therapy. Cancer Res; 78(11); 2925–38. ©2018 AACR.
Estrogen Metabolism in Premenopausal Women Is Related to Early Life Body Fatness
Authors: Houghton Lauren C. , Sisti Julia S. , Hankinson Susan E. , Xie Jing , Xu Xia , Hoover Robert N. , Eliassen A. Heather , Ziegler Regina G. 
Published: March 2018

Abstract
Background: Estrogen metabolism in premenopausal women may be related to early life body fatness.
Methods: Premenopausal women participating in the Nurses' Health Study II recalled their body fatness at ages 5, 10, and 20 years using a validated 9-level pictogram. Fifteen estrogens and estrogen metabolites (EM) were measured using LC/MS-MS in luteal phase urines from 603 women ages 32–54 years. Geometric means of individual EM, metabolic pathway groups, and pathway ratios were examined by body fatness categories using linear mixed models.
Results: Body fatness at each age was inversely associated with adult concentrations of all EM combined, parent estrogens (estrone, estradiol), and the 2-hydroxylation pathway. Women in the top (vs. bottom) category of body fatness at age 10 had 21% lower levels of all EM (Ptrend = 0.003), 24% lower parent estrogens (Ptrend = 0.002), and 36% lower 2-pathway (Ptrend = 0.0003). Body fatness at age 10 was inversely associated with 2-catechols (35% lower, Ptrend = 0.0004) and 2-methylated catechols (30% lower, Ptrend = 0.002). After adjusting for premenopausal body mass index (BMI), these associations remained inverse but were attenuated; only parent estrogens remained statistically significant (21% lower, Ptrend = 0.01). Body fatness at ages 5 and 20 were similarly, but more weakly, associated with estrogen pathways.
Conclusions: Estimates of body fatness during early life were inversely associated with premenopausal levels of all EM combined, parent estrogens, and 2-pathway estrogen metabolites. These relationships were not fully explained by adult BMI.
Impact: These findings inform investigations of diseases linked to early life body fatness and estrogen metabolism. Cancer Epidemiol Biomarkers Prev; 27(5); 585–93. ©2018 AACR.
Metformin Is Not Associated with Incidence Risk of Non-Hodgkin Lymphomas among Diabetic Patients
Authors: Ye Xibiao , Zhang Geng , Righolt Christiaan , Johnston James B. , Banerji Versha , Gibson Spencer B. , Mahmud Salaheddin M. 
Published: March 2018

Abstract
Background: Several epidemiological studies have shown a positive association between diabetes and increased risk of non-Hodgkin lymphoma (NHL), but the effect of diabetic treatment drugs such as metformin on the risk is unknown.
Methods: We conducted a population-based nested case–control study involving 878 NHL cases and 4,364 controls diagnosed with diabetes. Use of metformin and other medications before diagnosis and medical condition histories were assessed using administrative databases. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for use of metformin, adjusting for confounders.
Results: Risk of total NHLs is not associated with ever use of metformin (OR, 0.93; 95% CI, 0.79–1.10) among diabetic patients. NHL subtypes were also not associated with metformin use.
Conclusions: Metformin use is not associated with overall or subtype NHL risk among diabetic patients.
Impact: NHLs are etiologically heterogeneous and larger scale studies are warranted to test the potential effect of metformin by NHL subtype. Cancer Epidemiol Biomarkers Prev; 27(5); 610–2. ©2018 AACR.
Contralesional Brain Activity in Acute Ischemic Stroke
Authors: Van Kaam Ruud C. , van Putten Michel J.A.M. , Vermeer Sarah E. , Hofmeijer Jeannette 
Published: March 2018

<b><i>Background:</i></b> The noninjured, contralateral hemisphere is increasingly acknowledged in the process of recovery from acute ischemic stroke. We estimated the value of conventional electroencephalography (EEG) recordings for identifying contralateral hemisphere involvement in relation to functional recovery. <b><i>Methods:</i></b> We analyzed 2-min epochs from 21 electrode EEG registrations of 18 patients with acute hemispheric ischemic stroke and compared with 18 age-matched controls. Outcome was dichotomized as good (modified Rankin Scale [mRS] 0–2) or poor (mRS 3–5 or death) at 3 months. Effects of the infarct on the ipsi-and contralateral hemispheres were analyzed by the delta/alpha ratio (DAR) and 2 measures of functional connectivity (magnitude squared coherence [MSC] and weighted phase lag index [WPLI]). <b><i>Results:</i></b> DAR was higher in patients than in controls, both in the ipsilateral and in the contralateral hemisphere (median 4.5 ± 6.7 ipsilateral and 2.4 ± 2.0 contralateral vs. 0.5 ± 0.5 in the control group, <i>p</i> &#x3c; 0.001), indicating robust EEG changes in both lesioned and non-lesioned hemisphere. MSC and WPLI in the alpha and beta frequency bands were lower in patients than in controls in both hemispheres, indicating clear disturbances of functional connectivity (<i>p</i> &#x3c; 0.05). In the poor outcome group, contralateral MSC and WPLI were lower than in the good outcome group, although these differences did not reach statistical significance. <b><i>Conclusions:</i></b> Short conventional EEG measurements show robust changes of brain activity and functional connectivity in both ipsilateral and contralateral hemispheres of patients with acute ischemic stroke. Changes of remote functional connectivity tend to interact with functional recovery. Future studies should estimate predictive values for individual patients and interactions with plasticity enhancing treatments.
Two new records of Gynandromorphs in Xylocopa (Hymenoptera, Apidae s.l.)
Authors: Almeida Rony Peterson Santos , Leite Luis Anderson Ribeiro , Ramos Kelli Dos Santos 
Published: March 2018

Two new records of gynandromorphs in Xylocopa Latreille, 1802 (Hymenoptera, Apidae). Gynandromorphs are deviant morphological individuals with genetically distinct male and female tissues. Records of sex anomalies seems to be important to better understand the mechanisms regulating phenotypic expression. Herein, two new cases of gynandromorphs in carpenter bee species of Xylocopa from Brazil are described and figured: a mixed gynandromorph of the X. (Neoxylocopa) brasilianorum (Linnaeus, 1767) from São Paulo and a bilateral gynandromorph of the X. (Neoxylocopa) ordinaria Smith, 1874 from Sergipe.
Desirable Low-Density Lipoprotein Cholesterol Levels for Preventing Stroke Recurrence
Authors: Hosomi Naohisa , Kitagawa Kazuo , Nagai Yoji , Nakagawa Yoko , Aoki Shiro , Nezu Tomohisa , Kagimura Tatsuo , Maruyama Hirofumi , Origasa Hideki , Minematsu Kazuo , Uchiyama Shinichiro , Matsumoto Masayasu 
Published: March 2018

Background and Purpose—
To define desirable target low-density lipoprotein (LDL) cholesterol levels for the prevention of stroke recurrence, a post hoc analysis was performed in the J-STARS study (Japan Statin Treatment Against Recurrent Stroke).

Methods—
Subjects (n=1578) were divided into groups based on mean value of postrandomized LDL cholesterol levels until the last observation in 20 mg/dL increments. Adjusted hazard ratios (HRs) and 95% confidence intervals were analyzed for each group, with adjustments for baseline LDL cholesterol, baseline body mass index, hypertension, diabetes mellitus, and statin usage.

Results—

The postrandomized LDL cholesterol level until the last observation were 104.1±19.3 mg/dL in the pravastatin group and 126.1±20.6 mg/dL in the control group. The adjusted HRs for stroke and transient ischemic attack and all vascular events decreased in the postrandomized LDL cholesterol level of 80 to 100 mg/dL (
P
=0.23 and 0.25 for the trend, respectively). The adjusted HR for atherothrombotic infarction significantly reduced with the usage of statin after adjusting baseline LDL cholesterol levels (HR, 0.39; 95% confidence intervals, 0.19–0.83). The adjusted HR for atherothrombotic infarction and intracranial hemorrhage were similar among the postrandomized LDL-cholesterol–level subgroups (
P
=0.50 and 0.37 for the trend, respectively). The adjusted HR for lacunar infarction decreased in the postrandomized LDL cholesterol level of 100 to 120 mg/dL (HR, 0.45; 95% confidence intervals, 0.20–0.99;
P
=0.41 for the trend).

Conclusions—
The composite risk of stroke and transient ischemic attack reduced in the postrandomized LDL cholesterol level of 80 to 100 mg/dL after adjusting for statin usage.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00221104.
Increased Risk of Pregnancy Complications After Stroke
Authors: van Alebeek Mayte E. , de Vrijer Myrthe , Arntz Renate M. , Maaijwee Noortje A.M.M. , Synhaeve Nathalie E. , Schoonderwaldt Hennie , van der Vlugt Maureen J. , van Dijk Ewoud J. , de Heus Roel , Rutten-Jacobs Loes C.A. , de Leeuw Frank-Erik 
Published: March 2018

Background and Purpose—
The study goal was to investigate the prevalence of pregnancy complications and pregnancy loss in women before, during, and after young ischemic stroke/transient ischemic attack.

Methods—
In the FUTURE study (Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation), a prospective young stroke study, we assessed the occurrence of pregnancy, miscarriages, and pregnancy complications in 223 women aged 18 to 50 years with a first-ever ischemic stroke/transient ischemic attack. Pregnancy complications (gestational hypertension, diabetes mellitus, preeclampsia, and hemolysis, elevated liver enzymes, low platelet count syndrome) were assessed before, during, and after stroke using standardized questionnaires. Primary outcome was occurrence of pregnancy complications and the rate of pregnancy loss compared with the Dutch population. Secondary outcome was the risk of recurrent vascular events after stroke, stratified by a history of hypertensive disorder in pregnancy.

Results—

Data were available for 213 patients. Mean age at event was 39.6 years (SD=7.8) and mean follow-up 9.5 years (SD=8.5). Miscarriages occurred in 35.2% and fetal death in 6.2% versus 13.5% and 0.9% in the Dutch population, respectively (
P
<0.05). In nulliparous women after stroke (n=22), in comparison with Dutch population, there was a high prevalence of hypertensive disorders in pregnancy (33.3 versus 12.2%;
P
<0.05), hemolysis, elevated liver enzymes, low platelet count syndrome (9.5 versus 0.5%;
P
<0.05), and early preterm delivery <32 weeks (9.0 versus 1.4%;
P
<0.05). In primi/multiparous women (n=141) after stroke, 29 events occurred (20-year cumulative risk 35.2%; 95% confidence interval, 21.3–49.0), none during subsequent pregnancies, and a history of a hypertensive disorder in pregnancy did not modify this risk (log-rank
P
=0.62).

Conclusions—
When compared with the general population, women with young stroke show higher rates of pregnancy loss throughout their lives. Also, after stroke, nulliparous women more frequently experienced serious pregnancy complications.
The ‘Stock Market of Diplomatic Reputation’: Reputation on Diplomacy’s Frontline
Authors: Robertson Jeffrey 
Published: March 2018

Summary
Diplomacy was in the midst of a transformation from ‘old diplomacy’ to ‘new diplomacy’ one century ago, yet the changes were not welcomed by everyone. The renowned diplomat Harold Nicolson lamented the loss of the ‘stock market of diplomatic reputation’, meaning the corporate estimate of character built up during a lifetime of frontline diplomatic service. As we progress through another period of remarkable transformation in diplomacy, what has become of the stock market of diplomatic reputation? This article undertakes a case study of diplomatic alumni from a public policy training institute. It investigates understandings of the construct of reputation, concern for reputation and use of reputation. It finds that reputation remains very important to practising diplomats. Reputation is indeed a timeless feature that is intrinsic to frontline diplomacy. Furthermore, Nicolson’s conceptualization of ideal diplomacy as a building block of reputation remains relevant and presents an appealing topic for future research.
Practice what you Preach? Limitations to Imposing Democratic Norms on ngos
Authors: Beijerman Martine 
Published: March 2018

Abstract
This paper challenges the scholarly tendency of imposing democratic norms on non-governmental organisations (ngos). For decades there has been a strong debate among International Relations and International Law scholars on the question of whether or not ngos contribute to the democratic legitimacy of international law. Notwithstanding different arguments, both critics of and adherents seem to be primarily occupied with theorising and criticising the internal democratic legitimacy of ngos. In this article I question whether this is justifiable. Imposed democratic norms conflict with the inherent unpredictable character of ngos. Whereas the unpredictability of ngos in terms of form and content is often perceived as unreliable, it characterises their essential voluntariness, which can be considered their main contribution to democracy.
Traduction et validation du Questionnaire sur l’engagement dans les activités signifiantes
Authors: Lacroix Pier-Anne , Pelletier Anne-Julie , Blondin Marie-Pier , Dugal Ariane , Langlois Claudine , Levasseur Mélanie , Larivière Nadine 
Published: March 2018

Description. Peu d’outils sont disponibles en français pour mesurer l’engagement dans des activités signifiantes, au cœur de l’ergothérapie. But. Cette étude visait à traduire l’Engagement in Meaningful Activities Survey et, ensuite, à vérifier la validité convergente et la cohérence interne de la version française. Méthodologie. Une traduction renversée a d’abord été réalisée. Pour ensuite évaluer la validité convergente du Questionnaire sur l’engagement dans des activités signifiantes (QEAS), l’Indice de la qualité de vie et la Mesure des habitudes de vie modifiée (participation sociale) ont été complétés par 84 adultes de la population générale. La cohérence interne a été mesurée avec l’alpha de Cronbach. Résultats. Un meilleur engagement dans les activités signifiantes est significativement associé à une qualité de vie ( r = 0,36; p = 0,001) et une satisfaction accrues envers la participation sociale (ρ = 0,40; p < 0,001). Le QEAS présente une bonne cohérence interne (∂ = 0,81). Conséquences. Le QEAS est un questionnaire valide qui permettra aux ergothérapeutes francophones de mieux comprendre l’engagement de leurs clients dans l’ensemble de leurs activités.
Long-Term Prognosis of Plantar Fasciitis: A 5- to 15-Year Follow-up Study of 174 Patients With Ultrasound Examination
Authors: Hansen Liselotte , Krogh Thøger Persson , Ellingsen Torkell , Bolvig Lars , Fredberg Ulrich 
Published: March 2018

Background: Plantar fasciitis (PF) affects 7% to 10% of the population. The long-term prognosis is unknown. Purpose: Our study had 4 aims: (1) to assess the long-term prognosis of PF, (2) to evaluate whether baseline characteristics (sex, body mass index, age, smoking status, physical work, exercise-induced symptoms, bilateral heel pain, fascia thickness, and presence of a heel spur) could predict long-term outcomes, (3) to assess the long-term ultrasound (US) development in the fascia, and (4) to assess whether US-guided corticosteroid injections induce atrophy of the heel fat pad. Study Design: Cohort study; Level of evidence, 3. Methods: From 2001 to 2011 (baseline), 269 patients were diagnosed with PF based on symptoms and US. At follow-up (2016), all patients were invited to an interview regarding their medical history and for clinical and US re-examinations. Kaplan-Meier survival estimates were used to estimate the long-term prognosis, and a multiple Cox regression analysis was used for the prediction model. Results: In all, 174 patients (91 women, 83 men) participated in the study. All were interviewed, and 137 underwent a US examination. The mean follow-up was 9.7 years from the onset of symptoms and 8.9 years from baseline. At follow-up, 54% of patients were asymptomatic (mean duration of symptoms, 725 days), and 46% still had symptoms. The risk of having PF was 80.5% after 1 year, 50.0% after 5 years, 45.6% after 10 years, and 44.0% after 15 years from the onset of symptoms. The risk was significantly greater for women ( P < .01) and patients with bilateral pain ( P < .01). Fascia thickness decreased significantly in both the asymptomatic and symptomatic groups ( P < .01) from 6.9 mm and 6.7 mm, respectively, to 4.3 mm in both groups. Fascia thickness ( P = .49) and presence of a heel spur ( P = .88) at baseline had no impact on prognosis. At follow-up, fascia thickness and echogenicity had normalized in only 24% of the asymptomatic group. The mean fat pad thickness was 9.0 mm in patients who had received a US-guided corticosteroid injection and 9.4 mm in those who had not been given an injection ( P = .66). Conclusion: The risk of having PF in this study was 45.6% at a mean 10 years after the onset of symptoms. The asymptomatic patients had PF for a mean 725 days. The prognosis was significantly worse for women and patients with bilateral pain. Fascia thickness decreased over time regardless of symptoms and had no impact on prognosis, and neither did the presence of a heel spur. Only 24% of asymptomatic patients had a normal fascia on US at long-term follow-up. A US-guided corticosteroid injection did not cause atrophy of the heel fat pad. Our observational study did not allow us to determine the efficacy of different treatment strategies.
Development of a Radiation Oncology–Specific Prospective Data Registry for Research and Quality Improvement: A Clinical Workflow-Based Solution
Authors: Chen Allen M. , Kupelian Patrick A. , Wang Pin-Cheih , Steinberg Michael L. 
Published: March 2018

Purpose The computerized paperless medical recording system has transformed the modern health information system and serves as an idea platform for registry development, particularly in a specialty such as radiation oncology, where technologic advances continue to generate unprecedented amounts of complex data. We present our single-institution experience with the development of a real-time observational registry fully integrated into the process of routine clinical workflow and show how this has the potential to transform research and quality assurance. Materials and Methods From May 2011 to May 2016, physicians prospectively inputted data during the process of routine charting on patients seen in clinic. Using a customized interface established between an in-house registry and a commercially available, hospital-based electronic medical record system (Epic Systems, Verona, WI), a departmentally based parser was created for automatic data deposition, which was also linked to the Aria Treatment Planning Station (Varian Medical Systems, Palo Alto, CA). The total number of data fields embedded per disease site ranged from nine to 73 (median, 21 fields). Results A total of 12,341 patients were logged into the registry, of whom 6,911 completed a course of radiation therapy. Primary disease sites were prostate (n = 2,340), breast (n = 2,159), head or neck (n = 1,426), primary CNS (n = 1,338), lung (n = 749), brain metastasis (n = 739), GI (n = 638), gynecologic (n = 534), and other or benign (n = 3,618). A total of 54 independent, investigator-initiated research studies have been initiated using queries supported by the registry from multiple access points, of which 23 were published in peer-reviewed journals. Conclusion The development of a radiation oncology–specific registry enhanced research efficiency and facilitated quality assurance by producing clear and quality information to guide clinical practice.
Policy Analysis in Government and Academia: Two Cultures
Authors: Glied Sherry 
Published: March 2018

Abstract
Despite concerns that the health policy academy is divorced from policy making, the articles in this special issue generally suggest that academic policy research played important roles in the development, implementation, and subsequent defense of the Affordable Care Act. One reason for this relative success was the presence of many “embedded academics”—researchers who took leaves from universities to spend time working for the Obama administration or Congress. Embedded academics can help bridge the wide gap between the institutional cultures of the academy and of government and can thus act as translators of academic research for policy-making purposes. This essay describes how the cultures of the academy and of government policy research differ and suggests ways to use those cultural differences to improve knowledge translation.