bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune approaches to the treatment of breast cancer, around the corner?
Authors: Criscitiello Carmen , Esposito Angela , Gelao Lucia , Fumagalli Luca , Locatelli Marzia , Minchella Ida , Adamoli Laura , Goldhirsch Aron , Curigliano Giuseppe 
Published: February 2014

AbstractImmunotherapy for the treatment of breast cancer can be categorized as either (a) specific stimulation of the immune system by active immunization, with cancer vaccines, or (b) passive immunization, such as tumor-specific antibodies (including immune modulators) or adoptive cell therapy that inhibit the function of, or directly kill, tumor cells. We will present the current information and the future perspectives of immunotherapy in patients with breast cancer, including the prognostic role of tumor infiltrating lymphocytes, immune signatures, targeted therapies modulating the immune system, and tumor antigen cancer vaccines. Active immunotherapy in breast cancer and its implementation into clinical trials have been largely a frustrating experience in the last decades. The concept that the immune system regulates cancer development is experiencing a new era of interest. It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. Also, the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resumes the complex interaction between tumor and immune system into three phases: elimination, equilibrium, and escape. Major topics in the field of immunology deserve a response: what do we know about tumor immunogenicity, and how might we therapeutically improve tumor immunogenicity? How can we modulate response of the immune system? Is there any gene signature predictive of response to immune modulators? The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor-rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signaling pathways that regulate immune responses in the tumor microenvironment.
Prospective Study of Fertility Concerns and Preservation Strategies in Young Women With Breast Cancer
Authors: Ruddy Kathryn J. , Gelber Shari I. , Tamimi Rulla M. , Ginsburg Elizabeth S. , Schapira Lidia , Come Steven E. , Borges Virginia F. , Meyer Meghan E. , Partridge Ann H. 
Published: February 2014

Purpose Most research regarding fertility in young women with breast cancer has focused on long-term survivors. Little is known about how fertility concerns affect treatment decisions or fertility preservation strategies at the time of initial cancer diagnosis. Patients and Methods As part of an ongoing prospective multicenter cohort study, we surveyed women with newly diagnosed early-stage breast cancer at age ≤ 40 years. The baseline survey included sociodemographic, medical, and treatment data as well as a modified Fertility Issues Survey, including fertility concern and preservation items. Univariable and multivariable modeling were used to investigate predictors of greater fertility concern. Results Among the first 620 eligible respondents included in this analysis, median age was 37 years (range, 17 to 40 years); 425 women (68%) discussed fertility issues with their physicians before starting therapy, and 319 (51%) were concerned about becoming infertile after treatment. Because of concerns about fertility, four women (1%) chose not to receive chemotherapy, 12 (2%) chose one chemotherapy regimen over another, six (1%) considered not receiving endocrine therapy, 19 (3%) decided not to receive endocrine therapy, and 71 (11%) considered receiving endocrine therapy for < 5 years; 65 (10%) used fertility preservation strategies. Greater concern about fertility was associated with younger age, nonwhite race, not having children, and receipt of chemotherapy. Conclusion Many young women with newly diagnosed breast cancer have concerns about fertility, and for some, these substantially affect their treatment decisions. Only a minority of women currently pursue available fertility preservation strategies in this setting.
Cost Effectiveness of EML4-ALK Fusion Testing and First-Line Crizotinib Treatment for Patients With Advanced ALK-Positive Non–Small-Cell Lung Cancer
Authors: Djalalov Sandjar , Beca Jaclyn , Hoch Jeffrey S. , Krahn Murray , Tsao Ming-Sound , Cutz Jean-Claude , Leighl Natasha B. 
Published: February 2014

Purpose ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion–positive non–small-cell lung cancer (NSCLC). We estimated the cost effectiveness of EML4-ALK fusion testing in combination with targeted first-line crizotinib treatment in Ontario. Patients and Methods A cost-effectiveness analysis was conducted using a Markov model from the Canadian Public health (Ontario) perspective and a lifetime horizon in patients with stage IV NSCLC with nonsquamous histology. Transition probabilities and mortality rates were calculated from the Ontario Cancer Registry and Cancer Care Ontario New Drug Funding Program (CCO NDFP). Costs were obtained from the Ontario Case Costing Initiative, CCO NDFP, University Health Network, and literature. Results Molecular testing with first-line targeted crizotinib treatment in the population with advanced nonsquamous NSCLC resulted in a gain of 0.011 quality-adjusted life-years (QALYs) compared with standard care. The incremental cost was Canadian $2,725 per patient, and the incremental cost-effectiveness ratio (ICER) was $255,970 per QALY gained. Among patients with known EML4-ALK–positive advanced NSCLC, first-line crizotinib therapy provided 0.379 additional QALYs, cost an additional $95,043 compared with standard care, and produced an ICER of $250,632 per QALY gained. The major driver of cost effectiveness was drug price. Conclusion EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.
Impact of Oophorectomy on Cancer Incidence and Mortality in Women With a BRCA1 or BRCA2 Mutation
Authors: Finch Amy P.M. , Lubinski Jan , Møller Pål , Singer Christian F. , Karlan Beth , Senter Leigha , Rosen Barry , Maehle Lovise , Ghadirian Parviz , Cybulski Cezary , Huzarski Tomasz , Eisen Andrea , Foulkes William D. , Kim-Sing Charmaine , Ainsworth Peter , Tung Nadine , Lynch Henry T. , Neuhausen Susan , Metcalfe Kelly A. , Thompson Islay , Murphy Joan , Sun Ping , Narod Steven A. 
Published: February 2014

Purpose The purposes of this study were to estimate the reduction in risk of ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2 mutation after oophorectomy, by age of oophorectomy; to estimate the impact of prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival associated with clinically detected ovarian, occult, and peritoneal cancers diagnosed in the cohort. Patients and Methods Women with a BRCA1 or BRCA2 mutation were identified from an international registry; 5,783 women completed a baseline questionnaire and ≥ one follow-up questionnaires. Women were observed until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and all-cause mortality associated with oophorectomy were evaluated using time-dependent survival analyses. Results After an average follow-up period of 5.6 years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13 to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95% CI, 0.13 to 0.39; P < .001). Conclusion Preventive oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality.
The legal status of regional or minority languages: Ukrainian and foreign experience
Authors: Витман Константин , Vitman Konstantin 
Published: February 2014

The legal status of regional or minority languages in
Ukraine, Post-Soviet space and European understanding is studied.
The author proves that Ukraine stretches the meaning of
regional languages, provided by European Charter for Regional
or Minority Languages. The regional languages rather play the
role of the largest national minorities’ languages than disappearing
ones in Ukraine. National minorities did not get appropriate
protection of their language rights that is why they had to take
advantage of international legal rules. Ukraine had to extend the
concept of “regional language” to the largest national minorities’
languages to use international law effectively. Thus, the legal status
of regional languages has been changed in national language
law.
Thanks to European Charter for Regional or Minority Languages
the idea of regional language got implanted in language policy terminology.
That is why the lawmakers decided not to decline it during
new language Act working out. The Ukrainian experience exemplifies
modification of the legal status of regional languages, its
adaptation to language situation and has no analogs in Post-Soviet
space.
On reception of the American two-party system experience in modern Russia: pros and cons
Authors: Байбакова Лариса , Baybakova Larisa 
Published: February 2014

Lately there has been a lot of talk in Russian political
circles about the desirability of transition from a multiparty to twoparty system. It is believed that today its American model is one of the most effective mechanisms of representative form of government.
Several attempts to create a two-party system have been undertaken
in Russia for the last decade and a half, but it was not possible
to implement this idea. After the elections in September 2013 a
number of politicians have proposed to create a two-party system
of government, considering that current ruling party «Yedinaya Rossiya
(United Russia)» requires an adequate party rival. In prospects
one cannot exclude the creation in Russia of a two-party system,
but in present conditions it is difficult to assess the degree of its
effectiveness. On the one hand, its functioning is conducive to a
Federal form of government and majority system of election of senior officials, and on the other, there are centrifugal trends in the
dynamics of political processes, strengthened after the laws adopted
over the last decade on the liberalization of procedure of
registration of political parties. In this regard a number of sociopolitical
movements demand to make amendments in the electoral
legislation, aimed at the consolidation of political forces or
parties with similar policy.
Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury
Authors: Hogendoorn S. , Duijnisveld B. J. , van Duinen S. G. , Stoel B. C. , van Dijk J. G. , Fibbe W. E. , Nelissen R. G. H. H. 
Published: February 2014

Objectives Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear cell injection in partially denervated biceps. Methods Nine brachial plexus patients with insufficient elbow flexion (i.e., partial denervation) received intramuscular escalating doses of autologous bone marrow-derived mononuclear cells, combined with tendon transfers. Effect parameters included biceps biopsies, motor unit analysis on needle electromyography and computerised muscle tomography, before and after cell therapy. Results No adverse effects in vital signs, bone marrow aspiration sites, injection sites, or surgical wound were seen. After cell therapy there was a 52% decrease in muscle fibrosis (p = 0.01), an 80% increase in myofibre diameter (p = 0.007), a 50% increase in satellite cells (p = 0.045) and an 83% increase in capillary-to-myofibre ratio (p < 0.001) was shown. CT analysis demonstrated a 48% decrease in mean muscle density (p = 0.009). Motor unit analysis showed a mean increase of 36% in motor unit amplitude (p = 0.045), 22% increase in duration (p = 0.005) and 29% increase in number of phases (p = 0.002). Conclusions Mononuclear cell injection in partly denervated muscle of brachial plexus patients is safe. The results suggest enhanced muscle reinnervation and regeneration. Cite this article: Bone Joint Res 2014;3:38–47.
Convergence and its driving factors in Iranian news websites
Authors: Mehrabi Meghdad 
Published: February 2014

Abstract
The term convergence has been widely used in communications to refer to different media issues such as conglomeration of media corporations, changing behaviour of new media users and use of technological affordances among other things. There are debates about driving forces of media convergence. Whereas media owners consider convergence as a tool for more profits, critics express concerns about media monopoly as a result of organizational convergence. However, journalists regard convergence as a way to present more attractive and precise news. This article is an attempt to explore main aspects of convergence related to relationship among media organizations and characteristics of media contents in the context of Iranian online news papers. I also analyse essential factors that drive convergence for Iranian online newspapers and compare the findings with conditions of online news media in the United States. This article is significant since it expands existing knowledge about media convergence in Iranian context. The findings of this research can be helpful for news organizations to improve the quality of their news websites through different forms of convergence. Finally, implications for future research on convergence in contexts similar to Iran are provided.
Efficient identification of context dependent subgroups of risk from genome-wide association studies
Authors: Dyson Greg , Sing Charles F. 
Published: February 2014

AbstractWe have developed a modified Patient Rule-Induction Method (PRIM) as an alternative strategy for analyzing representative samples of non-experimental human data to estimate and test the role of genomic variations as predictors of disease risk in etiologically heterogeneous sub-samples. A computational limit of the proposed strategy is encountered when the number of genomic variations (predictor variables) under study is large (>500) because permutations are used to generate a null distribution to test the significance of a term (defined by values of particular variables) that characterizes a sub-sample of individuals through the peeling and pasting processes. As an alternative, in this paper we introduce a theoretical strategy that facilitates the quick calculation of Type I and Type II errors in the evaluation of terms in the peeling and pasting processes carried out in the execution of a PRIM analysis that are under-estimated and non-existent, respectively, when a permutation-based hypothesis test is employed. The resultant savings in computational time makes possible the consideration of larger numbers of genomic variations (an example genome-wide association study is given) in the selection of statistically significant terms in the formulation of PRIM prediction models.
Less common genotype variants of TP53 polymorphisms are associated with poor outcome in adult patients with adrenocortical carcinoma
Authors: Heinze Britta , Herrmann Leonie J M , Fassnacht Martin , Ronchi Cristina L , Willenberg Holger S , Quinkler Marcus , Reisch Nicole , Zink Martina , Allolio Bruno , Hahner Stefanie 
Published: February 2014

ContextThe Li–Fraumeni tumor syndrome is strongly associated with adrenocortical carcinoma (ACC) and is caused by germline mutations in TP53 in 70% of cases. Also, TP53 polymorphisms have been shown to influence both cancer risk and clinical outcome in several tumor entities. We, therefore, investigated TP53 polymorphisms in a cohort of adult patients with ACC.ObjectiveEvaluation of the role of TP53 polymorphisms in adult patients with ACC.Subjects and methodsPeripheral blood for DNA extraction was collected from 72 ACC patients. Polymorphism analysis was carried out by amplification and sequencing of exons and adjacent intron sections of TP53. Results were correlated with clinical data and the distribution of the polymorphisms was compared with published Caucasian control groups.ResultsCompared with control groups, genotype frequencies of analyzed TP53 polymorphisms among ACC patients were significantly different in three out of four polymorphisms: IVS2+38G>C (G/G, P=0.0248), IVS3ins16 (NoIns/NoIns, P<0.0001; NoIns/Ins, P<0.0001), and IVS6+62A>G (G/G, P<0.0001; G/A, P<0.0001). Overall, the survival of ACC patients, which harbored at least one of the less frequent genotype variants of four analyzed polymorphisms (n=23), was significantly inferior (median survival: 81.0 months in patients with the common homozygous genotypes vs 20.0 months in patients with the less frequent genotypes, HR 2.56, 95% CI 1.66–7.07; P=0.001). These results were confirmed by multivariable regression analysis (HR 2.84, 95% CI 1.52–7.17; P=0.037).ConclusionSome TP53 polymorphisms seem to influence overall survival in ACC patients. This effect was observed for a combination of polymorphic changes rather than for single polymorphisms.
Growth Patterns of Large for Gestational Age Children up to Age 4 Years
Authors: Bocca-Tjeertes Inger F.A. , Kerstjens Jorien M. , Reijneveld Sijmen A. , Veldman Karin , Bos Arend F. , de Winter Andrea F. 
Published: February 2014

OBJECTIVE:
To determine how growth of large for gestational age (LGA) preterm (PT) children was affected by their PT birth and their LGA status.

METHODS:
This is a community-based cohort study of 1302 PT and 489 full-term (FT) children, born 2002 and 2003.

RESULTS:
We found that growth in height, weight, and head circumference of LGA PT children was well balanced during infancy and that only weight gain accelerated during subsequent years. This led to high BMIs comparable to those of LGA FT children. Being born both LGA and PT resulted in a median growth at the age of 4 years that was 0.1 SD lower for weight (P = .44), 0.1 SD lower for height (P = .48), and 0.5 SD lower for head circumference compared with LGA FT counterparts (P = .016), whereas BMI at age 4 years was equal. Compared with appropriate for gestational age (AGA) PT children, these measures for LGA PT children were 0.9 SD, 0.6 SD, and 0.4 SD (all P &lt; .001) higher, respectively. That led to the BMI of LGA PT children at age 4 years being significantly higher (0.9 points, ie, 0.7 SD) than that of AGA PT and also higher (0.6 points, ie, 0.4 SD) than that of AGA FT children.

CONCLUSIONS:
The growth patterns of LGA PT-born children are distinctly different from other PT or FT children. In particular, we found substantially greater weight gains and relatively higher BMIs among them, which added to their already increased metabolic risks based on their gestational age.
Epidemiology of Male Genital Abnormalities: A Population Study
Authors: Wan Shaw , Wang Yunchao , Gu Shuijun 
Published: February 2014

BACKGROUND:
We conducted genital health wellness screens in male kindergarten children between the ages of 3 and 6 years to assess the incidence of congenital abnormalities and their treatment.

METHODS:
We performed genital examinations on 2241 male children in 8 kindergartens. We screened for 4 conditions: phimosis, hypospadias, cryptorchidism, and hydrocele/hernia. We assessed the incidence of these conditions and the effectiveness or lack of their treatment.

RESULTS:
Among this sample, 55.5% children aged 3 to 4 years and 44.1% aged 5 to 6 years were found to have persistent phimosis. The circumcision rate, excluding those performed in conjunction with hypospadias repair, was 2.8%, but it carried a 3.2% complication rate. There was a lower incidence of hypospadias and cryptorchidism than reported in the literature at 0.2% and 0.4%, respectively. Our hypospadias repair rate was 60%, with a success rate of 66.7%. Our cryptorchidism repair rate was only 25%, and all repairs were performed above the age of 5 years. Incidence of hydrocele and hernias was 1.2%, and our treatment rate was 46.2%. Finally, we found high incidence of keloid formation, 73.3%, associated with inguinal incision.

CONCLUSIONS:
There was high prevalence of phimosis in Chinese boys, a natural physiologic condition, up to age 6. There appeared to be lower incidences of hypospadias and cryptorchidism in our screened population. However, there were opportunities for us to improve the diagnosis and treatment of these 2 conditions. Our hydrocele/hernia incidence was on par with literature, but we had a lower treatment rate. Finally, we found a high incidence of keloid formation associated with inguinal incision.
AAP Principles Concerning Retail-Based Clinics
Authors:   COMMITTEE ON PRACTICE AND AMBULATORY MEDICINE, Laughlin James J. , Simon Geoffrey R. , Baker Cynthia , Barden Graham , Brown Oscar W. , Hardin Amy , Lessin Herschel R. , Meade Kelley , Moore Scot , Rodgers Chadwick T. 
Published: February 2014

This Policy Statement was retired May 2017.
The American Academy of Pediatrics views retail-based clinics (RBCs) as an inappropriate source of primary care for pediatric patients, as they fragment medical care and are detrimental to the medical home concept of longitudinal and coordinated care. This statement updates the original 2006 American Academy of Pediatrics statement on RBCs, which flatly opposed these sites as appropriate for pediatric care, discussing the shift in RBC focus and comparing attributes of RBCs with those of the pediatric medical home.
A primer melanoma malignum ritka gastrointestinalis lokalizációi
Authors: Rózsa Árpád , Mellár Erzsébet , Poczik Sándor , Bánhegyi Róbert János , Soós Péter , Liechtenstein Zábrák József , Pikó Béla , Varga István , Ottlakán Aurél 
Published: February 2014

AbsztraktA mucosalis melanomák csoportjába tartozó primer gastrointestinalis (GI) melanomák előfordulása igen ritka. Az összes malignus melanomát tekintve – azok mintegy 5%-át teszik ki – legnagyobb részük (3%) a rectumban található. A prognózis rossz, az átlagos 5 éves túlélés rectalis melanoma esetén 10–20%. Közleményünkben három esetet mutatunk be. 1. A 68 éves férfi kórszövettanilag igazolt rectummelanoma miatt került műtétre. Radikális műtéti és onkológiai kezelés után a műtétet követően három évvel a primer tumor áttétes manifesztációját igazolták a gyomorban. Radikális gyomorkiirtást követően onkológiai kezelés történt. 2. Az 59 éves férfi betegnél appendicitisre utaló tünetek miatt appendectomiát végeztünk. A kórszövettani vizsgálat az appendix melanomáját véleményezte. A kivizsgálás során a primer tumor a gyomorban volt, és áttéteket igazoltak a tüdőben is. 3. A 82 éves nőbeteg végbélfájdalom, nyákos, gyakori székürítés, széklettartási nehézség miatt jelentkezett ambulanciánkon. A rectum alsó harmadában primer melanoma malignum igazolódott multiplex hepaticus áttétekkel. Bemutatásra szánt eseteink leginkább azért igen figyelemreméltóak, mert a malignus melanoma rendkívül ritka lokalizációiról van szó, különösen igaz ez a háromból két esetben, melyekben a primer GI melanoma metastasisa is a GI traktusban volt fellelhető.