bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tubular breast carcinoma: An argument against treatment de‐escalation
Authors: Hansen Carmen J , Kenny Liz , Lakhani Sunil R , Ung Owen , Keller Jacqui , Tripcony Lee , Cheuk Robyn , Grogan Michelle , Vargas Ana Cristina , Martin Jarad 
Published: February 2012

AbstractPurpose: To evaluate the role of adjuvant radiotherapy in management of patients with tubular carcinoma of the breast.Methods: One hundred seventy‐eight patients treated for tubular carcinoma were identified from the Queensland Radium Institute database. A retrospective review of medical records identified 115 patients meeting eligibility criteria: breast‐conserving surgery for a histological diagnosis of tubular carcinoma, minimum follow up of 12 months and adequate medical records.Results: Median follow up was 64 months. There were no significant differences between patient characteristics treated with and without radiotherapy. Median age at diagnosis was 54 (36–78) years. Ninety‐five percent tumours were T1 and four patients had positive axillary lymph nodes. Of 94 patients treated with adjuvant radiotherapy, one developed local relapse. Five of 21 patients who did not have adjuvant radiotherapy failed locally. Five‐year relapse‐free survival with and without radiotherapy was 100 and 89%, respectively (hazard ratio for radiotherapy: 0.06; 95% confidence interval 0.01–0.32, P = 0.001).Conclusion: Radiotherapy has a significant impact on relapse‐free survival in patients treated with breast‐conserving surgery for tubular carcinoma.
Value of fused positron emission tomography CT in detecting primaries in patients with primary unknown cervical lymph node metastasis
Authors: Chen Yue‐Hong , Yang Xin‐Ming , Li Shi‐Sheng , Wang Yuan‐Hua , He Jian‐Jun , Yang Yi‐Da , Wang Shuang , Liu Jia‐Jia , Zhang Xiao‐Li 
Published: February 2012

AbstractObjective: Identification of the primary tumour can prolong the life expectancy of patients with primary unknown cervical lymph node metastasis (PUCLNM) through targeted therapy. This study investigated the value of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET‐CT) at identifying primaries in patients with PUCLNM.Methods: Twenty‐seven patients (21 males and 6 females, median age 48.2 ± 16.3, age range 30–73) with PUCLNM underwent FDG PET‐CT to search for the primary tumour, which could not be detected by conventional diagnostic modalities. The results were analysed and correlated with either pathological findings or clinical follow up.Results: Pathological FDG uptake suspicious for the primary was detected in 13 cases, while the primary tumour remained occult in 14 cases. Eleven of 13 patients with suspected primaries were confirmed by histological findings. One with a coexisting second tumour and three with unexpected distant metastases were found in patients with confirmed primaries. The most common primary location in patients with PUCLNM found in our study was nasopharynx. In those 14 patients with negative FDG PET‐CT results, only one patient had a primary malignancy that was proven histologically after endoscopy with biopsy during a period of clinical follow up. The sensitivity, specificity, accuracy and positive predictive values of FDG PET‐CT were 91.7, 86.7, 88.9 and 84.6%, respectively.Conclusion: FDG PET‐CT is a useful tool to help search for unknown primaries in patients with cervical lymph node metastasis and has an acceptable diagnostic yield for the detection of distant malignancies.
Blindness of Johann Sebastian Bach
Authors: Tarkkanen Ahti 
Published: February 2012

Abstract.Johann Sebastian Bach (1685–1750) was one of the greatest composers of all time. Apart from performing as a brilliant organist, he composed over 1.100 works in almost every musical genre. He was known as a hardworking, deeply Christian person, who had to support his family of 20 children and many students staying at his home. At the age of 64 years, his vision started to decline. Old biographies claim that it was the result of overstressing his vision in poor illumination. By persuasion of his friends, he had his both eyes operated by a travelling British eye surgeon. A cataract couching was performed. After surgery, Bach was totally blind and unable to play an organ, compose or direct choirs and orchestras. He was confined to bed and suffering from immense pain of the eyes and the body. He died <4 months after surgery. In this paper, as the plausible diagnosis, intractable glaucoma because of pupillary block or secondary to phacoanaphylactic endophthalmitis is suggested.
Continuous glucose monitoring system: Is it really accurate, safe and clinically useful?
Authors: Sato Junko , Hirose Takahisa , Watada Hirotaka 
Published: February 2012

AbstractThe continuous glucose monitoring system (CGM) has been used for constant checking of glucose level by measuring interstitial glucose concentrations, since the early days of the 21st century. It can potentially improve diabetes care if used carefully with the understanding of the characteristics of this system. Although there is a time lag of approximately 5–15 min between blood and interstitial glucose levels, the system is considered the most suitable device for meticulous glucose control and prevention of hypoglycemia. A large number of studies have examined its accuracy, safety and clinical effectiveness. The continuous glucose‐error grid analysis (CG‐EGA), designed by WL Clarke, evaluates the clinical accuracy of CGM. It examines ‘temporal’ characteristics of the data, analyzing pairs of reference and sensor readings as a process in time represented by a ‘bidimensional’ time series and taking into account inherent physiological time lags. Investment in CG‐EGA is clearly meaningful, even though there are other methodologies for evaluation. The use of each method complementarily is the most effective way to prove the accuracy of the device. The device has improved gradually, and real‐time CGM, which allows real‐time monitoring of blood glucose level, is already available commercially. The use of real‐time CGM could potentially lead to over‐ or undertreatment with insulin. Patient education through proper and effective handling of the new device is essential to improve diabetes care. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00197.x, 2012)
BaSTA: an R package for Bayesian estimation of age‐specific survival from incomplete mark–recapture/recovery data with covariates
Authors: Colchero Fernando , Jones Owen R. , Rebke Maren 
Published: February 2012

Summary1. Understanding age‐specific survival in wild animal populations is crucial to the study of population dynamics and is therefore an essential component of several fields including evolution, management and conservation.2. We present Bayesian survival trajectory analysis (BaSTA), a free open‐source software package for estimating age‐specific survival from capture–recapture/recovery data under a Bayesian framework.3. The method copes with low recapture probabilities, unknown ages (e.g. because of left‐truncation) and unknown ages at death (e.g. because of right‐censoring). It estimates survival and detection parameters as well as the unknown birth and death times (i.e. latent states) while allowing users to test a range of survival models. In addition, the effect of continuous or categorical covariates can be evaluated.4. This tool facilitates the analysis of age patterns of survival in long‐term animal studies and will enable researchers to robustly infer the effect of covariates, even with large amounts of missing data.
Bats as bioindicators – the need of a standardized method for acoustic bat activity surveys
Authors: Stahlschmidt Peter , Brühl Carsten A. 
Published: February 2012

Summary1. The species‐rich group of bats fills a wide range of ecological niches and provides ecosystem services like pest control. Bats are known to be sensitive to environmental stressors and could, therefore, be used in assessing ecosystem quality. To use bats as bioindicators, a standardized bat survey method needs to be established as the existing approaches vary in their methodology, and results are, therefore, often not comparable.2. Generally, there are two different acoustic bat survey methods: the transect walk and the stationary measurement. By conducting transect surveys and simultaneously using several stationary systems, we measured bat activity within a homogeneous habitat and evaluated which method assessed the spatial bat activity patterns with highest precision. Also the survey tool – the detectors themselves – can be grouped into devices with two different methods of triggering the recording of ultrasonic signals: actively by a fieldworker or automatically by a built‐in recording control algorithm of the detector. We measured bat activity simultaneously and side by side with both methods for direct comparison.3. Our results indicate that the transect survey fails to represent the heterogeneous bat activity patterns in a homogeneous landscape. Furthermore, errors occur based on the subjective hearing of the active triggering of the data recording by the human operator.4. The application of several stationary and automatic sampling systems has the highest potential for standardized acoustic bat surveys. The general use of such an approach would enable us to understand bat activity at landscape scale and could lead to an improvement of bats as bioindicators.
Ovarian torsion among girls presenting with abdominal pain: a retrospective cohort study
Authors: McCloskey Kathleen , Grover Sonia , Vuillermin Peter , Babl Franz E 
Published: February 2012

BackgroundOvarian torsion (OT) is an important cause of abdominal pain in girls. Prompt recognition of OT may lead to higher rates of ovarian salvage.ObjectiveTo identify clinical and laboratory findings that may indicate OT among girls with abdominal pain.MethodsRetrospective review of two cohorts of girls aged 5–17 years admitted to a children's hospital.Cohort 1:Girls admitted with abdominal pain from the emergency department (2008).Cohort 2:Girls with a discharge diagnosis of OT (2003–9).ResultsCohort 1: 325 girls were admitted from the emergency department with abdominal pain during 2008. Of these, 9 (3%) were diagnosed with OT.Cohort 2:37 girls were diagnosed with OT during 2003–9. Clinical or laboratory features differentiating OT from all abdominal pain could not be identified. A comparison of girls admitted with confirmed appendicitis showed that OT was more likely to be associated with a mass (RR=4.2, 95% CI 1.1 to 17), and less likely to be associated with anorexia (RR=0.46, 95% CI 0.23 to 0.93), guarding (RR=0.53, 95% CI 0.34 to 0.85), an elevated C reactive protein (RR=0.32, 95% CI 0.14 to 0.83), or leucocytosis (RR=0.4, 95% CI 0.21 to 0.78). Findings were similar in girls with an admission diagnosis of ‘possible appendicitis’.ConclusionClinical or laboratory features that would identify cases of OT among girls admitted with abdominal pain could not be identified. Some findings help to differentiate OT from appendicitis, but there is a large degree of overlap. OT is an uncommon condition, but has important management implications, and should be considered inallgirls presenting with abdominal pain.
EMERGENCE OF RANDOMNESS FROM CHAOS
Authors: LOZI R. 
Published: February 2012

In systems theory and science, emergence is the way complex systems and patterns arise out of a multiplicity of relatively simple interactions. Emergence is central to the theories of integrative levels and of complex systems [Aziz-Alaoui & Bertelle, 2009]. In this paper, we use the emergent property of the ultra weak multidimensional coupling of p 1-dimensional dynamical chaotic systems which leads from chaos to randomness.Generation of random or pseudorandom numbers, nowadays, is a key feature of industrial mathematics. Pseudorandom or chaotic numbers are used in many areas of contemporary technology such as modern communication systems and engineering applications. More and more European or US patents using discrete mappings for this purpose are obtained by researchers of discrete dynamical systems [Petersen & Sorensen, 2007; Ruggiero et al., 2006]. Efficient Chaotic Pseudo Random Number Generators (CPRNG) have been recently introduced. They use the ultra weak multidimensional coupling of p 1-dimensional dynamical systems which preserve the chaotic properties of the continuous models in numerical experiments. Together with chaotic sampling and mixing processes, ultra weak coupling leads to families of (CPRNG) which are noteworthy [Hénaff et al., 2009a, 2009b, 2009c, 2010].In this paper we improve again these families using a double threshold chaotic sampling instead of a single one.We analyze numerically the properties of these new families and underline their very high qualities and usefulness as CPRNG when very long series are computed. Moreover, a determining property of such improved CPRNG is the high number of parameters used and the high sensitivity to the parameters value which allows choosing it as cipher-keys. It is why we call these families multiparameter chaotic pseudo-random number generators (M-p CPRNG).
OPEN EXTENSOR TENDON INJURIES: AN EPIDEMIOLOGIC STUDY
Authors: Patillo Dominic , Rayan Ghazi M. 
Published: February 2012

Purpose: To report the epidemiology, mechanism, anatomical location, distribution, and severity of open extensor tendon injuries in the digits, hand, and forearm as well as the frequency of associated injuries to surrounding bone and soft tissue.Methods: Retrospective chart review was conducted for patients who had operative repair of open digital extensor tendon injuries in all zones within an 11-year period. Data was grouped according to patient characteristics, zone of injury, mechanism of injury, and presence of associated injury. Statistical analysis was used to determine the presence of relevant associations.Results: Eighty-six patients with 125 severed tendons and 105 injured digits were available for chart reviews. Patients were predominantly males (83%) with a mean age of 34.2 years and the dominant extremity was most often injured (60%). The thumb was the most commonly injured (25.7%), followed by middle finger (24.8), whereas small finger was least affected (10.5%). Sharp laceration was the most common mechanism of injury (60%), and most of these occurred at or proximal to the metacarpophalangeal joints. Most saw injuries occurred distal to the metacarpophalangeal joint. Zone V was the most commonly affected in the fingers (27%) while zone VT was the most commonly affected in the thumb (69%). Associated injuries to bone and soft tissue occurred in 46.7% of all injuries with saw and crush/avulsions being predictive of fractures and damage to the underlying joint capsule.Conclusions: The extensor mechanism is anatomically complex, and open injuries to the dorsum of the hand, wrist, and forearm, especially of crushing nature and those inflicted by saws, must be thoroughly evaluated. Associated injuries should be ruled out in order to customize surgical treatment and optimize outcome.
p53/HMGB1 Complexes Regulate Autophagy and Apoptosis
Authors: Livesey Kristen M. , Kang Rui , Vernon Philip , Buchser William , Loughran Patricia , Watkins Simon C. , Zhang Lin , Manfredi James J. , Zeh Herbert J. , Li Luyuan , Lotze Michael T. , Tang Daolin 
Published: February 2012

Abstract
The balance between apoptosis (“programmed cell death”) and autophagy (“programmed cell survival”) is important in tumor development and response to therapy. Here, we show that high mobility group box 1 (HMGB1) and p53 form a complex that regulates the balance between tumor cell death and survival. We show that knockout of p53 in HCT116 cells increases expression of cytosolic HMGB1 and induces autophagy. Conversely, knockout of HMGB1 in mouse embryonic fibroblasts increases p53 cytosolic localization and decreases autophagy. p53 is thus a negative regulator of the HMGB1/Beclin 1 complex, and HMGB1 promotes autophagy in the setting of diminished p53. HMGB1-mediated autophagy promotes tumor cell survival in the setting of p53-dependent processes. The HMGB1/p53 complex affects the cytoplasmic localization of the reciprocal binding partner, thereby regulating subsequent levels of autophagy and apoptosis. These insights provide a novel link between HMGB1 and p53 in the cross-regulation of apoptosis and autophagy in the setting of cell stress, providing insights into their reciprocal roles in carcinogenesis. Cancer Res; 72(8); 1996–2005. ©2012 AACR.
CDK8 Maintains Tumor Dedifferentiation and Embryonic Stem Cell Pluripotency
Authors: Adler Adam S. , McCleland Mark L. , Truong Tom , Lau Shari , Modrusan Zora , Soukup Tim M. , Roose-Girma Merone , Blackwood Elizabeth M. , Firestein Ron 
Published: February 2012

AbstractCDK8 is a cyclin-dependent kinase that mediates transcriptional control of pathways linked to both cancer and stem cells. In this study, we show that CDK8 is required for both tumor growth and maintenance of tumor dedifferentiation in vivo and uncover a common role for CDK8 in controlling cancer and stem cell function. Acute CDK8 loss in vivo strongly inhibited tumor growth and promoted differentiation. Transcriptional profiling identified a set of embryonic stem cell–related genes that are activated by CDK8 in cancer. Consistent with this, we found that CDK8 expression correlated to the embryonic stem cell pluripotency state and loss of CDK8 caused embryonic stem cells to differentiate. This effect was, at least partially, mediated by the ability of CDK8 to regulate MYC protein and downstream MYC target gene expression. Similar regulation of MYC target genes by CDK8 was observed in colon tumor cells, and increased expression of a CDK8-regulated, embryonic stem cell MYC target gene signature was associated with loss of differentiation and poor outcome in primary human colon cancers. Together, these observations reveal that CDK8 acts, at least in part, through MYC to maintain both tumors and embryonic stem cells in an undifferentiated state. This raises the intriguing possibility that targeting CDK8 therapeutically may specifically inhibit the stem-like properties of cancer cells. Cancer Res; 72(8); 2129–39. ©2012 AACR.
Molecular Pathways: Regulation and Therapeutic Implications of Multidrug Resistance
Authors: Chen Kevin G. , Sikic Branimir I. 
Published: February 2012

Abstract
Multidrug transporters constitute major mechanisms of MDR in human cancers. The ABCB1 (MDR1) gene encodes a well-characterized transmembrane transporter, termed P-glycoprotein (P-gp), which is expressed in many normal human tissues and cancers. P-gp plays a major role in the distribution and excretion of drugs and is involved in intrinsic and acquired drug resistance of cancers. The regulation of ABCB1 expression is complex and has not been well studied in a clinical setting. In this review, we elucidate molecular signaling and epigenetic interactions that govern ABCB1 expression and the development of MDR in cancer. We focus on acquired expression of ABCB1 that is associated with genomic instability of cancer cells, including mutational events that alter chromatin structures, gene rearrangements, and mutations in tumor suppressor proteins (e.g., mutant p53), which guard the integrity of genome. In addition, epigenetic modifications of the ABCB1 proximal and far upstream promoters by either demethylation of DNA or acetylation of histone H3 play a pivotal role in inducing ABCB1 expression. We describe a molecular network that coordinates genetic and epigenetic events leading to the activation of ABCB1. These mechanistic insights provide additional translational targets and potential strategies to deal with clinical MDR. Clin Cancer Res; 18(7); 1863–9. ©2012 AACR.
miRNA Profiling in Colorectal Cancer Highlights miR-1 Involvement in MET-Dependent Proliferation
Authors: Reid James F. , Sokolova Viktorija , Zoni Eugenio , Lampis Andrea , Pizzamiglio Sara , Bertan Claudia , Zanutto Susanna , Perrone Federica , Camerini Tiziana , Gallino Gianfrancesco , Verderio Paolo , Leo Ermanno , Pilotti Silvana , Gariboldi Manuela , Pierotti Marco A. 
Published: February 2012

Abstract
Altered expression of miRNAs is associated with development and progression of various human cancers by regulating the translation of oncogenes and tumor suppressor genes. In colorectal cancer, these regulators complement the Vogelstein multistep model of pathogenesis and have the potential of becoming a novel class of tumor biomarkers and therapeutic targets. Using quantitative real-time PCR, we measured the expression of 621 mature miRNAs in 40 colorectal cancers and their paired normal tissues and identified 23 significantly deregulated miRNAs. We subsequently evaluated their association with clinical characteristics of the samples and presence of alterations in the molecular markers of colorectal cancer progression. Expression levels of miR-31 were correlated with CA19-9 and miR-18a, miR-21, and miR-31 were associated with mutations in APC gene. To investigate the downstream regulation of the differentially expressed miRNAs identified, we integrated putative mRNA target predictions with the results of a meta-analysis of seven public gene expression datasets of normal and tumor samples of colorectal cancer patients. Many of the colorectal cancer deregulated miRNAs computationally mapped to targets involved in pathways related to progression. Here one promising candidate pair (miR-1 and MET) was studied and functionally validated. We show that miR-1 can have a tumor suppressor function in colorectal cancer by directly downregulating MET oncogene both at RNA and protein level and that reexpression of miR-1 leads to MET-driven reduction of cell proliferation and motility, identifying the miR-1 downmodulation as one of the events that could enhance colorectal cancer progression. Mol Cancer Res; 10(4); 504–15. ©2012 AACR.
Thioredoxin-Interacting Protein Mediates Nuclear–to–Plasma Membrane Communication
Authors: Spindel Oded N. , Yan Chen , Berk Bradford C. 
Published: February 2012

Objective—
Thioredoxin-interacting protein (TXNIP) and poly-ADP-ribose polymerase 1 (PARP1) are both regulated by changes in cellular reduction-oxidation (redox) state and localize to the nucleus basally in human umbilical vein endothelial cells (HUVEC). Previously we showed a novel mechanism for PARP1 inhibition–mediated HUVEC survival through activation of vascular endothelial growth factor receptor 2 (VEGFR2) signaling in response to stress-induced apoptosis. In addition, we showed TXNIP translocation to the plasma membrane (PM) and activation of VEGFR2 in response to physiological stimuli. Because TXNIP is an α-arrestin that regulates VEGFR2 signaling, we hypothesized that PARP1 regulates TXNIP localization and function that might affect HUVEC stress-induced apoptosis.

Methods and Results—

HUVEC treated with 10 μmol/L PARP1 inhibitor (PJ34) were protected from TNF (10 ng/mL) or H
2
O
2
(300 μmol/L) mediated cell death. HUVEC transfected with TXNIP siRNA lost the protective effect of PARP1 inhibition, suggesting a protective role for TXNIP. Using immunofluorescence, cell fractionation analysis, and plasma membrane sheet assay, TXNIP was shown to translocate to the plasma membrane after PARP1 inhibition. TXNIP translocation was associated with activation of VEGFR2 signaling. Functionally, TXNIP-PARP1 interaction was decreased on PJ34 treatment, suggesting PARP1 as a novel regulator of TXNIP localization and function.

Conclusion—
These findings demonstrate a novel regulatory mechanism of TXNIP by PARP1 to mediate activation of plasma membrane signaling and cell survival.