bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymph node status as a prognostic indicator after preoperative neoadjuvant chemoradiotherapy of rectal cancer
Authors: Mirbagheri N. , Kumar B. , Deb S. , Poh B. R. , Dark J. G. , Leow C. C. , Teoh W. M. K. 
Published: June 2014

AbstractAimThe primary aim of this study was to examine lymph node status after neoadjuvant chemoradiotherapy (CRT) using a novel scoring system describing the pathological lymph node regression grade. The proposed scoring system was based on the percentage of fibrosis and the presence of residual tumour amount. The secondary aim of the study was to assess the oncological impact of this scoring system.MethodThe project was a retrospective cohort study over a 10‐year period. Two hundred and two patients with rectal cancer who had received CRT followed by curative surgery were included. A histopathologist prospectively scored each specimen and the impact of the scoring system on survival and recurrence was analysed.ResultsOne hundred and ninety patients completed long‐course preoperative CRT and formed the basis of the study. Overall, 40 recurrences (local and distant) were observed over a median follow‐up of 36 months. The lymph node regression score was a significant predictor of tumour recurrence (hazard ratio 1.273, 95% CI 1.048–1.548; P = 0.015). The overall mortality rate was 21%, and a lower lymph node regression score was correlated with an improved survival curve (P = 0.01).ConclusionThe results demonstrate that lymph node response to neoadjuvant CRT based on a nodal regression scoring system is related to recurrence.
The feasibility and clinical efficacy of intravenous iron administration for preoperative anaemia in patients with colorectal cancer
Authors: Keeler B. D. , Simpson J. A. , Ng S. , Tselepis C. , Iqbal T. , Brookes M. J. , Acheson A. G. 
Published: June 2014

AbstractAimThe study aimed to analyse the feasibility and efficacy of administration of a single intravenous iron infusion (IVI) in the preoperative optimization of colorectal cancer patients with anaemia.MethodTwenty patients were recruited at least 14 days before the planned date of surgery. A single 1000 mg dose of ferric carboxymaltose (Ferinject®) was administered as an outpatient procedure. Blood samples were taken at recruitment prior to drug administration (REC), on the day of surgery prior to any intervention (DOS) and on the first postoperative day. Allogeneic red blood cell transfusions (ARBT) and outcomes were recorded from recruitment throughout the study period.ResultsThere was a significant median rise in haemoglobin levels (Hb) from REC to DOS of 1.8 g/dl [interquartile range (IQR) 0.75–2.45, P < 0.001] for the entire cohort. Two patients received ARBT preoperatively, and for those not transfused preoperatively (n = 18), this incremental Hb rise remained significant (P < 0.001, median 1.65 g/dl, IQR 0.5–2.3). Of these patients, those who responded to IVI had higher erythropoietin (EPO) levels at recruitment (P < 0.01) and lower recruitment Hb values, transferrin‐saturation (TSAT) and C‐reactive protein (CRP) levels (P < 0.05). REC Hb (Rs = −0.62, P < 0.01), REC TSAT levels (Rs = −0.67, P < 0.01) and REC EPO (Rs = 0.69, P < 0.01) correlated with the magnitude of treatment change in Hb levels. Five patients received ARBT until the fourth postoperative day, which was significantly fewer than predicted (P < 0.05).ConclusionIVI can be administered preoperatively in the outpatient clinic to colorectal cancer patients with anaemia, with associated reduction in ARBT use and increase in Hb levels.
Large cell acanthoma: a variant of solar lentigo with cellular hypertrophy
Authors: Fraga Garth R. , Amin Sapna M. 
Published: June 2014

BackgroundLarge cell acanthoma (LCA) is an epidermal proliferation of enlarged keratinocytes. There is a lack of consensus on whether it represents a unique neoplasm or not. To determine whether it is a variant of solar lentigo, we compared macroscopic, microscopic and immunophenotypic attributes of LCA with conventional solar lentigo, seborrheic keratosis, actinic keratosis and Bowen disease.MethodsWe constructed tissue microarrays containing multiple cores of LCA, solar lentigo, seborrheic keratosis, actinic keratosis and Bowen disease. Tissue microarray sections were blindly analyzed for microscopic morphologic variables. Corresponding ex vivo dermoscopic images from the original cases were blindly analyzed for macroscopic morphologic variables. Immunostained sections from the tissue microarray were tested for keratin 10, keratin 5/6, Bcl‐2 and Ki‐67 expression by image analysis.ResultsThere were no significant differences in the studied morphologic attributes between LCA and solar lentigo. All other tumor classes showed at least one significant morphologic difference with LCA. LCA and solar lentigo showed different keratin 10 and Bcl‐2 signal intensities.ConclusionsLCA is best considered a variant of solar lentigo with cellular hypertrophy. The differences in immunophenotype and cell size could be because of differences in cell kinetics.
Economic determinants of fertility in Belarus
Authors: Amialchuk Aliaksandr , Lisenkova Katerina , Salnykov Mykhaylo , Yemelyanau Maksim 
Published: June 2014

AbstractThis study examines the determinants of births in Belarus in 1996–2007 by using detailed micro‐data from the Belarusian Household Budget Surveys (BHBS). The existing literature offers several explanations of the recent trends in fertility in Belarus and in other former Soviet Union countries. It is often argued that the collapse of the Soviet Union and the concomitant economic instability reduced fertility in the 1990s, while economic growth and stabilization were responsible for its recovery since 2005. We evaluate these and other hypotheses by looking at the determinants of the first, second and third births, separately for women aged below 30 years of age and above 30 years of age. We provide evidence on the presence and the relative importance of the economic determinants, including income and wages, economic uncertainty, maternity and child‐care benefits. Our findings could inform demographic policies in Belarus and in other transitional countries.
Treatment for continuous spikes and waves during sleep (CSWS): Survey on treatment choices in North America
Authors: Sánchez Fernández Iván , Chapman Kevin , Peters Jurriaan M. , Klehm Jacquelyn , Jackson Michele C. , Berg Anne T. , Loddenkemper Tobias 
Published: June 2014

SummaryObjectiveCurrent literature does not allow an evidence‐based approach to the treatment of continuous spikes and waves during sleep (CSWS). The aim of this study was to describe treatment choices made by clinicians caring for patients with CSWS in North America.MethodsA 24‐question survey on treatment choices for CSWS was distributed to the members of the American Epilepsy Society (AES). The survey presented a clinical vignette of CSWS. The questions addressed treatment choices for that clinical scenario. Surveys were self‐administered and collected using an online survey website (www.surveymonkey.com).ResultsTwo‐hundred thirty‐two surveys were completed. Prominent sleep‐potentiated spiking was considered to warrant treatment by 81% of respondents. The proportion of patients in whom cognitive improvement occurs when sleep‐potentiated spiking is effectively treated is in >75% of patients (according to 16% of respondents), in 25–75% of patients (according to 52% of respondents), in <25% of patients (according to 20% of respondents), and no or unclear cognitive changes (according to 12% of respondents). The preferred first choice to reduce sleep‐potentiated epileptiform activity was high‐dose benzodiazepines (47%), valproate (26%), and corticosteroids (15%). The preferred second‐choice was valproate (26%), high‐dose benzodiazepines (24%), and corticosteroids (23%). Among high‐dose benzodiazepines, the preferred one was diazepam 1 mg/kg for one night followed by 0.5 mg/kg/day. The preferred dose of valproate was 30–49 mg/kg/day. Among corticosteroids the preferred choice was oral prednisone 2 mg/kg/day. The most commonly considered endpoints of treatment efficacy were (in decreasing order): response of epileptiform activity in electroencephalography (EEG), cognitive function, and seizure reduction. Results were consistent among respondents with different levels of training and clinical experience. There were differences in conceptualization and treatment approaches between pediatric and adult neurologists.SignificanceMost clinicians considered that prominent sleep‐potentiated epileptiform activity should be treated. There was no agreement on best treatment, but potential candidates included high‐dose benzodiazepines, valproate, levetiracetam, and corticosteroids.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Conversion to lacosamide monotherapy in the treatment of focal epilepsy: Results from a historical‐controlled, multicenter, double‐blind study
Authors: Wechsler Robert T. , Li George , French Jacqueline , O'Brien Terence J. , D'Cruz O'Neill , Williams Paulette , Goodson Robin , Brock Melissa ,   the ALEX‐MT Study Group
Published: June 2014

SummaryObjectiveTo evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy.MethodsThis historical‐controlled, double‐blind study (NCT00520741) enrolled patients aged 16–70 years on stable doses of 1–2 antiepileptic drugs (AEDs) and experiencing 2–40 partial‐onset seizures per 28 days during the 8‐week prospective Baseline. Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose. Patients then withdrew background AEDs over 6 weeks and entered a 10‐week Monotherapy Phase. The primary assessment was the Kaplan‐Meier–predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥1 predefined seizure‐related exit criterion by day 112, compared with the historical‐control threshold (65.3%).ResultsFour hundred twenty‐five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥1 exit criterion; the Kaplan‐Meier–predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6–35.5%) was lower than the historical control. When exit events, withdrawal due to treatment‐emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8–37.8%) was also lower than the historical control. Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%). Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild‐to‐moderate in intensity. Seventy‐two patients (16.9%) discontinued due to TEAEs. Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs.SignificanceLacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
RsaM: a transcriptional regulator of Burkholderia spp. with novel fold
Authors: Michalska Karolina , Chhor Gekleng , Clancy Shonda , Jedrzejczak Robert , Babnigg Gyorgy , Winans Stephen C. , Joachimiak Andrzej 
Published: June 2014

Burkholderia cepacia complex is a set of closely related bacterial species that are notorious pathogens of cystic fibrosis patients, responsible for life‐threatening lung infections. Expression of several virulence factors of Burkholderia cepacia complex is controlled by a mechanism known as quorum sensing (QS). QS is a means of bacterial communication used to coordinate gene expression in a cell‐density‐dependent manner. The system involves the production of diffusible signaling molecules (N‐acyl‐l‐homoserine lactones, AHLs), that bind to cognate transcriptional regulators and influence their ability to regulate gene expression. One such system that is highly conserved in Burkholderia cepacia complex consists of CepI and CepR. CepI is AHL synthase, whereas CepR is an AHL‐dependent transcription factor. In most members of the Burkholderia cepacia complex group, the cepI and cepR genes are divergently transcribed and separated by additional genes. One of them, bcam1869, encodes the BcRsaM protein, which was recently postulated to modulate the abundance or activity of CepI or CepR. Here, we show the crystal structure of BcRsaM from B. cenocepacia J2315. It is a single‐domain protein with unique topology and presents a novel fold. The protein is a dimer in the crystal and in solution. This regulator has no known DNA‐binding motifs and direct binding of BcRsaM to the cepI promoter could not be detected in in vitro assays. Therefore, we propose that the modulatory action of RsaM might result from interactions with other components of the QS machinery rather than from direct association with the DNA promoter.DatabaseThe atomic coordinates and structure factors have been deposited in the Protein Data Bank under entry 4O2H.Structured digital abstract

BcRsaM and BcRsaM bind by x-ray crystallography (View interaction)

BcRsaM and BcRsaM bind by molecular sieving (View interaction)
Combining physiological threshold knowledge to species distribution models is key to improving forecasts of the future niche for macroalgae
Authors: Martínez Brezo , Arenas Francisco , Trilla Alba , Viejo Rosa M. , Carreño Francisco 
Published: June 2014

AbstractSpecies distribution models (SDM) are a useful tool for predicting species range shifts in response to global warming. However, they do not explore the mechanisms underlying biological processes, making it difficult to predict shifts outside the environmental gradient where the model was trained. In this study, we combine correlative SDMs and knowledge on physiological limits to provide more robust predictions. The thermal thresholds obtained in growth and survival experiments were used as proxies of the fundamental niches of two foundational marine macrophytes. The geographic projections of these species’ distributions obtained using these thresholds and existing SDMs were similar in areas where the species are either absent‐rare or frequent and where their potential and realized niches match, reaching consensus predictions. The cold‐temperate foundational seaweed Himanthalia elongata was predicted to become extinct at its southern limit in northern Spain in response to global warming, whereas the occupancy of southern‐lusitanic Bifurcaria bifurcata was expected to increase. Combined approaches such as this one may also highlight geographic areas where models disagree potentially due to biotic factors. Physiological thresholds alone tended to over‐predict species prevalence, as they cannot identify absences in climatic conditions within the species’ range of physiological tolerance or at the optima. Although SDMs tended to have higher sensitivity than threshold models, they may include regressions that do not reflect causal mechanisms, constraining their predictive power. We present a simple example of how combining correlative and mechanistic knowledge provides a rapid way to gain insight into a species’ niche resulting in consistent predictions and highlighting potential sources of uncertainty in forecasted responses to climate change.
Dickkopf‐1 expression is down‐regulated during the colorectal adenoma–carcinoma sequence and correlates with reduced microvessel density and VEGF expression
Authors: Liu Zhiyong , Sun Baocun , Qi Lisha , Li Yixian , Zhao Xiulan , Zhang Danfang , Zhang Yanhui 
Published: June 2014

AimsDickkopf‐1 (Dkk1), an antagonist of the Wnt–β‐catenin signalling pathway, has been reported to play a role in cancer progression. However, little is known about the role of Dkk1 during the colorectal adenoma–carcinoma sequence. This study aimed to elucidate the role of Dkk1 in tumorigenesis and angiogenesis in colorectal cancer.Methods and resultsWe examined Dkk1 expression immunohistochemically in 476 colorectal tissue samples, including 46 sets of matched specimens. Dkk1 expression was down‐regulated during the colorectal adenoma–carcinoma sequence, both among the 476 samples and in the 46 sets of matched specimens. Dkk1 expression was correlated with decreased microvessel density (P < 0.05) and VEGF expression. In‐vitro 3D coculture experiments showed that Dkk1 overexpression in HCT116 cells inhibited tube‐like structure formation and down‐regulated VEGF expression in human umbilical vein endothelial cells. Xenografts of Dkk1‐overexpressing colorectal cancer cells were smaller, and showed lower microvessel density and VEGF expression levels, than those of control cells.ConclusionsThis study is the first to show the roles of Dkk1 during the colorectal adenoma–carcinoma sequence, which may involve suppression of the tumorigenesis and angiogenesis of CRC. Dkk1 could therefore serve as a potential target for tumour therapy.
Association of PTPN22+1858C/T polymorphism with Type 1 diabetes in the North Indian population
Authors: Kumar N. , Kaur G. , Kanga U. , Tandon N. , Caillat‐Zucman S. , Mehra N. K. 
Published: June 2014

SummaryA nonsynonymous SNP +1858C/T (rs2476601) in the protein tyrosine phosphatase, nonreceptor type 22(PTPN22) gene leading to Arg 620 Trp substitution is known to be associated with susceptibility to type 1 diabetes (T1D) and several other autoimmune diseases. We studied this polymorphism in 145 T1D patients and 210 healthy controls from North India. The minor allele +1858T was observed to be significantly increased among patients as compared to healthy controls (2.76% vs 0.5%, P = 0.027, OR = 5.93; 95% CI = 1.4–24.8). The association was also observed at the level of heterozygous C/T genotype (5.5% vs 0.95%, P = 0.026, OR = 6.07; 95% CI = 1.43–25.6). The T allele and C/T genotype were predominantly found among patients who were positive for both glutamic acid decarboxylase 65 (GAD65) and insulin antigen 2 (IA2) autoantibodies and showed significantly increased frequencies (10%, P = 0.034, OR = 11.67; 95% CI = 1.58–84.1 and 20%, P = 0.031, OR = 13.0; 95% CI = 1.66–97.5, respectively) as compared to patients negative for these autoantibodies (0.95% and 1.9%, respectively). The results suggest that the PTPN22+1858T allele is positively associated with T1D in the North Indian population.
Relevance of Osmotic and Frost Protecting Compounds for the Winter Hardiness of Autumn Sown Sugar Beet
Authors: Loel J. , Hoffmann C. M. 
Published: June 2014

AbstractThe cultivation of autumn sown sugar beet (winter beet) is supposed to result in a marked yield increase compared with spring sown sugar beet. Although the importance of the growth stage reached before winter for the survival of autumn sown sugar beet has already been shown, it is not clear to which extent osmotic and potentially frost protecting compounds may contribute to winter hardiness. The study thus aimed to analyse the acclimatization process of sugar beet to low temperatures and to identify compounds which are important for survival of frost. Field trials with autumn sown sugar beet were conducted at eleven environments in Germany from 2009/10 to 2012/13, which were accompanied by greenhouse experiments with controlled temperature regimes. In the field trials, the survival rates after winter varied from 0 % to 99 %, but only in four environments differences between the five genotypes occurred. During acclimatization, betaine, glutamine, proline and raffinose were markedly accumulated and osmolality was enhanced. In particular betaine, amino acids and osmolality showed a positive correlation to the survival rate and were thus identified as potentially frost protecting substances for sugar beet. In contrast, raffinose and proline seem to act rather as stress indicators as they were negatively related to survival. Possible frost protecting substances were identified which can be used in breeding to improve the winter hardiness of sugar beet.
Physiological and Growth Responses of Sugarcane Genotypes to Nitrogen Rate on a Sand Soil
Authors: Zhao D. , Glaz B. , Comstock J. C. 
Published: June 2014

AbstractYields of sugarcane (a complex hybrid of Saccharum spp.) in FL, USA, are lower on sand soils than on organic (muck) soils. Nitrogen (N) supply may limit sugarcane growth and yields on these sand soils. A 2‐year pot study was conducted to determine sugarcane genotypic variation in response to N rate on a sand soil. Treatments included four N rates (0, 75, 150 and 225 kg ha−1) and three sugarcane genotypes (CP 80‐1743, CP 01‐2390 and TCP 87‐3388). Nitrogen fertilizer was equally split and applied at about 55 and 125 days after planting (DAP) for each treatment. During the experiment, the number of nodes and length of the primary stalks and tillers were recorded. Leaf relative chlorophyll (soil plant analysis development (SPAD)) and net photosynthetic rate (Pn) were measured biweekly. All plants were harvested at 183 DAP to measure green leaf area (GLA), shoot biomass accumulation and partitioning, and fertilizer N use efficiency (NUE). Genotypes differed significantly in leaf SPAD, Pn, GLA, and shoot biomass accumulation and partitioning. CP 01‐2390 had the highest leaf Pn and shoot biomass, and CP 80‐1743 had the lowest GLA, shoot biomass and NUE among genotypes. Nitrogen rate affected leaf SPAD, GLA, shoot biomass and NUE, but had much less effect on leaf Pn. Green leaf area and biomass increased with increasing N rates. Our results suggest that a two‐pronged approach, selection of genotypes with high NUE while working to optimize N rates and delivery can improve sugarcane yields on sand soils.
Internalization of isolated functional mitochondria: involvement of macropinocytosis
Authors: Kitani Tomoya , Kami Daisuke , Matoba Satoaki , Gojo Satoshi 
Published: June 2014

AbstractIn eukaryotic cells, mitochondrial dysfunction is associated with a variety of human diseases. Delivery of exogenous functional mitochondria into damaged cells has been proposed as a mechanism of cell transplant and physiological repair for damaged tissue. We here demonstrated that isolated mitochondria can be transferred into homogeneic and xenogeneic cells by simple co‐incubation using genetically labelled mitochondria, and elucidated the mechanism and the effect of direct mitochondrial transfer. Intracellular localization of exogenous mitochondria was confirmed by PCR, real‐time PCR, live fluorescence imaging, three‐dimensional reconstruction imaging, continuous time‐lapse microscopic observation, flow cytometric analysis and immunoelectron microscopy. Isolated homogeneic mitochondria were transferred into human uterine endometrial gland‐derived mesenchymal cells in a dose‐dependent manner. Moreover, mitochondrial transfer rescued the mitochondrial respiratory function and improved the cellular viability in mitochondrial DNA‐depleted cells and these effects lasted several days. Finally, we discovered that mitochondrial internalization involves macropinocytosis. In conclusion, these data support direct transfer of exogenous mitochondria as a promising approach for the treatment of various diseases.