bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1
Authors: Ngiow Shin Foong , Young Arabella , Jacquelot Nicolas , Yamazaki Takahiro , Enot David , Zitvogel Laurence , Smyth Mark J. 
Published: July 2015

Abstract
Despite successes, thus far, a significant proportion of the patients treated with anti-PD1 antibodies have failed to respond. We use mouse tumor models of anti-PD1 sensitivity and resistance and flow cytometry to assess tumor-infiltrating immune cells immediately after therapy. We demonstrate that the expression levels of T-cell PD1 (PD1lo), myeloid, and T-cell PDL1 (PDL1hi) in the tumor microenvironment inversely correlate and dictate the efficacy of anti-PD1 mAb and function of intratumor CD8+ T cells. In sensitive tumors, we reveal a threshold for PD1 downregulation on tumor-infiltrating CD8+ T cells below which the release of adaptive immune resistance is achieved. In contrast, PD1hi T cells in resistant tumors fail to be rescued by anti-PD1 therapy and remain dysfunctional unless intratumor PDL1lo immune cells are targeted. Intratumor Tregs are partly responsible for the development of anti-PD1–resistant tumors and PD1hi CD8+ T cells. Our analyses provide a framework to interrogate intratumor CD8+ T-cell PD1 and immune PDL1 levels and response in human cancer. Cancer Res; 75(18); 3800–11. ©2015 AACR.
The 1,2-Diaminocyclohexane Carrier Ligand in Oxaliplatin Induces p53-Dependent Transcriptional Repression of Factors Involved in Thymidylate Biosynthesis
Authors: Kiyonari Shinichi , Iimori Makoto , Matsuoka Kazuaki , Watanabe Sugiko , Morikawa-Ichinose Tomomi , Miura Daisuke , Niimi Shinichiro , Saeki Hiroshi , Tokunaga Eriko , Oki Eiji , Morita Masaru , Kadomatsu Kenji , Maehara Yoshihiko , Kitao Hiroyuki 
Published: July 2015

Abstract
Platinum-based chemotherapeutic drugs are widely used as components of combination chemotherapy in the treatment of cancer. One such drug, oxaliplatin, exerts a synergistic effect against advanced colorectal cancer in combination with 5-fluorouracil (5-FU) and leucovorin. In the p53-proficient colorectal cancer cell line HCT116, oxaliplatin represses the expression of deoxyuridine triphosphatase (dUTPase), a ubiquitous pyrophosphatase that catalyzes the hydrolysis of dUTP to dUMP and inhibits dUTP-mediated cytotoxicity. However, the underlying mechanism of this activity has not been completely elucidated, and it remains unclear whether factors other than downregulation of dUTPase contribute to the synergistic effect of 5-FU and oxaliplatin. In this study, we found that oxaliplatin and dachplatin, platinum-based drugs containing the 1,2-diaminocyclohexane (DACH) carrier ligand, repressed the expression of nuclear isoform of dUTPase (DUT-N), whereas cisplatin and carboplatin did not. Oxaliplatin induced early p53 accumulation, upregulation of primary miR-34a transcript expression, and subsequent downregulation of E2F3 and E2F1. Nutlin-3a, which activates p53 nongenotoxically, had similar effects. Introduction of miR-34a mimic also repressed E2F1 and DUT-N expression, indicating that this miRNA plays a causative role. In addition to DUT-N, oxaliplatin repressed, in a p53-dependent manner, the expression of genes encoding enzymes involved in thymidylate biosynthesis. Consequently, oxaliplatin significantly decreased the level of dTTP in the dNTP pool in a p53-dependent manner. These data indicate that the DACH carrier ligand in oxaliplatin triggers signaling via the p53–miR-34a–E2F axis, leading to transcriptional regulation that ultimately results in accumulation of dUTP and reduced dTTP biosynthesis, potentially enhancing 5-FU cytotoxicity. Mol Cancer Ther; 14(10); 2332–42. ©2015 AACR.
Pancreatic Cancer Metastases Harbor Evidence of Polyclonality
Authors: Maddipati Ravikanth , Stanger Ben Z. 
Published: July 2015

Abstract
Studies of the cancer genome have demonstrated that tumors are composed of multiple subclones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these subclones. To understand the cellular dynamics that drive metastasis, we used multicolor lineage-tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity decreases during premalignant progression. Furthermore, we present evidence that a significant fraction of metastases are polyclonally seeded by distinct tumor subclones. Finally, we show that clonality during metastatic growth—leading to either monoclonal or polyclonal expansion—differs based on the site of metastatic invasion. These results provide an unprecedented window into the cellular dynamics of tumor evolution and suggest that heterotypic interactions between tumor subpopulations contribute to metastatic progression in native tumors.
Significance: Studies of tumor heterogeneity indicate that distinct tumor subclones interact during cancer progression. Here, we demonstrate by lineage tracing that metastases often involve seeding by more than one clone and that subsequent cellular outgrowth depends on the metastatic site. These findings provide insight into clonal diversity and evolution in metastatic disease. Cancer Discov; 5(10); 1086–97. ©2015 AACR.
This article is highlighted in the In This Issue feature, p. 1005
Dynamical Response to the QBO in the Northern Winter Stratosphere: Signatures in Wave Forcing and Eddy Fluxes of Potential Vorticity
Authors: White Ian P. , Lu Hua , Mitchell Nicholas J. , Phillips Tony 
Published: July 2015

Abstract
Wave–mean flow interactions associated with the Holton–Tan effect (HTE), whereby the tropical quasi-biennial oscillation (QBO) modulates the Northern Hemisphere wintertime stratospheric polar vortex, are studied using the ERA-Interim dataset. Significant evidence of the HTE in isentropic coordinates is found, with a weaker and warmer polar vortex present when the lower-stratospheric QBO is in its easterly phase (QBOe). For the first time, the authors quantify the QBO modulation of wave propagation, wave–mean flow interaction, and wave decay/growth via a calculation of potential vorticity (PV)-based measures, the zonal-mean momentum budget, and up-/downgradient eddy PV fluxes. The effect of the tropospheric subtropical jet on QBO modulation of the wave activity is also investigated. In the subtropical-to-midlatitude lower stratosphere, QBOe is associated with an enhanced upward flux of wave activity, and corresponding wave convergence and wave growth, which leads to a stronger poleward zonal-mean meridional circulation and consequently a warmer polar region. In the middle stratosphere, QBOe is associated with increased poleward wave propagation, leading to enhanced wave convergence and in situ wave growth at high latitudes and contributing to the weaker polar vortex. In agreement with recent studies, the results suggest that the critical-line effect cannot fully account for these wave anomalies associated with the HTE. Instead, it is suggestive of a new, additional mechanism that hinges on the QBO-induced meridional circulation effect on the latitudinal positioning of the subtropical jet. Under QBOe, the QBO-induced meridional circulation causes a poleward shift of the subtropical jet, encouraging more waves to propagate into the stratosphere at midlatitudes.
Predictive Skill for Regional Interannual Steric Sea Level and Mechanisms for Predictability*
Authors: Polkova Iuliia , Köhl Armin , Stammer Detlef 
Published: July 2015

Abstract
Based on decadal hindcasts initialized every five years over the period 1960–2000, the predictive skill of annual-mean regional steric sea level and associated mechanisms are investigated. Predictive skill for steric sea level is found over large areas of the World Ocean, notably over the subtropical Atlantic and Pacific Oceans, along the path of the North Atlantic Current, and over the Indian and Southern Oceans. Mechanisms for the predictability of the thermosteric and halosteric contributions to the steric signal are studied by separating these components into signals originating from processes within and beneath the mixed layer. Contributions originating from below the mixed layer are further decomposed into density-related (isopycnal motion term) and density-compensated (spice term) changes. In regions of the subtropical Pacific and Atlantic Oceans, predictive skill results from the interannual variability associated with the contribution from isopycnal motion to thermosteric sea level. Skill related to thermosteric mixed layer processes is found to be important in the subtropical Atlantic, while the spice contribution shows skill over the subpolar North Atlantic. In the subtropics, the high predictive skill can be rationalized in terms of westward-propagating baroclinic Rossby waves for a lead time of 2–5 yr, as demonstrated using an initialized Rossby wave model. Because of the low Rossby wave speed in high latitudes, this process is not separable from the persistence there.
Calibrated Forecasts of Extreme Windstorms Using the Extreme Forecast Index (EFI) and Shift of Tails (SOT)
Authors: Boisserie Marie , Descamps Laurent , Arbogast Philippe 
Published: July 2015

Abstract
This study presents a method that improves extreme windstorm early warning in regards to past events that hit France during the last 30 years. From a 21-member ensemble forecast, the extreme forecast index (EFI) and the shift of tails (SOT) are used to produce calibrated forecasts for a selection of 59 windstorm cases. The EFI and SOT forecasts are evaluated for windstorms of different levels of severity and for various forecast index thresholds using the Heidke skill score (HSS), hit rate (HR), and false alarm rate (FA). The HR and FA show that a “zero misses” level always goes conjointly with a high level of false alarms. The HSS shows maxima that are associated with EFI (or SOT) thresholds that could be used as a rationale for decision-makers to issue warnings. For most extreme events, it is found that a higher level of HR can be achieved using the SOT rather than the EFI. Overall, most of the windstorms are well anticipated 3–4 days ahead. To facilitate the use of EFI or SOT forecasts, it is suggested that extra information in the form of conditional probabilities be added, hence linking the EFI (or SOT) values to a risk of occurrence of a severe event. Finally, this anticipation of extreme events is illustrated by maps of EFI and SOT for four historical windstorms.
Laparoscopic colorectal surgery: Is it beneficial in the over 80s?
Authors: Tabbakh Y , Ihedioha U , Panteleimonitis S , Gevech Z , Evans J , Kang P 
Published: July 2015

Introduction Advanced age is often associated with higher incidence of co-morbidities, advanced cancer and post-operative complications. The aim of this study was to compare the differences in pre-operative, co-morbidities, cancer stage and surgical outcome measures between patients over the age of 80 and those below 80 undergoing elective laparoscopic colorectal resection. Method Data were analysed from a prospectively maintained database between February 2011 and June 2012 and patients were subdivided into two groups (over 80 and under 80). All patients underwent laparoscopic colorectal surgery. Their length of stay, high dependency unit/intensive therapy unit stay, American Society of Anaesthesiologists grade, co-morbidities, conversion rates, Dukes’ stage and post-operative complication rates were compared. Results Of the 67 patients in the study, 57 were <80 at the time of surgery. Their American Society of Anaesthesiologists grade prior to surgery, as expected, was better than that of the >80 group, with 23% having an American Society of Anaesthesiologists grade of 3 compared to 60% in the >80%. The prognosis of the patients in the two groups based on Dukes’ stage was similar, with 63% of the <80 s having a good prognosis, compared to 80% in the >80 s. (Good prognosis = Dukes’ A or B). The conversion rates were similar (26% of the <80 s compared to 20% of the > 80 s) Post-operative length of stay was also similar in both groups (<80 s vs. >80 s: median 5 vs. 5; p = 0.33). Post-operative complication rates were similar (17% of the <80 s vs. 20% of the >80 s). Conclusion The short-term outcomes following laparoscopic colorectal surgery in the elderly are similar to that of younger patients. Laparoscopic surgery should therefore be offered to all patients irrespective of age.
Comparison of Intraoperative versus Postoperative Parathyroid Hormone Levels to Predict Hypocalcemia Earlier after Total Thyroidectomy
Authors: Lee David R. , Hinson Andrew M. , Siegel Eric R. , Steelman Susan C. , Bodenner Donald L. , Stack Brendan C. 
Published: July 2015

ObjectiveTo determine differences in the mean parathyroid hormone (PTH) levels for normocalcemic and hypocalcemic total thyroidectomy patients who were tested for PTH during the intraoperative or early postoperative period.Data SourcesMEDLINE, the Cochrane Database, and other databases from 1960 to 2014 in the English language and specific to humans for relevant articles.Review MethodsStudies were included if PTH was obtained within 24 hours of thyroidectomy. Studies were excluded (1) if only a hemithyroidectomy was performed, (2) if means of studied PTH values were not reported in the article, or (3) if the time of the PTH draw fell outside of defined “intraoperative” or “early postoperative” windows. PTH values were divided into 3 groups: preoperative (control group), intraoperative (ie, discharge decisions were based on PTH values drawn in the operating room), and early postoperative (ie, PTH values at 1 to 4 hours after surgery were used as a guide).ResultsThe reported means of perioperative PTH levels and percentage of patients who developed hypocalcemia were collected from 14 studies. PTH evaluated at both the intraoperative and early postoperative periods was significantly lower in patients who became hypocalcemic versus patients who remained normocalcemic. There was no significant difference when PTH was measured intraoperatively or early postoperatively.ConclusionIntraoperative PTH has no significant disadvantage versus early postoperative PTH when used as a clinical guide for discharge after thyroidectomy.
Improving quality of a rural CAMHS service using the Choice and Partnership Approach
Authors: Naughton Jonine , Basu Soumya , O’Dowd Frank , Carroll Matthew , Maybery Darryl 
Published: July 2015

Objective: This study outlines the service issues and adjustments associated with the implementation of Choice and Partnership Approach (CAPA) into a rural Child and Adolescent Mental Health Service (CAMHS). Method: A mixed-methods approach examined the impacts of the CAPA implementation. A qualitative review of the minutes from team and implementation group meetings illustrated themes according to 11 key CAPA components. Quantitative internal audit data illustrated waiting list times. Results: Findings showed that inclusive language has replaced the traditional, pathology-driven psychiatric discourse, though this has been met with mixed response from CAMHS clinicians, service users and referrers. Data also showed that a waiting list for clinician allocation has been eliminated, and the waiting time between the referral date and the first face-to-face contact has decreased from 63.9 days to 10.7 days. Conclusion: A modified CAPA Choice appointment system has allowed quick access without a waiting list, in line with government guidelines. A full-booking system and focussed, goal-oriented interventions has led to lower caseloads and optimum use of CAMHS clinician skillsets.
Disciplinary and Legal Actions Against Dermatologists in Canada
Authors: Nasseri Eiman 
Published: July 2015

Background: Dermatologists face a litany of professional and legal risks in practice. Objective: To review cases of disciplinary and legal action against dermatologists in Canada. Methods: The Canadian Medical Protective Association, all 10 provincial medical colleges, and the Canadian Legal Information Institute were contacted to obtain data on legal or disciplinary action taken against dermatologists in their records. A literature review was performed regarding litigation against dermatologists in other countries. Results: Six dermatologists in Canada faced disciplinary action in the last 5 to 30 years. Seven dermatologists and 5 other specialists in Canada faced lawsuits relating to dermatology in the last 1 to 144 years. Procedures and therapy are the most frequently sources of lawsuits against dermatologists both at home and abroad. Conclusion: Dermatologists need to remain vigilant to avoid disciplinary action and lawsuits from their increasing and varied interactions with patients.
Use of carbonated water in reduction of adjacent gastric activity in 456 consecutive technetium-99m myocardial perfusion imaging studies
Authors: Thomas Dustin M. , Lee Joshua S. , Charmforoush Anthony , Rubal Bernard J. , Rosenblatt Stephen A. , Butler Joshua T. , Clemenshaw Michael , Cheezum Michael K. , Slim Ahmad M. 
Published: July 2015

Background: Small, observational trials have suggested a reduction in adjacent gastric activity with ingestion of soda water in myocardial perfusion imaging (MPI). We report our findings prior to and after implementation of soda water in 467 consecutive MPI studies. Methods: Consecutive MPI studies performed at a high-volume facility referred for vasodilator (VD) or exercise treadmill testing (ETT) were retrospectively reviewed before and after implementation of the soda water protocol. Patients undergoing the soda water protocol received 100 ml of soda water administered 30 min prior to image acquisition and after stress. Studies were performed using a same day rest/stress protocol. Incidence of adjacent gastric activity, diaphragmatic attenuation, stress and rest perfusion defects, and major adverse cardiovascular events (MACE) outcomes defined as death, myocardial infarction, stroke, reevaluation for chest pain, and late revascularization (>90 days from MPI) were abstracted using International Classification of Diseases, Ninth Revision (ICD-9) search. Results: Two hundred and eighteen studies were performed prior to implementation of the soda water protocol and 249 studies were performed with the use of soda water. Baseline demographic data were equal between the groups with the exception of more patients undergoing VD stress receiving soda water ( p < 0.001). Soda water was not associated with a decreased incidence of adjacent gastric activity with stress (54.7% versus 61.9% with no soda water, p = 0.129) or rest (68.6% versus 69.5% with no soda water, p = 0.919) imaging. Less adjacent gastric activity was observed with patients undergoing ETT who received soda water (42.5% versus 56.9% with no soda water, p = 0.031), but no difference was observed between the groups with VD stress (69.0% versus 68.1% with no soda water, p = 1.000). Conclusion: The use of soda water prior to technetium-99m MPI was associated with lower rates of adjacent gastric activity only in patients undergoing ETT stress but not rest or VD stress. This differs from previously published data.
Diffusion of innovation: customer relationship management adoption in supply chain organizations
Authors: Gu Vicky Ching , Schniederjans Marc J , Cao Qing 
Published: July 2015

Abstract
The successful diffusion of innovations in rapidly changing supply chain technological environments is essential to support operations and supply chain management functions. In this paper we conceptualize and develop a framework for research into the diffusion of innovations in organizations pertaining to software adoption in supply chain management. Incorporating Task-Technology Fit theory with a network externalities model, we develop a novel approach in customer relations management (CRM) software adoption. An empirical study using Partial Least Squares (PLS) on data from US supply chain managers is utilized to confirm the usability of the proposed framework as well as confirming the efficacy of the proposed combined methodological approach suggested in this paper. The results also show the direct and indirect network externalities of system quality, ease of use, system reliability, and authority can moderate the CRM adoption relationship in organizations, suggesting the possibility that other moderating network externality variables may impact CRM adoption.
Rank aggregation with ties
Authors: Brancotte Bryan , Yang Bo , Blin Guillaume , Cohen-Boulakia Sarah , Denise Alain , Hamel Sylvie 
Published: July 2015

The problem of aggregating multiple rankings into one consensus ranking is an active research topic especially in the database community. Various studies have implemented methods for rank aggregation and may have come up with contradicting conclusions upon which algorithms work best. Comparing such results is cumbersome, as the original studies mixed different approaches and used very different evaluation datasets and metrics. Additionally, in real applications, the rankings to be aggregated may not be permutations where elements are strictly ordered, but they may have ties where some elements are placed at the same position. However, most of the studies have not considered ties.
This paper introduces the first large scale study of algorithms for rank aggregation with ties. More precisely, (i) we review rank aggregation algorithms and determine whether or not they can handle ties; (ii) we propose the first implementation to compute the exact solution of the Rank Aggregation with ties problem; (iii) we evaluate algorithms for rank aggregation with ties on a very large panel of both real and carefully generated synthetic datasets; (iv) we provide guidance on the algorithms to be favored depending on dataset features.
Long-term treatment for hyperphenylalaninemia and phenylketonuria: a risk for nutritional vitamin B12 deficiency?
Authors: Procházková Dagmar , Jarkovský Jiří , Haňková Zdena , Konečná Petra , Benáková Hana , Vinohradská Hana , Mikušková Alena 
Published: July 2015

AbstractThe objective of the study was to determine the incidence of vitamin BThe group consisted of 51 PKU (n=29) and HPA (n=22) patients aged 3–48 years (28 children, 23 adults).A significant difference in serum folate levels was discovered between adult HPA patients and PKU patients (p=0.004, Mann-Whitney U-test). A significant difference in plasma homocysteine concentrations within the normal levels (p=0.032, χWe have proven that adult patients with PKU and HPA are at risk of vitamin B
Hawkinsinuria in two unrelated Greek newborns: identification of a novel variant, biochemical findings and treatment
Authors: Thodi Georgia , Schulpis Kleopatra H. , Dotsikas Yannis , Pavlides Christiane , Molou Elina , Chatzidaki Maria , Triantafylli Olga , Loukas Yannis L. 
Published: July 2015

AbstractHawkinsinuria is a rare inborn error of tyrosine metabolism.To study novel hawkinsinuria cases by monitoring their biochemical profile and conducting a mutation analysis.Among 92,519 newborns that underwent expanded newborn screening, two unrelated cases with high tyrosine blood levels were further investigated by chromatographic techniques and via genetic testing for 4-hydroxyphenylpyruvate dioxygenase (HPD) gene.Elevated levels were monitored for blood/plasma tyrosine and for the specific diagnostic markers in urine. The two newborns were put on a special low tyrosine diet. Till completion of the 1st year of their life, liver function tests and brain MRI were normal. The mutation A33T was identified in both cases, while one neonate carried an additional novel mutation ofTwo mutations of