bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 Expression in Triple-Negative Breast Cancer
Authors: Mittendorf Elizabeth A. , Philips Anne V. , Meric-Bernstam Funda , Qiao Na , Wu Yun , Harrington Susan , Su Xiaoping , Wang Ying , Gonzalez-Angulo Ana M. , Akcakanat Argun , Chawla Akhil , Curran Michael , Hwu Patrick , Sharma Padmanee , Litton Jennifer K. , Molldrem Jeffrey J. , Alatrash Gheath 
Published: January 2014

Abstract
Early-phase trials targeting the T-cell inhibitory molecule programmed cell death ligand 1 (PD-L1) have shown clinical efficacy in cancer. This study was undertaken to determine whether PD-L1 is overexpressed in triple-negative breast cancer (TNBC) and to investigate the loss of PTEN as a mechanism of PD-L1 regulation. The Cancer Genome Atlas (TCGA) RNA sequencing data showed significantly greater expression of the PD-L1 gene in TNBC (n = 120) compared with non-TNBC (n = 716; P &lt; 0.001). Breast tumor tissue microarrays were evaluated for PD-L1 expression, which was present in 19% (20 of 105) of TNBC specimens. PD-L1+ tumors had greater CD8+ T-cell infiltrate than PD-L1− tumors (688 cells/mm vs. 263 cells/mm; P &lt; 0.0001). To determine the effect of PTEN loss on PD-L1 expression, stable cell lines were generated using PTEN short hairpin RNA (shRNA). PTEN knockdown led to significantly higher cell-surface PD-L1 expression and PD-L1 transcripts, suggesting transcriptional regulation. Moreover, phosphoinositide 3-kinase (PI3K) pathway inhibition using the AKT inhibitor MK-2206 or rapamycin resulted in decreased PD-L1 expression, further linking PTEN and PI3K signaling to PD-L1 regulation. Coculture experiments were performed to determine the functional effect of altered PD-L1 expression. Increased PD-L1 cell surface expression by tumor cells induced by PTEN loss led to decreased T-cell proliferation and increased apoptosis. PD-L1 is expressed in 20% of TNBCs, suggesting PD-L1 as a therapeutic target in TNBCs. Because PTEN loss is one mechanism regulating PD-L1 expression, agents targeting the PI3K pathway may increase the antitumor adaptive immune responses. Cancer Immunol Res; 2(4); 361–70. ©2014 AACR.
Lower Levels of Sodium Intake and Reduced Cardiovascular Risk
Authors: Cook Nancy R. , Appel Lawrence J. , Whelton Paul K. 
Published: January 2014

Background—
Recent studies have raised the possibility of adverse effects of low sodium, particularly <2300 mg/d, on cardiovascular disease; however, these paradoxical findings might have resulted from suboptimal measurement of sodium and potential biases related to indication or reverse causation.

Methods and Results—

Phases 1 and 2 of the Trials of Hypertension Prevention (TOHP) collected multiple 24-hour urine specimens among prehypertensive individuals. During extended posttrial surveillance, 193 cardiovascular events or cardiovascular disease deaths occurred among 2275 participants not in a sodium reduction intervention with 10 (TOHP II) or 15 (TOHP I) years of posttrial follow-up. Median sodium excretion was 3630 mg/d, with 1.4% of the participants having intake <1500 mg/d and 10% <2300 mg/d, consistent with national levels. Compared with those with sodium excretion of 3600 to <4800 mg/d, risk for those with sodium <2300 mg/d was 32% lower after multivariable adjustment (hazard ratio, 0.68; 95% confidence interval, 0.34–1.37;
P
for trend=0.13). There was a linear 17% increase in risk per 1000 mg/d increase in sodium (
P
=0.05). Spline curves supported a linear association of sodium with cardiovascular events, which continued to decrease from 3600 to 2300 and 1500 mg/d, although the data were sparse at the lowest levels. Controlling for creatinine levels had little effect on these results.

Conclusions—
Results from the TOHP studies, which overcome the major methodological challenges of prior studies, are consistent with overall health benefits of reducing sodium intake to the 1500 to 2300 mg/d range in the majority of the population, in agreement with current dietary guidelines.
Timing and Patterns of the ENSO Signal in Africa over the Last 30 Years: Insights from Normalized Difference Vegetation Index Data
Authors: Philippon N. , Martiny N. , Camberlin P. , Hoffman M. T. , Gond V. 
Published: January 2014

Abstract
A more complete picture of the timing and patterns of the ENSO signal during the seasonal cycle for the whole of Africa over the three last decades is provided using the normalized difference vegetation index (NDVI). Indeed, NDVI has a higher spatial resolution and is more frequently updated than in situ climate databases, and highlights the impact of ENSO on vegetation dynamics as a combined result of ENSO on rainfall, solar radiation, and temperature.
The month-by-month NDVI–Niño-3.4 correlation patterns evolve as follows. From July to September, negative correlations are observed over the Sahel, the Gulf of Guinea coast, and regions from the northern Democratic Republic of Congo to Ethiopia. However, they are not uniform in space and are moderate (~0.3). Conversely, positive correlations are recorded over the winter rainfall region of South Africa. In October–November, negative correlations over Ethiopia, Sudan, and Uganda strengthen while positive correlations emerge in the Horn of Africa and in the southeast coast of South Africa. By December with the settlement of the ITCZ south of the equator, positive correlations over the Horn of Africa spread southward and westward while negative correlations appear over Mozambique, Zimbabwe, and South Africa. This pattern strengthens and a dipole at 18°S is well established in February–March with reduced (enhanced) greenness during ENSO years south (north) of 18°S. At the same time, at ~2°N negative correlations spread northward. Last, from April to June negative correlations south of 18°S spread to the north (to 10°S) and to the east (to the south of Tanzania).
Uncertainties, Correlations, and Optimal Blends of Drought Indices from the NLDAS Multiple Land Surface Model Ensemble
Authors: Xia Youlong , Ek Michael B. , Mocko David , Peters-Lidard Christa D. , Sheffield Justin , Dong Jiarui , Wood Eric F. 
Published: January 2014

AbstractThis study analyzed uncertainties and correlations over the United States among four ensemble-mean North American Land Data Assimilation System (NLDAS) percentile-based drought indices derived from monthly mean evapotranspiration ET, total runoff Q, top 1-m soil moisture SM1, and total column soil moisture SMT. The results show that the uncertainty is smallest for SM1, largest for SMT, and moderate for ET and Q. The strongest correlation is between SM1 and SMT, and the weakest correlation is between ET and Q. The correlation between ET and SM1 (SMT) is strongest in arid–semiarid regions, and the correlation between Q and SM1 (SMT) is strongest in more humid regions in the Pacific Northwest and the Southeast. Drought frequency analysis shows that SM1 has the most frequent drought occurrence, followed by SMT, Q, and ET. The study compared the NLDAS drought indices (a research product) with the U.S. Drought Monitor (USDM; an operational product) in terms of drought area percentage derived from each product. It proposes an optimal blend of NLDAS drought indices by searching for weights for each index that minimizes the RMSE between NLDAS and USDM drought area percentage for a 10-yr period (2000–09) with a cross validation. It reconstructed a 30-yr (1980–2009) Objective Blended NLDAS Drought Index (OBNDI) and monthly drought percentage. Overall, the OBNDI performs the best with the smallest RMSE, followed by SM1 and SMT. It should be noted that the contribution to OBNDI from different variables varies with region. So a single formula is probably not the best representation of a blended index. The representation of a blended index using the multiple formulas will be addressed in a future study.
Effects of Irrigation in India on the Atmospheric Water Budget
Authors: Tuinenburg O. A. , Hutjes R. W. A. , Stacke T. , Wiltshire A. , Lucas-Picher P. 
Published: January 2014

Abstract
The effect of large-scale irrigation in India on the moisture budget of the atmosphere was investigated using three regional climate models and one global climate model, all of which performed an irrigated run and a natural run without irrigation. Using a common irrigation map, year-round irrigation was represented by adding water to the soil moisture to keep it at 90% of the maximum soil moisture storage capacity, regardless of water availability. For two focus regions, the seasonal cycle of irrigation matched that of the reference dataset, but irrigation application varied between the models by up to 0.8 mm day−1. Because of the irrigation, evaporation increased in all models, but precipitation decreased because of a strong decrease in atmospheric moisture convergence. A moisture tracking scheme was used to track individual evaporated moisture parcels through the atmosphere to determine where these lead to precipitation. Up to 35% of the evaporation moisture from the Ganges basin is recycling within the river basin. However, because of a decreased moisture convergence into the river basin, the total amount of precipitation in the Ganges basin decreases. Although a significant fraction of the evaporation moisture recycles within the river basin, the changes in large-scale wind patterns due to irrigation shift the precipitation from the eastern parts of India and Nepal to the northern and western parts of India and Pakistan. In these areas where precipitation increases, the relative precipitation increase is larger than the relative decrease in the areas where precipitation decreases. It is concluded 1) that the direct effects of irrigation on precipitation are small and are not uniform across the models; 2) that a fraction of up to 35% of any marginal evaporation increase (for example, due to irrigation) will recycle within the river basin; and 3) that when irrigation is applied on a large scale, the dominant effect will be a change in large-scale atmospheric flow that decreases precipitation in eastern India and increases it in western and northern India.
A Procedure for Operational Use of Wave Hindcasts to Identify Landfall of Heavy Swell
Authors: Innocentini Valdir , Caetano Ernesto , Carvalho Jonas Takeo 
Published: January 2014

Abstract
The wave pattern on the Brazilian coastline is composed of both wind waves and swell. The wave systems (WSs), extracted from the spectra near the coast produced by numerical wave models, reveal the occasional presence of intense swells, with small significant wave height (HS) and large average period (Ta). This kind of event has nearly no effect over deep water, but its landfall can be accompanied by inundation, mainly when coupled with favorable tides and storm surge. Since these events are not clearly evident in the bulk parameters, this study proposes a methodology (i) to identify intense swells simulated by a coarse grid resolution wave modeling system (CWS) and (ii) to evaluate their importance. In this methodology, monitoring sites are defined along a 100-m isobath contouring the Brazilian coast, where the CWS hindcasts the spectra for a 31-yr period, from 1979 to 2009, obtained by the WAVEWATCH wave model. The spectra are partitioned into WSs, which are used to build cumulative distribution tables (CDTs) for each site. The variable used in the CDT is the flux of energy per unit length perpendicular to the wave propagation (PW), which contains in its definition both HS and Ta. The direction of propagation of a WS is used to compute the components of PW parallel and perpendicular to the coast. From the CDT of the perpendicular component of PW, the percentile of an incoming WS can be found and its intensity ranked. To illustrate the feasibility of this proposal, the method is used to find the 50 most powerful distantly generated swells for two sites: one on the northern and another on the southern Brazilian coast. In addition, the method is applied in two case studies, both accompanied by coastal flooding and erosion: one represents a very powerful WS arriving at the northern coast and the other a less energetic event occurring on the southeastern coast. The analysis of bulk parameters fails to identify the second case as potentially destructive, while the proposed methodology clearly gives some indication.
Fit for purpose? Validation of a conceptual framework for personal recovery with current mental health consumers
Authors: Bird Victoria , Leamy Mary , Tew Jerry , Le Boutillier Clair , Williams Julie , Slade Mike 
Published: January 2014

Objective: Mental health services in the UK, Australia and other Anglophone countries have moved towards supporting personal recovery as a primary orientation. To provide an empirically grounded foundation to identify and evaluate recovery-oriented interventions, we previously published a conceptual framework of personal recovery based on a systematic review and narrative synthesis of existing models. Our objective was to test the validity and relevance of this framework for people currently using mental health services. Method: Seven focus groups were conducted with 48 current mental health consumers in three NHS trusts across England, as part of the REFOCUS Trial. Consumers were asked about the meaning and their experience of personal recovery. Deductive and inductive thematic analysis applying a constant comparison approach was used to analyse the data. The analysis aimed to explore the validity of the categories within the conceptual framework, and to highlight any areas of difference between the conceptual framework and the themes generated from new data collected from the focus groups. Results: Both the inductive and deductive analysis broadly validated the conceptual framework, with the super-ordinate categories Connectedness, Hope and optimism, Identity, Meaning and purpose, and Empowerment (CHIME) evident in the analysis. Three areas of difference were, however, apparent in the inductive analysis. These included practical support; a greater emphasis on issues around diagnosis and medication; and scepticism surrounding recovery. Conclusions: This study suggests that the conceptual framework of personal recovery provides a defensible theoretical base for clinical and research purposes which is valid for use with current consumers. However, the three areas of difference further stress the individual nature of recovery and the need for an understanding of the population and context under investigation.
Pharmacological management of pain in chronic pancreatitis
Authors: Paisley P , Kinsella J 
Published: January 2014

Introduction: Chronic pancreatitis is a condition that is rising in incidence in the Western World. It is predominated by severe intractable abdominal pain that presents a significant impact on patients’ quality of life and physical functioning. The pain is persistent in many patients, requiring admission to hospital for the majority at some stage in their illness. There is no current NICE or SIGN guideline with associated grading for the pharmacological management of this symptom. This paper aims to investigate and summarise the current pharmacological therapies for pain control in an attempt to formulate the levels of evidence supporting their use. Methods: The online digital archives PubMed, Science Direct, Medscape and the Cochrane Library were searched for the keywords pain and chronic pancreatitis. Hand searches of relevant journals and citations were used to complete the investigation of current literature on the topic. Relevant articles and studies were critically analysed in a standard format with relation to study type, population, number, end point and outcomes. Publications not relevant to the management of pain in chronic pancreatitis were excluded. Results: Medical therapies, including oral analgesics and enzyme preparations, were included in the analysis of current modalities for treating pain in chronic pancreatitis. Conclusions: A summary of the evidence base for different pharmacological treatments in the context of chronic pancreatitis has shown that large number trials evaluating their efficacy in managing pain are lacking and offer scope for future research on this topic. The use of ‘alternative’ treatments such as antioxidant preparations and enzyme antagonists has shown promise. With regard to opioids, tramadol is as effective as morphine with less neuropsychiatric and gastrointestinal side effects. Oxycodone may derive more benefit than morphine due to an additional Κ-agonist effect.
Hereditary multiple exostoses: anatomical distribution and burden of exostoses is dependent upon genotype and gender
Authors: Clement ND , Porter DE 
Published: January 2014

Background and aims We describe the novel anatomical distribution of exostoses in patients with hereditary multiple exostoses according to their gender and genotype. Methods and results A prospective database of 143 patients from 65 families with hereditary multiple exostoses was compiled. Patient demographics, genotype and number of exostoses according to anatomical site were recorded. The hand was affected by the greatest proportion of exostoses for both EXT1 (19%) and EXT2 (14%) genotypes and was the most prevalent site for exostoses in patients with an EXT1 genotype (92%). Patients with an EXT1 genotype had a significantly greater number of exostoses compared to those with an EXT2 genotype (2680 vs. 1828, p = 0.006); however, this was only significantly different for 10 of the 19 anatomical regions examined. Male patients with an EXT1 genotype had a significantly ( p < 0.05) greater number of exostoses affecting their hands, distal radius, proximal humerus, scapular and ribs compared to female patients with the same genotype and males with an EXT2 genotype. Conclusion The anatomical distribution of exostoses varies according to genotype and gender; however, the reason for this difference is not clear and may relate to different biochemical pathways.
Caseload of a land-based trauma team
Authors: Maddock A , Donald M 
Published: January 2014

Background and aims Pre-hospital care is provided by a variety of models worldwide. The Tayside Trauma Team responds from Ninewells Hospital in Dundee to provide a physician-led pre-hospital care service targeted primarily at trauma patients. We present a description of the functions of the team, and data detailing the clinical work of the Team over a six-month period. Methods and results The Team was called out 35 times in six months and attended 22 incidents, some involving multiple casualties. 34 patients received treatment at the scene of an incident. Most incidents were road traffic collisions, although the team also attended falls from height, an assault and a vascular injury. Eight patients (24%) met Injury Severity Score criteria for major trauma (ISS>15). Mean time from 999 calls to Team activation was 20 (range 4–79) min; and mean time from Team dispatch to ‘Team mobile’ was 4.6 (2–21) min. Conclusion The Tayside Trauma Team provides a physician-led pre-hospital care response on demand from the Scottish Ambulance Service. It provides critical care interventions at the scene of various incidents (primarily traumatic) to attempt to improve patient outcome. Response times are favourable.
Health Literacy Among Insulin-Taking African Americans
Authors: Piatt Gretchen A. , Valerio Melissa A. , Nwankwo Robin , Lucas Stephanie M. , Funnell Martha M. 
Published: January 2014

Aims To determine the levels of functional health literacy (FHL) among insulin-taking African Americans with diabetes from an urban medical practice and to determine if associations exist between FHL levels and glycemic control. Methods Seventy insulin-taking African Americans seen for diabetes management comprised the analysis cohort. Patients were 18 years or older, African American, had diabetes, and currently using insulin via syringe, pen, or insulin pump. All participants completed a one-time assessment of FHL levels, using the Newest Vital Sign (NVS). Scores ranged from 0 to 6 (0-1 = high likelihood of limited FHL; 2-3 = possibility of limited FHL; 4-6 = adequate FHL). A combination of t tests, Pearson’s chi-square tests, and multivariate logistic regression models were used to determine associations between glycemic control and FHL. Results Average age was 58.7, 59.1% were female, 90.8% with type 2 diabetes, and 15.1% using an insulin pump. Glycemic control was: A1C < 7%: 22.9%, A1C < 8%: 47.1%. Of participants, 47.1% had adequate FHL, 31.4% had possible limited FHL, and 21.4% had a high likelihood of limited FHL. Also, 67.7% of participants with A1C ≥ 8% had a high likelihood of limited FHL. After adjusting for age and gender, participants with a high likelihood of limited FHL were 6.2 times (95% confidence interval [CI], 1.4-28.3) more likely to have A1C ≥ 8%. Conclusions Insulin-taking African Americans with a high likelihood of limited FHL are approximately 6 times more likely to have an A1C ≥ 8% compared to patients with a possibility of limited FHL, or adequate FHL, demonstrating the need for focused interventions tailored to FHL needs.
Kanamycin‐Furosemide Ototoxicity in the Mouse Cochlea: A 3‐Dimensional Analysis
Authors: Schmitz Heather M. , Johnson Shane B. , Santi Peter A. 
Published: January 2014

ObjectiveAdministration of an aminoglycoside antibiotic and loop diuretic causes damage to hair cells in the organ of Corti, resulting in their death and the death of their corresponding spiral ganglion neurons. While this phenomenon has been studied previously, analysis of its effects in the whole cochlea has not been reported. The authors sought to evaluate the effects of a combination dose of kanamycin and furosemide in mice cochlea using an imaging system and computer analysis that allowed for nondestructive, whole‐cochlea visualization.Study DesignStudy using an animal model.SettingCochlear analysis laboratory.Subjects and MethodsFive mice received kanamycin and furosemide and 3 mice received saline. Cochleas were harvested and imaged with scanning thin‐sheet laser imaging microscopy (sTSLIM) to analyze sensory cells and cochlea structures.ResultsThe drug‐treated animals showed substantial loss of inner hair cells and complete outer hair cell loss. All treated mice showed spiral ganglion neuron loss with fewer neurons than control animals and decreased cell density in the middle turn of the cochlea. The spiral ligament and spiral limbus in the treated animals also showed a decrease in fibrocyte cell density in the middle to apical portion of the cochlea. The stria vascularis appeared normal in all animals.ConclusionImaging methods that allow for whole‐cochlea analysis provide insight into changes that occur in the cochlea after ototoxic insult. Trends that may not be apparent in cross‐section samples of the cochlea can be observed. Computer analysis of these trends allows them to be assessed accurately.