bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAF Inhibition Stimulates Melanoma-Associated Macrophages to Drive Tumor Growth
Authors: Wang Tao , Xiao Min , Ge Yingbin , Krepler Clemens , Belser Eric , Lopez-Coral Alfonso , Xu Xiaowei , Zhang Gao , Azuma Rikka , Liu Qin , Liu Rui , Li Ling , Amaravadi Ravi K. , Xu Wei , Karakousis Giorgos , Gangadhar Tara C. , Schuchter Lynn M. , Lieu Melissa , Khare Sanika , Halloran Molly B. , Herlyn Meenhard , Kaufman Russel E. 
Published: January 2015

AbstractPurpose: To investigate the roles of melanoma-associated macrophages in melanoma resistance to BRAF inhibitors (BRAFi).Experimental Design: An in vitro macrophage and melanoma cell coculture system was used to investigate whether macrophages play a role in melanoma resistance to BRAFi. The effects of macrophages in tumor resistance were examined by proliferation assay, cell death assay, and Western blot analyses. Furthermore, two mouse preclinical models were used to validate whether targeting macrophages can increase the antitumor activity of BRAFi. Finally, the number of macrophages in melanoma tissues was examined by immunohistochemistry.Results: We demonstrate that in BRAF-mutant melanomas, BRAFi paradoxically activate the mitogen-activated protein kinase (MAPK) pathway in macrophages to produce VEGF, which reactivates the MAPK pathway and stimulates cell growth in melanoma cells. Blocking the MAPK pathway or VEGF signaling then reverses macrophage-mediated resistance. Targeting macrophages increases the antitumor activity of BRAFi in mouse and human tumor models. The presence of macrophages in melanomas predicts early relapse after therapy.Conclusions: Our findings demonstrate that macrophages play a critical role in melanoma resistance to BRAFi, suggesting that targeting macrophages will benefit patients with BRAF-mutant melanoma. Clin Cancer Res; 21(7); 1652–64. ©2015 AACR.
The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs
Authors: Boi Michela , Gaudio Eugenio , Bonetti Paola , Kwee Ivo , Bernasconi Elena , Tarantelli Chiara , Rinaldi Andrea , Testoni Monica , Cascione Luciano , Ponzoni Maurilio , Mensah Afua Adjeiwaa , Stathis Anastasios , Stussi Georg , Riveiro María Eugenia , Herait Patrice , Inghirami Giorgio , Cvitkovic Esteban , Zucca Emanuele , Bertoni Francesco 
Published: January 2015

AbstractPurpose: In cancer cells, the epigenome is often deregulated, and inhibition of the bromodomain and extra-terminal (BET) family of bromodomain-containing proteins is a novel epigenetic therapeutic approach. Preliminary results of an ongoing phase I trial have reported promising activity and tolerability with the new BET bromodomain inhibitor OTX015.Experimental Design: We assessed the preclinical activity of OTX015 as single agent and in combination in mature B-cell lymphoma models and performed in vitro and in vivo experiments to identify the mechanism of action and the genetic features associated with sensitivity to the compound.Results: OTX015 showed antiproliferative activity in a large panel of cell lines derived from mature B-cell lymphoid tumors with median IC50 of 240 nmol/L, without significant differences among the different histotypes. In vitro and in vivo experiments showed that OTX015 targeted NFKB/TLR/JAK/STAT signaling pathways, MYC- and E2F1-regulated genes, cell-cycle regulation, and chromatin structure. OTX015 presented in vitro synergism with several anticancer agents, especially with mTOR and BTK inhibitors. Gene expression signatures associated with different degrees of sensitivity to OTX015 were identified. Although OTX015 was mostly cytostatic, the compound induced apoptosis in a genetically defined subgroup of cells, derived from activated B-cell–like diffuse large B-cell lymphoma, bearing wtTP53, mutations in MYD88, and CD79B or CARD11.Conclusions: Together with the data coming from the ongoing phase I study, the in vitro and in vivo data presented here provide the basis for further clinical investigation of OTX015 as single agent and in combination therapies. Clin Cancer Res; 21(7); 1628–38. ©2015 AACR.
Predicting Cancer Drug Response: Advancing the DREAM
Authors: Altman Russ B. 
Published: January 2015

Abstract
Summary: The DREAM challenge is a community effort to assess current capabilities in systems biology. Two recent challenges focus on cancer cell drug sensitivity and drug synergism, and highlight strengths and weaknesses of current approaches. Cancer Discov; 5(3); 237–8. ©2015 AACR.
A review of the species of Oreichthys (Teleostei: Cyprinidae) in the Western Ghats, India
Authors: KNIGHT J. D. MARCUS , KUMAR RAHUL G. 
Published: January 2015

Fishes currently assigned to Oreichthys cosuatis from the Western Ghats are shown to belong to a closely-related group of three valid species: Puntius coorgensis, which is raised from synonymy, and two new species, O. duospilus and O. incognito. Oreichthys coorgensis can be distinguished from its congeners by a combination of characters that include 22–23+1–2 scales in the longitudinal series with 5–8 pored scales; ½3/1/2½ scales in the transverse row; 6–7 predorsal scales and usually a faint blackish spot on the caudal-fin base. Oreichthys duospilus, sp. nov., can be distinguished by possessing an almost complete lateral line with 11–21 pored scales and two black spots: one on the dorsal fin and the other on the anal fin. Oreichthys incognito, sp. nov., can be distinguished by a lateral line with 5 pored scales; ½3/1/1½ scales in the transverse row; 8 predorsal scales and a vertical black bar on the dorsal fin.
Microphysical Constraints on Millimeter-Wavelength Scattering Properties of Snow Particles
Authors: Wood Norman B. , L’Ecuyer Tristan S. , Heymsfield Andrew J. , Stephens Graeme L. 
Published: January 2015

AbstractA Bayesian optimal estimation retrieval is used to determine probability density functions of snow microphysical parameters from ground-based observations taken during four snowfall events in southern Ontario, Canada. The retrieved variables include the parameters of power laws describing particle mass and horizontally projected area. The results reveal nontrivial correlations between mass and area parameters that were not apparent in prior studies. The observations provide information mainly about the mass coefficient , somewhat less information about the mass exponent and the projected area coefficient , and minimal information about the projected area exponent . The expected values for retrieved mass power-law parameters = 0.003 28 and = 2.25 are consistent with those from several prior studies that looked at the mass of aggregate-like particles and precipitating ice aloft as functions of maximum particle dimension. Differences from other studies appear related to differences in the dimensions used to define particle size. The retrieval allows the analysis of relatively large volumes of continuous observations, greatly enhancing sampling relative to single-particle analyses. The retrieved properties are used to constrain 94-GHz (W band) radar scattering properties for a variety of snow particle shapes. Synthetic reflectivities calculated using these scattering properties and observed particle size distributions show that a branched, spatial aggregate-like particle produces good agreement with coincident observed W-band reflectivities. Uncertainties in the synthetic reflectivities, estimated by applying a simple error-propagation model, are substantial and are dominated by the uncertainties in and .
Ice Crystal Habits and Growth Processes in Stratiform Clouds with Embedded Convection Examined through Aircraft Observation in Northern China
Authors: Zhu Shichao , Guo Xueliang , Lu Guangxian , Guo Lijun 
Published: January 2015

Abstract
Ice crystal habits and growth processes in two cases of stratiform clouds with embedded convection are investigated using data observed simultaneously from three aircraft on 18 April 2009 and 1 May 2009 as part of the Beijing Cloud Experiment (BCE). The results show that the majority of ice crystal habits found in the two cases at temperatures between 0° and −16°C included platelike, needle column, capped column, dendrite, and irregular. A mixture of several ice crystal habits was identified in all of the clouds studied. However, the ice crystals recorded in the embedded convection regions contained more dendrites and possessed heavier riming degrees, and the ice crystals identified in the stratiform clouds contained more hexagonal plate crystals. Both riming and aggregation processes played central roles in the broadening of particle size distributions (PSDs), and these processes were more active in embedded convection regions than in stratiform regions. However, riming was more prevalent in the 18 April case than aggregation, though aggregates were evident. In contrast, the 1 May case had a more dominant aggregation processes, but also riming. With the decrease in height, PSDs broadened in both embedded convection regions and stratiform regions, but the broadening rates between 4.8 km (T ≈ −11.6°C) and 4.2 km (T ≈ −8°C) were larger than those between 4.2 km (T ≈ −8°C) and 3.6 km (T ≈ −5°C). In addition, the broadening rates of PSDs in the embedded convection regions were larger than those in the stratiform clouds, as the aggregation and riming processes of ice particles in embedded convection regions were active. High supercooled water content is critical to enhancing riming and aggregation processes in embedded convection regions.
How Robust Are Trends in the Brewer–Dobson Circulation Derived from Observed Stratospheric Temperatures?
Authors: Ossó Albert , Sola Yolanda , Rosenlof Karen , Hassler Birgit , Bech Joan , Lorente Jerónimo 
Published: January 2015

AbstractMost global circulation models and climate–chemistry models forced with increasing greenhouse gases predict a strengthening of the Brewer–Dobson circulation (BDC) in the twenty-first century, and some of them claim that such strengthening has already begun at the end of the twentieth century. However, observational evidence for such a trend remains inconclusive. The goal of this paper is to examine the evidence for observed trends in the stratospheric overturning circulation using a suite of currently available observational stratospheric temperature data. Trends are examined as “departures” from the global mean temperature, since such trends reflect the effects of dynamics and spatially inhomogeneous radiative forcing and are to first order independent of the direct radiative effects of increasing well-mixed greenhouse gas concentrations.The primary conclusion of the study is that temperature observations do not reveal statistically significant trends in the Brewer–Dobson circulation over the period from 1979 to the present, as covered by Microwave Sounding Unit and Stratospheric Sounding Unit temperatures. The estimated trends in the BDC are weak in all datasets and not statistically significant at the 95% confidence level. In many cases, different data products yield very different results, particularly when the trends are stratified by season. Implications for the interpretation of recent stratospheric climate change are discussed. The results illustrate the essential need to better constrain the accuracy of future stratospheric temperature datasets.
Use and misuse of glucocorticoids in the community of Raxaul Block, North Bihar
Authors: Masih Shelesh , Cynthia Stephen Sharon , Joy Armstrong Lois , Finny Philip 
Published: January 2015

Background Glucocorticoid misuse is widely recognised but inadequately addressed issue in India. This study reports the use and misuse of glucocorticoids in Raxaul Block, North Bihar, India. Methods A two-stage sampling method was used to interview 240 households during April and May 2013. In each household, anyone who had been sick in the last 6 months had their medication use recorded. Results In total, 113 out of 334 (33·8%) were found to have taken a glucocorticoid in the last 6 months (95% CI: 28.7–38.9%). One hundred (88.4%) of these were considered to be inappropriate. Seventy-nine percent had been using glucocorticoids for more than 1 month; 60.2% were prescribed by local, unlicensed practitioners. Conclusions Glucocorticoid misuse will contribute to the burden of hypertension, diabetes, osteoporotic fracture, tuberculosis, cataracts and deaths due to hypoadrenal crisis. One in 15 people in Raxaul Block are likely to have a suppressed hypothalamo-pituitary-adrenal axis.
Pre-existing Lumbar Spine Diagnosis as a Predictor of Outcomes in National Football League Athletes
Authors: Schroeder Gregory D. , Lynch T. Sean , Gibbs Daniel B. , Chow Ian , LaBelle Mark , Patel Alpesh A. , Savage Jason W. , Hsu Wellington K. , Nuber Gordon W. 
Published: January 2015

Background: It is currently unknown how pre-existing lumbar spine conditions may affect the medical evaluation, draft status, and subsequent career performance of National Football League (NFL) players. Purpose: To determine if a pre-existing lumbar diagnosis affects a player’s draft status or his performance and longevity in the NFL. Study Design: Cohort study; Level 3. Methods: The investigators evaluated the written medical evaluations and imaging reports of prospective NFL players from a single franchise during the NFL Scouting Combine from 2003 to 2011. Players with a reported lumbar spine diagnosis and with appropriate imaging were included in this study. Athletes were then matched to control draftees without a lumbar spine diagnosis by age, position, year, and round drafted. Career statistics and performance scores were calculated. Results: Of a total of 2965 athletes evaluated, 414 were identified as having a pre-existing lumbar spine diagnosis. Players without a lumbar spine diagnosis were more likely to be drafted than were those with a diagnosis (80.2% vs 61.1%, respectively, P < .001). Drafted athletes with pre-existing lumbar spine injuries had a decrease in the number of years played compared with the matched control group (4.0 vs 4.3 years, respectively, P = .001), games played (46.5 vs 50.8, respectively, P = .0001), and games started (28.1 vs 30.6, respectively, P = .02) but not performance score (1.4 vs 1.8, respectively, P = .13). Compared with controls, players were less likely to be drafted if they had been diagnosed with spondylosis (62.37% vs 78.55%), a lumbar herniated disc (60.27% vs 78.43%), or spondylolysis with or without spondylolisthesis (64.44% vs 78.15%) ( P < .001 for all), but there was no appreciable effect on career performance; however, the diagnosis of spondylolysis was associated with a decrease in career longevity ( P < .05). Notably, 2 athletes who had undergone posterior lateral lumbar fusion were drafted. One played in 125 games, and the other is still active and has played in 108 games. Conclusion: The data in this study suggest that athletes with pre-existing lumbar spine conditions were less likely to be drafted and that the diagnosis is associated with a decrease in career longevity but not performance. Players with lumbar fusion have achieved successful careers in the NFL.
Parenting Interventions for Indigenous Child Psychosocial Functioning: A Scoping Review
Authors: Macvean Michelle , Shlonsky Aron , Mildon Robyn , Devine Ben 
Published: January 2015

Objectives: To scope evaluations of Indigenous parenting programs designed to improve child psychosocial outcomes. Methods: Electronic databases, gray literature, Indigenous websites and journals, and reference lists were searched. The search was restricted to high-income countries with a history of colonialism. Results: Sixteen studies describing evaluations of 13 programs were found. Most were controlled studies from United States and Australia, targeting child social, emotional, behavioral and mental health outcomes, and these were delivered to groups of parents. Program content focused most often on child development and learning, child behavior management, and parent–child interactions. Some studies reported improvements in child and parent outcomes, though the majority used self-report measures and some were noncontrolled studies. Conclusions: This scoping review provides the first known map of evaluations of programs targeting parents of Indigenous children. There were few rigorous evaluations of effectiveness. A rigorous systematic review is needed to evaluate the strength and extent of these findings.
Social work in acute hospital settings in Northern Ireland: The views of service users, carers and multi-disciplinary professionals
Authors: McLaughlin John 
Published: January 2015

Summary Little is known about social work in acute hospital settings in Northern Ireland and the impact of the community care reforms on the hospital discharge process. This article presents findings of a small-scale exploratory study of the hospital social work service in two acute hospitals in Northern Ireland. The views of service users, carers, health and social care professionals and hospital and community based social workers were sought on the value, strengths and limitations of the service in one of the local board areas using focus groups, questionnaires and semi-structured interviews. Findings The results indicate that hospital social workers are highly valued by service users for their responsiveness, emotional support and practical help during the process of hospitalisation. While empowering practice was reported by some carers, discharge pressures had the potential to undermine person-centred practice in the care management process. Healthcare professionals valued hospital social workers for their assessment skills and commitment to patient care while community based colleagues perceived them as being particularly skilled in inter-disciplinary and inter-agency collaboration. Hospital social workers reported that their role had become increasingly proceduralised within a target culture, leaving less time to address the emotional needs of users and carers. Applications Policy, practice and research implications of the study are discussed. It is argued that hospital social workers locally and nationally could benefit from forming strategic alliances, in partnership with service users and carers, to explore ways to collectively resist neoliberal policy developments at the health and social care interface.
Patellar Tendinopathy
Authors: Schwartz Aaron , Watson Jonathan N. , Hutchinson Mark R. 
Published: January 2015

Context: Patellar tendinopathy is a common condition. There are a wide variety of treatment options available, the majority of which are nonoperative. No consensus exists on the optimal method of treatment. Evidence Acquisition: PubMed spanning 1962-2014. Study Design: Clinical review. Level of Evidence: Level 4. Results: The majority of cases resolve with nonoperative therapy: rest, physical therapy with eccentric exercises, cryotherapy, anti-inflammatories, corticosteroid injections, extracorporeal shockwave therapy, glyceryl trinitrate, platelet-rich plasma injections, and ultrasound-guided sclerosis. Refractory cases may require either open or arthroscopic debridement of the patellar tendon. Corticosteroid injections provide short-term pain relief but increase risk of tendon rupture. Anti-inflammatories and injectable agents have shown mixed results. Surgical treatment is effective in many refractory cases unresponsive to nonoperative modalities. Conclusion: Physical therapy with an eccentric exercise program is the mainstay of treatment for patellar tendinopathy. Platelet-rich plasma has demonstrated mixed results; evidence-based recommendations on its efficacy cannot be made. In the event that nonoperative treatment fails, surgical intervention has produced good to excellent outcomes in the majority of patients.
Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?
Authors: Udy Andrew A , Lipman Jeffrey , Jarrett Paul , Klein Kerenaftali , Wallis Steven C , Patel Kashyap , Kirkpatrick Carl MJ , Kruger Peter S , Paterson David L , Roberts Michael S , Roberts Jason A 
Published: January 2015

Abstract
Introduction
The aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT>MIC)) in critically ill patients with sepsis receiving intermittent dosing.

Methods
To be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CLCR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values.

Results
In total, 48 patients provided data. Increasing CLCR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CLCR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures.

Conclusions
Standard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.
Influence of the route of exposure and the matrix on the sensitisation potency of a major cows’ milk allergen
Authors: Wavrin Sophie , Bernard Herve , Wal Jean‐Michel , Adel‐Patient Karine 
Published: January 2015

AbstractBackgroundAllergic sensitisation to food may occur through non‐gastrointestinal routes such as via skin or lung. We recently demonstrated in mice that cutaneous or respiratory pre‐exposures to peanut proteins on intact epithelia induce a Th2 priming and allow subsequent oral sensitization without the use of adjuvant. We then aimed to assess the impact of a similar pattern of exposure to another relevant food allergen, cows’ milk.FindingsThe humoral and cellular immune response induced in BALB/cJ mice after repeated cutaneous applications on intact skin or after intranasal administration of cows’ milk proteins was analysed. In order to assess the potential effect of the food matrix, we used either a purified major cows’ milk allergen, β‐lactoglobulin (BLG), or whole cows’ milk containing the same amount of BLG. We then studied the impact of these pre‐exposures on a subsequent oral exposure to milk in the presence or absence of the mucosal Th2 adjuvant, Cholera toxin (CT). Cutaneous applications of milk induced production of BLG‐specific IgE and IgG1 in 5 and 8 mice out of 20 respectively, whereas purified BLG alone did not. Intranasal exposure to milk, but not to BLG, led to BLG‐specific IgG1 production in 8 out of 20 mice. Notably, cutaneous pre‐exposure to milk favours further oral sensitisation without CT, while intra‐nasal pre‐exposure to BLG prevents further experimental sensitisation.ConclusionsAltogether, our results thus demonstrated that the immune response induced after non‐gastrointestinal exposure to food depends on the allergen, the matrix and the route of exposure.