bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCR2 Chemokine Receptors Enhance Growth and Cell-Cycle Progression of Breast Cancer Cells through SRC and PKC Activation
Authors: Yao Min , Fang Wei , Smart Curtis , Hu Qingting , Huang Shixia , Alvarez Nehemiah , Fields Patrick , Cheng Nikki 
Published: November 2018

Abstract

Basal-like breast cancers are an aggressive breast cancer subtype, which often lack estrogen receptor, progesterone receptor, and Her2 expression, and are resistant to antihormonal and targeted therapy, resulting in few treatment options. Understanding the underlying mechanisms that regulate progression of basal-like breast cancers would lead to new therapeutic targets and improved treatment strategies. Breast cancer progression is characterized by inflammatory responses, regulated in part by chemokines. The CCL2/CCR2 chemokine pathway is best known for regulating breast cancer progression through macrophage-dependent mechanisms. Here, we demonstrated important biological roles for CCL2/CCR2 signaling in breast cancer cells. Using the MCF10CA1d xenograft model of basal-like breast cancer, primary tumor growth was significantly increased with cotransplantation of patient-derived fibroblasts expressing high levels of CCL2, and was inhibited with CRISP/R gene ablation of stromal CCL2. CRISP/R gene ablation of CCR2 in MCF10CA1d breast cancer cells inhibited breast tumor growth and M2 macrophage recruitment and validated through CCR2 shRNA knockdown in the 4T1 model. Reverse phase protein array analysis revealed that cell-cycle protein expression was associated with CCR2 expression in basal-like breast cancer cells. CCL2 treatment of basal-like breast cancer cell lines increased proliferation and cell-cycle progression associated with SRC and PKC activation. Through pharmacologic approaches, we demonstrated that SRC and PKC negatively regulated expression of the cell-cycle inhibitor protein p27KIP1, and are necessary for CCL2-induced breast cancer cell proliferation.

Implications:
This report sheds novel light on CCL2/CCR2 chemokine signaling as a mitogenic pathway and cell-cycle regulator in breast cancer cells.
Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?
Authors: Kooman Jeroen P. , Usvyat Len A. , Dekker Marijke J.E. , Maddux Dugan W. , Raimann Jochen G. , van der Sande Frank M. , Ye Xiaoling , Wang Yuedong , Kotanko Peter 
Published: November 2018

Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1–2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning ­approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.
Patellar Tendon–Lateral Trochlear Ridge Distance: A Novel Measurement of Patellofemoral Instability
Authors: Mistovich R. Justin , Urwin John W. , Fabricant Peter D. , Lawrence J. Todd R. 
Published: November 2018

Background: Abnormalities in the trochlea-patella-tibia relationship have been shown to be risk factors for recurrent patellofemoral instability, although no current measurements quantify patellar containment in the trochlea. Standard measurements, such as tibial tubercle–trochlear groove (TT-TG) distance, do not account for the containment of the patella by the trochlea. Our goal was to develop a measurement to assess how well the trochlea contained the extensor mechanism. Hypothesis: A novel measurement describing the amount of the patellar tendon lateral to the lateral trochlear ridge (PT-LTR) would be a reliable measurement and significantly greater among patients with patellofemoral instability. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The authors analyzed radiology records from 2005 to 2014 for patients aged 5 to 18 years with and without patellofemoral dislocations who had knee magnetic resonance imaging (MRI). Two blinded reviewers evaluated 215 MRI studies. Standard and novel morphology measurements were calculated for each knee and compared in a case-control design. Interobserver reliability of each measure was assessed by the intraclass correlation coefficient. Predictability for patellofemoral dislocation was calculated with 2-tailed independent-samples Student t tests. Discriminative capacity was calculated with receiver operating characteristic analyses and area under the curve (AUC). An optimal measurement cutoff with resultant sensitivity and specificity was calculated. Results: Standard measurements of TT-TG distance, tangential axial width of the patella (TAWP), and tangential axial trochlear width (TATW) had excellent agreement between raters; lateral femoral condyle length had good agreement; and the novel measurement—width of the tendon beyond the lateral femoral condyle (PT-LTR)—also had excellent agreement. These underwent predictability and discriminative capacity analyses. TT-TG, TAWP, TATW, and PT-LTR were significant predictors of patellofemoral instability. In receiver operating characteristic analysis, TAWP had an AUC of 0.65, below the 0.8 threshold. TATW had an AUC of 0.814 and, when <32.5 mm, was 76% sensitive and 77% specific for dislocations. TT-TG demonstrated an AUC of 0.806. TT-TG ≥13.5 mm was 76% sensitive and 76% specific for dislocations. PT-LTR demonstrated an AUC of 0.876 and, when ≥5.55 mm, was 73% sensitive and 89% specific for patellofemoral dislocation. Conclusion: PT-LTR is reliable, predictable, and discriminative for patellofemoral dislocations. This measurement had sensitivity similar to that of TT-TG but with higher specificity.
Use of maropitant for the control of pruritus in non-flea, non-food-induced feline hypersensitivity dermatitis: an open-label, uncontrolled pilot study
Authors: Maina Elisa , Fontaine Jacques 
Published: November 2018

Objectives Non-flea, non-food-induced hypersensitivity dermatitis (NFNFIHD) is a common inflammatory and pruritic skin disease in cats. When avoidance and conventional systemic immunosuppressive treatments fail to control the clinical signs, there are limited treatment options. The aim of this study was to evaluate the efficacy and tolerability of maropitant in feline NFNFIHD. Methods In an open-label, uncontrolled study, cats with proven non-seasonal NFNFIHD were treated with maropitant 2 mg/kg PO q24h for 4 weeks. Clinical lesions were evaluated with the Scoring Feline Allergic Dermatitis (SCORFAD) system and pruritus was evaluated with a 10 cm visual analogue scale (VAS) before and at the end of the study. Owners assessed global efficacy and tolerability with a 4-point scale at the end of the study. Adverse events and body weight changes were recorded. Results Twelve cats were treated with a mean initial maropitant dose of 2.22 mg/kg PO q24h. The treatment decreased both SCORFAD and pruritus VAS (pVAS) scores in all cats except one, in which only pruritus was reduced. The efficacy and the tolerability of the treatment were judged as excellent or good by 83.3% of owners. Treatment did not cause any side effects other than, in a few cases, short-time, self-limiting sialorrhoea. Conclusions and relevance Maropitant seems to be an effective, well-tolerated therapeutic option to control pruritus in cats. Caution is needed in interpreting the results as the pVAS score system has not yet been validated in cats and the trial was uncontrolled. A further, controlled study is required to confirm our findings.
Surgical timing and presence of a vitreoretinal fellow on postoperative adverse events following pars plana vitrectomy
Authors: Shields Ryan A , Ludwig Cassie A , Powers Matthew A , Tijerina Jonathan D , Schachar Ira H , Moshfeghi Darius M 
Published: November 2018

Introduction: To evaluate the adverse event rate following pars plana vitrectomy as a function of surgical start time and the presence of a vitreoretinal fellow. Methods: Single-institution retrospective cohort study of patients undergoing pars plana vitrectomy from 1 January 2016 to 31 December 2016 at Stanford University School of Medicine (Palo Alto, CA, USA). Records were reviewed for surgical start time, the presence of vitreoretinal fellow, and postoperative adverse events defined as any finding deviating from the expected postoperative course requiring observation or intervention. Results: A total of 310 pars plana vitrectomies were performed. There was no statistical difference in the rate of any adverse event when comparing cases starting after 16:01 (9/13, 69.2%) and after 12:01 (42/99, 42.4%) to a morning start time (69/198, 34.9%, adjusted p = 0.083). There was a statistically significant increase in the risk of postoperative vitreous hemorrhage with afternoon and evening cases as compared to morning cases (adjusted p = 0.021). In addition, there was no difference in any adverse event with a fellow present (93/244, 38.1%) compared to without (27/66, 40.9%, adjusted p = 0.163). There was a higher risk of postoperative hypotony when a fellow was involved (6.6% vs 0%, p = 0.028), though this difference disappeared after adjusting for confounders (adjusted p = 0.252). There was no difference in the length of surgery with and without a fellow (49 vs 54 min, respectively; p = 0.990). Discussion: Afternoon start time and the presence of a fellow were not independent risk factors for postoperative adverse events.
Prevalence and significance of T-wave inversion in Arab and Black paediatric athletes: Should anterior T-wave inversion interpretation be governed by biological or chronological age?
Authors: McClean Gavin , Riding Nathan R , Pieles Guido , Sharma Sanjay , Watt Victoria , Adamuz Carmen , Johnson Amanda , Tramullas Antonio , George Keith P , Oxborough David , Wilson Mathew G 
Published: November 2018

Background International electrocardiographic (ECG) recommendations regard anterior T-wave inversion (ATWI) in athletes under 16 years to be normal. Design The aim of this study was to identify the prevalence, distribution and determinants of TWI by ethnicity, chronological and biological age within paediatric athletes. A second aim was to establish the diagnostic accuracy of international ECG recommendations against refinement within athletes who present with ECG variants isolated to ATWI (V1–V4) using receiver operator curve analysis. Clinical context was calculated using Bayesian analysis. Methods Four hundred and eighteen Arab and 314 black male athletes (11–18 years) were evaluated by ECG, echocardiogram and biological age (by radiological X-ray) assessment. Results A total of 116 (15.8%) athletes presented with ATWI (V1–V4), of which 96 (82.8%) were observed in the absence of other ECG findings considered to be abnormal as per international recommendations for ECG interpretation in athletes; 91 (12.4%) athletes presented with ATWI confined to V1–V3, with prevalence predicted by black ethnicity (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.3–3.5) and biological age under 16 years (OR 2.0, 95% CI 1.2–3.3). Of the 96 with ATWI (V1–V4) observed in the absence of other ECG findings considered to be abnormal, as per international recommendations for ECG interpretation in athletes, diagnostic accuracy was ‘fail’ (OR 0.47, 95% CI 0.00–1.00) for international recommendations and ‘excellent’ (OR 0.97, 95% CI 0.92–1.00) when governed by biological age under 16 years, providing a positive and negative likelihood ratio of 15.8 (95% CI 1.8–28.1) and 0.0 (95% CI 0.0–0.8), respectively. Conclusion Interpretation of ECG variants isolated with ATWI (V1–V4) using international recommendations (chronological age <16 years) warrants caution, but governance by biological age yielded an ‘excellent’ diagnostic accuracy. In the clinical context, the ‘chance’ of detecting cardiac pathology within a paediatric male athlete presenting with ATWI in the absence of other ECG findings considered to be abnormal, as per international recommendations for ECG interpretation in athletes (positive likelihood ratio 15.8), was 14.4%, whereas a negative ECG (negative likelihood ratio 0.0) was 0%.
Cardiovascular disease in nonagenarians: Prevalence and utilization of preventive therapies
Authors: Mostaza Jose M , Lahoz Carlos , Salinero-Fort Miguel A , Cardenas Juan 
Published: November 2018

Aims Nonagenarians are a fast growing segment of industrialized countries' populations. Despite a greater risk of cardiovascular disease, there are limited data about their use of preventive therapies and factors guiding decisions regarding their prescription. The aim of this study was to evaluate the prevalence of cardiovascular diseases and the patterns of use of cardiovascular treatments in subjects ≥90 years old. Methods Population-based, cross-sectional study, in all nonagenarians residing in the Community of Madrid (Spain). Data were obtained from their electronic clinical records in primary care. Results Data were available from 59,423 subjects (mean age 93.3 years, 74.2% female, 13.5% with dementia). Prevalence of cardiovascular disease was 24.1% (10.9% with coronary artery disease (CAD), 13.1% with cerebrovascular disease (CVD) and 2.7% with peripheral artery disease(PAD)). In primary prevention, the use of statins and antiplatelet agents was 21.9% and 26.7%, respectively. Of subjects with vascular disease 27.7% were receiving a combined preventive strategy (use of antithrombotics, plus statins, plus blood pressure below 140/90 mmHg). Factors favourably associated with a combined preventive strategy were: female sex (odds ratio (OR) 1.29; 95% confidence interval (CI): 1.11–1.49), being independent versus totally dependent (OR 1.94; 95% CI: 1.43–2.65), diabetes (OR 1.42; 95% CI: 1.20–1.68), and negatively, age (OR 0.87; 95% CI: 0.85–0.90), CVD versus CAD (OR 0.41; 95% CI: 0.35–0.47), PAD versus CAD (OR 0.23; 95% CI: 0.18–0.30), dementia (OR 0.61; 95% CI: 0.49–0.76) and nursing home residency (OR 0.73; 95% CI: 0.57–0.93). Conclusion Nonagenarians have a great burden of cardiovascular diseases and receive a great number of preventive therapies, even in primary prevention, despite their unproven efficacy at these ages.
13910C>T and 22018G>A LCT gene polymorphisms in diagnosing hypolactasia in children
Authors: Tomczonek-Moruś J , Wojtasik A , Zeman K , Smolarz B , Bąk-Romaniszyn L 
Published: November 2018

BackgroundPrimary lactose intolerance (PLI) is a gradual decrease of lactase activity that usually manifests at the age of 1–5 years. It has been proved that PLI is related to a single‐nucleotide polymorphism of the lactase (LCT) gene.ObjectiveAn evaluation was performed on the usefulness of genetic tests in detecting LCT 13910C>T and 22018G>A polymorphisms in diagnosing lactose intolerance in children.MethodsThe study group included 99 children aged from 2 months to 16.5 years with different digestive tract symptoms. In all patients a hydrogen breath test (HBT) was conducted and blood samples were collected to determine LCT polymorphisms. PLI was defined as the presence of the 13910CC and/or 22018GG polymorphism in patients with a positive HBT result.ResultsIn the group younger than 6 years, no statistically significant correlation was observed between the 13910CC and/or 22018GG LCT polymorphisms and HBT result. In the group of children older than 6, a statistically significant correlation between the 13910CC (p = 0.0011) and 22018GG (p = 0.003) LCT polymorphisms and HBT result was detected.ConclusionsIn children older than 6, the result of genetic testing based on LCT 13910C>T and 22018G>A polymorphisms may diagnose lactose intolerance.
Direct Rap1/Talin1 interaction regulates platelet and neutrophil integrin activity in mice
Authors: Bromberger Thomas , Klapproth Sarah , Rohwedder Ina , Zhu Liang , Mittmann Laura , Reichel Christoph A. , Sperandio Markus , Qin Jun , Moser Markus 
Published: November 2018

Abstract
Targeting Talin1 to the plasma membrane is a crucial step in integrin activation, which in leukocytes is mediated by a Rap1/RIAM/Talin1 pathway, whereas in platelets, it is RIAM independent. Recent structural, biochemical, and cell biological studies have suggested direct Rap1/Talin1 interaction as an alternative mechanism to recruit Talin1 to the membrane and induce integrin activation. To test whether this pathway is of relevance in vivo, we generated Rap1 binding–deficient Talin1 knockin (Tln13mut) mice. Although Tln13mut mice showed no obvious abnormalities, their platelets exhibited reduced integrin activation, aggregation, adhesion, and spreading, resulting in prolonged tail-bleeding times and delayed thrombus formation and vessel occlusion in vivo. Surprisingly, neutrophil adhesion to different integrin ligands and β2 integrin–dependent phagocytosis were also significantly impaired, which caused profound leukocyte adhesion and extravasation defects in Tln13mut mice. In contrast, macrophages exhibited no defect in adhesion or spreading despite reduced integrin activation. Taken together, our findings suggest that direct Rap1/Talin1 interaction is of particular importance in regulating the activity of different integrin classes expressed on platelets and neutrophils, which both depend on fast and dynamic integrin-mediated responses.
Use of Next-Generation Sequencing Tests to Guide Cancer Treatment: Results From a Nationally Representative Survey of Oncologists in the United States
Authors: Freedman Andrew N. , Klabunde Carrie N. , Wiant Kristine , Enewold Lindsey , Gray Stacy W. , Filipski Kelly K. , Keating Nancy L. , Leonard Debra G.B. , Lively Tracy , McNeel Timothy S. , Minasian Lori , Potosky Arnold L. , Rivera Donna R. , Schilsky Richard L. , Schrag Deborah , Simonds Naoko I. , Sineshaw Helmneh M. , Struewing Jeffery P. , Willis Gordon , de Moor Janet S. 
Published: November 2018

Purpose There are no nationally representative data on oncologists’ use of next-generation sequencing (NGS) testing in practice. The purpose of this study was to investigate how oncologists in the United States use NGS tests to evaluate patients with cancer and to inform treatment recommendations. Methods The study used data from the National Survey of Precision Medicine in Cancer Treatment, which was mailed to a nationally representative sample of oncologists in 2017 (N = 1,281; cooperation rate = 38%). Weighted percentages were calculated to describe NGS test use. Multivariable modeling was conducted to assess the association of test use with oncologist practice characteristics. Results Overall, 75.6% of oncologists reported using NGS tests to guide treatment decisions. Of these oncologists, 34.0% used them often to guide treatment decisions for patients with advanced refractory disease, 29.1% to determine eligibility for clinical trials, and 17.5% to decide on off-label use of Food and Drug Administration–approved drugs. NGS test results informed treatment recommendations often for 26.8%, sometimes for 52.4%, and never or rarely for 20.8% of oncologists. Oncologists younger than 50 years of age, holding a faculty appointment, having genomics training, seeing more than 50 unique patients per month, and having access to a molecular tumor board were more likely to use NGS tests. Conclusion In 2017, most oncologists in the United States were using NGS tests to guide treatment decisions for their patients. More research is needed to establish the clinical usefulness of these tests, to develop evidence-based clinical guidelines for their use in practice, and to ensure that patients who can benefit from these new technologies receive appropriate testing and treatment.
Making a point: shared mechanics underlying the diversity of biological puncture
Authors: Anderson Philip S. L. 
Published: November 2018

ABSTRACTA viper injecting venom into a target, a mantis shrimp harpooning a fish, a cactus dispersing itself via spines attaching to passing mammals; all these are examples of biological puncture. Although disparate in terms of materials, kinematics and phylogeny, all three examples must adhere to the same set of fundamental physical laws that govern puncture mechanics. The diversity of biological puncture systems is a good case study for how physical laws can be used as a baseline for comparing disparate biological systems. In this Review, I explore the diversity of biological puncture and identify key variables that influence these systems. First, I explore recent work on biological puncture in a diversity of organisms, based on their hypothesized objectives: gripping, injection, damage and defence. Variation within each category is discussed, such as the differences between gripping for prey capture, gripping for dispersal of materials or gripping during reproduction. The second half of the Review is focused on specific physical parameters that influence puncture mechanics, such as material properties, stress, energy, speed and the medium within which puncture occurs. I focus on how these parameters have been examined in biology, and how they influence the evolution of biological systems. The ultimate objective of this Review is to outline an initial framework for examining the mechanics and evolution of puncture systems across biology. This framework will not only allow for broad biological comparisons, but also create a baseline for bioinspired design of both tools that puncture efficiently and materials that can resist puncture.