bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome response of human skeletal muscle to divergent exercise stimuli
Authors: Dickinson Jared M. , D’Lugos Andrew C. , Naymik Marcus A. , Siniard Ashley L. , Wolfe Amanda J. , Curtis Donald R. , Huentelman Matthew J. , Carroll Chad C. 
Published: March 2018

Aerobic (AE) and resistance exercise (RE) elicit unique adaptations in skeletal muscle that have distinct implications for health and performance. The purpose of this study was to identify the unique transcriptome response of skeletal muscle to acute AE and RE. In a counterbalanced, crossover design, six healthy, recreationally active young men (27 ± 3 yr) completed acute AE (40 min of cycling, ∼70% maximal HR) and RE [8 sets, 10 reps, ∼65% 1-repetition maximum (1RM)], separated by ∼1 wk. Muscle biopsies (vastus lateralis) were obtained before and at 1 and 4 h postexercise. Whole transcriptome RNA sequencing (HiSeq2500; Illumina) was performed on cDNA synthesized from skeletal muscle RNA. Sequencing data were analyzed using HTSeq, and differential gene expression was identified using DESeq2 [adjusted P value (FDR) <0.05, >1.5-fold change from preexercise]. RE resulted in a greater number of differentially expressed genes at 1 (67 vs. 48) and 4 h (523 vs. 221) compared with AE. We identified 348 genes that were differentially expressed only following RE, whereas 48 genes were differentially expressed only following AE. Gene clustering indicated that AE targeted functions related to zinc interaction, angiogenesis, and ubiquitination, whereas RE targeted functions related to transcription regulation, cytokine activity, cell adhesion, kinase activity, and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. ESRRG and TNFSRF12A were identified as potential targets related to the specific response of skeletal muscle to AE and RE, respectively. These data describe the early postexercise transcriptome response of skeletal muscle to acute AE and RE and further highlight that different forms of exercise stimulate unique molecular activity in skeletal muscle.NEW & NOTEWORTHY Whole transcriptome RNA sequencing was used to determine the early postexercise transcriptome response of skeletal muscle to acute aerobic (AE) and resistance exercise (RE) in untrained individuals. Although a number of shared genes were stimulated following both AE and RE, several genes were uniquely responsive to each exercise mode. These findings support the need for future research focused to better identify the role of exercise mode as it relates to targeting specific cellular skeletal muscle abnormalities.
Exercise and weight loss effects on cardiovascular risk factors in overweight men
Authors: Rosenkilde Mads , Rygaard Lisbeth , Nordby Pernille , Nielsen Lars Bo , Stallknecht Bente 
Published: March 2018

Both exercise training and weight loss reduce cardiovascular risk, but the independent importance of the two strategies is unclear. We aimed to investigate independent and combined effects of exercise training and weight loss on lipoproteins and dyslipidemia in overweight sedentary men. Sixty individuals were randomized to 12 wk of endurance training (T), energy-reduced diet (D), training and energy increased diet (T-iD), or control (C). Equal energetic deficits (−600 kcal/day) were prescribed by exercise for T and caloric restriction for D. T-iD completed similar exercise but remained in energy balance due to the dietary replacement of calories expended during exercise. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo)B and A1, pre-β-HDL, and susceptibility of LDL-C to oxidation were measured. Body weight was reduced similarly between T (−5.9 ± 0.7 kg) and D (−5.2 ± 0.8 kg), whereas T-iD (−1.0 ± 0.5 kg) and C (0.1 ± 0.6 kg) remained weight stable. Plasma TC, LDL-C, and apolipoprotein B were reduced in T compared with C ( P < 0.001 for both), but this was not observed for D ( P > 0.17). Changes in TC and LDL-C were associated with changes in body weight and body fat ( P < 0.01). In T-iD, increases in HDL-C and apolipoprotein A1 were observed ( P < 0.001). In conclusion, an exercise-induced decline in body weight reduces proatherogenic apoB-containing lipoproteins, whereas exercise compensated by energy intake increases the key component of reverse cholesterol transport, i.e., apoA1-containing HDL-C.NEW & NOTEWORTHY Exercise has additive effects in lowering plasma lipoprotein particles to diet-induced weight loss in individuals with increased cardiovascular risk. In the present study, we investigated whether training per se would have beneficial cardiovascular effects. We found that 3 mo of exercise-induced weight loss reduced proatherogenic lipoproteins, whereas endurance training without weight loss improved factors involved in reverse cholesterol transport in a group of overweight sedentary men.
Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture
Authors: Myung Ja Hye , Eblan Michael J. , Caster Joseph M. , Park Sin-Jung , Poellmann Michael J. , Wang Kyle , Tam Kevin A. , Miller Seth M. , Shen Colette , Chen Ronald C. , Zhang Tian , Tepper Joel E. , Chera Bhishamjit S. , Wang Andrew Z. , Hong Seungpyo 
Published: March 2018

Abstract
Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment.
Experimental Design: Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to five time points, including before radiotherapy, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of radiotherapy. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR.
Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK+/CD45−/DAPI+) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before radiotherapy to 32 CTCs/mL at completion of radiotherapy (P = 0.001). CTCs declined throughout radiotherapy in patients with complete clinical and/or radiographic response, in contrast with an elevation in CTCs at mid or post-radiotherapy in the two patients with known pathologic residual disease.
Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared with multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment. Clin Cancer Res; 24(11); 2539–47. ©2018 AACR.
Therapeutic Effect of Quinacrine, an Antiprotozoan Drug, by Selective Suppression of p-CHK1/2 in p53-Negative Malignant Cancers
Authors: Park Soyoung , Oh Ah-Young , Cho Jung-Hyun , Yoon Min-Ho , Woo Tae-Gyun , Kang So-mi , Lee Ho-Young , Jung Youn-Jin , Park Bum-Joon 
Published: March 2018

Abstract
Quinacrine (QNC), antiprotozoan drug commonly used against Malaria and Giardiasis, has been recently tried for rheumatics and prion diseases via drug repositioning. In addition, several reports suggest antitumor effects of QNC through suppression of NF-κB and activation of p53. This study demonstrates the anticancer effect of QNC via a novel pathway through the elimination of checkpoint kinase 1/2 (Chk1/2) under p53-inactivated conditions. Inhibition of p53 by PFT-α or siRNA promotes QNC-induced apoptosis in normal fibroblast and p53-intact cancer cells. Considering that Chk1/2 kinases exert an essential role in the control of cell cycle, inhibition of Chk1/2 by QNC may induce cell death via uncontrolled cell cycle progression. Indeed, QNC reduces Chk1/2 expression under p53-impaired cancer cells and induces cell death in the G2–M phase. QNC increases the binding between p-Chk1/2 and β-TrCP and promotes proteasome-dependent degradation. Moreover, QNC treatment displayed antitumor effects in a Villin-Cre;p53+/LSL-R172H intestinal cancer mouse model system as well as HCT116 p53−/− xenografts.
Implications: QNC has been used for the past over 70 years without obvious side effects, as such it is a plausible drug candidate for relapsed cancers, small-cell lung cancer, breast cancer as well as various p53-inactivated human malignancies. Mol Cancer Res; 16(6); 935–46. ©2018 AACR.
Inhibition of Endothelial SCUBE2 (Signal Peptide-CUB-EGF Domain-Containing Protein 2), a Novel VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) Coreceptor, Suppresses Tumor Angiogenesis
Authors: Lin Yuh-Charn , Liu Chun-Yu , Kannagi Reiji , Yang Ruey-Bing 
Published: March 2018

Objective—
SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), expressed on the endothelial cell surface, functions as a novel coreceptor for VEGFR2 (vascular endothelial growth factor receptor 2) and enhances VEGF-induced signaling in adult angiogenesis. However, whether SCUBE2 plays a role in pathological angiogenesis and whether anti-SCUBE2 antibody is an effective strategy for blocking tumor angiogenesis remain unknown. The aim of this study was to investigate the pathological role and targeting therapy of SCUBE2 in tumor vasculature.

Approach and Results—
Immunohistochemistry revealed that SCUBE2 is highly expressed in endothelial cells of numerous carcinomas. Genetic endothelial cell knockout of SCUBE2 and pharmacological inhibition with the anti-SCUBE2 monoclonal antibody SP.B1 significantly reduced xenograft tumor growth, decreased tumor vascular density, increased apoptosis, and decreased the proliferation of tumor cells. Mechanistic studies revealed that SP.B1 binds to SCUBE2 and induces its internalization for lysosomal degradation, thereby reducing its cell surface level and inhibiting the binding of and downstream signaling of VEGF, including VEGFR2 phosphorylation and AKT/MAPK (mitogen-activated protein kinase) activation. Importantly, dual combination therapy with anti-SCUBE2 monoclonal antibody and anti-VEGF antibody or chemotherapy was more effective than single-agent therapy.

Conclusions—
Endothelial cell surface SCUBE2 is a VEGFR2 coreceptor essential for pathological tumor angiogenesis, and anti-SCUBE2 monoclonal antibody acting as an internalization inducer may provide a potent combination therapy for tumor angiogenesis.
Pain Management in Cancer Center Inpatients: A Cluster Randomized Trial to Evaluate a Systematic Integrated Approach—The Edinburgh Pain Assessment and Management Tool
Authors: Fallon Marie , Walker Jane , Colvin Lesley , Rodriguez Aryelly , Murray Gordon , Sharpe Michael ,   for the Edinburgh Pain Assessment and Management Tool Study Group
Published: March 2018

Purpose Pain is suboptimally managed in patients with cancer. We aimed to compare the effect of a policy of adding a clinician-delivered bedside pain assessment and management tool (Edinburgh Pain Assessment and management Tool [EPAT]) to usual care (UC) versus UC alone on pain outcomes. Patients and Methods In a two-arm, parallel group, cluster randomized (1:1) trial, we observed pain outcomes in 19 cancer centers in the United Kingdom and then randomly assigned the centers to either implement EPAT or to continue UC. The primary outcome was change in the percentage of study participants in each center with a clinically significant (≥ 2 point) improvement in worst pain (using the Brief Pain Inventory Short Form) from admission to 3 to 5 days after admission. Secondary outcomes included quality of analgesic prescribing and opioid-related adverse effects. Results Ten centers were randomly assigned to EPAT, and nine were assigned to UC. We enrolled 1,921 patients and obtained outcome data from 93% (n = 1,795). Participants (mean age, 60 years; 49% women) had a variety of cancer types. For centers randomly assigned to EPAT, the percentage of participants with a clinically significant improvement in worst pain increased from 47.7% to 54.1%, and for those randomly assigned to continue UC, this percentage decreased from 50.6% to 46.4%. The absolute difference was 10.7% (95% CI, 0.2% to 21.1%; P = .046) and it increased to 15.4% (95% CI, 5.8% to 25.0%; P = .004) when two centers that failed to implement EPAT were excluded. EPAT centers had greater improvements in prescribing practice and in the Brief Pain Inventory Short Form pain subscale score. Other pain and distress outcomes and opioid adverse effects did not differ between EPAT and UC. Conclusion A systematic integrated approach improves pain outcomes for inpatients in cancer centers without increasing opioid adverse effects.
Developing Media to Promote Community Awareness of Early Detection of Kaposi’s Sarcoma in Africa
Authors: Laker-Oketta Miriam , Butler Lisa , Makanga Philippa , Maurer Toby , Mbidde Edward , Martin Jeffrey 
Published: March 2018

Abstract 44 Purpose Despite overt presentation on the skin, most Kaposi’s sarcoma (KS) in Africa is diagnosed too late for treatment to be effective. Training health care workers to recognize KS early can increase knowledge, but is only clinically impactful if providers actually encounter early KS—that is, if patients with early KS present to care. Indeed, recent work from Zimbabwe has shown that facility-based KS training failed to increase early diagnosis, which is unsurprising given the public’s lack of awareness of KS. We hypothesized that educating affected populations about KS is critical to making progress in early detection and that enhanced community awareness about KS can be achieved through exposure to common media. Methods Working in Uganda, we used community-engaged research to learn about health-related behaviors in the context of skin disease, craft a culturally appropriate educational theme regarding the detection of KS, and develop three forms of media. We interacted with survivors of KS, HIV-infected patients, facility-based and community health workers, traditional healers, and media professionals. We tested our media among adults at community-based venues in rural Uganda. Participants were randomly assigned to be exposed to one of the three media and were evaluated for changes in knowledge and attitudes concerning KS before and after exposure to media. Results In comics, 90-second radio plays, and a 10-minute film, we developed a three-part theme that was aimed at the public: “look,” meaning to regularly examine one’s skin and mouth; “show” to bring to the attention of a health care worker any skin changes; and “test” to remind providers about skin biopsy for diagnosis. Among the 240 participants who were exposed to media, median age was 30 years, 50% were women, 6% were HIV infected, and 60% were literate. Exposure to media resulted in increases in the ability to recognize and/or name KS (+47%), awareness that anyone is at risk for KS (+15%), and knowledge of how to prevent KS from becoming a substantial problem (+34%). Conclusion Featuring the theme, “Look, show, and test,” we developed media—comics, radio plays, and film—for the public in Africa about the early detection of KS. Exposure to these media resulted in increases in knowledge and changes in attitudes concerning KS. Although the increases in knowledge were not large, they may be as much as can be expected from a single exposure. Optimal outcomes will likely require multiple exposures and facilitated discussions. Media elements are freely available online. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.
Impact of Pharmacist Participation on Chemotherapy Administration Outcomes in a Low-Resource Setting
Authors: Downey-Wall Kathryn , Hilary Keneth , Katabalo Deo , Masalu Nestory , Schroeder Kristin 
Published: March 2018

Abstract 50 Purpose Implementation of specialty oncology pharmacy services is associated with improved patient care and reduced medical errors. Pharmacy capacity is limited in many low-resource countries, with chemotherapy preparation and administration often being performed by other allied health care providers. At Bugando Medical Center in Tanzania, both nurses and pharmacists are responsible for mixing and administering chemotherapy; however, most nurses do not have specialized oncology training, which increases the risk for medication errors. The purpose of the current study was to assess the effects of pharmacist participation on therapeutic outcomes, including verified dosage calculations, chemotherapy administration adherence, and dose documentation. Methods Chemotherapy encounters were observed over a 1-month period. Recorded observations included adherence to prescribed chemotherapy administration times; errors, including spills and extravasation; and administrative adherence, including dose verification and documentation. Results There were 53 observed encounters—32 with a pharmacist and 21 without; 15 were for pediatric patients. Pharmacist participation increased adherence to prescribed administration time (54% v 19%; P = .009) and decreased errors (zero v two extravasations; zero v one spill). Pharmacist participation improved chemotherapy administration documentation (96.8% v 76.2%; P = .049); however, patient safety measures, including intravenous catheter placement verification, secondary dose check, and toxicity monitoring during administration, were not done with or without pharmacist participation. Conclusion Pharmacist participation increased adherence to prescribed chemotherapy administration and documentation, and reduced extravasation; however, additional patient safety training is needed. A larger study can further evaluate the impact of the participation of a specialty pharmacist on patient-related outcomes. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.
Access to Cancer Medicine Issues: Implication for Policy and Practice in Ethiopia
Authors: Tegegn Henok Getachew , Reda Hailemariam Lemma , Tilahun Yared 
Published: March 2018

Abstract 55 Purpose Cancer currently is a major public health problem in developing countries. In Ethiopia, cancer is responsible for 5.8% of total national deaths. Patients often present with advanced stage cancer and have limited access to screening, diagnosis, and treatment. Access to affordable cytotoxic medicines is a major challenge in the care of patients with cancer, especially in resource-poor settings, such as Ethiopia. This aim of this study was to explore perceived challenges in the accessibility of cancer chemotherapy drugs among different stakeholders in Ethiopia. Methods A qualitative study was performed using face-to-face in-depth interviews with such key informants as health care providers, supply chain management experts, and decision makers working in the Ministry of Health. Results A total of six key informants participated in this case report, with two oncology pharmacists, two supply chain management experts, one expert from the Ministry of Health, and one private supplier. Challenges were explored and viewed from the perspectives of policy, supply chain management, and health service. The most frequently identified challenges were the presence of inconsistent services and few currently active cancer centers, such as Tikur Anbesa Specialized Hospital, Gondar University Hospital, and Jimma University Hospital; difficulties in cancer commodity management; implementation challenges with cancer medicine cost subsidy programs; lack of an efficient stock status reporting system; supplementary medicine requirements; an inefficient market (costly, few suppliers, and noneconomic quantities); the need for combinations of cancer medicines; and a lack of national treatment guidelines. Conclusion Respondents suggested ways forward that included the participation of relevant and specific stakeholders, such as government and private pharmaceutical suppliers, the Ministry of Health, nongovernmental organizations, and hospitals. Strengthening supply chain management at all levels and sustainable subsidy programs for cancer medicines should be sought to avoid frequent interruptions in the availability of chemotherapy drugs. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.
Age-Standardized Mortality Rates in the Caribbean: One Source, Three Different Interpretations
Authors: Wolf Nicholas G. , Morgan Camille , Flanigan John S. 
Published: March 2018

Abstract 74 Purpose A recent publication in the Morbidity and Mortality Weekly Report (MMWR) provided the opportunity to calculate differences in published cancer mortality estimates for Caribbean jurisdictions from three organizations, MMWR, the International Agency for Research on Cancer, and the Institute for Health Metrics and Evaluation. This comparison study serves to educate end users of these data. Methods We downloaded the publicly available cancer mortality estimates for 15 jurisdictions and the United States from the three organizations. We compared reported age-standardized mortality rates for each jurisdiction, and calculated the range among the estimates for each jurisdiction. We repeated this analysis after applying the same world population standard to all estimates. Results For males, ranges of Caribbean estimates were between 49% (Grenada and Trinidad) and 201% (US Virgin Islands) of the MMWR value, with an average of 88%. For females, ranges were between 15% (Trinidad) and 171% (US Virgin Islands) of the MMWR value, with an average of 64%. After all estimates were compared using the same population standard, ranges of Caribbean estimates for males were between 6% (Grenada) and 111% (US Virgin Islands) of the MMWR value, with an average of 34%. For females, ranges were between 7% (Grenada) and 97% (US Virgin Islands), with an average of 28%. Conclusion The use of different standard populations complicates comparisons across organizations. Data modeling does not completely compensate for the quality of source data, as our analysis has demonstrated by the differences in mortality rates despite the good quality of the vital registration in the Caribbean. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.
Saving the Security State
Authors: Grewal Inderpal 
Published: March 2018

In Saving the Security State Inderpal Grewal traces the changing relations between the US state and its citizens in an era she calls advanced neoliberalism. Marked by the decline of US geopolitical power, endless war, and increasing surveillance, advanced neoliberalism militarizes everyday life while producing the “exceptional citizens”—primarily white Christian men who reinforce the security state as they claim responsibility for protecting the country from racialized others. Under advanced neoliberalism, Grewal shows, others in the United States strive to become exceptional by participating in humanitarian projects that compensate for the security state’s inability to provide for the welfare of its citizens. In her analyses of microfinance programs in the global South, security moms, the murders at a Sikh temple in Wisconsin, and the post-9/11 crackdown on Muslim charities, Grewal exposes the fissures and contradictions at the heart of the US neoliberal empire and the centrality of race, gender, and religion to the securitized state.