bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Impact of Symptom Prevalence and Chronic Conditions on Quality of Life in Cancer Survivors and Non-Cancer Individuals: A Population Study
Authors: Huang I-Chan , Hudson Melissa M. , Robison Leslie L. , Krull Kevin R. 
Published: March 2017

Abstract
Background: To compare associations of symptom prevalence, chronic conditions, and health-related quality of life (HRQOL) between cancer survivors and non-cancer individuals using the U.S. National Health Interview Survey.
Methods: Study samples comprised 604 survivors and 6,166 non-cancer individuals. Symptoms included sensation abnormality, pain, fatigue, cognitive disturbance, depression, and anxiety. Physical and mental HRQOL was measured by the Patient-Reported Outcomes Measurement Information System.
Results: Compared with non-cancer individuals, survivors had higher prevalence in sensation abnormality (OR = 2.4; 95% CI = 1.9 to 3.0), pain (OR = 2.1; 95% CI = 1.7 to 2.6), fatigue (OR = 1.4; 95% CI = 1.1 to 1.8), and decremented physical HRQOL (difference = −3.7; 95% CI = −4.7 to −2.6). The prevalence of individual symptoms was significantly associated with decremented physical HRQOL [range = −5.9 (anxiety) to −8.9 (pain)] and mental HRQOL [range = −4.7 (sensation) to −8.4 (depression)]. The association between cancer experience and physical and mental HRQOL was chiefly explained by the prevalence of six symptoms and presence of chronic conditions. Pain (β = −4.0; 95% CI = −4.5 to −3.6) and ≥2 chronic conditions (β = −9.2; 95% CI = −10.2 to −8.2) significantly decremented physical HRQOL. Depression (β = −5.2; 95% CI = −5.8 to −4.6) and ≥2 chronic conditions (β = −3.3; 95% CI = −4.4 to −2.3) significantly decremented mental HRQOL.
Conclusions: Cancer survivors experience more symptom burden than non-cancer individuals, which is associated with more chronic conditions and impaired HRQOL.
Impacts: Interventions to manage symptom prevalence especially for older cancer survivors and survivors with more chronic conditions may improve their HRQOL outcomes. Cancer Epidemiol Biomarkers Prev; 26(7); 1124–32. ©2017 AACR.
Identification of a Novel SYK/c-MYC/MALAT1 Signaling Pathway and Its Potential Therapeutic Value in Ewing Sarcoma
Authors: Sun Haibo , Lin De-Chen , Cao Qi , Pang Brendan , Gae David D. , Lee Victor Kwan Min , Lim Huey Jin , Doan Ngan , Said Jonathan W. , Gery Sigal , Chow Marilynn , Mayakonda Anand , Forscher Charles , Tyner Jeffrey W. , Koeffler H. Phillip 
Published: March 2017

Abstract
Purpose: Ewing sarcoma (EWS) is a devastating soft tissue sarcoma affecting predominantly young individuals. Tyrosine kinases (TK) and associated pathways are continuously activated in many malignancies, including EWS; these enzymes provide candidate therapeutic targets.
Experimental Design: Two high-throughput screens (a siRNA library and a small-molecule inhibitor library) were performed in EWS cells to establish candidate targets. Spleen tyrosine kinase (SYK) phosphorylation was assessed in EWS patients and cell lines. SYK was inhibited by a variety of genetic and pharmacological approaches, and SYK-regulated pathways were investigated by cDNA microarrays. The transcriptional regulation of MALAT1 was examined by ChIP-qPCR, luciferase reporter, and qRT-PCR assays.
Results: SYK was identified as a candidate actionable target through both high-throughput screens. SYK was highly phosphorylated in the majority of EWS cells, and SYK inhibition by a variety of genetic and pharmacologic approaches markedly inhibited EWS cells both in vitro and in vivo. Ectopic expression of SYK rescued the cytotoxicity triggered by SYK-depletion associated with the reactivation of both AKT and c-MYC. A long noncoding RNA, MALAT1, was identified to be dependent on SYK-mediated signaling. Moreover, c-MYC, a SYK-promoted gene, bound to the promoter of MALAT1 and transcriptionally activated MALAT1, which further promoted the proliferation of EWS cells.
Conclusions: This study identifies a novel signaling involving SYK/c-MYC/MALAT1 as a promising therapeutic target for the treatment of EWS. Clin Cancer Res; 23(15); 4376–87. ©2017 AACR.
Lectin, Galactoside-Binding Soluble 3 Binding Protein Promotes 17-N-Allylamino-17-demethoxygeldanamycin Resistance through PI3K/Akt Pathway in Lung Cancer Cell Line
Authors: Woo Jong Kyu , Jang Jeong-Eun , Kang Ju-Hee , Seong Je Kyung , Yoon Yeo Sung , Kim Hyoung-Chin , Lee Sang-Jin , Oh Seung Hyun 
Published: March 2017

Abstract
Heat shock protein 90 (HSP90) stabilizing oncoproteins has been an attractive target in cancer therapy. 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG), an HSP90 inhibitor, was tested in phase II/III clinical trials, but due to lack of efficacy, clinical evaluation of 17-AAG has achieved limited success, which led to resistance to 17-AAG. However, the mechanism of 17-AAG resistance has not clearly been identified. Here, we identified LGALS3BP (Lectin, galactoside-binding soluble 3 binding protein), a secretory glycoprotein, as a 17-AAG resistance factor. In the clinical reports, it was suggested that LGALS3BP was associated with low survival rate, development of cancer progression, and enhancement of metastasis in human cancers. As we confirmed that the LGALS3BP level was increased in 17-AAG–resistant cells (H1299_17R) compared with that of the parental cell line (H1299_17P), knockdown of LGALS3BP expression increased sensitivity to 17-AAG in H1299_17R cells. Overexpression of LGALS3BP also augmented PI3K/Akt and ERK signaling pathways. Furthermore, we determined that the PI3K/Akt signaling pathway was involved in LGALS3BP-mediated 17-AAG resistance in vitro and in vivo, demonstrating that LGALS3BP mediates the resistance against 17-AAG through PI3K/Akt activation rather than ERK activation. These findings suggest that LGALS3BP would be a target to overcome resistance to 17-AAG in lung cancer. For example, the combination of 17-AAG and PI3K/Akt inhibitor would effectively suppress acquired resistance to 17-AAG. In conclusion, targeting of LGALS3BP-mediated–specific survival signaling pathway in resistant cells may provide a novel therapeutic model for the cancer therapy. Mol Cancer Ther; 16(7); 1355–65. ©2017 AACR.
PMP22 Regulates Self-Renewal and Chemoresistance of Gastric Cancer Cells
Authors: Cai Wangyu , Chen Gang , Luo Qicong , Liu Jun , Guo Xiaofeng , Zhang Tian , Ma Fei , Yuan Liang , Li Boan , Cai Jianchun 
Published: March 2017

Abstract
Cancer stem cells possess self-renewal and chemoresistance activities. However, the manner in which these features are maintained remains obscure. We sought to identify cell surface protein(s) that mark self-renewing and chemoresistant gastric cancer cells using the explorer antibody microarray. We identified PMP22, a target gene of the Wnt/β-catenin pathway, as the most upregulated cell surface protein in gastric cancer xenografts exposed to cisplatin (DDP). PMP22 expression was markedly upregulated in tumorspheric cells and declined with differentiation. Infecting gastric cancer cells with lentivirus expressing PMP22 shRNAs reduced proliferation, tumorsphere formation, and chemoresistance to cisplatin in vitro and in NOD/SCID mice. When combined with bortezomib, a PMP22 inhibitor, the chemotherapeutic sensitivity to cisplatin treatment was dramatically increased by inducing cell apoptosis in cultured cells and xenograft mouse models. Finally, mRNA expression levels of PMP22 were detected in 38 tumor specimens from patients who received six cycles of perioperative chemotherapy. A strong correlation between PMP22 level and tumor recurrence was revealed, thus showing a pivotal role of PMP22 in the clinical chemoresistance of gastric cancer. Our study is the first to show the role of PMP22 in gastric cancer stemness and chemoresistance and reveals a potential new target for the diagnosis and treatment of recurrent gastric cancer. Mol Cancer Ther; 16(6); 1187–98. ©2017 AACR.
Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies
Authors: Jordan Emmet J. , Kim Hyunjae R. , Arcila Maria E. , Barron David , Chakravarty Debyani , Gao JianJiong , Chang Matthew T. , Ni Andy , Kundra Ritika , Jonsson Philip , Jayakumaran Gowtham , Gao Sizhi Paul , Johnsen Hannah C. , Hanrahan Aphrothiti J. , Zehir Ahmet , Rekhtman Natasha , Ginsberg Michelle S. , Li Bob T. , Yu Helena A. , Paik Paul K. , Drilon Alexander , Hellmann Matthew D. , Reales Dalicia N. , Benayed Ryma , Rusch Valerie W. , Kris Mark G. , Chaft Jamie E. , Baselga José , Taylor Barry S. , Schultz Nikolaus , Rudin Charles M. , Hyman David M. , Berger Michael F. , Solit David B. , Ladanyi Marc , Riely Gregory J. 
Published: March 2017

Abstract
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma, but the fraction of patients who derive clinical benefit remains undefined. Here, we report the experience of 860 patients with metastatic lung adenocarcinoma analyzed prospectively for mutations in &gt;300 cancer-associated genes. Potentially actionable genetic events were stratified into one of four levels based upon published clinical or laboratory evidence that the mutation in question confers increased sensitivity to standard or investigational therapies. Overall, 37.1% (319/860) of patients received a matched therapy guided by their tumor molecular profile. Excluding alterations associated with standard-of-care therapy, 14.4% (69/478) received matched therapy, with a clinical benefit of 52%. Use of matched therapy was strongly influenced by the level of preexistent clinical evidence that the mutation identified predicts for drug response. Analysis of genes mutated significantly more often in tumors without known actionable mutations nominated STK11 and KEAP1 as possible targetable mitogenic drivers.
Significance: An increasing number of therapies that target molecular alterations required for tumor maintenance and progression have demonstrated clinical activity in patients with lung adenocarcinoma. The data reported here suggest that broader, early testing for molecular alterations that have not yet been recognized as standard-of-care predictive biomarkers of drug response could accelerate the development of targeted agents for rare mutational events and could result in improved clinical outcomes. Cancer Discov; 7(6); 596–609. ©2017 AACR.
See related commentary by Liu et al., p. 555.
This article is highlighted in the In This Issue feature, p. 539
Lipoprotein(a) and HIV
Authors: Enkhmaa Byambaa , Anuurad Erdembileg , Zhang Wei , Li Chin-Shang , Kaplan Robert , Lazar Jason , Merenstein Dan , Karim Roksana , Aouizerat Brad , Cohen Mardge , Butler Kenneth , Pahwa Savita , Ofotokun Igho , Adimora Adaora A. , Golub Elizabeth , Berglund Lars 
Published: March 2017

Objective—
In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)–related elevated cardiovascular disease risk remain unclear.

Approach and Results—

The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima–media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women’s Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level (
P
=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (
P
=0.022) were significantly associated with carotid artery intima–media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4
+
T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) (
P
=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (
P
=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima–media thickness.

Conclusions—
Lp(a) and allele-specific apo(a) levels predict carotid artery intima–media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection.
Human MicroRNA-548p Decreases Hepatic Apolipoprotein B Secretion and Lipid Synthesis
Authors: Zhou Liye , Hussain M. Mahmood 
Published: March 2017

Objective—
MicroRNAs (miRs) play important regulatory roles in lipid metabolism. Apolipoprotein B (ApoB), as the only essential scaffolding protein in the assembly of very-low-density lipoproteins, is a target to treat hyperlipidemia and atherosclerosis. We aimed to find out miRs that reduce apoB expression.

Approach and Results—
Bioinformatic analyses predicted that hsa-miR-548p can interact with apoB mRNA. MiR-548p or control miR was transfected in human and mouse liver cells to test its role in regulating apoB secretion and mRNA expression levels. Site-directed mutagenesis was used to identify the interacting site of miR-548p in human apoB 3′-untranslated region. Fatty acid oxidation and lipid syntheses were examined in miR-548p overexpressing cells to investigate its function in lipid metabolism. We observed that miR-548p significantly reduces apoB secretion from human hepatoma cells and primary hepatocytes. Mechanistic studies showed that miR-548p interacts with the 3′-untranslated region of human apoB mRNA to enhance post-transcriptional degradation. Bioinformatic algorithms suggested 2 potential binding sites of miR-548p on human apoB mRNA. Site-directed mutagenesis studies revealed that miR-548p targets site I involving both seed and supplementary sequences. MiR-548p had no effect on fatty acid oxidation but significantly decreased lipid synthesis in human hepatoma cells by reducing HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and ACSL4 (Acyl-CoA synthetase long-chain family member 4) enzymes involved in cholesterol and fatty acid synthesis. In summary, miR-548p reduces lipoprotein production and lipid synthesis by reducing expression of different genes in human liver cells.

Conclusions—
These studies suggest that miR-548p regulates apoB secretion by targeting mRNA. It is likely that it could be useful in treating atherosclerosis, hyperlipidemia, and hepatosteatosis.
Urban and rural stroke mortality rates in China between 1988 and 2013: An age-period-cohort analysis
Authors: Li Jingjing , Li Boyang , Zhang Fengfan , Sun Yang 
Published: March 2017

Objective To evaluate effects attributable to age, time period and birth cohort, on stroke mortality data from urban and rural regions in China between 1988 and 2013. Methods Mortality data were obtained from the Chinese Health Statistics Annual Report (1987–2001) and Chinese Health Statistics Yearbooks (2003–2014). Population data were obtained from population censuses (i.e. 1982, 1990, 2000 and 2010). Data were analysed using an age-period-cohort (APC) model and intrinsic estimation (IE) method. Results The age effect suggested that all older residents had higher stroke mortality risk than younger residents. Period effect showed that compared with figures for 1988, stroke mortality in 2013 was 1.8 times higher for urban regions and 2.4 times higher for rural regions. After controlling for age and period effects, cohorts born before the Chinese economic reform had a steady decline in stroke mortality. However, mortality rates increased and fluctuated in post-reform cohorts. Conclusions This APC-IE analysis identified a modest period effect with large age and cohort contributions to both the overall mortality and the disparity between urban and rural stroke mortality. Identifying early life and cumulative risk factors for stroke, improving equality in stroke prevention and care are needed to reduce the stroke mortality in China.
The Proximal Tibiofibular Joint: A Biomechanical Analysis of the Anterior and Posterior Ligamentous Complexes
Authors: Marchetti Daniel Cole , Moatshe Gilbert , Phelps Brian M. , Dahl Kimi D. , Ferrari Marcio Balbinotti , Chahla Jorge , Turnbull Travis Lee , LaPrade Robert F. 
Published: March 2017

Background: Dislocation of the proximal tibiofibular joint is a complex injury that is often overlooked or misdiagnosed. Surgical management is recommended for severe acute or for chronic symptomatic instability of the proximal tibiofibular joint. Although the anterior ligamentous complex has been reported to be stronger than the posterior complex, biomechanical data are lacking. Purpose: To determine the ultimate load of the anterior and posterior ligamentous complexes of the proximal tibiofibular joint to determine optimal graft selection. Study Design: Controlled laboratory study. Methods: Ten nonpaired, fresh-frozen knee specimens were dissected to expose the anterior and posterior proximal tibiofibular ligamentous complexes. The tibia was split in the coronal plane to separate the anterior and posterior ligamentous complexes, and the fibula was left intact. Specimens were secured in a dynamic testing machine and preconditioned for 10 cycles between 2 and 10 N at 0.1 Hz followed by loading to failure at a rate of 25 mm/min. Results: The mean (±SD) ultimate load of the anterior complex (517 ± 144 N) was significantly greater than the mean ultimate load of the posterior complex (322 ± 160 N) ( P = .012). The mean surface areas of the anterior and posterior complexes were 761 ± 174 mm2 and 565 ± 103 mm2, respectively ( P = .008). The mean values for stiffness of the anterior (133 N/mm) and posterior (109 N/mm) complexes were similar ( P = .250). Conclusion: The ligaments of the human proximal tibiofibular joint were able to withstand a mean ultimate failure load of 517 ± 144 N for the anterior complex and 322 ± 160 N for the posterior complex. In this regard, it is recommended that the strengths of grafts chosen for proximal tibiofibular reconstructions meet or exceed these values. Clinical Relevance: The optimal surgical treatment for addressing residual proximal tibiofibular instability is not well defined. Before an anatomic reconstruction of the proximal tibiofibular ligament is developed, the individual biomechanical properties of the anterior and posterior ligamentous structures of the proximal tibiofibular joint need to be considered to facilitate an optimal reconstruction design.
Effect of Severe Vitamin D Deficiency at Admission on Shock Reversal in Children With Septic Shock: A Prospective Observational Study
Authors: Sankar Jhuma , Ismail Javed , Das Rashmi , Dev Nishanth , Chitkara Anubhuti , Sankar M. Jeeva 
Published: March 2017

Objectives: To evaluate the association of severe vitamin D deficiency with clinically important outcomes in children with septic shock. Methods: We enrolled children ≤17 years with septic shock prospectively over a period of 6 months. We estimated 25-hydroxyvitamin D [25 (OH) D] levels at admission and 72 hours. Severe deficiency was defined as serum 25 (OH) <10 ng/mL. We performed univariate and multivariate analysis to evaluate association with clinically important outcomes. Results: Forty-three children were enrolled in the study. The prevalence of severe vitamin D deficiency was 72% and 69% at admission and 72 hours, respectively. On univariate analysis, severe vitamin D deficiency at admission was associated with lower rates of shock reversal, 74% (23) versus 25% (3); relative risk (95% confidence interval [CI]): 2.9 (1.09-8.08), at 24 hours and greater need for fluid boluses (75 vs 59 mL/kg). On multivariate analysis, nonresolution of shock at 24 hours was significantly associated with severe vitamin D deficiency after adjusting for other key baseline and clinical variables, adjusted odds ratio (95% CI): 12 (2.01-87.01); 0.01. Conclusion: The prevalence of severe vitamin D deficiency is high in children with septic shock admitted to pediatric intensive care unit. Severe vitamin D deficiency at admission seems to be associated with lower rates of shock reversal at 24 hours of ICU stay. Our study provides preliminary data for planning interventional studies in children with septic shock and severe vitamin D deficiency.
Monitoring the World Health Organization Global Target 2025 for Exclusive Breastfeeding: Experience From the United States
Authors: Gupta Priya M. , Perrine Cria G. , Chen Jian , Elam-Evans Laurie D. , Flores-Ayala Rafael 
Published: March 2017

Background: Exclusive breastfeeding under 6 months, calculated from a single 24-hour recall among mothers of children 0 to 5 months of age, is a World Health Organization (WHO) indicator used to monitor progress on the 2025 global breastfeeding target. Many upper-middle-income and high-income countries, including the United States, do not have estimates for this indicator. Research aim: To describe the prevalence of exclusive breastfeeding under 6 months in the United States. Methods: We used a single 24-hour dietary recall from the National Health and Nutrition Examination Survey 2009-2012 to calculate the prevalence of exclusive breastfeeding under 6 months. We discuss our results in the context of routine breastfeeding surveillance, which is reported from a national survey with different methodology. Results: Among children younger than 6 months, 24.4%, 95% confidence interval [17.6, 31.1], were exclusively breastfed the previous day. Conclusion: To our knowledge, this is the first estimate of the WHO indicator of exclusive breastfeeding under 6 months for the United States. This study supports the global surveillance and data strategy for reporting to the WHO on the 2025 target for exclusive breastfeeding.
Uptake trends in the Scottish Bowel Screening Programme and the influences of age, sex, and deprivation
Authors: Quyn Aaron J , Fraser Callum G , Stanners Greig , Carey Francis A , Carden Claire , Shaukat Aasma , Steele Robert JC 
Published: March 2017

Objective Age, sex, and deprivation are known factors influencing colorectal (bowel) cancer screening uptake. We investigated the influence of these factors on uptake over time. Methods Data from the Scottish Bowel Screening Programme (SBoSP) were collected between 2007 and 2014. End-points for analysis were uptake, faecal occult blood test positivity, and disease detection, adjusted for age, sex, deprivation, and year of screening. Results From 5,308,336 individual screening episodes documented, uptake gradually increased with increasing age up to 65–69 and was lower in men than women (52.4% vs. 58.7%, respectively). Deprivation had a significant effect on uptake by men and women of all age groups, with the most deprived least likely to complete a screening test. Uptake has increased with time in both sexes and across the deprivation gradient. The number needed to screen to detect significant neoplasia was significantly lower in men than women overall (170 vs. 365), and this held over all age and deprivation groups. The number needed to screen was also lower in the more deprived population. Conclusions Although lower age, male sex, and increased deprivation are associated with lower bowel cancer screening uptake in Scotland, uptake has increased since SBoSP introduction in all age groups, both sexes, and across the deprivation gradient. Despite a lower uptake, the number needed to screen to find significant disease was lower in men and in those with higher levels of deprivation.