bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qualitative study to explore the health and well-being impacts on adults providing informal support to female domestic violence survivors
Authors: Gregory Alison , Feder Gene , Taket Ann , Williamson Emma 
Published: March 2017

ObjectivesDomestic violence (DV) is hazardous to survivors' health, from injuries sustained and from resultant chronic physical and mental health problems. Support from friends and relatives is significant in the lives of DV survivors; research shows associations between positive support and the health, well-being and safety of survivors. Little is known about how people close to survivors are impacted. The aim of this study was exploratory, with the following research question: what are the health and well-being impacts on adults who provide informal support to female DV survivors?DesignA qualitative study using semistructured interviews conducted face to face, by telephone or using Skype. A thematic analysis of the narratives was carried out.SettingCommunity-based, across the UK.ParticipantsPeople were eligible to take part if they had had a close relationship (either as friend, colleague or family member) with a woman who had experienced DV, and were aged 16 or over during the time they knew the survivor. Participants were recruited via posters in community venues, social media and radio advertisement. 23 participants were recruited and interviewed; the majority were women, most were white and ages ranged from mid-20s to 80.ResultsGenerated themes included: negative impacts on psychological and emotional well-being of informal supporters, and related physical health impacts. Some psychological impacts were over a limited period; others were chronic and had the potential to be severe and enduring. The impacts described suggested that those providing informal support to survivors may be experiencing secondary traumatic stress as they journey alongside the survivor.ConclusionsFriends and relatives of DV survivors experience substantial impact on their own health and well-being. There are no direct services to support this group. These findings have practical and policy implications, so that the needs of informal supporters are legitimised and met.
Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5′-UTR of TRIM22
Authors: Lim Keo-Heun , Park Eun-Sook , Kim Doo Hyun , Cho Kyung Cho , Kim Kwang Pyo , Park Yong Kwang , Ahn Sung Hyun , Park Seung Hwa , Kim Kee-Hwan , Kim Chang Wook , Kang Hong Seok , Lee Ah Ram , Park Soree , Sim Heewoo , Won Juhee , Seok Kieun , You Jueng Soo , Lee Jeong-Hoon , Yi Nam-Joon , Lee Kwang-Woong , Suh Kyung-Suk , Seong Baik L , Kim Kyun-Hwan 
Published: March 2017

ObjectiveInterferons (IFNs) mediate direct antiviral activity. They play a crucial role in the early host immune response against viral infections. However, IFN therapy for HBV infection is less effective than for other viral infections.DesignWe explored the cellular targets of HBV in response to IFNs using proteome-wide screening.ResultsUsing LC-MS/MS, we identified proteins downregulated and upregulated by IFN treatment in HBV X protein (HBx)-stable and control cells. We found several IFN-stimulated genes downregulated by HBx, including TRIM22, which is known as an antiretroviral protein. We demonstrated that HBx suppresses the transcription of TRIM22 through a single CpG methylation in its 5′-UTR, which further reduces the IFN regulatory factor-1 binding affinity, thereby suppressing the IFN-stimulated induction of TRIM22.ConclusionsWe verified our findings using a mouse model, primary human hepatocytes and human liver tissues. Our data elucidate a mechanism by which HBV evades the host innate immune system.
The effect of excise tax increases on cigarette prices in South Africa
Authors: Linegar Daniel J , van Walbeek Corne 
Published: March 2017

IntroductionThe effectiveness of excise tax increases as a tool for reducing tobacco consumption depends largely on how the tax increases impact the retail price. We estimate this relationship in South Africa for 2001–2015.DataStatistics South Africa provided disaggregated cigarette price data, used in the calculation of the Consumers’ Price Index. Data on the excise tax per cigarette were obtained from Budget Reviews prepared by the National Treasury of South Africa.MethodsRegression equations were estimated for each month. The month-on-month change in cigarette prices in February through April was regressed against March’s excise tax change to estimate the pass-through coefficient. For the other 9 months, the month-on-month change in cigarette price was regressed against monthly dummy variables to determine the size of the non-tax-related price increase in each of these months. The analysis was performed in both nominal and real (inflation-adjusted) terms.FindingsExpressed in real terms, the excise tax was undershifted. A R1.00 (one rand) increase in the excise tax is associated with an increase in the retail price of cigarettes of R0.90 in the pre-2010 period, and R0.49 in the post-2010 period. In the pre-2010 period, the tobacco industry increased the retail price of cigarettes in July/August, independent of the excise tax increase. The discretionary July/August price increases largely disappeared after 2010, primarily because the market became more competitive.ConclusionThe degree of excise tax pass-through, and the magnitude of discretionary increases in cigarette prices, is significantly determined by the competitive environment in the cigarette market.
Sciatic and femoral nerve blockade using bupivacaine alone, or in combination with dexmedetomidine or buprenorphine in cats
Authors: Evangelista M. C. , Doodnaught G. M. , Fantoni D. T. , Steagall P. V. M. 
Published: March 2017

The aim of this study was to determine the onset and offset of antinociception after sciatic (ScN) and femoral (FN) nerve blocks. Six healthy adult cats (4.8±1.3years; 4.3±0.4 kg) were included in a randomised, crossover, blinded and controlled study. Following sedation with dexmedetomidine (25 µg/kg, intramuscular), each ScN and FN injection was performed using 0.1 ml/kg of saline (CONTROL), bupivacaine (0.46 per cent, 0.46 mg/kg; BUPI), bupivacaine and dexmedetomidine (1 µg/kg; BUPI‐DEX) or bupivacaine and buprenorphine (2.5 µg/kg; BUPI‐BUPRE). Atipamezole (250 µg/kg) was administered after injections. Paw withdrawal thresholds (PWT) and motor blockade were evaluated before sedation and up to 24 hours. The PWT were significantly increased at half an hour in CONTROL, from two to four hours in BUPI and BUPI‐DEX when compared with baseline. Motor blockade was observed between one and three hours in treatments using bupivacaine. Ability to walk was significantly impaired in BUPI at half an hour to two hours, BUPI‐DEX at one to two hours and BUPI‐BUPRE at two hours. Antinociception was observed in BUPI between one and eight hours, and in BUPI‐DEX and BUPI‐BUPRE between one and four hours. This study could not demonstrate a benefit of administering bupivacaine with dexmedetomidine or buprenorphine in cats. Results in BUPI‐DEX may have been biased by the administration of atipamezole.
Microvascular leakage in acute myocardial infarction: characterization by histology, biochemistry, and magnetic resonance imaging
Authors: Gao Xiao-Ming , Wu Qi-Zhu , Kiriazis Helen , Su Yidan , Han Li-Ping , Pearson James Todd , Taylor Andrew J. , Du Xiao-Jun 
Published: March 2017

Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepentaacetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24–48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2%) was greater than that of infarct (47 ± 4%, P < 0.01) or MVO (36 ± 4%, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization ( r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology.NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.
Sept7bis required for the subcellular organization of cardiomyocytes and cardiac function in zebrafish
Authors: Dash Surjya Narayan , Narumanchi Suneeta , Paavola Jere , Perttunen Sanni , Wang Hong , Lakkisto Päivi , Tikkanen Ilkka , Lehtonen Sanna 
Published: March 2017

Myofibrils made up of actin, myosin, and associated proteins generate the contractile force in muscle, and, consequently, mutations in these proteins may lead to heart failure. Septins are a conserved family of small GTPases that associate with actin filaments, microtubules, and cellular membranes. Despite the importance of septins in cytoskeleton organization, their role in cardiomyocyte organization and function is poorly characterized. Here, we show that septin 7 is expressed in both embryonic and adult zebrafish hearts and elucidate the physiological significance of sept7b, the zebrafish ortholog of human septin 7, in the heart in embryonic and larval zebrafish. Knockdown of sept7b reduced F-actin and α-cardiac actin expression in the heart and caused disorganization of actin filaments. Electron microscopy of sept7b-depleted larvae showed disorganization of heart myofibrils and partial detachment from Z-disks. Functional studies revealed that knockdown of sept7b leads to reduced ventricular dimensions, contractility, and cardiac output. Furthermore, we found that depletion of sept7b diminished the expression of retinaldehyde dehydrogenase 2, which catalyzes the synthesis of retinoic acid necessary for heart morphogenesis. We further observed that the sept7b and retinoic acid signaling pathways converge to regulate cardiac function. Together, these results specify an essential role for sept7b in the contractile function of the heart.NEW & NOTEWORTHY Knockdown of the zebrafish ortholog of human septin 7 ( sept7b) destabilizes cardiac actin and reduces ventricular dimensions, contractility, and cardiac output in larval zebrafish, indicating that sept7b is essential for cardiac function. We further found that sept7b and retinoic acid signaling pathways converge to regulate cardiac function. These data prompt further studies defining the role of sept7b in cardiomyopathies.
Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis
Authors: Levin Lynn I. , Breen Elizabeth C. , Birmann Brenda M. , Batista Julie L. , Magpantay Larry I. , Li Yuanzhang , Ambinder Richard F. , Mueller Nancy E. , Martínez-Maza Otoniel 
Published: March 2017

AbstractBackground: We investigated whether an immune system environment characterized by elevated serum levels of B-cell activation molecules was associated with the subsequent development of classical Hodgkin lymphoma (cHL).Methods: We measured serum levels of B-cell–stimulatory cytokines, IL6 and IL10, soluble CD30 (sCD30), and total IgE prior to cHL diagnosis in 103 cases and 206 matched controls with archived specimens in the DoD Serum Repository.Results: Prediagnosis serum sCD30 and IL6 levels had strong positive associations with risk of a cHL diagnosis 0 to 1 year prior to diagnosis [sCD30 OR = 5.5; 95% confidence interval (CI), 3.4–9.0; IL6 OR = 4.6; 95% CI, 2.9–7.5] and &gt;1 year to 2 years pre-cHL diagnosis (sCD30 OR = 3.3; 95% CI, 1.6–6.7; IL6 OR = 2.9; 95% CI, 1.3–6.5). We observed similar, albeit not consistently significant positive associations, over 4 or more years preceding diagnosis. We did not observe a clear association with IgE levels. Of note, detectable IL10 levels were significantly associated with Epstein–Barr virus (EBV)-positive cHL cases compared with EBV-negative cases.Conclusion: In this prospective analysis, elevated sCD30 and IL6 levels and detectable IL10 preceded cHL diagnosis.Impact: The associations of these cytokines with cHL risk may reflect the production of these molecules by proliferating nascent cHL tumor cells, or by immune cells responding to their presence, prior to clinical detection. The stable elevation in cHL risk, 4 or more years prediagnosis, also suggests that a B-cell–stimulatory immune system milieu precedes, and may promote, lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1114–23. ©2017 AACR.
High Salt Intake Is Associated with Atrophic Gastritis with Intestinal Metaplasia
Authors: Song Ji Hyun , Kim Young Sun , Heo Nam Ju , Lim Joo Hyun , Yang Sun Young , Chung Goh Eun , Kim Joo Sung 
Published: March 2017

Abstract
Background: Although several studies have investigated excessive salt intake as a risk factor for gastric precancerous lesions, such as atrophic gastritis and intestinal metaplasia, the evidence is insufficient to make a conclusion. We evaluated the association between gastric precancerous lesions and salt intake.
Methods: From 2008 to 2015, the medical records of 728 subjects who underwent upper gastrointestinal endoscopy and sodium excretion in 24-hour urine tests were retrospectively reviewed. Sixty-six subjects were excluded due to diuretics use (n = 55), diagnosis with a gastric neoplasm (n = 4), or the cases of intestinal metaplasia in the absence of atrophy (n = 7), so 662 subjects were included. Atrophic gastritis and intestinal metaplasia were diagnosed by endoscopic findings. The subjects were grouped into three levels by tertiles of 24-hour urine sodium excretion.
Results: A total of 192 (29.0%) had atrophic gastritis without intestinal metaplasia and 112 (16.9%) had atrophic gastritis with intestinal metaplasia. A total of 276 subjects (61.5%) were infected with Helicobacter pylori (H. pylori). In multivariate analyses, H. pylori infection [OR = 14.17; 95% confidence interval (CI), 7.12–28.22) was associated with atrophic gastritis without intestinal metaplasia. Highest levels of sodium excretion (OR = 2.870; 95% CI, 1.34–6.14), heavy smoking (≥20 pack-years) (OR = 2.75; 95% CI, 1.02–7.39), and H. pylori infection (OR = 3.96; 95% CI, 2.02–7.76) were associated with atrophic gastritis with intestinal metaplasia.
Conclusions: Our endoscopy-based study suggested that high salt intake could be associated with an increased risk of atrophic gastritis with intestinal metaplasia.
Impact: Low salt diet might be helpful to prevent gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1133–8. ©2017 AACR.
The Promise of Targeting Macrophages in Cancer Therapy
Authors: Brown J. Martin , Recht Lawrence , Strober Samuel 
Published: March 2017

AbstractCancer therapy has developed around the concept of killing, or stopping the growth of, the cancer cells. Molecularly targeted therapy is the modern expression of this paradigm. Increasingly, however, the realization that the cancer has co-opted the normal cells of the stroma for its own survival has led to the concept that the tumor microenvironment (TME) could be targeted for effective therapy. In this review, we outline the importance of tumor-associated macrophages (TAM), a major component of the TME, in the response of tumors to cancer therapy. We discuss the normal role of macrophages in wound healing, the major phenotypes of TAMs, and their role in blunting the efficacy of cancer treatment by radiation and anticancer drugs, both by promoting tumor angiogenesis and by suppressing antitumor immunity. Finally, we review the many preclinical studies that have shown that the response of tumors to irradiation and anticancer drugs can be improved, sometimes markedly so, by depleting TAMs from tumors or by suppressing their polarization from an M1 to an M2 phenotype. The data clearly support the validity of clinical testing of combining targeting TAMs with conventional therapy. Clin Cancer Res; 23(13); 3241–50. ©2017 AACR.
Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor
Authors: Perera Timothy P.S. , Jovcheva Eleonora , Mevellec Laurence , Vialard Jorge , De Lange Desiree , Verhulst Tinne , Paulussen Caroline , Van De Ven Kelly , King Peter , Freyne Eddy , Rees David C. , Squires Matthew , Saxty Gordon , Page Martin , Murray Christopher W. , Gilissen Ron , Ward George , Thompson Neil T. , Newell David R. , Cheng Na , Xie Liang , Yang Jennifer , Platero Suso J. , Karkera Jayaprakash D. , Moy Christopher , Angibaud Patrick , Laquerre Sylvie , Lorenzi Matthew V. 
Published: March 2017

Abstract
Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor (FGFR) family members are associated with increased tumor growth, metastasis, angiogenesis, and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases. JNJ-42756493 shows rapid uptake into the lysosomal compartment of cells in culture, which is associated with prolonged inhibition of FGFR signaling, possibly due to sustained release of the inhibitor. In xenografts from human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations, JNJ-42756493 administration results in potent and dose-dependent antitumor activity accompanied by pharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors. The results of the current study provide a strong rationale for the clinical investigation of JNJ-42756493 in patients with tumors harboring FGFR pathway alterations. Mol Cancer Ther; 16(6); 1010–20. ©2017 AACR.
Tumor-Associated Macrophages Can Contribute to Antitumor Activity through FcγR-Mediated Processing of Antibody–Drug Conjugates
Authors: Li Fu , Ulrich Michelle , Jonas Mechthild , Stone Ivan J. , Linares Germein , Zhang Xinqun , Westendorf Lori , Benjamin Dennis R. , Law Che-Leung 
Published: March 2017

AbstractThe primary mechanism of antibody–drug conjugates (ADC) is targeted delivery of a cytotoxic payload to tumor cells via cancer-associated membrane receptors. However, the tumor microenvironment likely plays a role in ADC penetration, distribution, and processing and thus impacts the overall antitumor activity. Here, we report on the potential contribution of Fc–FcγR interactions between ADCs and tumor-associated macrophages (TAM) to the preclinical antitumor activities of ADCs. In the CD30+ L-428 Hodgkin lymphoma model, anti-CD30-vcMMAE and a non-binding control (hIgG-vcMMAE) demonstrated similar antitumor activity as well as similar payload release in the tumors. IHC analysis revealed L-428 tumors contained highly abundant TAMs, which were confirmed to bind ADCs by IHC and flow cytometry. The infiltration of TAMs was further found to correlate with the antitumor activity of the non-binding hIgG-vcMMAE in five additional xenograft models. hIgG1V1-vcMMAE, bearing a mutation in the Fc region which ablates Fc gamma receptor (FcγR) binding, lost antitumor activity in three TAM-high xenograft models, suggesting Fc–FcγR interactions modulate the TAM-ADC interaction. Our results suggest that TAMs can contribute to ADC processing through FcγR interaction in preclinical tumor models and may represent an important additional mechanism for drug release from ADCs. Correlative studies in clinical trials will further shed light on whether TAMs play a role in patients' response to ADC therapies. Mol Cancer Ther; 16(7); 1347–54. ©2017 AACR.
An
NPPB
Promoter Polymorphism Associated With Elevated N‐Terminal pro–B‐Type Natriuretic Peptide and Lower Blood Pressure, Hypertension, and Mortality
Authors: Seidelmann Sara B. , Vardeny Orly , Claggett Brian , Yu Bing , Shah Amil M. , Ballantyne Christie M. , Selvin Elizabeth , MacRae Calum A. , Boerwinkle Eric , Solomon Scott D. 
Published: March 2017

Background

Elevated B‐type natriuretic peptide (
BNP
) levels are associated with heart failure and increased mortality in the general population. We investigated rs198389, a functional variant in the promoter region of the
BNP
gene (

NPPB

), in patients from the Atherosclerosis Risk in Communities Study to investigate associations with N‐terminal pro‐BNP (NT‐pro
BNP)
levels and outcomes.

Methods and Results

A total of 11 361 black and white patients with rs198389 genotyping attended visit 1 (aged 45–64 years; 1987–1989), with follow‐up visits occurring every 3 years (visit 2–visit 4, 1990–1999), followed by visit 5 (2011–2013).
NT
‐pro
BNP
levels were measured at visits 2, 4, and 5. At visit 2, the
GG
genotype (frequency 18%) was associated with a 41% higher mean plasma level of
NT
‐pro
BNP
compared with the
AA
genotype (frequency 34%), with intermediate values observed in
AG
s (
P
=4.2×10
−52
). The
GG
genotype was associated with reduced systolic blood pressure (−1.6 mm Hg,
P
=0.006), diastolic blood pressure (−1 mm Hg,
P
=0.003), antihypertension medication use (odds ratio, 0.85; 95%
CI
, 0.74–0.97 [
P
=0.02]), and hypertension (odds ratio, 0.81; 95%
CI
, 0.72–0.92 [
P
=0.002]) compared with the
AA
genotype with intermediate values in
AG
s. These relationships persisted throughout subsequent visits. After a median follow‐up of 23 years, there were 4031 deaths. With and without covariate adjustment, the
GG
genotype was associated with modestly lower mortality (hazard ratio, 0.86; 95% CI, 0.78–0.95), primarily reflective of cardiovascular death (hazard ratio, 0.75; 95% CI, 0.61–0.92), and increased residual lifespan of 8 months from 50 years of age (
P
=0.02) versus
AA
s.

Conclusions

The rs198389 G allele in the

NPPB

promoter is associated with elevated levels of
NT
‐pro
BNP
throughout adult life, reduced blood pressure, hypertension and cardiovascular mortality, and increased lifespan.