bluuebunny/crossref_metadata_2025_split huggingface dataset:
EF Hand Protein IBA2 Promotes Cell Proliferation in Breast Cancers via Transcriptional Control of Cyclin D1
Authors: Zhang Ying , Wang Shuling , Li Lingsong 
Published: June 2016

AbstractEF hand (EFh) domain–containing proteins have been implicated in malignant progression, but their precise functional contributions are uncertain. Here, we report evidence that the EFh protein IBA2 promotes the proliferation of breast cancer cells by facilitating their transit through the G1–S cell-cycle transition. Mechanistic investigations revealed that IBA2 acted at the transcriptional level to promote the expression of the critical cell-cycle regulator cyclin D1. Clinically, we found that levels of IBA2 were significantly upregulated in breast cancer specimens, where its expression correlated positively with histologic grade. Our results suggest a key role for IBA2 in mammary tumorigenesis. Cancer Res; 76(15); 4535–45. ©2016 AACR.
A Novel Chemotherapeutic Agent to Treat Tumors with DNA Mismatch Repair Deficiencies
Authors: Zhang Yongliang , Fox Jennifer T. , Park Young-Un , Elliott Gene , Rai Ganesha , Cai Mengli , Sakamuru Srilatha , Huang Ruili , Xia Menghang , Lee Kyeryoung , Jeon Min Ho , Mathew Bijoy P. , Park Hee Dong , Edelmann Winfried , Park Chan Young , Hong Sung You , Maloney David , Myung Kyungjae 
Published: June 2016

Abstract
Impairing the division of cancer cells with genotoxic small molecules has been a primary goal to develop chemotherapeutic agents. However, DNA mismatch repair (MMR)-deficient cancer cells are resistant to most conventional chemotherapeutic agents. Here we have identified baicalein as a small molecule that selectively kills MutSα-deficient cancer cells. Baicalein binds preferentially to mismatched DNA and induces a DNA damage response in a MMR-dependent manner. In MutSα-proficient cells, baicalein binds to MutSα to dissociate CHK2 from MutSα leading to S-phase arrest and cell survival. In contrast, continued replication in the presence of baicalein in MutSα-deficient cells results in a high number of DNA double-strand breaks and ultimately leads to apoptosis. Consistently, baicalein specifically shrinks MutSα-deficient xenograft tumors and inhibits the growth of AOM-DSS–induced colon tumors in colon-specific MSH2 knockout mice. Collectively, baicalein offers the potential of an improved treatment option for patients with tumors with a DNA MMR deficiency. Cancer Res; 76(14); 4183–91. ©2016 AACR.
AIMP2 Controls Intestinal Stem Cell Compartments and Tumorigenesis by Modulating Wnt/β-Catenin Signaling
Authors: Yum Min Kyu , Kang Jong-Seol , Lee Al-Eum , Jo Young-Woo , Seo Ji-Yun , Kim Hyun-A , Kim Yoon-Young , Seong Jinwoo , Lee Eun Byul , Kim Ji-Hoon , Han Jung Min , Kim Sunghoon , Kong Young-Yun 
Published: June 2016

Abstract
Wnt/β-catenin (CTNNB1) signaling is crucial for the proliferation and maintenance of intestinal stem cells (ISC), but excessive activation leads to ISC expansion and eventually colorectal cancer. Thus, negative regulators are required to maintain optimal levels of Wnt/β-catenin signaling. Aminoacyl-tRNA synthetase–interacting multifunctional proteins (AIMP) function in protein synthesis, but have also been implicated in signaling cascades affecting angiogenesis, immunity, and apoptosis. In this study, we investigated the relationship between AIMP2 and Wnt/β-catenin signaling in a murine model of intestinal homeostasis and tumorigenesis. Hemizygous deletion of Aimp2 resulted in enhanced Wnt/β-catenin signaling, increased proliferation of cryptic epithelial cells, and expansion of ISC compartments. In an ApcMin/+ background, Aimp2 hemizygosity increased adenoma formation. Mechanistically, AIMP2 disrupted the interaction between AXIN and Dishevelled-1 (DVL1) to inhibit Wnt/β-catenin signaling by competing with AXIN. Furthermore, AIMP2 inhibited intestinal organoid formation and growth by suppressing Wnt/β-catenin signaling in an Aimp2 gene dosage-dependent manner. Collectively, our results showed that AIMP2 acts as a haploinsufficient tumor suppressor that fine-tunes Wnt/β-catenin signaling in the intestine, illuminating the regulation of ISC abundance and activity. Cancer Res; 76(15); 4559–68. ©2016 AACR.
Interferon-γ Production by Peripheral Lymphocytes Predicts Survival of Tumor-Bearing Mice Receiving Dual PD-1/CTLA-4 Blockade
Authors: McNamara Michael J. , Hilgart-Martiszus Ian , Barragan Echenique Diego M. , Linch Stefanie N. , Kasiewicz Melissa J. , Redmond William L. 
Published: June 2016

Abstract
Immune checkpoint inhibitors are transforming the way cancer is treated. However, these therapies do not benefit all patients and frequently cause significant immune-related adverse events. Biomarkers that identify patients with a favorable early response to therapy are essential for guiding treatment decisions and improving patient outcomes. In this report of our study, we present evidence that shortly after administration of dual PD-1/CTLA-4 blockade, the proinflammatory capacity of peripheral lymphocytes is predictive of tumor progression and survival outcomes in multiple murine models. Specifically, we observed that the quantity of interferon-γ (IFNγ) produced by peripheral lymphocytes in response to CD3/CD28 stimulation was robustly correlated with subsequent survival outcomes. In the tumor models and early time points assessed in this study, this relationship was considerably more predictive than a host of other potential biomarkers, several of which have been previously reported. Overall, these findings suggest that measuring the capacity of peripheral lymphocytes to produce IFNγ may help identify which patients are benefitting from combination anti–PD-1/anti–CTLA-4 immunotherapy. Cancer Immunol Res; 4(8); 650–7. ©2016 AACR.
Concentration of Positive Ground State Solutions for Schrödinger–Maxwell Systems with Critical Growth
Authors: Yang Minbo 
Published: June 2016

Abstract
In this paper, we study the following Schrödinger–Maxwell system with critical exponents in

ℝ
3

${\mathbb{R}^{3}}$

:

{

-

ε
2

⁢
Δ
⁢
u

+

V
⁢

(
x
)

⁢
u

+

K
⁢

(
x
)

⁢
ϕ
⁢
u

=

P
⁢

(
x
)

⁢
g
⁢

(
u
)

+

Q
⁢

(
x
)

⁢

|
u
|

4

⁢
u

,

-

ε
2

⁢
Δ
⁢
ϕ

=

K
⁢

(
x
)

⁢

u
2

.

$\left\{\begin{aligned} &\displaystyle{-}\varepsilon^{2}\Delta u+V(x)u+K(x)\phi u% =P(x)g(u)+Q(x)|u|^{4}u,\\ &\displaystyle{-}\varepsilon^{2}\Delta\phi=K(x)u^{2}.\end{aligned}\right.$

Under suitable assumptions on the potentials

V
⁢

(
x
)

${V(x)}$

,

K
⁢

(
x
)

${K(x)}$

,

P
⁢

(
x
)

${P(x)}$

and

Q
⁢

(
x
)

${Q(x)}$

, we are able to prove the existence of semiclassical ground state solutions

(

u
ε

,

ϕ
ε

)

${(u_{\varepsilon},\phi_{\varepsilon})}$

with the maximum points

x
ε

${x_{\varepsilon}}$

of

u
ε

${u_{\varepsilon}}$

concentrating at a special set M described by these potential functions. Moreover, setting

v
ε

⁢

(
x
)

:=

u
ε

⁢

(

ε
⁢
x

+

x
ε

)

${v_{\varepsilon}(x):=u_{\varepsilon}(\varepsilon x+x_{\varepsilon})}$

for any sequence

x
ε

→

x
0

∈
M

${x_{\varepsilon}\to x_{0}\in M}$

, the solutions

(

v
ε

,

ϕ
ε

)

${(v_{\varepsilon},\phi_{\varepsilon})}$

converge strongly in

H
1

⁢

(

ℝ
3

)

${H^{1}(\mathbb{R}^{3})}$

to a solution

(
u
,
ϕ
)

${(u,\phi)}$

of

{

-

Δ
⁢
v

+

V
⁢

(

x
0

)

⁢
v

+

K
⁢

(

x
0

)

⁢
ϕ
⁢
v

=

P
⁢

(

x
0

)

⁢
g
⁢

(
v
)

+

Q
⁢

(

x
0

)

⁢

|
v
|

4

⁢
v

,

-

Δ
⁢
ϕ

=

K
⁢

(

x
0

)

⁢

v
2

.

$\left\{\begin{aligned} &\displaystyle{-}\Delta v+V(x_{0})v+K(x_{0})\phi v=P(x_% {0})g(v)+Q(x_{0})|v|^{4}v,\\ &\displaystyle{-}\Delta\phi=K(x_{0})v^{2}.\end{aligned}\right.$
Molecular mechanisms redirecting the GLP-1 receptor signalling profile in pancreatic β-cells during type 2 diabetes
Authors: Roussel Morgane , Mathieu Julia , Dalle Stéphane 
Published: June 2016

Abstract
Treatments with β-cell preserving properties are essential for the management of type 2 diabetes (T2D), and the new therapeutic avenues, developed over the last years, rely on the physiological role of glucagon-like peptide-1 (GLP-1). Sustained pharmacological levels of GLP-1 are achieved by subcutaneous administration of GLP-1 analogues, while transient and lower physiological levels of GLP-1 are attained following treatment with inhibitors of dipeptidylpeptidase 4 (DPP4), an endoprotease which degrades the peptide. Both therapeutic classes display a sustained and durable hypoglycaemic action in patients with T2D. However, the GLP-1 incretin effect is known to be reduced in patients with T2D, and GLP-1 analogues and DPP4 inhibitors were shown to lose their effectiveness over time in some patients. The pathological mechanisms behind these observations can be either a decrease in GLP-1 secretion from intestinal L-cells and, as a consequence, a reduction in GLP-1 plasma concentrations, combined or not with a reduced action of GLP-1 in the β-cell, the so-called GLP-1 resistance. Much evidence for a GLP-1 resistance of the β-cell in subjects with T2D have emerged. Here, we review the potential roles of the genetic background, the hyperglycaemia, the hyperlipidaemia, the prostaglandin E receptor 3, the nuclear glucocorticoid receptor, the GLP-1R desensitization and internalisation processes, and the β-arrestin-1 expression levels on GLP-1 resistance in β-cells during T2D.
Investigations on Surface Roughness Measurement in Minimum Quantity Lubrication Turning of Titanium Alloys Using Response Surface Methodology and Box–Cox Transformation
Authors: Gupta Munish Kumar , Sood P. K. , Sharma Vishal S. 
Published: June 2016

AbstractIn the present work, an attempt has been made to establish the accurate surface roughness (Ra, Rq and Rz) prediction model using response surface methodology with Box–Cox transformation in turning of Titanium (Grade-II) under minimum quantity lubrication (MQL) conditions. This surface roughness model has been developed in terms of machining parameters such as cutting speed, feed rate and approach angle. Firstly, some experiments are designed and conducted to determine the optimal MQL parameters of lubricant flow rate, input pressure and compressed air flow rate. After analyzing the MQL parameter, the final experiments are performed with cubic boron nitride (CBN) tool to optimize the machining parameters for surface roughness values i. e., Ra, Rq and Rz using desirability analysis. The outcomes demonstrate that the feed rate is the most influencing factor in the surface roughness values as compared to cutting speed and approach angle. The predicted results are fairly close to experimental values and hence, the developed models using Box-Cox transformation can be used for prediction satisfactorily.
HMGB1, nucleosomes and sRAGE as new prognostic serum markers after multiple trauma
Authors: Stahl Juliane Barbara , Hoecherl Eduard F. , Durner Jürgen , Nagel Dorothea , Wolf Konrad , Holdenrieder Stefan 
Published: June 2016

Abstract

Background: The prognostic relevance of blood markers in multiple trauma is still a matter of controversial debate. Besides clinical scores new biomarkers indicating the disease severity and the prognosis during the first hours of therapy are highly needed to improve individual patient management.

Methods: In prospectively collected sera of 164 patients, among them 115 with multiple trauma, the values of circulating nucleosomes, high-mobility-group-box protein 1 (HMGB1) and soluble receptor of advanced glycation end products (sRAGE) were determined at time of admission to the resuscitation room. Disease severity and clinical status were quantified by injury severity score (ISS) and Glasgow Coma Scale (GCS). As controls, 24 patients with femoral neck fractures and 25 patients with ankle fractures (AFs) were included.

Results: Patients with severe multiple trauma (SMT) showed significantly higher HMGB1 and sRAGE levels than patients with moderate trauma and single fractures. Interestingly, HMGB1 and nucleosomes (R=0.56; p<0.01) as well as HMGB1 and sRAGE (R=0.44; p<0.01) correlated significantly with each other. In multiple trauma patients, high HMGB1 and sRAGE levels were significantly associated with more severe trauma according ISS (both p<0.01) and more severe traumatic brain injury (TBI) (GCS≤8; both p<0.01). Thirteen of the multiple injured patients died during the first week after trauma. Non-surviving patients showed significantly higher values of HMGB1, nucleosomes, and sRAGE than survivors (p<0.01; p=0.01; p=0.02). Best prediction of first-week mortality was obtained in receiver operating characteristic (ROC) curves for HMGB1 that yielded an area under the curve (AUC) of 90.6%.

Conclusions: HMGB1, nucleosomes and sRAGE are valuable biomarkers indicating trauma severity and prognosis of trauma patients.
Impact of rest breaks on musculoskeletal discomfort of Chikan embroiderers of West Bengal, India: a follow up field study
Authors: Chakrabarty Sabarni , Sarkar Krishnendu , Dev Samrat , Das Tamal , Mitra Kalpita , Sahu Subhashis , Gangopadhyay Somnath 
Published: June 2016

ObjectivesThis study aimed to determine risk factors that predict musculoskeletal discomfort in Chikan embroiderers of West Bengal, India, and to compare the effect of two rest break schedules to reduce these symptoms.MethodsThe Nordic musculoskeletal questionnaire was performed on 400 Chikan embroiderers at baseline containing questions on job autonomy, working behavior, and work stress factors. Relative risk was calculated to identify prognostic factors for musculoskeletal discomfort in different body regions. Two groups of workers received two rest break schedules for 4 months and compared in a between‐subject design. Outcome variables were scores of Body Part Discomfort (BPD) scale.ResultsChikan embroiderers are afflicted with musculoskeletal discomfort mainly in the lower back, neck/shoulder and wrist/forearm region, which is attributed to their prolonged working timeinvolving hands and wrists, being in a static seating posture. Rigidity in working methods, prolonged working time, inadequate rest break during the working day, dissatisfaction regarding earning, monotonous work, static sitting posture, and repetitive movement of wrist and forearm were the significant predictors of these symptom developments. Rest break schedule 1 with more frequent and shorter breaks had more significant improvement on the severity of these musculoskeletal discomforts.ConclusionsChikan embroiderers perform a highly dreary occupation and various ergonomics conditions work as predictors for developing musculoskeletal discomforts among them. Design of proper rest break schedule involving shorter and frequent breaks was competent for reducing these discomforts to a certain extent.
Validity and reproducibility of self‐reported working hours among Japanese male employees
Authors: Imai Teppei , Kuwahara Keisuke , Miyamoto Toshiaki , Okazaki Hiroko , Nishihara Akiko , Kabe Isamu , Mizoue Tetsuya , Dohi Seitaro ,   Japan Epidemiology Collaboration on Occupational Health Study Group
Published: June 2016

ObjectiveWorking long hours is a potential health hazard. Although self‐reporting of working hours in various time frames has been used in epidemiologic studies, its validity is unclear. The objective of this study was to examine the validity and reproducibility of self‐reported working hours among Japanese male employees.MethodsThe participants were 164 male employees of four large‐scale companies in Japan. For validity, the Spearman correlation between self‐reported working hours in the second survey and the working hours recorded by the company was calculated for the following four time frames: daily working hours, monthly overtime working hours in the last month, average overtime working hours in the last 3 months, and the frequency of long working months (>45 h/month) within the last 12 months. For reproducibility, the intraclass correlation between the first (September 2013) and second surveys (December 2013) was calculated for each of the four time frames.ResultsThe Spearman correlations between self‐reported working hours and those based on company records were 0.74, 0.81, 0.85, and 0.89 for daily, monthly, 3‐monthly, and yearly time periods, respectively. The intraclass correlations for self‐reported working hours between the two questionnaire surveys were 0.63, 0.66, 0.73, and 0.87 for the respective time frames.ConclusionsThe results of the present study among Japanese male employees suggest that the validity of self‐reported working hours is high for all four time frames, whereas the reproducibility is moderate to high.
Comparison of biomarkers in serum and induced sputum of patients with occupational asthma and chronic obstructive pulmonary disease
Authors: Kleniewska Aneta , Walusiak‐Skorupa Jolanta , Piotrowski Wojciech , Nowakowska‐Świrta Ewa , Wiszniewska Marta 
Published: June 2016

ObjectivesOccupational asthma and chronic obstructive pulmonary disease (COPD) are associated with the airway inflammatory process. The aim of this study was to compare the sputum and serum markers of inflammation in patients with occupational asthma and COPD.MethodsThe study group included 20 patients with stable COPD, 24 patients with asthma, and 22 healthy subjects. Interleukin (IL)‐6, IL‐1β, tumor necrosis factor (TNF)‐α, matrix metalloproteinase (MMP)‐9 levels in serum and induced sputum as well as fibrinogen and CRP in serum were determined in all the subjects.ResultsHigher concentrations of IL‐1β, IL‐6, TNF‐α, and MMP‐9 in induced sputum and an increased concentration of acute‐phase proteins in serum were observed in COPD patients compared with healthy subjects. Higher concentrations of IL‐1β and MMP‐9 in induced sputum and a higher concentration of C‐reactive protein (CRP) were detected in COPD patients than in asthmatic subjects. Never smokers with COPD had significantly higher levels of IL‐1β and MMP‐9 in induced sputum than never smoker controls. There was no significant difference between the serum and sputum levels of cytokines and MMP‐9 of never smokers and smokers with COPD.ConclusionsHigher concentrations of IL‐1β and MMP‐9 in induced sputum and a higher concentration of CRP in serum allow distinguishing between biomarker profiles of COPD patients and asthmatic patients. Occupational exposure induces a systemic proinflammatory state with increased levels of acute‐phase proteins in stable COPD patients. MMP‐9 and IL‐1β concentrations are increased in induced sputum of never smokers with COPD, which is associated with occupational exposure.
Can leisure‐time physical activity improve health checkup results? Evidence from Japanese occupational panel data
Authors: Oshio Takashi , Tsutsumi Akizumi , Inoue Akiomi 
Published: June 2016

ObjectivesWe examined the extent to which changes in worker health, as measured by health checkup items, were associated with increased intensity of leisure‐time physical activity (LTPA) after controlling for individual time‐invariant attributes.MethodsWe used panel data from two to four waves of a Japanese occupational cohort survey, focusing on 30,206 observations of 10,106 individuals (7,669 men and 2,437 women) aged 18‐76 years. We estimated first‐difference and mean‐centered fixed effects models to examine how changes in 10 health checkup items were associated with changes in LTPA intensity. We considered four LTPA intensity levels (none, low, moderate, and vigorous), based on self‐reported assessments.ResultsFor men, low‐density lipoprotein cholesterol levels, glycated hemoglobin levels, body mass index, and waist circumference improved when LTPA intensity was increased even at a low level, whereas triglyceride, high‐density lipoprotein cholesterol, and fasting blood glucose levels improved when LTPA intensity was increased to moderate or vigorous levels. Blood pressure (both systolic and diastolic) and total cholesterol levels were only modestly responsive to changes in LTPA intensity. For women, blood pressure (both systolic and diastolic) and waist circumference were negatively associated with LTPA intensity, whereas the other variables showed more modest effects.ConclusionsThe results suggest that even low‐to moderate‐intensity LTPA can improve health checkup results; however, the lowest LTPA intensity associated with improvement in health depends on healthrisk factors as well as gender.
Resilience, post‐traumatic growth, and work engagement among health care professionals after the Great East Japan Earthquake: A 4‐year prospective follow‐up study
Authors: Nishi Daisuke , Kawashima Yuzuru , Noguchi Hiroko , Usuki Masato , Yamashita Akihiro , Koido Yuichi , Matsuoka Yutaka J 
Published: June 2016

ObjectivesAlthough attention has been paid to post‐traumatic stress disorder (PTSD) among health care professionals after disasters, the impact of traumatic events on their work has not been elucidated. The aim of this study was to examine whether disaster‐related distress, resilience, and post‐traumatic growth (PTG) affect work engagement among health care professionals who had been deployed to the areas affected by the Great East Japan Earthquake that occurred on March 11, 2011.MethodsWe recruited disaster medical assistance team members who were engaged in rescue activities after the earthquake. The short version of the Resilience Scale (RS‐14) and Peritraumatic Distress Inventory (PDI) were administered one month after the earthquake, and the short form of Posttraumatic Growth Inventory (SF‐PTGI) and Utrecht Work Engagement Scale (UWES) were administered four years after the earthquake. Work engagement is composed of vigor, dedication, and absorption. Regression analyses were used to examine the relationship of UWES with RS‐14, PDI, and SF‐PTGI.ResultsWe obtained baseline data of 254 participants in April 2011, and 191 (75.2%) completed the follow‐up assessment between December 2014 and March 2015. The results showed that RS‐14 predicted vigor, dedication, and absorption; in addition, SF‐PTGI was positively related with these three parameters (p<0.01 for all).ConclusionsResilience at baseline and PTG after rescue activities may increase work engagement among health care professionals after disasters. These findings could be useful for establishing a support system after rescue activities during a largescale disaster and for managing work‐related stress among health care professionals.
Differential gene expression associated with inflammation in peripheral blood cells of patients with pneumoconiosis
Authors: Liu Shu‐jun , Wang Ping , Jiao Jie , Han Lin , Lu Yu‐min 
Published: June 2016

ObjectivesTo study expression changes in inflammation‐related genes in peripheral blood of patients with pneumoconiosis and to explore the possibility of these genes as pneumoconiosis biomarkers.MethodsPeripheral blood samples of patients with pneumoconiosis patients and controls were collected, and total RNA of the blood cells were extracted and reverse transcribed to cDNA. Screenings of deferentially expressed genes associated with inflammation between patients with pneumoconiosis and controls were performed using real‐time quantitative PCR array and the expressions of the three most upregulated genes were confirmed by real‐time PCR.ResultsThe expression of 11 genes was significantly altered in patients with pneumoconiosis compared with those of the control. Among these 11 genes, 8 genes were upregulated and 3 were downregulated. Preliminary results indicated that interleukin 6 (IL‐6) mRNA expression in patients with pneumoconiosis was higher than that in controls (P=0.019). The level of IL6 mRNA expression in the patients was higher than that in non‐smoking controls, but it was neither affected by type and stage of pneumoconiosis nor by time of contact with dust.ConclusionsIL6 was possibly involved in the development of pneumoconiosis.