bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen but not testosterone preserves myofilament function from doxorubicin-induced cardiotoxicity by reducing oxidative modifications
Authors: Rattanasopa Chutima , Kirk Jonathan A. , Bupha-Intr Tepmanas , Papadaki Maria , de Tombe Pieter P. , Wattanapermpool Jonggonnee 
Published: November 2018

Here, we aimed to explore sex differences and the impact of sex hormones on cardiac contractile properties in doxorubicin (DOX)-induced cardiotoxicity. Male and female Sprague-Dawley rats were subjected to sham surgery or gonadectomy and then treated or untreated with DOX (2 mg/kg) every other week for 10 wk. Estrogen preserved maximum active tension (Tmax) with DOX exposure, whereas progesterone and testosterone did not. The effects of sex hormones and DOX correlated with both altered myosin heavy chain isoform expression and myofilament protein oxidation, suggesting both as possible mechanisms. However, acute treatment with oxidative stress (H2O2) or a reducing agent (DTT) indicated that the effects on Tmaxwere mediated by reversible myofilament oxidative modifications and not only changes in myosin heavy chain isoforms. There were also sex differences in the DOX impact on myofilament Ca2+sensitivity. DOX increased Ca2+sensitivity in male rats only in the absence of testosterone and in female rats only in the presence of estrogen. Conversely, DOX decreased Ca2+sensitivity in female rats in the absence of estrogen. In most instances, this mechanism was through altered phosphorylation of troponin I at Ser23/Ser24. However, there was an additional DOX-induced, estrogen-dependent, irreversible (by DTT) mechanism that altered Ca2+sensitivity. Our data demonstrate sex differences in cardiac contractile responses to chronic DOX treatment. We conclude that estrogen protects against chronic DOX treatment in the heart, preserving myofilament function.NEW & NOTEWORTHY We identified sex differences in cardiotoxic effects of chronic doxorubicin (DOX) exposure on myofilament function. Estrogen, but not testosterone, decreases DOX-induced oxidative modifications on myofilaments to preserve maximum active tension. In rats, DOX exposure increased Ca2+sensitivity in the presence of estrogen but decreased Ca2+sensitivity in the absence of estrogen. In male rats, the DOX-induced shift in Ca2+sensitivity involved troponin I phosphorylation; in female rats, this was through an estrogen-dependent mechanism.
P209L mutation in Bag3 does not cause cardiomyopathy in mice
Authors: Fang Xi , Bogomolovas Julius , Zhou Paul Shichao , Mu Yongxin , Ma Xiaolong , Chen Zee , Zhang Lunfeng , Zhu Mason , Veevers Jennifer , Ouyang Kunfu , Chen Ju 
Published: November 2018

Bcl-2-associated athanogene 3 (BAG3) is a cochaperone protein and a central player of the cellular protein quality control system. BAG3 is prominently expressed in the heart and plays an essential role in cardiac protein homeostasis by interacting with chaperone heat shock proteins (HSPs) in large, functionally distinct multichaperone complexes. The BAG3 mutation of proline 209 to leucine (P209L), which resides in a critical region that mediates the direct interaction between BAG3 and small HSPs (sHSPs), is associated with cardiomyopathy in humans. However, the mechanism by which the BAG3 P209L missense mutation leads to cardiomyopathy remains unknown. To determine the molecular basis underlying the cardiomyopathy caused by the BAG3 P209L mutation, we generated a knockin (KI) mouse model in which the endogenous Bag3 gene was replaced with mutant Bag3 containing the P215L mutation, which is equivalent to the human P209L mutation. We performed physiological, histological, and biochemical analyses of Bag3 P209L KI mice to determine the functional, morphological, and molecular consequences of the P209L mutation. We found that Bag3 P209L KI mice exhibited normal cardiac function and morphology up to 16 mo of age. Western blot analysis further revealed that levels of sHSPs, stress-inducible HSPs, ubiquitinated proteins, and autophagy were unaffected in P209L mutant mouse hearts. In conclusion, the P209L mutation in Bag3 does not cause cardiomyopathy in mice up to 16 mo of age under baseline conditions. NEW & NOTEWORTHY Bcl-2-associated athanogene 3 (BAG3) P209L mutation is associated with human cardiomyopathy. A recent study reported that transgenic mice overexpressing human BAG3 P209L in cardiomyocytes have cardiac dysfunction. In contrast, our P209L mice that express mutant BAG3 at the same level as that of wild-type mice displayed no overt phenotype. Our results suggest that human cardiomyopathy may result from species-specific requirements for the conserved motif that is disrupted by P209L mutation or from genetic background-dependent effects.
Depression-Induced Neuropeptide Y Secretion Promotes Prostate Cancer Growth by Recruiting Myeloid Cells
Authors: Cheng Yan , Tang Xin-Ying , Li Yi-Xuan , Zhao Dan-Dan , Cao Qiu-Hua , Wu Hong-Xi , Yang Hong-Bao , Hao Kun , Yang Yong 
Published: November 2018

Abstract

Purpose:
Psychologic depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychologic depression alters the immune profiles in prostate cancer.

Experimental Design:
We used a murine model of depression in Myc-CaP tumor-bearing immunocompetent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and coculture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant, which correlated with immune cell infiltration, was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of patients with prostate cancer with a high score of psychologic depression.

Results:
Psychologic depression predominantly promoted tumor-associated macrophage (TAM) intratumor infiltrations, which resulted from spleen and circulating monocytic myeloid-derived suppressor cell mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL6 releasing, which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from patients with prostate cancer with higher score of depression revealed higher CD68+ TAM infiltration and stronger NPY and IL6 expression.

Conclusions:
Depression promotes myeloid cell infiltration and increases IL6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for patients with prostate cancer with high score of psychologic depression.
See related commentary by Mohammadpour et al., p. 2363
Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial
Authors: Bernard-Tessier Alice , Jeannot Emmanuelle , Guenat David , Debernardi Alice , Michel Marc , Proudhon Charlotte , Vincent-Salomon Anne , Bièche Ivan , Pierga Jean-Yves , Buecher Bruno , Meurisse Aurélia , François Éric , Cohen Romain , Jary Marine , Vendrely Véronique , Samalin Emmanuelle , El Hajbi Farid , Baba-Hamed Nabil , Borg Christophe , Bidard François-Clément , Kim Stefano 
Published: November 2018

Abstract

Purpose:
Human papillomavirus (HPV) is found in 90% of squamous cell carcinomas of the anal canal (SCCA). We investigated the clinical validity of HPV circulating tumor DNA (ctDNA) detection in patients enrolled in the Epitopes-HPV02 trial that demonstrated the efficacy of docetaxel, cisplatin, and 5-FU as first-line chemotherapy in advanced SCCA.

Experimental Design:
According to the protocol, serum samples were collected before chemotherapy and on completion of chemotherapy. HPV16 ctDNA was quantified by droplet digital PCR (ddPCR) and correlated with prospectively registered patient characteristics and outcomes. A landmark was set at the time of chemotherapy completion for postchemotherapy progression-free survival (PFS) analyses.

Results:
Among 57 patients with HPV16-related advanced SCCA, HPV ctDNA was detected in 91.1% (95% confidence interval, 81.1–96.2) of baseline samples. Baseline HPV ctDNA levels were not associated with any patient characteristics; baseline ctDNA level below the cutoff obtained by AUC (area under the curve) was associated with a longer PFS (HR = 2.1; P = 0.04). Among the 36 patients who completed 5 months of chemotherapy, residual HPV ctDNA was detected after chemotherapy in 38.9% of patients. Residual HPV ctDNA detected at chemotherapy completion was associated with shorter postchemotherapy PFS (median PFS 3.4 months vs. not reached; HR = 5.5; P &lt; 0.001) and a reduction of 1-year overall survival rate (OR = 7.0; P = 0.02).

Conclusions:
This prospective study in advanced SCCA demonstrated a significant prognostic impact of HPV ctDNA level before first-line chemotherapy and HPV ctDNA negativity after chemotherapy completion. With a limited cost and short turnaround, this assay is a promising tool to optimize the therapeutic management of SCCA.
See related commentary by Morris, p. 2030
China in Latin America: South-South Cooperation with Chinese Characteristics
Authors: Vadell Javier A. 
Published: November 2018

The central questions for a critical analysis of the economic relations between China and Latin America and the Caribbean countries since the beginning of the twenty-first century are how to interpret the changes in them since the end of the commodities boom and whether they have resulted in the emulation in these countries of the Chinese model of development. Analysis suggests that, although the Chinese presence was welcome during the turbulence of the 2001 economic crisis, relations with China are becoming increasingly complex and reflect the political and economic principles of South-South cooperation. Las preguntas centrales para un análisis crítico de las relaciones económicas entre China y los países de América Latina y el Caribe desde principios del siglo XXI son cómo interpretar los cambios en ellos desde el final del auge de los productos básicos y si han resultado en la emulación en estos países del modelo de desarrollo chino. El análisis sugiere que, aunque la presencia china fue bienvenida durante la turbulencia de la crisis económica de 2001, las relaciones con China son cada vez más complejas y reflejan los principios políticos y económicos de la cooperación Sur-Sur.
Comparative efficacy and safety of NSAIDs-controlled acupuncture in the treatment of patients with primary dysmenorrhoea: a Bayesian network meta-analysis
Authors: Luo Falan , Huang Xinyu , Liu Xiaohui , Wang Lijun , Xu Nenggui 
Published: November 2018

Background Acupuncture and non-steroidal anti-inflammatory drugs (NSAIDs) are used frequently to treat primary dysmenorrhoea. However, it is unclear whether this treatment greatly reduces the risk of primary dysmenorrhoea. Methods Eight databases were searched up to January 2018. Pair-wise and network meta-analyses were conducted to synthesize data from eligible studies. Results Seventeen randomized controlled trials were included. The following acupuncture types showed more efficacy than NSAIDs in reducing primary dysmenorrhoea risk: traditional acupuncture (odds ratio [OR] = 6.70, 95% confidence interval [CI] 2.60–20.0), eye acupuncture (OR = 3.50, 95% CI 1.40–8.90), wrist–ankle acupuncture (OR = 6.00, 95% CI 1.30–32.0), superficial acupuncture (OR= 5.10, 95% CI 1.20–26.0), moxibustion (OR = 7.70, 95% CI 2.90–25.0), electroacupuncture (OR = 23.0, 95% CI 4.80–130), ear acupuncture (OR = 13.0, 95% CI 2.80–100) and abdominal acupuncture (OR = 5.30, 95% CI 2.10–16.0). Surface under the cumulative ranking curve values were traditional acupuncture (53.0%), eye acupuncture (22.0%), wrist–ankle acupuncture (81.5%), superficial acupuncture (50.0%), moxibustion (57.8%), electroacupuncture (99.9%), ear acupuncture (41.6%) and abdominal acupuncture (44.1%). Conclusion Acupuncture is more efficacious than NSAIDs in reducing primary dysmenorrhoea risk. Acupuncture, particularly electroacupuncture, can decrease the risk of primary dysmenorrhoea.
Direct Comparison of Modified Jobe and Docking Ulnar Collateral Ligament Reconstruction at Midterm Follow-up
Authors: Arner Justin W. , Chang Edward S. , Bayer Stephen , Bradley James P. 
Published: November 2018

Background: The modified Jobe and docking techniques are the 2 most commonly employed techniques for ulnar collateral ligament (UCL) reconstruction among overhead athletes. However, no study has directly compared these techniques performed by a single surgeon. Current comparisons of these techniques have relied solely on systematic reviews and biomechanical studies. Hypothesis: There will be no difference in outcomes or return to play between the modified Jobe and docking techniques in elbow UCL reconstruction surgery. Study Design: Cohort study; Level of evidence, 3. Methods: Twenty-five modified Jobe and 26 docking UCL-reconstructive surgical procedures were performed by a single surgeon, each with a minimum 2-year follow-up. Kerlan-Jobe Orthopaedic Clinic (KJOC) score, Conway Scale, years played, sex, handedness, sport, position, palmaris versus gracilis graft type, concomitant or future arm/shoulder injuries, and need for additional surgery were compared between the groups. Patients who underwent future shoulder or elbow surgery, no matter the cause, were included. Results: No difference was seen between the modified Jobe and docking reconstruction cases in regard to KJOC scores (mean ± SD: 78.4 ± 19.5 vs 72.0 ± 26.0, P = .44), Conway Scale (return to play, any level: 84% vs 82%, P = .61), years played (14.7 ± 6.2 vs 15.2 ± 5.8, P = .52), sex ( P = .67), handedness ( P ≥ .999), sport ( P = .44), position ( P = .60), level of competition ( P = .59), and future surgery (12% vs 4%, P = .35). Palmaris graft type had significantly higher KJOC scores than hamstring grafts (82.3 ± 20.0 vs 57.9 ± 21.2, P = .001). The mean follow-up was 6.1 years in the modified Jobe group and 7.3 years in the docking group (mean = 6.7, P = .47). Conclusion: The modified Jobe and docking techniques are both suitable surgical options for elbow UCL reconstruction. There was no statistically significant difference between the techniques in regard to return to play, KJOC score, or need for subsequent surgery at 6.7-year follow-up. This is the first direct clinical comparison of these 2 techniques by a single surgeon at midterm follow-up.
Examining Changes in Healthy Days After Health Coaching
Authors: Cole Sam , Zbikowski Susan M. , Renda Andrew , Wallace Anne , Dobbins Jessica M. , Bogard Matt 
Published: November 2018

Purpose: To describe changes in health-related quality of life (HRQOL) related to variation in demographic characteristics, program goals, and program participation, among health coaching program participants. Design: A retrospective observational study of a health coaching program. Setting and Participants: A total of 2169 adults enrolled in an individually purchased or employer-sponsored health plan from a large health and well-being company, who participated in a health coaching program between January 2016 and April 2017. Intervention: The health coaching program used evidence-based behavior change strategies to encourage skill development, self-monitoring, and goal setting/achievement. Health coaching program modalities included online and telephonic coaching sessions. Measures: Demographic characteristics (gender, age, race, income), goal categories (weight management, fitness, nutrition, stress management, other), program modality (online, telephonic, both), engagement level (low, medium, high), and Healthy Days, a validated HRQOL measure developed by the Centers for Disease Control and Prevention. Analysis: t Tests, mixed analysis of variance (ANOVA). Results: There were significant ( P < .05) reductions in average total unhealthy days (UHDs) across all goal categories. Mixed ANOVAs identified a significant main effect for time, for all demographic characteristics ( P values < .05), and a significant effect for program modality ( P < .0001), time ( P < .0001), and interaction effects, between program modality and time, on average UHD ( P = .01). Conclusion: Our findings indicate significant reductions in UHD, following 6 months of health coaching, and support the use of HRQOL measures, which are known to be highly correlated with traditional measures of health, to evaluate health coaching programs.
Horses for Courses: Setting Tasks for Spotting Talent
Authors: Ghosh Saptarshi P. 
Published: November 2018

We investigate a distortion in the labour market that is rampant in developing countries and occurs in the form of inaccurate estimation of the innate talents of employees. We characterise the optimal level of difficulty in a predictive task that an employer, who acts as the evaluator, must choose in order to have the least noise in the talent estimation process. Contrary to the standard noise minimization result, our model re affirms the staffing policy of throwing employees in the deep end. We also find that the evaluator will not benefit from knowing the result of the predictive task set from beforehand. JEL: D82, D83
Using Fast Frequency Household Survey Data to Estimate the Impact of Demonetisation on Employment
Authors: Vyas Mahesh 
Published: November 2018

Centre for Monitoring Indian Economy Pvt. Ltd conducts a large longitudinal household survey, Consumer Pyramids Household Survey (CPHS). Since January 2016 it has been producing fast-frequency measures of unemployment by using the CPHS. This article attempts to understand the impact of demonetisation announced on 8 November 2016, if any, on employment by using the results from CPHS. We use data on two waves preceding demonetisation and two waves after demonetisation, that is, seven quarters—3 before and 4 after demonetisation—and also monthly and weekly data to understand the impact of demonetisation. The evidence indicates a substantial loss of jobs and labour participation after demonetisation. JEL: J640, J08, J210
Femoral head material loss at the head-neck junction in total hip arthroplasty: the effect of head size, stem material and stem offset
Authors: Valente Giuseppe , Lanting Brent , MacDonald Steven , Teeter Matthew G , Van Citters Douglas , Howard James 
Published: November 2018

Introduction: Material loss at the head-neck junction in total hip arthroplasty may cause adverse clinical symptoms and implant failure. The purpose of this study was to quantitatively examine the effects of head size, stem material and stem offset on material loss of the head-neck taper interface of a single trunnion design in retrieval implants of metal on polyethylene bearing surfaces. Methods: A retrieval study was performed to identify all 28-mm and 32-mm femoral heads from a single implant/taper design implanted for >2 years. This included n = 56 of the 28-mm heads and n = 23 of the 32-mm heads. The 28-mm femoral heads were matched to 32-mm femoral heads based on time in vivo and head length. A coordinate measuring machine was used to determine maximum linear corrosion depth (MLD). Differences in MLD for head diameter, stem material, and stem offset were determined. Results: There were no differences between groups for age, gender, BMI, or implantation time. There was no difference in MLD between 28 mm and 32 mm matched paired head diameters ( p = 0.59). There was also no difference in MLD between titanium or cobalt-chromium stems ( p = 0.79), and regular or high-offset stems ( p = 0.95). Conclusion: There is no statistical difference in femoral head MLD at the head-neck junction in THA between 28-mm and 32-mm matched paired femoral heads, similar or mixed alloy coupled femoral head stem constructs, and regular or high offset stems.
The Care Ecosystem: Promoting self-efficacy among dementia family caregivers
Authors: Merrilees Jennifer J , Bernstein Alissa , Dulaney Sarah , Heunis Julia , Walker Reilly , Rah Esther , Choi Jeff , Gawlas Katherine , Carroll Savannah , Ong Paulina , Feuer Julie , Braley Tamara , Clark Amy M , Lee Kirby , Chiong Winston , Bonasera Stephen J , Miller Bruce L , Possin Katherine L 
Published: November 2018

Objectives To illustrate specific psychosocial interventions aimed at improving self-efficacy among family caregivers enrolled in the Care Ecosystem, a model of navigated care designed to support persons with dementia and their primary caregivers. Enrolled family caregivers work with unlicensed care team navigators who are trained in dementia care and provide information, linkages to community resources, and emotional support by phone and email. Method We conducted focus groups and interviews with the care team navigators to identify the approaches they used to target caregiver self-efficacy. We assessed mean self-efficacy scores in a sample of 780 family caregivers and selected three exemplary cases in which the caregivers had low self-efficacy scores at baseline with significantly higher scores after six months of participation in the Care Ecosystem intervention. Results Multiple psychosocial strategies were utilized by care team navigators working with patients with dementia and their family caregivers. Using thematic coding we identified three categories of Care Team Navigator intervention: emotional, informational, and instrumental support. These are consistent with a psychosocial approach to building self-efficacy. Discussion Self-efficacy represents a family caregiver’s knowledge and preparedness in managing the challenges of care. Psychosocial support shows benefit in improving caregiver self-efficacy that in turn, may positively influence caregiver health and well-being. The findings in this manuscript demonstrate how a model of navigated care can positively impact self-efficacy among dementia family caregivers.
Identifying Brain Connectivity Using Network-Based Statistics in Amnestic Mild Cognitive Impairment Stratified by β-Amyloid Positivity
Authors: Kim Ji Eun , Kim Sung-Woo , Choi Minsuk , Seong Joon-Kyung , Lee Jae-Hong 
Published: November 2018

Background: The aim of this study was to identify white matter structural networks of amnestic mild cognitive impairment (aMCI) dichotomized by β amyloid (Aβ) status and compare them using network-based statistics (NBS). Methods: Patients underwent whole-brain diffusion-weighted magnetic resonance imaging, detailed neuropsychological test and [18F]-Florbetaben amyloid positron emission tomography. We performed the NBS analysis to compare the whole-brain white matter structural networks extracted from diffusion tensor images. Results: One hundred sixteen participants (Aβ− cognitively normal [CN], n = 35; Aβ− aMCI, n = 42; Aβ+ aMCI, n = 39) were included. There was no subnetwork showing significant difference between Aβ+ aMCI and Aβ− aMCI. However, by comparing each aMCI group with control group, we found that supplementary motor areas were common hub regions. Intriguingly, Aβ+ aMCI showed reduced connectivity mainly in the medial frontal regions, while Aβ− aMCI showed somewhat uniform disruption when compared to CN. Conclusion: Structural network analysis using network-based approach in aMCI may shed light on further understanding of white matter disruption in the prodromal stage of Alzheimer’s disease.