bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgenic overexpression of active HDAC4 in the heart attenuates cardiac function and exacerbates remodeling in infarcted myocardium
Authors: Zhang Ling X. , Du Jianfeng , Zhao Yu Tina , Wang Jianguo , Zhang Shouyan , Dubielecka Patrycja M. , Wei Lei , Zhuang Shougang , Qin Gangjian , Chin Y. Eugene , Zhao Ting C. 
Published: October 2018

Histone deacetylases (HDACs) play a critical role in modulating cardiac function and ischemic injury. HDAC4 was found to be elevated and activated in response to injury. However, whether HDAC4 mediates cardiac function is currently unknown. In this study, we created myocyte-specific activated HDAC4 transgenic mice to examine the role of HDAC4 in mediating cardiac function during development and response to infarction. There are no differences in cardiac function and gross phenotype between wild-type and cardiomyocyte-specific HDAC4 transgenic mice at 1 mo of age. However, cardiac dysfunction and vascular growth deficiency were displayed in 6-mo-old HDAC4-transgenic mice compared with wild-type mice. Activation of HDAC4 increased heart and myocyte size, hypertrophic proteins, and interstitial fibrosis in 6-mo-old mice but not in 1-mo-old mice. To further define whether activated HDAC4 in the heart could impact myocardial function and remodeling, myocardial infarction was created in both wild-type and cardiomyocyte-specific HDAC4-transgenic mice. In myocardial infarction, the overexpression of activated HDAC4 exacerbated cardiac dysfunction and augmented cardiac remodeling and interstitial fibrosis, which was associated with the reduction of cardiokines in the heart. These results indicate the activation of HDAC4 as a crucial regulator for cardiac function in development and myocardial infarction. NEW & NOTEWORTHY We created myocyte-specific activated HDAC4-transgenic mice to examine the function of HDAC4 in mediating cardiac function. HDAC4 overexpression led to cardiac dysfunction, which was associated with increased hypertrophy and myocardial fibrosis. Furthermore, the overexpression of activated HDAC4 exacerbated cardiac dysfunction, augmented remodeling, and increased apoptosis in the infarcted heart. This is the first demonstration that transgenic overexpression of HDAC4 is crucial for modulation of cardiac function and remodeling.
Modelling mucosal surface roughness in the human velopharynx: a computational fluid dynamics study of healthy and obstructive sleep apnea airways
Authors: Lambeth Christopher , Wang Ziyu , Kairaitis Kristina , Moshfegh Abouzar , Jabbarzadeh Ahmad , Amis Terence 
Published: October 2018

We previously published a unique methodology for quantifying human velopharyngeal mucosal surface topography and found increased mucosal surface roughness in patients with obstructive sleep apnea (OSA). In fluid mechanics, surface roughness is associated with increased frictional pressure losses and resistance. This study used computational fluid dynamics (CFD) to analyze the mechanistic effect of different levels of mucosal surface roughness on velopharyngeal airflow. Reconstructed velopharyngeal models from OSA and control subjects were modified, giving each model three levels of roughness, quantified by the curvature-based surface roughness index (CBSRI0.6) (range 24.8–68.6 mm−1). CFD using the k-ω shear stress transport turbulence model was performed (unidirectional, inspiratory, steady-state, 15l/min volumetric flow rate), and the effects of roughness on flow velocity, intraluminal pressure, wall shear stress, and velopharyngeal resistance ( Rv) were examined. Across all models, increasing roughness increased maximum flow velocity, wall shear stress, and flow disruption while decreasing intraluminal pressures. Linear mixed effects modeling demonstrated a log-linear relationship between CBSRI0.6and Rv, with a common slope (log( Rv)/CBSRI0.6) of 0.0079 [95% confidence interval (CI) 0.0015–0.0143; P = 0.019] for all subjects, equating to a 1.9-fold increase in Rvwhen roughness increased from control to OSA levels. At any fixed CBSRI0.6, the estimated difference in log( Rv) between OSA and control models was 0.9382 (95% CI 0.0032–1.8732; P = 0.049), equating to an 8.7-fold increase in Rv. This study supports the hypothesis that increasing mucosal surface roughness increases velopharyngeal airway resistance, particularly for anatomically narrower OSA airways, and may thus contribute to increased vulnerability to upper airway collapse in patients with OSA.NEW & NOTEWORTHY Increased mucosal surface roughness in the velopharynx of patients with obstructive sleep apnea (OSA) has recently been identified, but its role in OSA pathogenesis is unknown. This is the first study to model the impact of increased roughness on airflow mechanics in the velopharynx. We report that increasing roughness significantly affects airflow, increasing velopharyngeal resistance and potentially increasing the vulnerability to upper airway collapse, particularly in those patients with an already compromised anatomy.
Arrested Developments: CDK4/6 Inhibitor Resistance and Alterations in the Tumor Immune Microenvironment
Authors: Teh Jessica L.F. , Aplin Andrew E. 
Published: October 2018

Abstract
The uncontrolled proliferation of cancer cells has led to the development of small-molecule inhibitors to target cell-cycle progression. Palbociclib, ribociclib, and abemaciclib are ATP-competitive inhibitors of cyclin-dependent kinases 4/6 (CDK4/6), which function early within the G1 phase of the cell cycle. Recently, CDK4/6 inhibitors have gained FDA approval in postmenopausal estrogen receptor (ER)–positive/human epidermal growth factor receptor 2 (HER2)–negative breast cancer and testing in other cancer types is underway. However, resistance to CDK4/6 inhibitors frequently develops. In addition, targeting CDK4/6 may augment the action of immune checkpoint blockade agents. Here, we review recent studies that provide the preclinical rationale for treatment combinations and schedules that include CDK4/6 inhibitors. Furthermore, we discuss inhibitor effects on tumor-infiltrating lymphocytes as a preclinical rationale for targeting CDK4/6 in combination with anti–PD-1 or anti–CTLA-4 antibodies.
Evidence for Chemopreventive and Resilience Activity of Licorice: Glycyrrhiza Glabra and G. Inflata Extracts Modulate Estrogen Metabolism in ACI Rats
Authors: Wang Shuai , Dunlap Tareisha L. , Huang Lingyi , Liu Yang , Simmler Charlotte , Lantvit Daniel D. , Crosby Jenna , Howell Caitlin E. , Dong Huali , Chen Shao-Nong , Pauli Guido F. , van Breemen Richard B. , Dietz Birgit M. , Bolton Judy L. 
Published: October 2018

Abstract
Women are increasingly using botanical dietary supplements (BDS) to reduce menopausal hot flashes. Although licorice (Glycyrrhiza sp.) is one of the frequently used ingredients in BDS, the exact plant species is often not identified. We previously showed that in breast epithelial cells (MCF-10A), Glycyrrhiza glabra (GG) and G. inflata (GI), and their compounds differentially modulated P450 1A1 and P450 1B1 gene expression, which are responsible for estrogen detoxification and genotoxicity, respectively. GG and isoliquiritigenin (LigC) increased CYP1A1, whereas GI and its marker compound, licochalcone A (LicA), decreased CYP1A1 and CYP1B1. The objective of this study was to determine the distribution of the bioactive licorice compounds, the metabolism of LicA, and whether GG, GI, and/or pure LicA modulate NAD(P)H quinone oxidoreductase (NQO1) in an ACI rat model. In addition, the effect of licorice extracts and compounds on biomarkers of estrogen chemoprevention (CYP1A1) as well as carcinogenesis (CYP1B1) was studied. LicA was extensively glucuronidated and formed GSH adducts; however, free LicA as well as LigC were bioavailable in target tissues after oral intake of licorice extracts. GG, GI, and LicA caused induction of NQO1 activity in the liver. In mammary tissue, GI increased CYP1A1 and decreased CYP1B1, whereas GG only increased CYP1A1. LigC may have contributed to the upregulation of CYP1A1 after GG and GI administration. In contrast, LicA was responsible for GI-mediated downregulation of CYP1B1. These studies highlight the polypharmacologic nature of botanicals and the importance of standardization of licorice BDS to specific Glycyrrhiza species and to multiple constituents.
Social conformity affects experimental measurement of boldness in male but not female monk parakeets (Myiopsitta monachus)
Authors: Kerman Kaan , Sieving Kathryn E. , St. Mary Colette , Avery Michael L. 
Published: October 2018

AbstractThe standard approach for characterizing boldness rarely considers the influence of social environment on the expression of boldness in group-living animals. We studied a wild-caught, captive population of monk parakeets (Myiopsitta monachus) to investigate the impact of conspecific presence on boldness — a personality trait in monk parakeets — in a controlled environment. We quantified seven boldness metrics across three types of behavioural assay: novel object, emergence, and predator exposure tests in the presence of a companion pair of flock mates. Because of the high degree of sociality in this species, we hypothesized that the presence of companion birds would facilitate the focal individuals’ behavioural responses (i.e., increase the average boldness level). We found that behavioural response in a risky foraging context was inversely correlated between solitary and social condition in males, but not in females. Our results have implications for characterizing sex-specific differences of risk-taking behaviour in social animals.
Integrating a nationally scaled workforce of community health workers in primary care: a modelling study
Authors: Hayhoe Benedict , Cowling Thomas E , Pillutla Virimchi , Garg Priya , Majeed Azeem , Harris Matthew 
Published: October 2018

Objective To model cost and benefit of a national community health worker workforce. Design Modelling exercise based on all general practices in England. Setting United Kingdom National Health Service Primary Care. Participants Not applicable. Data sources Publicly available data on general practice demographics, population density, household size, salary scales and screening and immunisation uptake. Main outcome measures We estimated numbers of community health workers needed, anticipated workload and likely benefits to patients. Results Conservative modelling suggests that 110,585 community health workers would be needed to cover the general practice registered population in England, costing £2.22bn annually. Assuming community health workerss could engage with and successfully refer 20% of eligible unscreened or unimmunised individuals, an additional 753,592 cervical cancer screenings, 365,166 breast cancer screenings and 482,924 bowel cancer screenings could be expected within respective review periods. A total of 16,398 additional children annually could receive their MMR1 at 12 months and 24,716 their MMR2 at five years of age. Community health workerss would also provide home-based health promotion and lifestyle support to patients with chronic disease. Conclusion A scaled community health worker workforce integrated into primary care may be a valuable policy alternative. Pilot studies are required to establish feasibility and impact in NHS primary care.
The nerve root sedimentation sign in diagnosis of lumbar spinal stenosis
Authors: Piechota Małgorzata , Król Robert , Elias David A. , Wawrzynek Wojciech , Lekstan Andrzej 
Published: October 2018

Background The nerve root sedimentation sign is a magnetic resonance (MR) sign, shown to be present in central lumbar spinal stenosis. The lack of sedimentation of the nerve roots to the dorsal part of the dural sac is consistent with the positive nerve root sedimentation sign. Purpose To validate the reliability of the nerve root sedimentation sign in diagnosis of different grades of lumbar spinal canal stenosis. Material and Methods This study was a retrospective review of 101 consecutive MR imaging (MRI) studies obtained on patients with clinically suspected lumbar canal stenosis. Based on the minimum anteroposterior (AP) diameter of the dural sac the study sample was classified into two groups: a group with morphological lumbar spinal stenosis; and the group of patients free from stenosis (AP > 12 mm). Patients with stenosis were further subclassified based on its severity: severe stenosis (AP ≤ 10 mm); and moderate stenosis (AP > 10 mm to ≤ 12 mm). Results Positive sedimentation sign was identified in 81% of patients with severe lumbar spinal stenosis and 14% of patients with moderate stenosis. No patients without lumbar spinal stenosis had a positive nerve root sedimentation sign. Of patients with a positive nerve root sedimentation sign, 89% presented with neurological claudication. Conclusion The nerve root sedimentation is a useful tool for identification of patients with both severe clinical and morphological lumbar spinal stenosis; however, its performance in the diagnosis of patients with moderate morphological spinal stenosis is poor.
Has the implementation of the Minamata convention had an impact on the practice of operative dentistry in Jordan?
Authors: Al-Asmar Ayah Abdullah , Al-Khatib Khaled M , Al-Amad Tareq Z , Sawair Faleh A 
Published: October 2018

Objective To assess Jordanian dentists’ current perception and attitudes towards amalgam and composite restorations four years after the Minamata treaty was endorsed and suggest decision making factors that may influence the type of restoration requested by patients. Methods The cross-sectional study was conducted through structured questionnaires distributed to dentists in Amman, Jordan from June 2017 to February 2018. Results Of the 1686 dentists who were contacted 758 dentists (response rate 45%) responded to the questionnaire either by email or via field visits. Jordanian dentists used more composite restorations than amalgam. Recurrent caries followed by fracture of the restoration were the main reasons for replacement of both fillings by dentists. However, dentists suggested that the main reason patients requested replacement of amalgam was for ‘staining’. In addition, a large proportion of the dentists had experienced patients who had asked either for replacement of amalgam (77%) or refused an amalgam filling (99%) for aesthetic reasons. In the opinion of the dentists, only 20% patients requested replacement of amalgam because of the mercury content. Conclusion The findings of this survey suggest that a ‘phase-down’ of dental amalgam is being implemented in Jordan's dental clinics but it is not associated with commitment to the Minamata Convention, rather to current dental practice trends and patients’ aesthetic demands.
Emergency Department Presentations and Youth Suicide: A Case-Control Study
Authors: Rhodes Anne E. , Sinyor Mark , Boyle Michael H. , Bridge Jeffrey A. , Katz Laurence Y. , Bethell Jennifer , Newton Amanda S. , Cheung Amy , Bennett Kathryn , Links Paul S. , Tonmyr Lil , Skinner Robin 
Published: October 2018

Objective: We estimate associations between emergency department (ED) diagnoses and suicide among youth to guide ED care. Method: This ED-based case-control study used data from the Office of the Chief Coroner and all EDs in Ontario, Canada. Cases ( n = 697 males and n = 327 females) were aged 10 to 25 years who died by suicide in Ontario between April 2003 and March 2014, with an ED contact in the year before their death. Same-aged ED-based controls were selected during this time frame. Crude and adjusted odds ratios (aORs) and 95% confidence intervals were calculated. Results: Among youth diagnosed with a mental health problem at their most recent ED contact (41.9% cases, 5% controls), suicide was elevated among nonfatal self-inflicted: ‘other’ injuries, including hanging, strangulation, and suffocation in both sexes (aORs > 14); cut/pierce injuries in males (aOR > 5); poisonings in both sexes (aORs > 2.2); and mood and psychotic disorders in males (aORs > 1.7). Among those remaining, ‘undetermined’ injuries and poisonings in both sexes (aORs > 5), ‘unintentional’ poisonings in males (aOR = 2.1), and assault in both sexes (aORs > 1.8) were significant. At least half of cases had ED contact within 106 days. Conclusions: The results highlight the need for timely identification and treatment of mental health problems. Among those with an identified mental health problem, important targets for suicide prevention efforts are youth with self-harm and males with mood and psychotic disorders. Among others, youth with unintentional poisonings, undetermined events, and assaults should raise concern.
Systemic lupus erythematosus is a risk factor for cardiovascular disease: a nationwide, population-based study in Korea
Authors: Lim S Y , Bae E H , Han K-D , Jung J-H , Choi H S , Kim HY , Kim C S , Ma S K , Kim S W 
Published: October 2018

Objective To investigate the incidence and clinical significance of cardiovascular disease in systemic lupus erythematosus patients. Methods We included systemic lupus erythematosus patients ( n = 18,575) without previous cardiovascular disease and age- and sex-matched individuals without systemic lupus erythematosus (controls; n = 92,875) from the Korean National Health Insurance Service database (2008–2014). Both cohorts were followed up for incident cardiovascular disease and death until 2015. Results During follow up, myocardial infarction occurred in 203 systemic lupus erythematosus patients and 325 controls (incidence rate: 1.76 and 0.56 per 1000 person-years, respectively), stroke occurred in 289 patients and 403 controls (incidence rate: 2.51 and 0.70 per 1000 person-years, respectively), heart failure occurred in 358 patients and 354 controls (incidence rate 3.11 and 0.61 per 1000 person-years, respectively), and death occurred in 744 patients and 948 controls (incidence rate 6.54 and 1.64 per 1000 person-years, respectively). Patients with systemic lupus erythematosus had higher risks for myocardial infarction (hazard ratio: 2.74, 95% confidence interval: 2.28–3.37), stroke (hazard ratio: 3.31, 95% confidence interval: 2.84–3.86), heart failure (hazard ratio: 4.60, 95% confidence interval: 3.96–5.35), and cardiac death (hazard ratio: 3.98, 95% confidence interval: 3.61–4.39). Conclusions Here, systemic lupus erythematosus was an independent risk factor for cardiovascular disease, thus cardiac assessment and management are critical in systemic lupus erythematosus patients.
Characteristics, diagnoses, illness course and risk profiles of inpatients admitted for at least 21 days to an Australian private psychiatric hospital
Authors: Keks Nicholas A , Hope Judy , Pring William , Damodaran Saji , Varma Shashjit , Adamopoulos Voula 
Published: October 2018

Objectives: To perform a clinical and risk audit of private hospital inpatients staying in hospital at least 21 days. Methods: Of 492 admissions for ≥21 days in 2016, 40 were randomly selected for audit. Characteristics, illness severity and course using the Clinical Global Impression severity (CGI-S) subscale and improvement (CGI-I) subscale, and clinical risk profiles were ascertained at admission, day 15 and discharge by two psychiatrists. Results: The cases were 65% female, age 50.0±16.2 years (range 24–86), 43% in relationships, and 28% on disability support. The length of stay was 29±7 days. On admission 88% were severely or markedly ill on the CGI-S subscale. Thirty-nine of 40 cases had ≥3 psychiatric diagnoses: 93% depression, 48% bipolar, 15% schizophrenia. High risk was present in suicide risk (48%), illness-induced dysfunction risk (78%) and physical risk (28%). By day 15, 63% were not improved or marginally worse. Suicide ratings were unimproved. By the time of discharge, illness severity and risk ratings were significantly reduced. Conclusion: Private hospital inpatients staying ≥21 days were predominantly female and had severe, diagnostically complex illnesses and high risk ratings. Most were still seriously unwell after 15 days. Patients improved significantly by the time of discharge (though were by no means recovered), indicating that the duration of hospitalisation was appropriate.
Retrospective analysis of effects of sodium-glucose co-transporter 2 inhibitor in Japanese type 2 diabetes mellitus patients with chronic kidney disease
Authors: Kobayashi Kazuo , Toyoda Masao , Kimura Moritsugu , Hatori Nobuo , Furuki Takayuki , Sakai Hiroyuki , Takihata Masahiro , Umezono Tomoya , Ito Shun , Suzuki Daisuke , Takeda Hiroshi , Kanamori Akira , Degawa Hisakazu , Yamamoto Hareaki , Machimura Hideo , Mokubo Atsuko , Chin Keiichi , Obana Mitsuo , Hishiki Toshimasa , Aoyama Kouta , Nakajima Shinichi , Umezawa Shinichi , Shimura Hidetoshi , Aoyama Togo , Sato Kazuyoshi , Miyakawa Masaaki 
Published: October 2018

Aim: The aim of this study was to assess the renal effects of the glucose-lowering SGLT2 inhibitors in Japanese type 2 diabetes mellitus patients with chronic kidney disease. Methods: The Kanagawa Physicians Association maintains a registry of patients who visit their 31 clinics. Clinical data of type 2 diabetes mellitus patients with chronic kidney disease, who were prescribed SGLT2 inhibitors in addition to other treatments, were collected and analysed. Results: SGLT2i was associated with a fall in HbA1c from 64.1 ± 16.7 mmol/mol (8.0 ± 1.5%) to 56.5 ± 12.9 mmol/mol (7.3 ± 1.2%) ( p < 0.01) in 869 analysed cases, a decrease in urine albumin-creatinine ratio from a median of 47.1 to 41.1 mg/gCr, and decrease in estimated glomerular filtration rate from 77.7 ± 23.9 to 75.0 ± 23.9 mL/min/1.73 m2 ( p < 0.01). The effect on albumin-creatinine ratio was independent of age or stage of estimated glomerular filtration; however, there was a significant negative correlation between albumin-creatinine ratio at the initiation of SGLT2 inhibitor and change in ACR. Multiple linear regression analysis identified use of empagliflozin, β-blockers, and sulphonylureas, Δsystolic blood pressure at office, serum Cr and albumin-creatinine ratio value at initiation of SGLT2 inhibitor as independent and significant determinants of change in ACR. Conclusions: This study confirmed that the beneficial renal effects of SGLT2 inhibitor in Japanese type 2 diabetes mellitus patients with chronic kidney disease, similar to those reported in large-scale clinical trials conducted in Western countries.
What are the determinants of a concerned vision of the future when living with type 2 diabetes? Results from the E3N-AfterDiab study
Authors: Fagherazzi Guy , Chambraud Clélia , Dow Courtney , Mancini Francesca Romana , Affret Aurélie , Balkau Beverley , Magliano Dianna J , Boutron-Ruault Marie-Christine , Bonnet Fabrice 
Published: October 2018

Objectives Identification of characteristics associated with a negative experience with type 2 diabetes may help to develop novel intervention to improve the outlook of people with the disease. Our aim was to identify determinants of a self-reported concerned vision about the future when living with type 2 diabetes. Methods In 2630 women with type 2 diabetes from the E3N-AfterDiab study, we used multivariable logistic regression models to derive odds-ratios and 95% confidence intervals. Results Women with elevated HbA1c levels (OR = 2.42 (1.67–3.49) for ≥7.2% when compared to <6.2%), or treated with injected glucose lowering treatments (OR = 1.37 [1.05–1.81]) had a higher risk of a concerned vision of the future. Age and obesity were associated with a decreased risk. Hypertension, duration of diabetes, smoking, fasting glucose levels, and years of education were not associated with a concerned vision of the future. Discussion Our findings highlight the importance of both glycemic control and the type of treatment on the perception of the future when living with type 2 diabetes. Subgroups of patients based on these characteristics may receive a specific attention from healthcare professionals to address potential concerns related with diabetes management or the fear of complications.