bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality and quality of death certification in a cohort of patients with Parkinson’s disease and matched controls in North Wales, UK at 18 years: a community-based cohort study
Authors: Hobson Peter , Meara Jolyon
Published: February 2018

Objective

This investigation reports the cause and the quality of death certification in a community cohort of patients with Parkinson’s disease (PD) and controls at 18 years.

Setting

Denbighshire North Wales, UK.

Participants

The community-based cohorts consisted of 166 patients with PD and 102 matched controls.

Primary outcomes

All-cause mortality was ascertained at 18 years by review of hospitals’ primary care records and examination of death certificates obtained from the UK General Register Office. Mortality HRs were estimated using Cox proportional regression, controlling for covariates including age at study entry, age at death, gender, motor function, mood, health-related quality of life (HRQoL) and cognitive function.

Results

After 18 years, 158 (95%) of patients in the PD cohort and 34 (33%) in the control cohort had died. Compared with the general UK population, the PD cohort had a higher risk of mortality (standard mortality rate, 1.82, 95% CI 1.55 to 2.13). As the primary or underlying cause of death, PD was not reported in 75/158 (47%) of the death certificates. In addition, although 144/158 (91%) of the PD cohort had a diagnosis of dementia, this was reported in less than 10% of death certificates. The main cause of death reported in the PD cohort was pneumonia (53%), followed by cardiac-related deaths (21%). Compared with controls, patients with PD had a greater risk of pneumonia (2.03, 95% CI 1.34 to 3.6), poorer HRQoL and more likely to reside in institutional care at death (P<0.01).

Conclusion

This investigation found that PD was associated with an excess risk of mortality compared with the general population. However, PD as a primary or underlying cause of death recorded on certificates was found to be suboptimal. This suggests that the quality of mortality statistics drawn from death certificates alone is not a valid or reliable source of data.
Longitudinal changes in intraocular pressure and association with systemic factors and refractive error: Lingtou Eye Cohort Study
Authors: Han Xiaotong , Yang Tangjian , Zhang Jian , Yu Sha , Guo Xinxing , Yan William , Hu Yin , He Mingguang
Published: February 2018

Objectives

To investigate the longitudinal changes in intraocular pressure (IOP) and its associations with refractive error and systemic determinants in a Chinese geriatric population.

Design

Prospective cohort study.

Setting

Guangzhou Government Servant Physical Check-up Center, Guangzhou, China.

Participants

4413 government employees aged no less than 40 years (41.9% female) attending annual physical and eye examinations were included in this study. The inclusion criterion was having attended the 2010 follow-up examination. The exclusion criteria include glaucoma or intraocular surgery history, IOP >21 mm Hg at any visit or without available IOP data at all visits from 2010 to 2014.

Primary and secondary outcome measures

The outcome measure was IOP at each follow-up visit from 2010 to 2014. Mixed-effect model was used to assess the relationship between longitudinal changes in IOP and potential risk factors.

Results

For the 2653 participants who had available IOP data at both the 2010 and 2014 follow-up visits, the average change in IOP was an increase of 0.43 (95% CI 0.36 to 0.50) mm Hg. For the whole study population and in the optimised mixed model, there was a non-linear increase of IOP with age (P<0.001), with greater changes in younger subjects and in women (P<0.001 and P=0.002, respectively). Elevations in systolic blood pressure, diastolic blood pressure, body mass index (BMI) and fasting plasma glucose (FPG), as well as a myopic shift (all with P<0.001), during the follow-up were associated with an increasing trend of IOP, while serum lipids were found to be not significantly associated.

Conclusions

In this cohort of elderly Chinese adults, IOP increases non-linearly with ageing. People with increasing blood pressure, BMI, FPG and myopic progression are more likely to have IOP elevation over time.
Task sharing to improve the prevention, diagnosis and management of rheumatic heart disease: a systematic review protocol
Authors: Abdullahi Leila Hussein , Smit Inge , Engel Mark E , Watkins David A , Zühlke Liesl Joanna
Published: February 2018

Introduction

Rheumatic heart disease (RHD) remains an important cause of cardiovascular morbidity and mortality globally due to weak health systems in many countries. RHD can be effectively prevented and managed; however, RHD-related interventions have not been widely adopted in countries with severe human resource constraints. Task sharing is a recognised approach to personnel shortages that could prove effective for RHD and has, anecdotally, been attempted in a few settings. We propose a systematic review and meta-analysis protocol to assess models that use non-physician workers to expand access to, and quality of, RHD-related healthcare.

Methods

We will include randomised controlled trials (RCT), cluster RCTs, quasi-experimental and controlled before and after studies providing information on the effectiveness of non-physician workers in providing care for streptoccocal pharyngitis, rheumatic fever and RHD. We will search relevant electronic databases and grey literature using medical subject headings. Standardised data extraction forms will be used to collect effect sizes that will be pooled in random-effects models. We will also conduct subgroup analyses and note other important quantitative findings, such as cost reduction, and qualitative findings, such as patient satisfaction. We will also assess study quality and risk of bias and metabias.

Ethics and dissemination

Ethics approval is not required for this systematic review of previously published literature. The results of the systematic review will be broadly disseminated via conference presentations, multidisciplinary workshops and peer-reviewed publications.

PROSPERO registration number

CRD42017072989.
Randomised controlled pragmatic clinical trial evaluating the effectiveness of a discharge follow-up phone call on 30-day hospital readmissions: balancing pragmatic and explanatory design considerations
Authors: Yiadom Maame Yaa A B , Domenico Henry , Byrne Daniel , Hasselblad Michele Marie , Gatto Cheryl L , Kripalani Sunil , Choma Neesha , Tucker Sarah , Wang Li , Bhatia Monisha C , Morrison Johnston , Harrell Frank E , Hartert Tina , Bernard Gordon
Published: February 2018

Introduction

Hospital readmissions within 30 days are a healthcare quality problem associated with increased costs and poor health outcomes. Identifying interventions to improve patients’ successful transition from inpatient to outpatient care is a continued challenge.

Methods and analysis

This is a single-centre pragmatic randomised and controlled clinical trial examining the effectiveness of a discharge follow-up phone call to reduce 30-day inpatient readmissions. Our primary endpoint is inpatient readmission within 30 days of hospital discharge censored for death analysed with an intention-to-treat approach. Secondary endpoints included observation status readmission within 30 days, time to readmission, all-cause emergency department revisits within 30 days, patient satisfaction (measured as mean Hospital Consumer Assessment of Healthcare Providers and Systems scores) and 30-day mortality. Exploratory endpoints include the need for assistance with discharge plan implementation among those randomised to the intervention arm and reached by the study nurse, and the number of call attempts to achieve successful intervention delivery. Consistent with the Learning Healthcare System model for clinical research, timeliness is a critical quality for studies to most effectively inform hospital clinical practice. We are challenged to apply pragmatic design elements in order to maintain a high-quality practicable study providing timely results. This type of prospective pragmatic trial empowers the advancement of hospital-wide evidence-based practice directly affecting patients.

Ethics and dissemination

Study results will inform the structure, objective and function of future iterations of the hospital’s discharge follow-up phone call programme and be submitted for publication in the literature.

Trial registration number

NCT03050918; Pre-results.
Evaluation of California’s ‘Tobacco 21’ law
Authors: Zhang Xueying , Vuong Tam D , Andersen-Rodgers Elizabeth , Roeseler April
Published: February 2018

Introduction

California’s law raising the minimum tobacco sales age to 21 went into effect on 9 June 2016. This law, known as ‘Tobacco 21’ or ‘T21’, also expanded the definition of tobacco to include electronic smoking devices. This paper describes the T21 evaluation plan and initial evaluation results.

Methods

An evaluation plan and logic model were created to evaluate T21. A tobacco retailer poll was conducted 7 months after the law went into effect to assess awareness, support and implementation; an online survey of California adults was fielded to provide data on tobacco use and attitudinal changes before and after T21 implementation; and tobacco purchase surveys were conducted to assess the retailer violation rate (RVR). Multivariate models estimated the odds of RVR and odds of being aware, agreeing with and observing advertisements related to T21.

Results

Seven months after the T21 effective date, 98.6% of retailers were aware of the law and 60.6% supported the law. Furthermore, 66.2% of retailers agreed that people who start smoking before 21 would become addicted to tobacco products. The RVR using youth decoys under age 18 statistically decreased from 10.3% before T21 to 5.7% after T21 (P=0.002). Furthermore, the RVR using young adult decoys ages 18–19 was 14.2% (95% CI 9.3% to 19.1%) for traditional tobacco and 13.1% (95% CI 10.2% to 16.1%) for electronic smoking devices.

Conclusions

Survey findings suggest that the high awareness and support for the law may have contributed to reducing illegal tobacco sales to youth under 18 and achieving widespread retailer conformity with the new law disallowing sales to young adults under 21.
Morphology and longevity of different-order fine roots in poplar (Populus×euramericana) plantations with contrasting forest productivities
Authors: Zhu Wanrui , Sang Ya Lin , Zhu Qiliang , Duan Baoli , Wang Yanping
Published: February 2018

Fine roots play important roles in the allocation of forest net primary productivity. Here, to provide insights into the intrinsic and extrinsic factors affecting the root growth, we examined the morphology and longevity of different-order fine roots in two poplar (Populus × euramericana (Dode) Guinier) plantations with contrasting forest productivities. The results indicated that the biomass of fine roots decreased significantly as the root orders increased (P < 0.05). In the plantation with relatively high productivity, the specific root length of the first- and second-order roots was significantly greater than that of the third- to fifth-order roots (P < 0.05). Observations of minirhizotrons showed that roots of the third-order and higher lived longer than the first- and second-order roots. Compared with those in the plantation with relatively low productivity, the cumulative survival rate of the first-order roots was significantly higher in the plantation with relatively high productivity, while that of the third-order or higher roots was lower. The life-span of the first-order roots correlated negatively with soil available inorganic nitrogen, while that of the second-order roots correlated positively with the soil phenolic acid content. A Cox proportional hazards analysis revealed that soil conditions, root orders, season of root birth, and soil depth significantly affected fine-root longevity. These findings suggest that roots of different orders contribute unequally to the poplar plantation productivity.
Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations
Authors: Oh Dool-Ri , Kim Yujin , Choi Eun-Jin , Jung Myung-A , Oh Kyo-Nyeo , Hong Ji-Ae , Bae Donghyuck , Kim Kwangsu , Kang Huwon , Kim Jaeyong , Kim Young Ran , Cho Seung Sik , Choi Chul-Young
Published: February 2018

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT-induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT[Formula: see text] receptor.
Investigation of different physical aspects such as structural, mechanical, optical properties and Debye temperature of Fe2ScM (M=P and As) semiconductors: A DFT-based first principles study
Authors: Ali Md. Lokman , Rahaman Md. Zahidur
Published: February 2018

By using first principles calculation dependent on the density functional theory (DFT), we have investigated the mechanical, structural properties and the Debye temperature of Fe2ScM (M=P and As) compounds under various pressures up to 60 GPa. The optical properties have been investigated under zero pressure. Our calculated optimized structural parameters of both the materials are in good agreement with other theoretical predictions. The calculated elastic constants show that Fe2ScM (M=P and As) compounds are mechanically stable under external pressure below 60 GPa. From the elastic constants, the shear modulus G, the bulk modulus B, Young’s modulus E, anisotropy factor A and Poisson’s ratio [Formula: see text] are calculated by using the Voigt–Reuss–Hill approximation. The Debye temperature and average sound velocities are also investigated from the obtained elastic constants. The detailed analysis of all optical functions reveals that both compounds are good dielectric material.
Performance Analysis of Handover Schemes in Heterogeneous Networks
Authors: Bagubali A. , Verma Tanmay , Anand Anurag , Prithiviraj V. , Mallick P. S.
Published: February 2018

Internet protocol (IP)-based mobile systems are ushering new and faster technologies in wireless mobile networking. Therefore, the expectations from these network services with respect to data transfer rate and quality of service (QoS) are high. As such, meeting these requirements is the recent trend in modern wireless technologies. An important aspect regarding such improvements is the modification of handoff schemes between different networks. In this paper, we are focusing on the recent trends based on seamless handoff scheme in heterogeneous networks such as worldwide interoperability for microwave access (WiMAX) and long term evolution (LTE). The development of the session initiation protocol (SIP) Prior-INVITE scheme is an improvement on the earlier used SIP Re-INVITE method, which comes a long way in decreasing the average handoff delay. The performance analysis using software simulation on account of various parameters, such as handoff delay, cost of signaling and packet loss rate are accomplished in this work. The performance analysis demonstrates that the proposed scheme outperforms the ordinary cross-layer scheme and noncross-layer scheme in a vertical handover scenario.
A Low-Power Ring Oscillator with Temperature Compensation for IR-UWB Applications
Authors: Sakka Zied , Gargouri Nadia , Samet Mounir
Published: February 2018

This paper presents a 4[Formula: see text]GHz low-power ring oscillator with supply and temperature compensation for use in impulse-radio ultra-wideband (IR-UWB) applications. Simulations using TSMC 0.18[Formula: see text][Formula: see text]m CMOS technology show that this configuration is able to achieve a 94.87% reduction in the variation of the center frequency of the uncompensated VCO and 25[Formula: see text]ppm/[Formula: see text]C temperature stability. Monte Carlo simulations have also been performed, and demonstrate a 3[Formula: see text] deviation of about 7.26%. The power for the proposed circuit is only 4.5[Formula: see text]mW at 27[Formula: see text]C.
2017 update of the discoveries of nuclides
Authors: Thoennessen M.
Published: February 2018

The 2017 update of the discovery of nuclide project is presented. 34 new nuclides were observed for the first time in 2017. However, the assignment of six previously identified nuclides had to be retracted.
Is combined CBT therapy more effective than drug therapy alone for ADHD in children? A meta-analysis
Authors: Ding Qiang , Li Mengyao , Zhu Daqian
Published: February 2018

Based on published research on the combined cognitive behavioral therapy (CBT) versus drug therapy alone in children with attention deficit/hyperactivity disorder (ADHD), we systematically reviewed and analyzed the efficacy of two treatment methods in children with ADHD. The literature as at the end of 10 July 2017 in multiple databases was systematically searched. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated. The results indicated that combined CBT therapy was efficacious in reducing symptoms of ADHD (SDM [Formula: see text]0.48, 95% CI [Formula: see text]0.80 to [Formula: see text]0.17). The executive function scores were not improved more in the combined CBT (SMD [Formula: see text]0.34; 95% CI [Formula: see text]0.71 to 0.03). This study suggests that combined CBT seems more efficacious in some domains affecting children with ADHD, but further evaluation is needed.
Alamandine acts via MrgD to induce AMPK/NO activation against ANG II hypertrophy in cardiomyocytes
Authors: Jesus Itamar Couto Guedes de , Scalzo Sérgio , Alves Fabiana , Marques Kariny , Rocha-Resende Cibele , Bader Michael , Santos Robson A. Souza , Guatimosim Silvia
Published: February 2018

The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. New members of this system have been characterized and shown to have biologically relevant actions. Alamandine and its receptor MrgD are recently identified components of RAS. In the cardiovascular system, alamandine actions included vasodilation, antihypertensive, and antifibrosis effects. Currently, the actions of alamandine on cardiomyocytes are unknown. Here our goal was twofold: 1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; and 2) to evaluate the ability of this axis to prevent angiotensin II (ANG II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by d-Pro7-ANG-(1–7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine-induced NO production was preserved in Mas−/− myocytes and lost in MrgD−/− cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD−/− myocytes. We also assessed the consequences of prolonged alamandine exposure to cultured neonatal rat cardiomyocytes (NRCMs) treated with ANG II. Treatment of NRCMs with alamandine prevented ANG II-induced hypertrophy. Moreover, the antihypertrophic actions of alamandine were mediated via MrgD and NO, since they could be prevented by d-Pro7-ANG-(1–7) or inhibitors of NO synthase or AMPK. β-Alanine, a MrgD agonist, recapitulated alamandine’s cardioprotective effects in cardiomyocytes. Our data show that alamandine via MrgD induces AMPK/NO signaling to counterregulate ANG II-induced hypertrophy. These findings highlight the therapeutic potential of the alamandine/MrgD axis in the heart.
Erythropoietin, a putative neurotransmitter during hypoxia, is produced in RVLM neurons and activates them in neonatal Wistar rats
Authors: Oshima Naoki , Onimaru Hiroshi , Yamagata Akira , Itoh Seigo , Matsubara Hidehito , Imakiire Toshihiko , Nishida Yasuhiro , Kumagai Hiroo
Published: February 2018

Recent studies indicate that erythropoietin (EPO) is present in many areas of the brain and is active in the restoration of impaired neurons. In this study, we examined the presence of EPO and its role in bulbospinal neurons in the rostral ventrolateral medulla (RVLM). Hypoxia is often accompanied by a high blood pressure (BP). We hypothesized that EPO is produced in response to hypoxia in RVLM neurons and then activates them. To investigate whether RVLM neurons are sensitive to EPO, we examined the changes in the membrane potentials (MPs) of bulbospinal RVLM neurons using the whole cell patch-clamp technique during superfusion with EPO. A brainstem-spinal cord preparation was used for the experiments. EPO depolarized the RVLM neurons, and soluble erythropoietin receptor (SEPOR), an antagonist of EPO, hyperpolarized them. Furthermore, hypoxia-depolarized RVLM neurons were significantly hyperpolarized by SEPOR. In histological examinations, the EPO-depolarized RVLM neurons showed the presence of EPO receptor (EPOR). The RVLM neurons that possessed EPORs showed the presence of EPO and hypoxia-inducible factor (HIF)-2α. We also examined the levels of HIF-2α and EPO messenger RNA (mRNA) in the ventral sites of the medullas (containing RVLM areas) in response to hypoxia. The levels of HIF-2α and EPO mRNA in the hypoxia group were significantly greater than those in the control group. These results suggest that EPO is produced in response to hypoxia in RVLM neurons and causes a high BP via the stimulation of those neurons. EPO may be one of the neurotransmitters produced by RVLM neurons during hypoxia.
VEGF therapy for the kidney: emerging strategies
Authors: Guise Erika , Chade Alejandro R.
Published: February 2018

Renovascular disease (RVD), which is prevalent in the elderly, significantly increases cardiovascular risk and can progressively deteriorate renal function. The loss of renal function in patients with RVD is associated with a progressive dysfunction, damage, and loss of renal microvessels, which can be combined with decreased renal bioavailability of vascular endothelial growth factor (VEGF) and a defective vascular repair and proliferation. This association has been the impetus for recent efforts that have focused on developing methods to stop the progression of renal injury by protecting the renal microvasculature. This mini-review focuses on recent studies supporting potential applications of VEGF therapy for the kidney and discusses underlying mechanisms of renoprotection.
Neurogenesis: remembering all or forgetting some
Authors: Goodwin Shikha Jain
Published: February 2018

Research over the last 20 years has begun to elucidate the importance of adult neurogenesis in cognition. Three studies recently asked what might be happening to memories formed before neurogenesis in the hippocampus (Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro A, Hsiang HL, Wheeler AL, Guskjolen A, Niibori Y, Shoji H, Ohira K, Richards BA, Miyakawa T, Josselyn SA, Frankland PW. Science 344: 598–602, 2014; Epp JR, Silva Mera R, Köhler S, Josselyn SA, Frankland PW. Nat Commun 7: 10838, 2016; Kodali M, Megahed T, Mishra V, Shuai B, Hattiangady B, Shetty AK. J Neurosci 36: 8112–8122, 2016). These studies found conflicting results: running (which increases neurogenesis) induced forgetting in two studies, but there was no difference in memory retrieval after exercise in another. To reconcile these studies, one must understand the processes behind memory maintenance and recall and consider context, species, and other factors.
Neutrophils Release Metalloproteinases during Adhesion in the Presence of Insulin, but Cathepsin G in the Presence of Glucagon
Authors: Fedorova Natalia V. , Ksenofontov Alexander L. , Serebryakova Marina V. , Stadnichuk Vladimir I. , Gaponova Tatjana V. , Baratova Ludmila A. , Sud’ina Galina F. , Galkina Svetlana I.
Published: February 2018

In patients with reperfusion after ischemia and early development of diabetes, neutrophils can attach to blood vessel walls and release their aggressive bactericide agents, which damage the vascular walls. Insulin and 17β-estradiol (E2) relieve the vascular complications observed in metabolic disorders. In contrast, glucagon plays an essential role in the pathophysiology of diabetes. We studied the effect of hormones on neutrophil secretion during adhesion to fibronectin. Amino acid analysis revealed that proteins secreted by neutrophils are characterized by a stable amino acid profile enriched with glutamate, leucine, lysine, and arginine. The total amount of secreted proteins defined as the sum of detected amino acids was increased in the presence of insulin and reduced in the presence of glucagon. E2 did not affect the amount of protein secretion. Proteome analysis showed that in the presence of insulin and E2, neutrophils secreted metalloproteinases MMP-9 and MMP-8 playing a key role in modulation of the extracellular matrix. In contrast, glucagon induced the secretion of cathepsin G, a key bactericide protease of neutrophils. Cathepsin G can promote the development of vascular complications because of its proinflammatory activity and ability to stimulate neutrophil adhesion via the proteolysis of surface receptors.
Performance of Geosynthetic‐Reinforced and Cement‐Fly Ash‐Gravel Pile‐Supported Embankments over Completely Decomposed Granite Soil: A Case Study
Authors: Wu Lijun
Published: February 2018

This paper presents a full‐scale test of the high‐speed railway embankment to investigate the performance of cement‐fly ash‐gravel (CFG) pile‐supported embankments over completely decomposed granite (CDG) soils. The authors compared the embankments built on CDG soils reinforced by geogrid only and geogrid and CFG piles in terms of ground settlement, layer settlement, and pile efficacy. Experimental results show that the CFG pile‐supported embankment built on CDG soils performs well. The soil arching of CFG piled reinforcement is effective and significantly increases with surrounding soil consolidation. Furthermore, the increase in the soil arching effect is heavily dependent on differential settlements between surrounding soils and piles. Five methods widely adopted in current designing were used to calculate the pile efficacy. The prediction for pile efficacy by the Nordic method, BS8006, and its modified version is significantly higher than measured values. By contrast, the calculation by the EBGEO and CA model method is more approximate to the measured results in both the pattern and the value at the end of construction. Therefore, the adaptability of the EBGEO and CA model method outperformed that of the Nordic method, BS8006, and its modified version. Finally, in this case, the CA model method was recommended to estimate the pile efficacy of CFG pile‐supported embankments built on CDG soils.
Improved Unsupervised Color Segmentation Using a Modified HSV Color Model and a Bagging Procedure in K-Means++ Algorithm
Authors: Chavolla Edgar , Valdivia Arturo , Diaz Primitivo , Zaldivar Daniel , Cuevas Erik , Perez Marco A.
Published: February 2018

Accurate color image segmentation has stayed as a relevant topic between the researches/scientific community due to the wide range of application areas such as medicine and agriculture. A major issue is the presence of illumination variations that obstruct precise segmentation. On the other hand, the machine learning unsupervised techniques have become attractive principally for the easy implementations. However, there is not an easy way to verify or ensure the accuracy of the unsupervised techniques; so these techniques could lead to an unknown result. This paper proposes an algorithm and a modification to the HSV color model in order to improve the accuracy of the results obtained from the color segmentation using the K-means++ algorithm. The proposal gives better segmentation and less erroneous color detections due to illumination conditions. This is achieved shifting the hue and rearranging the H equation in order to avoid undefined conditions and increase robustness in the color model.
Sarcoid-Like Mediastinal Lymphadenopathy in Gynecologic Malignancy
Authors: Lashari Bilal H. , Asai Megumi , Randleman Gissele , Sack Martha , Patel Rajeshkumar
Published: February 2018

Noncaseating granulomas are seen surrounding tumors with varying frequency, possibly as part of an immune response to tumor cells. However, data about the association of sarcoid with gynecologic malignancy is sparse. We performed a search of our institutional database for all EBUS-TBNA biopsies conducted within the past five years that revealed granulomatous inflammation. All adult female patients with a history of gynecologic malignancy were included. Patients with a history of sarcoidosis or fungal or mycobacterial infection were excluded. All patients with evidence of malignant cells on TBNA specimen were excluded. Our results revealed 65 patients with histologic diagnosis of a noncaseating granuloma on EBUS-TBNA. Five patients (7.69%) had a history of gynecologic malignancy. Two patients had evidence of PET-positive nodes on surveillance scans, which led directly to the examination. Our findings suggest that distant malignancies may cause granulomatous lymphadenitis, through yet undefined mechanisms. As such, patients with evidence of mediastinal lymphadenopathy could benefit from routine sampling and histologic examination to define the pathology in the correct clinical context.
Energy-Aware VM Initial Placement Strategy Based on BPSO in Cloud Computing
Authors: Fu Xiong , Zhao Qing , Wang Junchang , Zhang Lin , Qiao Lei
Published: February 2018

In recent years, high energy consumption has gradually become a prominent problem in a data center. With the advent of cloud computing, computing and storage resources are bringing greater challenges to energy consumption. Virtual machine (VM) initial placement plays an important role in affecting the size of energy consumption. In this paper, we use binary particle swarm optimization (BPSO) algorithm to design a VM placement strategy for low energy consumption measured by proposed energy efficiency fitness, and this strategy needs multiple iterations and updates for VM placement. Finally, the strategy proposed in this paper is compared with other four strategies through simulation experiments. The results show that our strategy for VM placement has better performance in reducing energy consumption than the other four strategies, and it can use less active hosts than others.
Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML
Authors: Björklund Andreas T. , Carlsten Mattias , Sohlberg Ebba , Liu Lisa L. , Clancy Trevor , Karimi Mohsen , Cooley Sarah , Miller Jeffrey S. , Klimkowska Monika , Schaffer Marie , Watz Emma , Wikström Kristina , Blomberg Pontus , Wahlin Björn Engelbrekt , Palma Marzia , Hansson Lotta , Ljungman Per , Hellström-Lindberg Eva , Ljunggren Hans-Gustaf , Malmberg Karl-Johan
Published: February 2018

Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell–based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients.

Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2–activated haploidentical NK cells.

Results: NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients. Six patients achieved objective responses with complete remission (CR), marrow CR, or partial remission (PR). Five patients proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Three patients are still free from disease >3 years after treatment. All evaluable patients with objective responses (5/5 evaluable) had detectable donor NK cells at days 7/14 following infusion and displayed reduction of tumor cell clones, some of which carried poor prognosis mutations. Residual lin−CD34+CD123+CD45RA+ blast cells in responders had increased total HLA class I and HLA-E expression. Responding patients displayed less pronounced activation of CD8+ T cells and lower levels of inflammatory cytokines following NK-cell infusion. Intriguingly, despite omission of systemic IL2, all patients displayed increased frequencies of activated Ki-67+CD127−FoxP3+CD25hiCD4+ Treg cells of recipient origin following NK-cell therapy.

Conclusions: Overall, this study suggests that high-risk MDS is responsive to NK-cell therapy and supports the use of haploidentical NK-cell infusions as a bridge to HSCT in refractory patients. Objective clinical responses and reduction of high-risk clones were associated with detectable donor-derived NK cells, immunoediting of residual blast cells, and less pronounced host immune activation. Clin Cancer Res; 24(8); 1834–44. ©2018 AACR.
NEO212 Inhibits Migration and Invasion of Glioma Stem Cells
Authors: Marín-Ramos Nagore I. , Thein Thu Zan , Cho Hee-Yeon , Swenson Stephen D. , Wang Weijun , Schönthal Axel H. , Chen Thomas C. , Hofman Florence M.
Published: February 2018

Glioblastoma multiforme is a malignant brain tumor noted for its extensive vascularity, aggressiveness, and highly invasive nature, suggesting that cell migration plays an important role in tumor progression. The poor prognosis in GBM is associated with a high rate of tumor recurrence, and resistance to the standard of care chemotherapy, temozolomide (TMZ). The novel compound NEO212, a conjugate of TMZ and perillyl alcohol (POH), has proven to be 10-fold more cytotoxic to glioma stem cells (GSC) than TMZ, and is active against TMZ-resistant tumor cells. In this study, we show that NEO212 decreases migration and invasion of primary cultures of patient-derived GSCs, in both mesenchymal USC02 and proneural USC04 populations. The mechanism by which NEO212 reduces migration and invasion appears to be independent of its DNA alkylating effects, which cause cytotoxicity during the first hours of treatment, and is associated with a decrease in the FAK/Src signaling pathway, an effect not exhibited by TMZ. NEO212 also decreases the production of matrix metalloproteinases MMP2 and MMP9, crucial for GSC invasion. Gene expression analysis of epithelial and mesenchymal markers suggests that NEO212 increases the expression of epithelial-like characteristics, suggesting a reversion of the epithelial-to-mesenchymal transition process. Furthermore, in an in vivo orthotopic glioma model, NEO212 decreases tumor progression by reducing invasion of GSCs, thereby increasing survival time of mice. These studies indicate that NEO212, in addition to cytotoxicity, can effectively reduce migration and invasion in GSCs, thus exhibiting significant clinical value in the reduction of invasion and malignant glioma progression. Mol Cancer Ther; 17(3); 625–37. ©2018 AACR.
MI130004, a Novel Antibody–Drug Conjugate Combining Trastuzumab with a Molecule of Marine Origin, Shows Outstanding In Vivo Activity against HER2-Expressing Tumors
Authors: Avilés Pablo , Domínguez Juan Manuel , Guillén María José , Muñoz-Alonso María José , Mateo Cristina , Rodriguez-Acebes Raquel , Molina-Guijarro José Manuel , Francesch Andrés , Martínez-Leal Juan Fernando , Munt Simon , Galmarini Carlos M. , Cuevas Carmen
Published: February 2018

In the search for novel payloads to design new antibody–drug conjugates (ADC), marine compounds represent an interesting opportunity given their unique chemical features. PM050489 is a marine compound that binds β-tubulin at a new site and disrupts the microtubule network, hence leading to mitotic aberrations and cell death. PM050489 has been conjugated to trastuzumab via Cys residues through a noncleavable linker, and the resulting ADC, named MI130004, has been studied. Analysis of MI130004 delivered data consistent with the presence of two molecules of PM050489 per antibody molecule, likely bound to both sides of the intermolecular disulfide bond connecting the antibody light and heavy chains. The antitumor activity of MI130004 was analyzed in vitro and in vivo in different cell lines of diverse tumor origin (breast, ovary, and gastric cancer) expressing different levels of HER2. MI130004 showed very high in vitro potency and good selectivity for tumor cells that overexpressed HER2. At the cellular level, MI130004 impaired tubulin polymerization, causing disorganization and disintegration of the microtubule network, which ultimately led to mitotic failure, mirroring the effect of its payload. Treatment with MI130004 in mice carrying histologically diverse tumors expressing HER2 induced a long-lasting antitumor effect with statistically significant inhibition of tumor growth coupled with increases in median survival time compared with vehicle or trastuzumab. These results strongly suggest that MI130004 is endowed with remarkable anticancer activity and confirm the extraordinary potential of marine compounds for the design of new ADCs. Mol Cancer Ther; 17(4); 786–94. ©2018 AACR.
In Vitro and In Vivo Activity of IMGN853, an Antibody–Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers
Authors: Altwerger Gary , Bonazzoli Elena , Bellone Stefania , Egawa-Takata Tomomi , Menderes Gulden , Pettinella Francesca , Bianchi Anna , Riccio Francesco , Feinberg Jacqueline , Zammataro Luca , Han Chanhee , Yadav Ghanshyam , Dugan Katherine , Morneault Ashley , Ponte Jose F. , Buza Natalia , Hui Pei , Wong Serena , Litkouhi Babak , Ratner Elena , Silasi Dan-Arin , Huang Gloria S. , Azodi Masoud , Schwartz Peter E. , Santin Alessandro D.
Published: February 2018

Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. The in vitro cytotoxic activity and bystander effect were studied in primary uterine cancer cell lines expressing differential levels of FRα. In vivo antitumor efficacy of IMGN853 was evaluated in xenograft/patient-derived xenograft (PDX) models. Semiquantitative IHC analysis indicated that 41% of the USC patients overexpress FRα. Further, overexpression of FRα (i.e., 2+) was detected via flow cytometry in 22% (2/9) of primary endometrioid and in 27% (3/11) of primary USC cell lines. Increased cytotoxicity was seen with IMGN853 treatment compared with control in 2+ expressing uterine tumor cell lines. In contrast, tumor cell lines with low FRα showed no difference when exposed to IMGN853 versus control. IMGN853 induced bystander killing of FRα = 0 tumor cells. In an endometrioid xenograft model (END(K)265), harboring 2+ FRα, IMGN853 treatment showed complete resolution of tumors (P < 0.001). Treatment with IMGN853 in the USC PDX model (BIO(K)1), expressing 2+ FRα, induced twofold increase in median survival (P < 0.001). IMGN853 shows impressive antitumor activity in biologically aggressive FRα 2+ uterine cancers. These preclinical data suggest that patients with chemotherapy resistant/recurrent endometrial cancer overexpressing FRα may benefit from this treatment. Mol Cancer Ther; 17(5); 1003–11. ©2018 AACR.
Quercetin Therapy for Selected Patients with PIM1 Kinase-Positive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pilot Study
Authors: Baron Beverly W. , Thirman Michael J. , Giurcanu Mihai C. , Baron Joseph M.
Published: February 2018

We reported that PIM1 kinase is expressed in the lymphocytes of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Quercetin, a naturally occurring flavonoid, is a dietary supplement and inhibits many kinases, including PIM1, in vitro. Under an Institutional Review Board-approved protocol, we performed an open-label, single-arm pilot study to evaluate the antitumor activity of quercetin in patients with CLL/SLL. Q-ForceTM chews were administered orally, 500 mg twice daily, for 3 months. Eligible patients had failed prior therapies, had had no other standard treatment, or refused other therapies. Response was assessed based on objective change in disease parameters. Patients were included if their lymphocyte counts were rising and ≥10,000/µL but not > 100,000/µL. Three patients received quercetin treatment. There was no toxicity. Two responded with stabilization of rising lymphocyte counts (p < 0.001 for each), which remained stable during their follow-up (5 and 11 months after cessation of treatment, respectively). The CLL cells in the nonresponder harbored a TP53 mutation. Although our data from this pilot translational study are based on a small sample, further studies of quercetin as a potential therapeutic agent in selected patients with CLL/SLL appear warranted.
The Impact of Advanced Age on Driving Safety in Adults with Medical Conditions
Authors: Moon Sanghee , Ranchet Maud , Akinwuntan Abiodun Emmanuel , Tant Mark , Carr David Brian , Raji Mukaila Ajiboye , Devos Hannes
Published: February 2018

Background: Adults aged 85 and older, often referred to as the oldest-old, are the fastest-growing segment of the population. The rapidly increasing number of older adults with chronic and multiple medical conditions poses challenges regarding their driving safety. Objective: To investigate the effect of advanced age on driving safety in drivers with medical conditions. Methods: We categorized 3,425 drivers with preexisting medical conditions into four age groups: middle-aged (55–64 years, n = 1,386), young-old (65–74 years, n = 1,013), old-old (75–84 years, n = 803), or oldest-old (85 years and older, n = 223). All underwent a formal driving evaluation. The outcome measures included fitness to drive recommendation by the referring physician, comprehensive fitness to drive decision from an official driving evaluation center, history of motor vehicle crashes (MVCs), and history of traffic violations. Results: The oldest-old reported more cardiopulmonary and visual conditions, but less neurological conditions than the old-old. Compared to the middle-aged, the oldest-old were more likely to be considered unfit to drive by the referring physicians (odds ratio [OR] = 4.47, 95% confidence interval [CI] 2.20–9.10) and by the official driving evaluation center (OR = 2.74, 95% CI 1.87–4.03). The oldest-old reported more MVCs (OR = 2.79, 95% CI 1.88–4.12) compared to the middle-aged. Conclusion: Advanced age adversely affected driving safety outcomes. The oldest-old are a unique age group with medical conditions known to interfere with safe driving. Driving safety strategies should particularly target the oldest-old since they are the fastest-growing group and their increased frailty is associated with severe or fatal injuries due to MVCs.
Readmissions Following a Hospitalization for Cardiovascular Events in Dialysis Patients: A Retrospective Cohort Study
Authors: Wetmore James B. , Molony Julia T. , Liu Jiannong , Peng Yi , Herzog Charles A. , Collins Allan J. , Gilbertson David T.
Published: February 2018

Background

Hospitalization for cardiovascular disease (
CVD
) is common among patients receiving maintenance dialysis, but patterns of readmissions following cardiovascular events are underexplored.

Methods and Results

In this retrospective analysis of prevalent, Medicare‐eligible patients receiving dialysis in 2012–2013, all live‐discharge hospitalizations attributed to
CVD
were ascertained. Rates of all‐cause,
CVD
‐related, and non–
CVD
‐related readmissions and death in the ensuing 10 and 30 days were calculated. Multinomial logistic modeling was used to assess the relationship between potential explanatory factors and outcomes of interest. Among 142 210 analyzed hospitalizations, mean age at time of index
CVD
hospitalization was 64.9±14.1 years; 50.4% of index hospitalizations were for women, and 41.4% were for white patients. Fully 15.6% and 34.2% of
CVD
hospitalizations resulted in readmission within 10 and 30 days, respectively; less than half of readmissions were
CVD
related (42.5%, 10 days; 43.1%, 30 days). Death within 30 days, regardless of readmission, occurred after 4.5% of index hospitalizations; 51.2% were attributed to
CVD
. Compared with ages 65 to 69 years, younger age tended to be associated with increased readmission risk (adjusted relative risk for ages 18–44 years: 1.55; 95% confidence interval, 1.48–1.63). Readmission risk did not differ between white and black patients, but risk of death without readmission was markedly lower for black patients (relative risk: 0.60; 95% confidence interval, 0.55–0.67).

Conclusions

Roughly 1 in 3
CVD
hospitalizations resulted in 30‐day readmission; nearly 1 in 20 was followed by death within 30 days. Risk of death without readmission was higher for white than black patients, despite no difference in risk of readmission.