bluuebunny/crossref_metadata_2025 huggingface dataset:
Astatine
Authors: Meyer Geerd‐J
Published: October 2017

This educational review describes and summarizes the historic discovery of element 85, the experiments leading to its physical and chemical characterization and comparison with its lighter homologue iodine. The half‐lives of its longest living isotopes 210At and 211At with 8.3 and 7.22 hours respectively together with their alpha decay characteristics made these isotopes interesting for radiation biological research. However, the lack of stable isotopes of astatine presents a strong challenge for all characterizations. Nevertheless, the decay characteristics especially of 211At stimulated several research groups to develop labelling strategies for the preparation of astatinated radiopharmaceuticals for targeted alpha radiation therapy. Because of the distinct differences in the chemical behaviour of astatine, when compared with iodine, these approaches are quite challenging. Accordingly, quite different labelling strategies have been tested, namely nucleophilic and electrophilic substitution reactions as well as complex forming strategies. Classic and new developments for the preparation of these compounds are reviewed.
Probabilistic tractography‐based thalamic parcellation in healthy newborns and newborns with congenital heart disease
Authors: Jaimes Camilo , Cheng Henry H. , Soul Janet , Ferradal Silvina , Rathi Yogesh , Gagoski Borjan , Newburger Jane W. , Grant P. Ellen , Zöllei Lilla
Published: October 2017

Background

Given the central role of the thalamus in motor, sensory, and cognitive development, methods to study emerging thalamocortical connectivity in early infancy are of great interest.

Purpose

To determine the feasibility of performing probabilistic tractography‐based thalamic parcellation (PTbTP) in typically developing (TD) neonates and to compare the results with a pilot sample of neonates with congenital heart disease (CHD).

Study type

Institutional Review Board (IRB)‐approved cross‐sectional study.

Model

We prospectively recruited 20 TD neonates and five CHD neonates (imaged preoperatively).

Field Strength/Sequence

MRI was performed at 3.0T including diffusion‐weighted imaging (DWI) and 3D magnetization prepared rapid gradient‐echo (MPRAGE).

Assessment

A radiologist and trained research assistants segmented the thalamus and seven cortical targets for each hemisphere. Using the thalami as seeds and the cortical labels as targets, FSL library tools were used to generate probabilistic tracts. A Hierarchical Dirichlet Process algorithm was then used for clustering analysis. A radiologist qualitatively assessed the results of clustering. Quantitative analyses were also performed.

Statistical Tests

We summarized the demographic data and results of clustering with descriptive statistics. Linear regressions covarying for gestational age were used to compare groups.

Results

In 17 of 20 TD neonates, we identified five connectivity‐determined clusters, which correlate with known thalamic nuclei and subnuclei. In four neonates with CHD we observed a spectrum of abnormalities including fewer and disorganized clusters or small supernumerary clusters (up to seven per thalamus). After covarying for differences in corrected gestational age (cGA), the fractional anisotropy (FA), volume, and normalized thalamic volume were significantly lower in CHD neonates (P < 0.01).

Data Conclusions

Using PTbTP clusters, correlating well with the location and connectivity of known thalamic nuclei, were identified in TD neonates. Differences in thalamic clustering outputs were identified in four neonates with CHD, raising concern for disordered thalamic connectivity. PTbTP is feasible in TD and CHD neonates. Preliminary findings suggest the prenatal origins of altered connectivity in CHD.

Level of Evidence: 2

Technical Efficacy: Stage 4

J. Magn. Reson. Imaging 2018;47:1626–1637.
The unfolded protein response mediated by PERK is casually related to the pathogenesis of intervertebral disc degeneration
Authors: Fujii Takeshi , Fujita Nobuyuki , Suzuki Satoshi , Tsuji Takashi , Takaki Takashi , Umezawa Kazuo , Watanabe Kota , Miyamoto Takeshi , Horiuchi Keisuke , Matsumoto Morio , Nakamura Masaya
Published: October 2017

Although the number of patients with intervertebral disc (IVD) degeneration is increasing in aging societies, its etiology and pathogenesis remain elusive and there is currently no effective treatment to prevent this undesirable condition. The unfolded protein response (UPR) is a cellular machinery that plays critical roles in handling endoplasmic reticulum (ER) stress, a condition caused by the accumulation of unfolded proteins in the ER lumen. This study aimed to elucidate the potential role of the UPR mediated by pancreatic endoplasmic reticulum kinase (PERK), one of the major ER stress sensors in mammalian cells, in the development of IVD degeneration. IVD degeneration was artificially induced in Wister rats by percutaneously puncturing the coccyx IVDs and human IVDs were collected from patients who underwent spinal surgery. Expression of the UPR target genes was elevated in degenerative IVDs in both humans and rats. The induction of ER stress in annulus fibrosus cells significantly increased the transcripts for tumor necrosis factor alpha (TNF‐α) and interleukin 6 (IL‐6) in a nuclear factor (NF)‐κB pathway‐dependent manner. The expression of TNF‐α and IL‐6 was significantly reduced by treatment with a selective PERK inhibitor, GSK2606414, and by gene silencing against PERK and activating transcription factor 4 (ATF4) transcripts. Our findings indicate that the UPR mediated by the PERK pathway is causally related to the development of IVD degeneration, suggesting that PERK may be a potential molecular target for suppressing the degenerative changes in IVDs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1334–1345, 2018.
Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks
Authors: Francisco Vera , Pérez Tamara , Pino Jesús , López Verónica , Franco Eloy , Alonso Ana , Gonzalez‐Gay Miguel Angel , Mera Antonio , Lago Francisca , Gómez Rodolfo , Gualillo Oreste
Published: October 2017

Osteoarthritis is a high‐incidence painful and debilitating disease characterized by progressive degeneration of articular joints, which indicates a breakdown in joint homeostasis favoring catabolic processes. Biomechanical loading, associated with inflammatory and metabolic imbalances of joint, strongly contributes to the initiation and progression of the disease. Obesity is a primary risk factor for disease onset, and mechanical factors increased the risk for disease progression. Moreover, inflammatory mediators, in particular, adipose tissue‐derived cytokines (better known as adipokines) play a critical role linking obesity and osteoarthritis. The present article summarizes the knowledge about the role of adipokines in cartilage and bone function, highlighting their contribution to the imbalance of joint homeostasis and, consequently, pathogenesis of osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
36:594–604, 2018.
A static headspace GC‐MS/MS method for the determination of ethanol, iso‐butanol, and n‐butanol at nanomolar concentrations in aqueous environmental samples
Authors: Mead Ralph N. , Cala John M. , Felix J. David , Shimizu Megumi S. , Casas Matthew S. , Lathrope Thomas , Avery G. Brooks , Kieber Robert J. , Willey Joan D.
Published: October 2017

The increased use of small molecular weight alcohols such as ethanol and potentially butanol isomers as biofuels has raised questions about the fate of these compounds in the environment once emitted. In order to address these questions, a method for the simultaneous determination of nanomolar concentrations of ethanol, n‐butanol, and iso‐butanol in aqueous environmental matrices is presented. The method consists of static headspace gas chromatograph‐mass spectrometer/mass spectrometer (GC‐MS/MS) analysis with detection limits of 28 nM for ethanol and 9 nM for each butanol isomer. Accuracy of the new method was verified by comparing ethanol concentrations in authentic environmental samples by an independent technique utilizing solid phase microextraction (SPME). Results of an intercomparison study between the static headspace GC‐MS/MS and SPME analyses produced a trend line with a slope of unity demonstrating that the methods produced statistically equivalent ethanol concentrations. Spiked additions of each alcohol in a variety of aqueous environmental matrices gave recoveries greater than 90% validating the accuracy of the headspace GC‐MS/MS analysis. The new static headspace GC‐MS/MS analysis represents the first methodology available with demonstrated accuracy in an array of environmental matrices with the requisite limit of detection capable of quantifying several alcohols in one analysis with minimal sample preparation and sample size requirement.
Technical Note: On the efficiency of variance reduction techniques for Monte Carlo estimates of imaging noise
Authors: Sharma Diksha , Sempau Josep , Badano Aldo
Published: October 2017

Purpose

Monte Carlo simulations require large number of histories to obtain reliable estimates of the quantity of interest and its associated statistical uncertainty. Numerous variance reduction techniques (VRTs) have been employed to increase computational efficiency by reducing the statistical uncertainty. We investigate the effect of two VRTs for optical transport methods on accuracy and computing time for the estimation of variance (noise) in x‐ray imaging detectors.

Methods

We describe two VRTs. In the first, we preferentially alter the direction of the optical photons to increase detection probability. In the second, we follow only a fraction of the total optical photons generated. In both techniques, the statistical weight of photons is altered to maintain the signal mean. We use fastdetect2, an open‐source, freely available optical transport routine from the hybridmantis package. We simulate VRTs for a variety of detector models and energy sources. The imaging data from the VRT simulations are then compared to the analog case (no VRT) using pulse height spectra, Swank factor, and the variance of the Swank estimate.

Results

We analyze the effect of VRTs on the statistical uncertainty associated with Swank factors. VRTs increased the relative efficiency by as much as a factor of 9. We demonstrate that we can achieve the same variance of the Swank factor with less computing time. With this approach, the simulations can be stopped when the variance of the variance estimates reaches the desired level of uncertainty.

Conclusion

We implemented analytic estimates of the variance of Swank factor and demonstrated the effect of VRTs on image quality calculations. Our findings indicate that the Swank factor is dominated by the x‐ray interaction profile as compared to the additional uncertainty introduced in the optical transport by the use of VRTs. For simulation experiments that aim at reducing the uncertainty in the Swank factor estimate, any of the proposed VRT can be used for increasing the relative efficiency.
Technical Note: Sequential combination of parallel imaging and dynamic artificial sparsity framework for rapid free‐breathing golden‐angle radial dynamic MRI: K‐T ARTS‐GROWL
Authors: Chen Zhifeng , Kang Liyi , Xia Ling , Wang Qiuliang , Li Yi , Hu Xinning , Liu Feng , Huang Feng
Published: October 2017

Purpose

To develop and validate a fast dynamic MR imaging scheme. A novel approach termed K‐T ARTificial Sparsity enhanced GROWL (K‐T ARTS‐GROWL) is proposed that integrates dynamic artificial sparsity and GROWL‐based parallel imaging (PI).

Methods

Golden‐angle radial k‐space data are acquired with the free‐breathing sampling scheme and then sorted into a time series by grouping consecutive spokes into temporal frames. The reconstruction framework sequentially applies PI and dynamic artificial sparsity. In the implementation, GROWL is taken as a special PI instance for its high computational efficiency and the K‐T sparse is exploited to improve the PI reconstruction performance, because the dynamic MR images are often sparse in the x‐f domain. In the final reconstruction procedure, artificial sparsity is constructed and fed back to the previous reconstruction.

Results

The K‐T ARTS‐GROWL results in high spatial and temporal resolution reconstructions. By exploiting dynamic artificial sparsity, the acceleration capability is further improved compared to the PI alone. The experimental results demonstrate that K‐T ARTS‐GROWL leads to significantly better image quality (P < 0.05) than the frame‐by‐frame GROWL and frame‐by‐frame ARTS‐GROWL for in vivo liver imaging. Compared with the tested K‐T reconstruction algorithms, the K‐T ARTS‐GROWL results in a better or comparable image quality and temporal resolution with greatly decreased computational costs.

Conclusion

The proposed technique enables sparse, fast imaging of high spatial, high temporal resolutions for dynamic MRI.
Low‐dose CT perfusion with projection view sharing
Authors: Martin Thomas , Hoffman John , Alger Jeff R. , McNitt‐Gray Michael , Wang Danny JJ
Published: October 2017

Purpose

CT Perfusion (CTP) is a widely used clinical imaging modality. However, CTP typically involves the use of substantial radiation dose (CTDIvol ≥~200 mGy). The purpose of this study is to present a low‐dose CTP technique using a projection view‐sharing reconstruction algorithm originally developed for dynamic MRI — “K‐space Weighted Image Contrast” (KWIC).

Methods

The KWIC reconstruction is based on an angle‐bisection scheme. In KWIC, a Fourier transform was performed along each projection to form a “k‐space”‐like CT data space, based on the central‐slice theorem. As a projection view‐sharing technique, KWIC preserves the spatiotemporal resolution of undersampled CTP data by progressively increasing the number of projection views shared for more distant regions of “k‐space”. KWIC reconstruction was evaluated on a digital FORBILD head phantom with numerically simulated time‐varying objects. The numerically simulated scans were undersampled using the angle‐bisection scheme to achieve 50%, 25%, and 12.5% of the original dose (288, 144, and 72 projections, respectively). The area‐under‐the‐curve (AUC), time‐to‐peak (TTP), and full width half maximum (FWHM) were measured in KWIC recons and compared to fully sampled filtered back projection (FBP) reconstructions. KWIC reconstruction and dose reduction was also implemented for three clinical CTP cases (45 s, 1156 projections per turn, 1 s/turn, CTDIvol 217 mGy). Quantitative perfusion metrics were computed and compared between KWIC reconstructed CTP data and those of standard FBP reconstruction.

Results

The AUC, TTP, and FWHM in the numerical simzulations were unaffected by the undersampling/dose reduction (down to 12.5% dose) with KWIC reconstruction compared to the fully sampled FBP reconstruction. The normalized root‐mean‐square‐error (NRMSE) of the AUC in the FORBILD head phantom is 0.04, 0.05, and 0.07 for 50%, 25%, and 12.5% KWIC, respectively, as compared to FBP reconstruction. The cerebral blood flow (CBF) and cerebral blood volume had no significant difference between FBP and 50%, 25%, and 12.5% KWIC reconstructions (P > 0.05).

Conclusions

This study demonstrates that KWIC preserves perfusion metrics for CTP with substantially reduced dose. Clinical implementation will require further investigation into methods of rapid switching of a CT x‐ray source.
Distinct Metabolic Profiles are Associated with Colorectal Adenomas and Serrated Polyps
Authors: Fliss‐Isakov Naomi , Zelber‐Sagi Shira , Webb Muriel , Halpern Zamir , Shibolet Oren , Kariv Revital
Published: October 2017

Objective

Prevention of colorectal cancer (CRC) by colonoscopy is recommended according to age and personal/familial history. Metabolic alterations are associated with colorectal adenomas, but data are scarce regarding serrated polyps and advanced polyps. The aim of this study was to evaluate the association between metabolic alterations and colorectal polyp type and advanced polyps.

Methods

A case‐control study was conducted among consecutive subjects, 40 to 70 years old, who underwent screening/diagnostic colonoscopy from 2010 to 2015. Subjects who were treated for diabetes, who had a family/personal history of CRC, and who were at high risk for CRC were excluded. Participants underwent anthropometric, laboratory, and ultrasonographic evaluations and a medical and lifestyle interview. Polyps were histologically classified as adenomatous or serrated polyps and divided into advanced and non‐advanced categories.

Results

The study included 828 participants (58.4 ± 6.6 years, 50.4% men). Abdominal obesity (odds ratio [OR] = 1.67, 95% CI: 1.20‐2.30), hypertension (OR = 1.47, 95% CI: 1.03‐2.09), and a high glycosylated hemoglobin percentage (HbA1c%) (OR = 1.57, 95% CI: 1.06‐2.34) were independently associated with colorectal adenomas, whereas a high triglyceride to high‐density lipoprotein cholesterol (TG/HDL) ratio was independently associated with serrated polyps (OR = 2.31, 95% CI: 1.32‐4.03). A combination of three metabolic alterations was strongly associated with colorectal polyps.

Conclusions

Abdominal obesity, hypertension, and a high HbA1c% are independently associated with adenomas, whereas a high TG/HDL ratio is associated with serrated polyps. These parameters are easily accessible in clinical practice and may help define high‐risk groups for CRC.
Change in Physical Activity During a Weight Management Intervention for Breast Cancer Survivors: Association with Weight Outcomes
Authors: Fazzino Tera L. , Fabian Carol , Befort Christie A.
Published: October 2017

Objective

This study examined the effects of a group phone‐based weight management intervention on change in physical activity as measured via accelerometer and self‐report in rural breast cancer survivors. The study also evaluated the role of physical activity on clinically meaningful cut points for weight loss (baseline to 6 months) and weight loss maintenance (6 to 18 months).

Methods

Participants were breast cancer survivors in a weight management intervention who provided valid weight and accelerometer data (N = 142). Participants were categorized into four groups based on weight loss ≥10% and weight regain ≥5% at 18 months.

Results

Accelerometer‐measured moderate‐to‐vigorous physical activity (MVPA) significantly increased from baseline to 6 months (+46.9 minutes). MVPA declined during maintenance but remained significantly greater than baseline. Self‐reported MVPA followed a similar pattern as accelerometer MVPA, but estimates were significantly higher. Participants in the high loss, low regain group had significantly higher MVPA at all points.

Conclusions

A distance‐based weight management intervention for survivors improved physical activity outcomes over 18 months. Self‐reported physical activity was substantially higher than accelerometer measured. Findings highlight the importance of device‐based measurement for characterizing the magnitude of physical activity change as well as the role of physical activity in weight management outcomes.
Morphological and Functional Changes in the Peritumoral Adipose Tissue of Colorectal Cancer Patients
Authors: Zoico Elena , Rizzatti Vanni , Darra Elena , Budui Simona Luciana , Franceschetti Guido , Vinante Fabrizio , Pedrazzani Corrado , Guglielmi Alfredo , De Manzoni Giovanni , Mazzali Gloria , Rossi Andrea Petronio , Fantin Francesco , Zamboni Mauro
Published: October 2017

Objective

The role of peritumoral adipose tissue (AT) has not been extensively studied in colorectal cancer (CRC).

Methods

This study was conducted in 20 male subjects undergoing elective surgery for CRC. The differences between the peritumoral visceral adipose tissue (P‐VAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) of the patients were described via immunohistochemistry and molecular biology analyses. The interactions between adipocytes and a colon cancer cell line were also investigated by using anin vitrococulture system.

Results

The analyses revealed that adipocytes near the tumor were significantly smaller than the adipocytes from other sites. The P‐VAT was preferentially infiltrated by a CD68+/CD163+/IDO‐ macrophage subset with a prevalent reparative inflammatory response, while the macrophages identified in VAT and SAT mainly presented inflammatory features. Furthermore, the P‐VAT presented a higher expression of adiponectin compared with other sites. Morphological analysisin vitroshowed that after a few days of coculture, 3T3‐L1 adipocytes were reduced in number and size with an increase in lipolysis rate and dedifferentiation phenomena.

Conclusions

This study reveals important morphological and functional changes in the AT surrounding the tumor as an increase in lipolysis and in adiponectin‐producing adipocytes, preferentially infiltrated by a macrophage subset, with prevalent reparative inflammatory response.
Cardiorespiratory Fitness, Adiposity, and Cancer Mortality in Men
Authors: Vainshelboim Baruch , Chen Zhongming , Lee Yvonne Nicole , Sorayya Aryo , Kokkinos Peter , Nead Kevin T. , Chester Cariad , Myers Jonathan
Published: October 2017

Objective

This study sought to evaluate the association between cardiorespiratory fitness (CRF) and cancer mortality in men with overweight and obesity.

Methods

Maximal exercise testing was performed in 3,610 men (58.8 ± 17.5 years) (n = 2,100 with overweight and n = 1,510 with obesity) free from malignancy at baseline who were followed for 12.3 ± 7.4 years. Body mass index of 25.0 to 29.9 kg/m2 for overweight and ≥ 30.0 for obesity categories was used. Hazard ratios and population‐attributable risks (PAR) were determined.

Results

During the follow‐up period, 11.1% and 9.1% died from cancer among those who had overweight and obesity, respectively. CRF had an inverse and graded association with cancer mortality. Compared with low CRF (< 5 metabolic equivalents), moderate and high CRF levels were associated with 48% and 79% reduced risks for cancer mortality in men who had overweight (P < 0.001) and 55% and 83% lower risks in those who had obesity (P < 0.001), respectively. Low CRF had PARs of 9.3% and 10.5% for cancer mortality in subjects who had overweight and obesity, respectively.

Conclusions

Among men with overweight and obesity, higher CRF is associated with lower cancer mortality. Eliminating low CRF as a risk factor would potentially prevent a considerable number of cancer deaths and reduce the associated societal and economic burden in these high‐risk populations.
Effect of Adolescent Bariatric Surgery on the Brain and Cognition: A Pilot Study
Authors: Pearce Alaina L. , Mackey Eleanor , Cherry J. Bradley C. , Olson Alexandra , You Xiaozhen , Magge Sheela N. , Mietus‐Snyder Michele , Nadler Evan P. , Vaidya Chandan J.
Published: October 2017

Objective

Neurocognitive deficits in pediatric obesity relate to poor developmental outcomes. We sought preliminary evidence for changes in brain and cognitive functioning relevant to obesogenic behavior following vertical sleeve gastrectomy (VSG) in adolescents relative to wait‐listed (WL) and healthy controls (HC).

Methods

Thirty‐six adolescents underwent fMRI twice 4 months apart, during executive, reward, and episodic memory encoding, in addition to behavioral testing for reward‐related decision making.

Results

VSG adolescents lost weight, while WL gained weight and HC did not change between time points. Gains in executive and reward‐related performance were larger in VSG than control groups. Group × Time interaction (P < 0.05 corrected) in left prefrontal cortex during N‐back showed greater presurgical activation and postsurgical reduction comparable to HC levels but increased in WL between time points. Similarly, left striatal parametric response to reward value reduced after surgery to HC levels; WL did not change. Memory‐related medial temporal activation did not change in any group.

Conclusions

Results provide pilot evidence for functional brain changes induced by VSG in adolescents with severe obesity. Weight loss and gain were paralleled by reduced and increased prefrontal activation, respectively, suggesting neural plasticity related to metabolic change.
A Randomized, Controlled, Multicenter Study of Technology‐Based Weight Loss Interventions among Endometrial Cancer Survivors
Authors: Haggerty Ashley F. , Hagemann Andrea , Barnett Matthew , Thornquist Mark , Neuhouser Marian L. , Horowitz Neil , Colditz Graham A. , Sarwer David B. , Ko Emily M. , Allison Kelly C.
Published: October 2017

Objective

The aim of this study was to test the efficacy of technology‐based weight loss interventions for endometrial cancer (EC) survivors with obesity.

Methods

EC survivors with obesity (n = 196) from three medical centers completed assessments for knowledge of obesity as a risk for EC and interest in weight management. Forty‐one women were randomized to a 6‐month intervention: telemedicine with Wi‐Fi scales, text messaging (texting), or enhanced usual care (EUC). Changes in anthropometrics and psychosocial measures were analyzed.

Results

One‐third of survey participants lacked awareness that obesity increased the risk of EC, and 40% misclassified their body mass. There were no significant differences in weight loss across interventions (mean = −4.4 kg, SD = 6.5 kg). Telemedicine showed improvements in physical health and cancer‐related body image (Ps = 0.04) compared to texting and in sexual functioning compared to EUC (P = 0.03). Total physical activity was increased in EUC compared with telemedicine (P = 0.01), and vigorous physical activity was increased in EUC compared with both interventions (P = 0.01‐0.03); walking significantly increased in texting compared with telemedicine (P = 0.02).

Conclusions

Technology‐based lifestyle interventions in EC survivors with obesity were accessible and resulted in weight loss and improved quality of life. EUC also produced weight loss, demonstrating a potential for beginning weight management with information on specific diet and exercise goals.
Evaluation of patritumab with or without erlotinib in combination with standard cytotoxic agents against pediatric sarcoma xenograft models
Authors: Bandyopadhyay Abhik , Favours Edward , Phelps Doris A. , Pozo Vanessa Del , Ghilu Samson , Kurmashev Dias , Michalek Joel , Trevino Aron , Guttridge Denis , London Cheryl , Hirotani Kenji , Zhang Ling , Kurmasheva Raushan T. , Houghton Peter J.
Published: October 2017

Background

Integrating molecularly targeted agents with cytotoxic drugs used in curative treatment of pediatric cancers is complex. An evaluation was undertaken with the ERBB3/Her3‐specific antibody patritumab (P) either alone or with the ERBB1/epidermal growth factor receptor inhibitor erlotinib (E) in combination with standard cytotoxic agents, cisplatin, vincristine, and cyclophosphamide, in pediatric sarcoma xenograft models that express receptors and ligands targeted by these agents.

Procedures

Tumor models were selected based upon ERBB3 expression and phosphorylation, and ligand (heregulin) expression. Patritumab, E, or these agents combined was evaluated without or with concomitant cytotoxic agents using procedures developed by the Pediatric Preclinical Testing Program.

Results

Full doses of cytotoxic agents were tolerated when combined with P, whereas dose reductions of 25% (vincristine, cisplatin) or 50% (cyclophosphamide) were required when combined with P + E. Patritumab, E alone, or in combination did not significantly inhibit growth of any tumor model, except for Rh18 xenografts (E alone). Patritumab had no single‐agent activity and marginally enhanced the activity of vincristine and cisplatin only in Ewing sarcoma ES‐4. P + E did not increase the antitumor activity of vincristine or cisplatin, whereas dose‐reduced cyclophosphamide was significantly less active than cyclophosphamide administered at its maximum tolerated dose when combined with P + E.

Conclusions

P had no single‐agent activity, although it marginally potentiated the activity of vincristine and cisplatin in one of three models studied. However, the addition of E necessitated dose reduction of each cytotoxic agent, abrogating the enhancement observed with P alone.
Comparison of first‐tier cell‐free DNA screening for common aneuploidies with conventional publically funded screening
Authors: Langlois Sylvie , Johnson JoAnn , Audibert François , Gekas Jean , Forest Jean‐Claude , Caron André , Harrington Keli , Pastuck Melanie , Meddour Hasna , Tétu Amélie , Little Julian , Rousseau François
Published: October 2017

Objective

This study evaluates the impact of offering cell‐free DNA (cfDNA) screening as a first‐tier test for trisomies 21 and 18.

Methods

This is a prospective study of pregnant women undergoing conventional prenatal screening who were offered cfDNA screening in the first trimester with clinical outcomes obtained on all pregnancies.

Results

A total of 1198 pregnant women were recruited. The detection rate of trisomy 21 with standard screening was 83% with a false positive rate (FPR) of 5.5% compared with 100% detection and 0% FPR for cfDNA screening. The FPR of cfDNA screening for trisomies 18 and 13 was 0.09% for each. Two percent of women underwent an invasive diagnostic procedure based on screening or ultrasound findings; without the cfDNA screening, it could have been as high as 6.8%. Amongst the 640 women with negative cfDNA results and a nuchal translucency (NT) ultrasound, only 3 had an NT greater or equal to 3.5 mm: one had a normal outcome and two lost their pregnancy before 20 weeks.

Conclusions

cfDNA screening has the potential to be a highly effective first‐tier screening approach leading to a significant reduction of invasive diagnostic procedures. For women with a negative cfDNA screening result, NT measurement has limited clinical utility.
Preparation of PA6‐g‐LCX‐PAH fiber for removing formaldehyde
Authors: Zhang Yi‐An , Di Jianfeng , Du Wenqin
Published: October 2017

The innovative formaldehyde removal fibers (PA6‐g‐LCX‐PAH) have been developed by grafting polyacryloyl hydrazid (PAH) onto the polyamide molecules with bridging agent of Polyketide amide (LCX). The effects of varied grafting parameters including reaction time, reaction temperature, the ratio of PAH/LCX, and pH value have been discussed in detail to optimizing the grafting conditions. PA6‐g‐LCX‐PAH can be easily regenerated after treatment of glacial acetic acid at ambient temperature and the formaldehyde removal rate still reached 79.6% after repeated use for 10 times. The structure and morphology of PA6‐g‐LCX‐PAH were characterized by SEM, DSC and FT‐IR spectroscopy. It is concluded that the PA6‐g‐LCX‐PAH is a suitable removal agent of high‐ or mid‐concentration formaldehyde in a living or industrial environment. POLYM. ENG. SCI., 58:1652–1658, 2018. © 2017 Society of Plastics Engineers
Visible light‐induced RAFT polymerization of methacrylates with benzaldehyde derivatives as organophotoredox catalysts
Authors: Yang Qian , Zhang Xianhong , Ma Wenchao , Ma Yuhong , Chen Dong , Wang Li , Zhao Changwen , Yang Wantai
Published: October 2017

The benzaldehyde derivatives, such as 2,4‐dimethoxy benzaldehyde (PC1) and p‐anisaldehyde (PC2), were successfully used as photoredox catalysts (PCs) in combination with typical RAFT agent 4‐cyano‐4‐(phenylcarbonothioylthio)pentanoic acid (CTP) for the controlled photoinduced electron transfer RAFT polymerization (PET‐RAFT) of methyl methacrylate (MMA) and benzyl methacrylate (BnMA) at room temperature. The kinetics of the polymerizations showed first order with respect to monomer conversions. Besides, the average number molecular weights (Mn) of the produced polymers increased linearly with the monomer conversions and kept relatively narrow polydispersity (PDI = Mw/Mn). For example, the Mn of PMMA increased from about 3400 to 17,300 g mol−1 with the increasing in monomer conversion from 11% to 85%, and the PDI maintained around 1.36. The living features of polymerizations with the PC1 and PC2 as catalysts have also been further supported by chain extension and synthesis of PMMA‐b‐PBnMA diblock copolymer. As a result, the simplicity and efficiency of benzaldehyde derivatives catalyzed PET‐RAFT polymerization have been demonstrated under mild conditions. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 229–236
Hydrogen bonding improved atom transfer radical polymerization of methyl methacrylate with a glycerol/1,3‐dimethyl‐2‐imidazolidinone green system
Authors: Tian Mengying , Wang Jirong , Zhou Jun , Han Jianyu , Du Feipeng , Xue Zhigang
Published: October 2017

1,3‐Dimethyl‐2‐imidazolidinone (DMI) was used as an efficient media in iron‐catalyzed atom transfer radical polymerizations (ATRPs) and AGET ATRPs of MMA. Both of these systems presented relatively high reaction rate and well controllability even in the presence of limited amount of DMI. In iron‐catalyzed AGET ATRPs, a variety of alcohols were served as reducing agents and all the polymerizations behaved excellent activity features, especially for glycerol. The hydrogen‐bond interaction between DMI and glycerol was also studied, which may release the reducing ability of glycerol by decreasing the viscosity of glycerol similar to deep eutectic solvents (DESs). © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 282–289
Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients
Authors: Tyagi Pradeep , Motley Saundra S. , Koyama Tatsuki , Kashyap Mahendra , Gingrich Jeffrey , Yoshimura Naoki , Fowke Jay H.
Published: October 2017

Purpose

Benign prostatic hyperplasia (BPH) is strongly associated with obesity and prostatic tissue inflammation, but the molecular underpinning of this relationship is not known. Here, we examined the association between urine levels of chemokines/adipokines with histological markers of prostate inflammation, obesity, and lower urinary tract symptoms LUTS in BPH patients.

Methods

Frozen urine specimens from 207 BPH/LUTS patients enrolled in Nashville Men's Health Study were sent for blinded analysis of 11 analytes, namely sIL‐1RA, CXC chemokines (CXCL‐1, CXCL‐8, CXCL‐10), CC chemokines (CCL2, CCL3, CCL5), PDGF‐BB, interleukins IL‐6, IL‐17, and sCD40L using Luminex™ xMAP® technology. After adjusting for age and medication use, the urine levels of analytes were correlated with the scales of obesity, prostate inflammation grade, extent, and markers of lymphocytic infiltration (CD3 and CD20) using linear regression.

Results

sIL‐1RA levels were significantly raised with higher BMI, waist circumference and waist‐hip ratio in BPH patients after correction for multiple testing (P = 0.02). Men with greater overall extent of inflammatory infiltrates and maximal CD3 infiltration were marginally associated with CXCL‐10 (P = 0.054) and CCL5 (P = 0.054), respectively. CCL3 in 15 patients with moderate to severe grade inflammation was marginally associated with maximal CD20 infiltration (P = 0.09), whereas CCL3 was undetectable in men with mild prostate tissue inflammation. There was marginal association of sCD40L with AUA‐SI scores (P = 0.07).

Conclusions

Strong association of sIL‐1RA in urine with greater body size supports it as a major molecular correlate of obesity in the urine of BPH patients. Increased urine levels of CXCL‐10, CCL5, and CCL3 were marginally associated with the scores for prostate tissue inflammation and lymphocytic infiltration. Overall, elevated urinary chemokines support that BPH is a metabolic disorder and suggest a molecular link between BPH/LUTS and prostatic inflammation.
Reducing Process Safety Events: An approach proven by sustainable results
Authors: Champion John , Van Geffen Sheila , Borrousch Lynnette
Published: October 2017

The Dow Chemical Company has significantly reduced the number of Tier 1 Process Safety events from 69 in 2008 to an average of 10 in 2013–2015. This paper will share some of the key elements that have led to this successful and sustainable reduction in incidents. The structure of the paper is focused around the concept of “Effective Process Safety Programs” published by Klein and Vaughen, Process Safety: Key Concepts and Practical Applications, CRC Press, 2017.

In this paper, we will provide details on Dow's Operational Discipline systems that enable success on a day‐to‐day basis. These systems include Procedure Use Culture, Process Safety Training programs, and Process Safety Collaboration Networks. We will also describe our Process Safety Management Systems that enable long‐term success including Dow's Loss Prevention Principles (LPP), use of Process Hazards Analysis (PHA), Layer of Protection Analysis (LOPA) and other tools to manage risk, and Dow's Mechanical Integrity program. The success is built on a strong foundation of Safety Culture and Leadership. This paper will illustrate how Dow is structured to support the Process Safety efforts and examples will be shared about how leadership at all levels of the organization is practiced and demonstrated. © 2017 American Institute of Chemical Engineers Process Saf Prog 36: 326–337, 2017
The effects of higher orders of perturbation theory on the correlation energy of atoms and bonds in molecules
Authors: Vincent Mark A. , Silva Arnaldo F. , McDonagh James L. , Popelier Paul L. A.
Published: October 2017

We examine, for the first time, the effects of higher orders of Møller–Plesset perturbation theory on the individual atoms within a molecule and the bonds between them, via the topological energy partitioning method of interacting quantum atoms. In real terms (i.e., not by absolute value) MP3 decreases the correlation energy of a bond, and MP4SDQ also decreases the energy of the atoms at either end of the bond. In addition, we investigated long‐range through‐space dispersive effects on a H2oligomer. Overall, MP3 is the largest correction to the correlation energy, and most of that energy is allocated to chemical bonds, reducing their values in actual terms. The MP4SDQ bond correlation correction, despite being relatively small, tends to have two effects: (i) for small or negative correlation energies MP4SDQ tends to decrease the bond correlation values even more, and (ii) for large (positive) bond correlation energies MP4SDQ tends to restore the bond correlation energies from the MP3 back toward the MP2 values. Furthermore, each individual part of a molecule or complex (atom or bond) has a specific convergence pattern for the MPnseries: through‐space interactions converge at MP2 but bonds converge at MP3 level. The atomic correlation energy appears to head toward convergence at the MP4 level.
Insight into the π‐hole···π‐electrons tetrel bonds between F2ZO (Z = C, Si, Ge) and unsaturated hydrocarbons
Authors: Shen Shaojie , Zeng Yanli , Li Xiaoyan , Meng Lingpeng , Zhang Xueying
Published: October 2017

The intermolecular π‐hole···π‐electrons interactions between F2ZO (Z = C, Si, Ge) molecules and unsaturated hydrocarbons including acetylene, ethylene, 1,3‐butadiene and benzene were constructed to reveal the differences of tetrel bonds forming by carbon and heavier tetrel atoms. The ab initio computation in association with topological analysis of electron density, natural bond orbital, and energy decomposition analysis demonstrate that the strength of Si···π and Ge···π tetrel bonds is much stronger than that of C···π tetrel bonds. The Si···π and Ge···π tetrel bonds exhibit covalent or partially covalent interaction nature, while the weak C···π tetrel bonds display the hallmarks of noncovalent interaction, the electrostatic interaction is the primary influencing factor. The Si···π and Ge···π interactions are determined by both the σ‐ and π‐electron densities, while the C···π interactions are dominated mainly by the π‐electron densities. The π‐hole···π‐electrons tetrel bonds are dominated by electrostatic interaction, and polarization has a comparable contribution in the Si···π and Ge···π tetrel bonds.
Microparticles Carrying Peroxisome Proliferator-Activated Receptor Alpha Restore the Reduced Differentiation and Functionality of Bone Marrow-Derived Cells Induced by High-Fat Diet
Authors: Vergori Luisa , Lauret Emilie , Soleti Raffaella , Andriantsitohaina Ramaroson , Carmen Martinez M.
Published: October 2017

Metabolic pathologies such as diabetes and obesity are associated with decreased level of circulating and bone marrow (BM)-derived endothelial progenitor cells (EPCs). It is known that activation of peroxisome proliferator-activated receptor alpha (PPARα) may stimulate cell differentiation. In addition, microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, are able to reprogram EPCs. Here, we evaluated the role of MPs carrying PPARα on both phenotype and function of progenitor cells from mice fed with a high-fat diet (HFD). HFD reduced circulating EPCs and, after 7 days of culture, BM-derived EPCs and monocytic progenitor cells from HFD-fed mice displayed impaired differentiation. At the same time, we show that MPs bearing PPARα, MPsPPARα+/+, increased the differentiation of EPCs and monocytic progenitors from HFD-fed mice, whereas MPs taken from PPARα knockout mice (MPsPPARα−/−) had no effect on the differentiation of all types of progenitor cells. Furthermore, MPsPPARα+/+ increased the ability of progenitor cells to promote in vivo angiogenesis in mice fed with HFD. The in vitro and in vivo effects of MPsPPARα+/+ were abolished in presence of MK886, a specific inhibitor of PPARα. Collectively, these data highlight the ability of MPs carrying PPARα to restore the failed differentiation and functionality of BM-derived cells induced by HFD.
Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial
Authors: Sun Jessica M. , Song Allen W. , Case Laura E. , Mikati Mohamad A. , Gustafson Kathryn E. , Simmons Ryan , Goldstein Ricki , Petry Jodi , McLaughlin Colleen , Waters-Pick Barbara , Chen Lyon W. , Wease Stephen , Blackwell Beth , Worley Gordon , Troy Jesse , Kurtzberg Joanne
Published: October 2017

Cerebral palsy (CP) is a condition affecting young children that causes lifelong disabilities. Umbilical cord blood cells improve motor function in experimental systems via paracrine signaling. After demonstrating safety, we conducted a phase II trial of autologous cord blood (ACB) infusion in children with CP to test whether ACB could improve function (ClinicalTrials.gov, NCT01147653; IND 14360). In this double-blind, placebo-controlled, crossover study of a single intravenous infusion of 1–5 × 107 total nucleated cells per kilogram of ACB, children ages 1 to 6 years with CP were randomly assigned to receive ACB or placebo at baseline, followed by the alternate infusion 1 year later. Motor function and magnetic resonance imaging brain connectivity studies were performed at baseline, 1, and 2 years post-treatment. The primary endpoint was change in motor function 1 year after baseline infusion. Additional analyses were performed at 2 years. Sixty-three children (median age 2.1 years) were randomized to treatment (n = 32) or placebo (n = 31) at baseline. Although there was no difference in mean change in Gross Motor Function Measure-66 (GMFM-66) scores at 1 year between placebo and treated groups, a dosing effect was identified. In an analysis 1 year post-ACB treatment, those who received doses ≥2 × 107/kg demonstrated significantly greater increases in GMFM-66 scores above those predicted by age and severity, as well as in Peabody Developmental Motor Scales-2 Gross Motor Quotient scores and normalized brain connectivity. Results of this study suggest that appropriately dosed ACB infusion improves brain connectivity and gross motor function in young children with CP.
Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue
Authors: Taraballi Francesca , Bauza Guillermo , McCulloch Patrick , Harris Josh , Tasciotti Ennio
Published: October 2017

Musculoskeletal reconstruction is an ongoing challenge for surgeons as it is required for one out of five patients undergoing surgery. In the past three decades, through the close collaboration between clinicians and basic scientists, several regenerative strategies have been proposed. These have emerged from interdisciplinary approaches that bridge tissue engineering with material science, physiology, and cell biology. The paradigm behind tissue engineering is to achieve regeneration and functional recovery using stem cells, bioactive molecules, or supporting materials. Although plenty of preclinical solutions for bone and cartilage have been presented, only a few platforms have been able to move from the bench to the bedside. In this review, we highlight the limitations of musculoskeletal regeneration and summarize the most relevant acellular tissue engineering approaches. We focus on the strategies that could be most effectively translate in clinical practice and reflect on contemporary and cutting-edge regenerative strategies in surgery.
A Potential Method Using Ge{iPrNC[N(SiMe3)2]NiPr}2, (Et3Si)2Te and Anhydrous Hydrazine for Germanium Tellurides
Authors: Du Liyong , Du Shulei , Ding Yuqiang
Published: October 2017

A germanium(II)‐guanidine derivative of formula Ge{iPrNC[N(SiMe3)2]NiPr}2 (1) was synthesized and characterized by 1H NMR, 13C NMR, elemental analysis, and X‐ray diffraction method. Thermal property was also studied to identify its thermal stability and volatility. More importantly, compound 1 was synthesized to develop a new method for germanium tellurides, where anhydrous hydrazine was introduced to prompt the activity of germanium(II) guanidines (or derivatives) towards (Et3Si)2Te. Solution reaction of compound 1, (Et3Si)2Te, and anhydrous hydrazine was investigated to pre‐identify the feasibility of this combination for ALD process. The EDS data of the black precipitate from this reaction verified the potential of this method to manufacture germanium tellurides.
Unusual Rhesus Antibodies as a Cause for Fetal Isoimmunisation
Authors: Raheja Aastha , Agarwal Krishna
Published: October 2017

Hemolytic disease of the newborn due to Rh isoimmunisation in a Rhesus D (Rh-D) negative mother with an Rh-D positive fetus is a well recognised entity. Although antibody to Rh-D antigen (anti-D antibody) was once the major cause of hemolytic disease of the fetus and newborn (HDFN), widespread adoption of antenatal and postnatal prophylactic anti-D immunoglobulin administration has resulted in a marked decrease in the prevalence of allo-immunisation due to the Rh-D antigen during pregnancy. However, at the same time, the maternal allo-immunisation to other red cell Rhesus antigens became more evident as a cause for HDFN, since no prophylactic immunoglobulins are available to prevent the formation of these antibodies. The authors report a case of a pregnant woman with AB negative blood group and positive indirect Coombs test (ICT) with rising middle cerebral artery peak systolic velocity (MCA-PSV) on follow up visits. Fetus required intrauterine transfusion. Fetal cord blood sampling revealed the fetus to be B negative and the direct Coombs test (DCT) was positive. On further testing, maternal serum was found to be positive for anti-D, anti-C and anti-G antibodies. Postnatally, the baby required double volume exchange transfusion. The authors highlight the importance of irregular antibody screening for women with obstetric history suggestive of HDNF. This could help in diagnosis and successful treatment of the affected fetus.