bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear growth following complicated severe malnutrition: 1-year follow-up cohort of Kenyan children
Authors: Ngari Moses M , Iversen Per Ole , Thitiri Johnstone , Mwalekwa Laura , Timbwa Molline , Fegan Greg W , Berkley James Alexander 
Published: August 2019

BackgroundStunting is the most common manifestation of childhood undernutrition worldwide. Children presenting with severe acute malnutrition (SAM) are often also severely stunted. We evaluated linear growth and its determinants after medically complicated SAM.MethodsWe performed secondary analysis of clinical trial data (NCT00934492) from HIV-uninfected Kenyan children aged 2–59 months hospitalised with SAM. Outcome was change in height/length-for-age z-score (HAZ) between enrolment and 12 months later. Exposures were demographic, clinical, anthropometric characteristics and illness episodes during follow-up.ResultsAmong 1169 children with HAZ values at month 12 (66% of those in original trial), median (IQR) age 11 (7–17) months and mean (SD) HAZ −2.87 (1.6) at enrolment, there was no change in mean HAZ between enrolment and month 12: −0.006Z (95% CI −0.07 to 0.05Z). While 262 (23%) children experienced minimal HAZ change (within ±0.25 HAZ), 472 (40%) lost >0.25 and 435 (37%) gained >0.25 HAZ. After adjusting for regression to the mean, inpatient or outpatient episodes of diarrhoea and inpatient severe pneumonia during follow-up were associated with HAZ loss. Premature birth and not being cared by the biological parent were associated with HAZ gain. Increases in mid-upper arm circumference and weight-for-age were associated with HAZ gain and protected against HAZ loss. Increase in weight-for-height was not associated with HAZ gain but protected against HAZ loss. No threshold of weight gain preceding linear catch-up growth was observed.ConclusionsInterventions to improve dietary quality and prevent illness over a longer period may provide opportunities to improve linear growth.
Intraocular pressure control and visual field changes in primary angle closure disease: the CUHK PACG Longitudinal (CUPAL) study
Authors: Cheung Carol Y , Li Sophia L , Chan Poemen Pui , Chan Noel C Y , Tan Shaoying , Man Xiaofei , Tham Clement C 
Published: August 2019

PurposeTo determine the relationship of intraocular pressure (IOP) control with subsequent visual field (VF) deterioration in patients with primary angle closure disease (PACD).Methods419 PACD eyes from 240 Chinese patients were included. Mean IOP and IOP fluctuation were calculated as the average and SD divided by mean IOP, respectively, of all the IOP measured in the initial 18 months for assessment of IOP control. The relationship between IOP control and subsequent VF parameters over time was examined using linear mixed models. VF deterioration was defined as IOP control associated with decreased VF parameters over time with a p value <0.05. We calculated the average of the mean IOPs and IOP fluctuations in the cohort and used these two average values as a cut-off point to define high-threshold (≥average value) or low-threshold (<average value) for mean IOP and IOP fluctuation for each PACD eye, respectively.ResultsGreater IOP fluctuation was significantly associated with VF deterioration, independent of mean IOP (mean deviation (MD) β=−6.36, p=0.03; VF index β=−16.41, p=0.04; and cataract-adjusted MD β=−6.96, p=0.02). In the categorical analysis, those with both high-threshold mean IOP and high-threshold IOP fluctuation had the most rapid VF deterioration, compared with eyes with low-threshold IOP fluctuation (p<0.05). Among eyes with high-threshold mean IOP, eyes with high-threshold IOP fluctuation had faster rate of VF deterioration compared with eyes with low-threshold IOP fluctuation (p=0.01).ConclusionsIOP fluctuation was a significant and independent predictor for subsequent VF deterioration in eyes with PACD.
Healthcare provider and service user perspectives on STI risk reduction interventions for young people and MSM in the UK
Authors: Roy Anupama , King Carina , Gilson Richard , Richardson Daniel , Burns Fiona , Rodger Alison , Clark Laura , Miners Alec , Pollard Alex , Desai Sarika , Bailey Julia , Shahmanesh Maryam , Llewellyn Carrie 
Published: August 2019

ObjectiveBehavioural interventions have been shown to reduce sexual behaviours associated with increased risk of sexually transmitted infections in young people (<25 years) and men who have sex with men (MSM) internationally, but evidence from England is limited. We aimed to explore service provider and user experiences and perspectives on behavioural interventions to reduce sexual behaviour risks, and the use of automated methods to triage individuals to these services.MethodsWe conducted a sequential mixed methods study with sexual health service providers and users in 2015/2016. Qualitative interviews with providers and service users (heterosexual young people and MSM) in London and Brighton allowed us to explore a range of experiences and expectations. A subsequent national web-survey of service providers measured the feasibility of delivery within existing resources and preferences for intervention attributes.ResultsWe conducted 35 service user (15 heterosexual young people; 20 MSM) and 26 provider interviews and had 100 web-survey responses. We found considerable heterogeneity in prevention services offered. Service users and providers were broadly supportive of tailoring interventions offered, but service users raised concerns about automated, data-driven triage, particularly around equity and fairness of service delivery. Digital technologies, including social media or apps, were appealing to providers, being less resource intensive. However, one-to-one talking interventions remained popular with both service users and providers, being familiar, trustworthy and personal. Key tensions between desirability of interventions and availability of resources to deliver them were acknowledged/recognised by providers and users.ConclusionOverall, behavioural interventions to reduce sexual behaviour risks were viewed favourably by service providers and users, with key considerations including: privacy, personalisation and convenience. However, introducing desirable targeted interventions within heterogeneous sexual health settings will require resources to adapt interventions and research to fully understand the barriers and facilitators to use within routine services.
Ambient air pollution exposure and risk and progression of interstitial lung abnormalities: the Framingham Heart Study
Authors: Rice Mary B , Li Wenyuan , Schwartz Joel , Di Qian , Kloog Itai , Koutrakis Petros , Gold Diane R , Hallowell Robert W , Zhang Chunyi , O'Connor George , Washko George R , Hunninghake Gary M , Mittleman Murray A 
Published: August 2019

BackgroundAmbient air pollution accelerates lung function decline among adults, however, there are limited data about its role in the development and progression of early stages of interstitial lung disease.AimsTo evaluate associations of long-term exposure to traffic and ambient pollutants with odds of interstitial lung abnormalities (ILA) and progression of ILA on repeated imaging.MethodsWe ascertained ILA on chest CT obtained from 2618 Framingham participants from 2008 to 2011. Among 1846 participants who also completed a cardiac CT from 2002 to 2005, we determined interval ILA progression. We assigned distance from home address to major roadway, and the 5-year average of fine particulate matter (PM2.5), elemental carbon (EC, a traffic-related PM2.5constituent) and ozone using spatio-temporal prediction models. Logistic regression models were adjusted for age, sex, body mass index, smoking status, packyears of smoking, household tobacco exposure, neighbourhood household value, primary occupation, cohort and date.ResultsAmong 2618 participants with a chest CT, 176 (6.7%) had ILA, 1361 (52.0%) had no ILA, and the remainder were indeterminate. Among 1846 with a preceding cardiac CT, 118 (6.4%) had ILA with interval progression. In adjusted logistic regression models, an IQR difference in 5-year EC exposure of 0.14 µg/m3was associated with a 1.27 (95% CI 1.04 to 1.55) times greater odds of ILA, and a 1.33 (95% CI 1.00 to 1.76) times greater odds of ILA progression. PM2.5and O3were not associated with ILA or ILA progression.ConclusionsExposure to EC may increase risk of progressive ILA, however, associations with other measures of ambient pollution were inconclusive.
Enhancing trap and fault seal analyses by integrating observations from HR3D seismic data with well logs and conventional 3D seismic data, Texas inner shelf
Authors: Osmond Johnathon L. , Meckel Timothy A. 
Published: August 2019

Abstract

An understanding of trap and fault seal quality is critical for assessing hydrocarbon prospectivity. To achieve this, modern analytical techniques leverage well data and conventional industry-standard 3D seismic data to evaluate the trap, and any faults displacing the reservoir and top seal intervals. Above all, geological interpretation provides the framework of trap and fault seal analyses, but can be hindered by the data resolution, quality and acquisition style of the conventional seismic data. Furthermore, limiting the analysis to only the petroleum system at depth may lead to erroneous perceptions because interpreting overburden features, such as shallow faults or gas chimneys, can provide valuable observations with respect to container performance, and can to help validate trap and fault seal predictions. A supplement to conventional 3D data are high-resolution 3D seismic (HR3D) data, which provide detailed images of the overburden geology. This study utilizes an HR3D seismic volume in the San Luis Pass area of the Texas inner shelf, where shallow fault tips and a sizeable gas chimney are interpreted over an unsuccessful hydrocarbon prospect. Static post-drill fault seal and trap analyses suggest that the primary fault displacing the structural closure could have withheld columns of gas
c.
100 m high, but disagree with our HR3D seismic interpretations and dry-well analyses. From our results, we hypothesize that tertiary gas migration through fault conduits reduced the hydrocarbon column in the prospective Early Miocene reservoir, and may have resulted from continued movement along the intersecting faults. Overall, this study reinforces the importance of understanding the overburden geology and geohistory of faulted prospects, and demonstrates the utility of pre-drill HR3D acquisition when conducting trap and fault seal analyses.
Behavioral training of marmosets and electrophysiological recording from the cerebellum
Authors: Sedaghat-Nejad Ehsan , Herzfeld David J. , Hage Paul , Karbasi Kaveh , Palin Tara , Wang Xiaoqin , Shadmehr Reza 
Published: August 2019

The common marmoset ( Callithrix jacchus) is a promising new model for study of neurophysiological basis of behavior in primates. Like other primates, it relies on saccadic eye movements to monitor and explore its environment. Previous reports have demonstrated some success in training marmosets to produce goal-directed actions in the laboratory. However, the number of trials per session has been relatively small, thus limiting the utility of marmosets as a model for behavioral and neurophysiological studies. In this article, we report the results of a series of new behavioral training and neurophysiological protocols aimed at increasing the number of trials per session while recording from the cerebellum. To improve the training efficacy, we designed a precisely calibrated food regulation regime that motivates the subjects to perform saccade tasks, resulting in ~1,000 reward-driven trials on a daily basis. We then developed a multichannel recording system that uses imaging to target a desired region of the cerebellum, allowing for simultaneous isolation of multiple Purkinje cells in the vermis. In this report, we describe 1) the design and surgical implantation of a computer tomography (CT)-guided, subject-specific head post, 2) the design of a CT- and MRI-guided alignment tool for trajectory guidance of electrodes mounted on an absolute encoder microdrive, 3) development of a protocol for behavioral training of subjects, and 4) simultaneous recordings from pairs of Purkinje cells during a saccade task. NEW & NOTEWORTHY Marmosets present the opportunity to investigate genetically based neurological disease in primates, in particular, diseases that affect social behaviors, vocal communication, and eye movements. All of these behaviors depend on the integrity of the cerebellum. We present training methods that better motivate the subjects, allowing for improved performance, and we also present electrophysiological techniques that precisely target the subject’s cerebellum, allowing for simultaneous isolation of multiple Purkinje cells.
Glutamatergic input varies with phrenic motor neuron size
Authors: Rana Sabhya , Mantilla Carlos B. , Sieck Gary C. 
Published: August 2019

Like all skeletal muscles, the diaphragm muscle accomplishes a range of motor behaviors by recruiting different motor unit types in an orderly fashion. Recruitment of phrenic motor neurons (PhMNs) is generally assumed to be based primarily on the intrinsic properties of PhMNs with an equal distribution of descending excitatory inputs to all PhMNs. However, differences in presynaptic excitatory input across PhMNs of varying sizes could also contribute to the orderly recruitment pattern. In the spinal cord of Sprague-Dawley rats, we retrogradely labeled PhMNs using cholera toxin B (CTB) and validated a robust confocal imaging-based technique that utilizes semiautomated processing to identify presynaptic glutamatergic (Glu) terminals within a defined distance around the somal membrane of PhMNs of varying size. Our results revealed an ~10% higher density of Glu terminals at PhMNs in the lower tertile of somal surface area. These smaller PhMNs are likely recruited first to accomplish lower force ventilatory behaviors of the diaphragm as compared with larger PhMNs in the upper tertile that are recruited to accomplish higher force expulsive behaviors. These results suggest that differences in excitatory synaptic input to PhMNs may also contribute to the orderly recruitment of diaphragm motor units.NEW & NOTEWORTHY The distribution of excitatory glutamatergic synaptic input to phrenic motor neurons differs across motor neurons of varying size. These findings support the size principle of motor unit recruitment that underlies graded force generation in a muscle, which is based on intrinsic electrophysiological properties of motor neurons resulting from differences in somal surface area. A higher density of glutamatergic inputs at smaller, more excitable motor neurons substantiates the earlier and more frequent recruitment of these units.
Abstract 1001: Functional and mechanistic interrogation of androgen receptor degraders for the treatment of metastatic castration resistant prostate cancer
Authors: Kregel Steven , Wang Chao , Fernandez-Salas Ester , Wilder-Romans Kari , Han Xin , Qin Chong , Xiang Weiguo , Tien Jean , Cao Xuhong , Speers Corey , Wang Shaomeng , Chinnaiyan Arul M. 
Published: August 2019

Abstract
The clinical development of second-generation androgen receptor (AR) antagonists, including enzalutamide, has confirmed that the AR remains a key oncogene in castration-resistant prostate cancer (CRPC). However, response to enzalutamide is temporary and incremental, and prostate cancer (PCa) cells usually maintain AR expression and signaling upon resistance to AR-targeted therapies. One novel strategy for targeting the AR axis in CRPC is to target proteins through proteasomal degradation, which improves the efficacy and specificity of standard inhibitors. We have developed compounds that bind to AR and engage the proteasomal degradation machinery to specifically degrade the AR protein. Based on this, we hypothesized that the pharmacologic degradation of AR represents an important advance in CRPC treatment, and may provide a novel therapeutic strategy for advanced prostate cancer. These compounds affect AR-positive prostate cancer cells by decreasing AR protein levels as well as disrupting oncogenic AR signaling and enzalutamide resistance. Nanomolar concentrations of AR degraders ultimately lead to decreases in PCa cell growth in vitro and in vivo. In conclusion, we developed highly potent small molecules that induced proteasomal degradation of AR proteins, thus demonstrating degrader compounds to be a potential therapeutic strategy for patients with CRPC.
Citation Format: Steven Kregel, Chao Wang, Ester Fernandez-Salas, Kari Wilder-Romans, Xin Han, Chong Qin, Weiguo Xiang, Jean Tien, Xuhong Cao, Corey Speers, Shaomeng Wang, Arul M. Chinnaiyan. Functional and mechanistic interrogation of androgen receptor degraders for the treatment of metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1001.
Abstract 1195: Stochastic co-evolution of the adaptive immune system and an evading cancer population
Authors: George Jason Thomas , Molldrem Jeffrey J. , Levine Herbert 
Published: August 2019

Abstract
Recent advances in immunotherapy have revolutionized modern cancer treatment. While encouraging, robust therapies that lead to durable remission outcomes still remain a challenge in curing many malignancies as cancer cells may acquire clones that effectively evade the immune system. Cancer immunotherapeutic treatment strategies are quite complex. In extreme cases, hematopoietic stem cell recipients enlist an entire allogeneic T-cell repertoire to fight against a growing malignancy. Perhaps most importantly, the adaptive nature of the immune system uniquely enables this treatment approach to co-evolve alongside an evasive threat. However, this process is poorly quantified and thus merits further study in order to maximally benefit cancer patients. Here, we develop a theoretical framework to quantify the dynamics between a growing collection of cancer cells capable of acquiring multiple evasive clones and a T-cell repertoire that may eventually recognize the evading populations. We create the first mathematical model of stochastic tumor-immune co-evolution by applying principles of stochastic process theory. We demonstrate that our model agrees with experimental time-course data in solid and liquid cancers and relate differences in branched vs. clonal evolution to the stringency of immunosurveillance present during early cancer progression. We argue that the clonal dynamics observed in leukemia patients treated with T-cell transplant therapy likely arise from the selection of pre-existent immune-evasive clones. In conclusion, our co-evolutionary model recapitulates empirical observations and offers a framework for quantifiable predictions to further improve cancer immunotherapy.
Citation Format: Jason Thomas George, Jeffrey J. Molldrem, Herbert Levine. Stochastic co-evolution of the adaptive immune system and an evading cancer population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1195.
Abstract 164: MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 and promotes colorectal cancer metastasis
Authors: Ji Qing , Cai Guoxiang , Liu Xuan , Zhang Yi , Wang Yan , Zhou Lihong , Sui Hua , Li Qi 
Published: August 2019

Abstract
Ectopic expression of lncRNA-MALAT1 has been discovered in recurrent colorectal cancer (CRC) and metastatic sites in post-surgical patients, however, its biological mechanism remained un-elucidated. Our study firstly revealed the novel mechanisms of MALAT1 in promoting CRC metastasis through at least the following two mechanisms: First of all, MALAT1 binds miR-15 family members, to “de-inhibit” their effect on LRP6 expression, enhances beta-catenin signaling, leading to elevated transcriptional levels of downstream target genes RUNX2. Secondly, MALAT1 binds SFPQ, dissociate SFPQ/PTBP2 dimer to release free PTBP2, which elevates translational levels of RUNX2, through interacting with IRES domain in the 5’UTR of the corresponding RUNX2 mRNAs. Moreover, elevated RUNX2 expression levels were detected in recurrent CRC tumors, which were closely associated with TMN stages and CRC patients’ survival. Our data demonstrated that, MALAT1 and RUNX2 may serve as two biomarkers for predicting the recurrence of CRC patients.
Note: This abstract was not presented at the meeting.
Citation Format: Qing Ji, Guoxiang Cai, Xuan Liu, Yi Zhang, Yan Wang, Lihong Zhou, Hua Sui, Qi Li. MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 and promotes colorectal cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 164.
Abstract 1736: Targeting Hsp90-Cdc37 complex overcomes drug resistance in glioma cells harboring FGFR3-TACC3 fusion gene
Authors: Li Tao , Mehraein-Ghomi Farideh , Namjoshi Sanjeev V. , Phillips Lynette M. , Ballard Elizabeth A. , Forbes Mary E. , Chou ping-Chieh , Yang Xuejun , Zhang Wei 
Published: August 2019

Abstract
Glioblastoma is one of the most lethal malignancies with the poorest prognosis among tumors of the central nervous system. Fusion genes are common chromosomal aberrations in many cancers that may give rise to an in-frame fusion protein with oncogenic function. These fusion genes can be used as prognostic markers as well as drug targets in clinical practice. The FGFR3-TACC3 (F3T3) fusion gene was discovered in glioblastoma, with an occurrence rate of up to 8.3% and leading to uncontrolled proliferation and chromosomal instability. Our studies have shown that glioblastoma cells harboring the F3T3 are resistant to the frontline glioblastoma drug Temozolomide (TMZ). Using the Comet assay, we show that TMZ-mediated DNA damage is repaired more rapidly in cells harboring the F3T3 compared to control. Our studies on the mechanism of this drug resistance show that the F3T3 confers an aberrant activation of FGFR and ERK pathways when treated with TMZ. To further explore druggable target(s) to overcome resistance caused by F3T3, we immunoprecipitated (IP) the proteins that interact with F3T3 in U251 glioblastoma cells overexpressing the F3T3 or wildtype FGFR3, followed by LC-MS/MS analyses. Our quantitative proteomic analysis revealed interactions of the F3T3 fusion protein with Hsp90α and Cdc37 proteins. These interactions were further validated by reciprocal IPs followed by Western blotting. Activation of many kinases, such as FGFRs, depends on their interaction with the Hsp90 molecular chaperone system. Hsp90 recruitment is mediated by the co-chaperone adaptor protein Cdc37, which simultaneously binds to both the kinase and Hsp90. To test inhibition of F3T3 association with the Hsp90-Cdc37 complex, we treated U251 cells constitutively expressing F3T3 with the Hsp90 inhibitor Onalespib. We show that Onalespib treatment at 26 nM significantly suppresses the proliferation of F3T3 expressing U251 cells in comparison to micromolar levels of the pan-FGFR inhibitor BGJ398 and PD173074. Our results provide evidence that the F3T3 fusion gene contributes to drug resistance via multiple chemo-resistance pathways. Importantly, our findings establish that F3T3 is an Hsp90 client that shows strong addiction to the Hsp90-Cdc37 complex for cell growth and suggests a novel strategy for targeting F3T3 fusion gene in glioma.
Citation Format: Tao Li, Farideh Mehraein-Ghomi, Sanjeev V. Namjoshi, Lynette M. Phillips, Elizabeth A. Ballard, Mary E. Forbes, ping-Chieh Chou, Xuejun Yang, Wei Zhang. Targeting Hsp90-Cdc37 complex overcomes drug resistance in glioma cells harboring FGFR3-TACC3 fusion gene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1736.