bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunonutrition for traumatic brain injury in children and adolescents: protocol for a systematic review and meta-analysis
Authors: Peng Rong , Li Hailong , Yang Lijun , Chen Xinwei , Zeng Linan , Bo Zhenyan , Zhang Lingli 
Published: September 2020

IntroductionTraumatic brain injury (TBI) is the leading cause of paediatric trauma death and disability worldwide. The ‘Guidelines for the Management of Severe Traumatic Brain Injury (Fourth Edition)’ recommend that nutritional goals should be achieved within 5–7 days of injury. Immune-enhancing nutrition or immunonutrition, referring to the addition of specialised nutrients, including glutamine, alanine, omega-3 fatty acids and nucleotides, to standard nutrition formulas, may improve surgical outcomes in the perioperative period. However, the role of immune-enhancing nutritional supplements for patients with paediatric TBI remains unclear. We will conduct a systematic review to determine the efficacy and safety of immunonutrition for patients with paediatric TBI and provide evidence for clinical decision-making.Methods and analysisStudies reporting immune-enhancing nutrition treatments for patients with paediatric TBI will be included. Outcomes of interest include the length of hospital stay, wound infections, all-cause mortality, non-wound infection, including pneumonia, urinary tract infection and bacteraemia, and the reports adverse events. Duration of follow-up has no restriction. Primary studies consisting of randomised controlled trials (RCTs) and non-RCTs will be eligible for this review, and only studies published in English will be included. We will search the Medline, Embase and Cochrane Library databases from their inception dates to January 2020. We will also search clinicaltrials.gov and the WHO International Clinical Trials Registry Platform for additional information. Two reviewers will independently select studies and extract data. Risk-of-bias will be assessed with tools based on the Cochrane risk-of-bias criteria and Newcastle-Ottawa Quality Assessment Scale. A meta-analysis will be used to pool data when there are sufﬁcient studies with homogeneity. Heterogeneity of the estimates across studies will be assessed; if necessary, a subgroup analysis will be performed to explore the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence obtained from this systematic review.Ethics and disseminationThe proposed systematic review and meta-analysis will be based on published data, and thus ethical approval is not required. The results of this review will be published.PROSPERO registration numberCRD42020154814.
Intermittent pneumatic compression for venous thromboembolism prevention: a systematic review on factors affecting adherence
Authors: Greenall Richard , Davis Rachel E 
Published: September 2020

ObjectiveVenous thromboembolism (VTE) is a potentially fatal complication of hospitalisation. Intermittent pneumatic compression (IPC) is one approach to reducing the likelihood of a VTE. Adherence to IPC is known to be inadequate though the reasons for this remain unclear. This systematic review explores factors that affect adherence to IPC in the inpatient context.MethodsInformation sources—EMBASE, MEDLINE and PsycINFO were searched for literature between January 1960 and May 2019. Eligibility criteria—studies were included if they focused on inpatient care and examined factors affecting adherence to IPC devices.ResultsIncluded studies—a total of 20 out of 1476 studies were included. Synthesis of results—eight factors were identified that affected adherence: patient discomfort (n=8), healthcare professionals’ knowledge and behaviours (n=6), mobilisation (n=6), equipment supply and demand (n=3), the use of guidelines (n=3), intensive care context (n=2), computer-assisted prescribing (n=2) and patients’ knowledge of IPC (n=1).ConclusionOverall while the evidence base is quite limited, a number of factors were shown to affect adherence to IPC. These findings could be used to inform future research and quality improvement efforts to increase adherence in this very important, but currently under-researched area.
Longitudinal association between food frequency and changes in body mass index: a prospective cohort study
Authors: Bernabe-Ortiz Antonio , Carrillo-Larco Rodrigo M 
Published: September 2020

ObjectivesAnalysing data of the Young Lives Study in Peru, we aimed at assessing the association between daily food frequency and body mass index (BMI) changes between 2006 and 2016.DesignSecondary analysis of a prospective ongoing cohort study.Setting20 sentinel sites in Peru.ParticipantsChildren enrolled in the younger cohort of the Young Lives Study. We used information from the second (2006–2007), third (2009–2010), fourth (2013–2014) and fifth (2016–2017) rounds of the younger cohort in Peru.Primary and secondary outcomesBMI as well as BMI-for-age z-score, both as numerical variables.ResultsData from 1948 children, mean age 4.3 (SD: 0.3) years and 966 (49.6%) women were included at baseline. In multivariable model, lower food consumption frequency was associated with increased BMI and BMI-for-age z-scores: children reporting <4 times of food consumption per day had a greater increase in BMI (β=0.39; 95% CI 0.17 to 0.62) and BMI-for-age z-score (β=0.07; 95% CI 0.01 to 0.13) compared with those reporting 5 per day. Results were consistent for those reporting exactly eating 4 times per day (β for BMI=0.16; 95% CI 0.02 to 0.30 and β for BMI-for-age z-score=0.05; 95% CI 0.01 to 0.09).ConclusionsChildren who eat <5 times per day, gain more BMI compared with those who eat ≥5 times. Parents should receive information to secure adequate nutrition for their children, both in terms of quality and quantity.
Profile and complexity of travel medicine consultations in Chile: unicentric cross-sectional study
Authors: Weitzel Thomas 
Published: September 2020

ObjectiveTo analyse the spectrum, vaccination needs and pretravel advice complexity of travellers presenting at a travel medicine clinic in Santiago, Chile.DesignCross-sectional study.SettingPretravel consultations in a private healthcare centre in Chile, an ‘emerging market’ country in South America.ParticipantsTravellers (n=1341) seeking pretravel advice at the Travel Medicine Program of Clínica Alemana, Santiago, from April 2016 to March 2018.Primary and secondary outcome measuresDemographical and travel characteristics, indications for travel vaccines and malaria prophylaxis, and complexity of travel consultations.ResultsOf 1341 travellers, 51% were female; the median age was 33 years. Most frequent travel reasons were tourism (67%) and business (20%). Median travel duration and time to departure were 21 days and 28 days, respectively. Most destinations were located in America (41%), followed by Asia (36%) and Africa (26%); 96% visited less developed countries, mostly in tropical regions, with risk of arboviral infections (94%) and malaria (69%). The indicated vaccine indications comprised hepatitis A (84%), yellow fever (58%), typhoid fever (51%), rabies (29%), polio (8%), Japanese encephalitis (6%) and meningococcal meningitis (5%). More than 60% of consultations were classified as complex.ConclusionThe studied population mostly visited less developed tropical regions, resulting in a high requirement of yellow fever and other travel-related vaccinations. Most consultations were complex and required a comprehensive knowledge and training in travel medicine.
Assisting beginners in root cause analysis operations: analysis and recommendations regarding the spread of COVID-19 in nursing facilities for the elderly
Authors: Tsuchiya Hitoshi 
Published: September 2020

BackgroundTo analyse a medical accident, much time and experience are needed. However, people without experience in analysis have difficulty understanding its conditions and methods, and as a result it takes longer to establish countermeasures. It must be noted that understanding conditions by simply aligning occurrences in the accident in a chronological order is difficult.PurposeA workflow chart that considers time was proposed so that individuals without adequate experience in analysis could easily carry out root cause analysis.MethodsIn the ‘workflow chart (WFC)’, the time sequence was described horizontally. On the vertical axis, the business manual, the occurrence of the accident, and the time of the occurrence are displayed. In the bottom column of patient event, information regarding damage to patients was written in accordance with time axis. Regarding the degree of damage, the time of error until the accident was identified was connected using a straight line (when the patient was not affected, a dotted line was used) in order to show the overall picture of the accident.ResultsAccording to the time flow chart, hints to identify potential risks were proposed. Focus was placed not only on the error event, but also on keywords such as manual inadequacy, time gap, degree of error and so on to easily lead to the question ‘why?’ To visualise this, I proposed an operation flow chart. By using time-WFC, even beginners can easily develop accident countermeasure strategies.ConclusionUsing a WFC that considers time, time of error and the occurrence of accident could be visualised. As a result, even individuals without experience in analysis could easily perform an analysis.
Impact of cytokine release syndrome on cardiac function following CD19 CAR-T cell therapy in children and young adults with hematological malignancies
Authors: Shalabi Haneen , Sachdev Vandana , Kulshreshtha Amita , Cohen Julia W , Yates Bonnie , Rosing Doug R , Sidenko Stanislav , Delbrook Cindy , Mackall Crystal , Wiley Brandon , Lee Daniel W , Shah Nirali N 
Published: September 2020

BackgroundChimeric antigen receptor (CAR) T-cell-associated cytokine release syndrome (CRS) may present with tachycardia, hemodynamic instability and reduced cardiac function. Pediatric CAR studies examining cardiac toxicity are limited.MethodsWe report on cardiac toxicity observed in children and young adults with hematologic malignancies enrolled in a CD19-28ζ CAR T-cell phase I trial (NCT01593696). All patients had a formal baseline echocardiogram. Real-time studies included echocardiograms on intensive care unit (ICU) transfer, and serial troponin and pro-B-type natriuretic peptide (pro-BNP) in the select patients.ResultsFrom July 2012 to March 2016, 52 patients, with a median age of 13.4 years (range 4.2–30.3) were treated. CRS developed in 37/52 (71%), which was grade 3–4 CRS in nine patients (17%). The median prior anthracycline exposure was 205 mg/m2 (range 70–620 mg/m2) in doxorubicin equivalents. The median baseline left ventricle ejection fraction (LVEF) and baseline LV global longitudinal strain (GLS) were 60% (range 50%–70%) and 16.8% (range 14.1%–23.5%, n=37) respectively. The majority, 78% (29/37), of patients had a reduced GLS <19% at baseline, and 6% (3/52) of patients had baseline LVEF <53%. ICU transfers occurred in 21 patients, with nine requiring vasoactive hemodynamic support and three necessitating >1 vasopressor. Six (12%) patients developed cardiac dysfunction (defined by >10% absolute decrease in LVEF or new-onset grade 2 or higher LV dysfunction, per CTCAE v4), among whom 4 had grade 3–4 CRS. Troponin elevations were seen in 4 of 13 patients, all of whom had low LVEF. Pro-BNP was elevated from baseline in 6/7 patients at the onset of CRS, with higher levels correlating with more severe CRS. Cardiac dysfunction fully resolved in all but two patients by day 28 post-CAR.ConclusionCardiac toxicity related to CD19-28ζ CAR T-cell-associated CRS was generally reversible by day 28 postinfusion. Implementation of more frequent monitoring with formal echocardiograms incorporating systemic analysis of changes in GLS, and cardiac biomarkers (troponin and proBNP) may help to earlier identify those patients at highest risk of severe cardiac systolic dysfunction, facilitating earlier interventions for CRS to potentially mitigate acute cardiac toxicity.
InSight
Authors: Janveja Ishani , Nambi Akshay , Bannur Shruthi , Gupta Sanchit , Padmanabhan Venkat 
Published: September 2020

Road safety is a major public health issue across the globe and over two-thirds of the road accidents occur at nighttime under low-light conditions or darkness. The state of the driver and her/his actions are the key factors impacting road safety. How can we monitor these in a cost-effective manner and in low-light conditions? RGB cameras present in smartphones perform poorly in low-lighting conditions due to lack of information captured. Hence, existing monitoring solutions rely upon specialized hardware such as infrared cameras or thermal cameras in low-light conditions, but are limited to only high-end vehicles owing to the cost of the hardware. We present InSight, a windshield-mounted smartphone-based system that can be retrofitted to the vehicle to monitor the state of the driver, specifically driver fatigue (based on frequent yawning and eye closure) and driver distraction (based on their direction of gaze). Challenges arise from designing an accurate, yet low-cost and non-intrusive system to continuously monitor the state of the driver.
In this paper, we present two novel and practical approaches for continuous driver monitoring in low-light conditions: (i) Image synthesis: enabling monitoring in low-light conditions using just the smartphone RGB camera by synthesizing a thermal image from RGB with a Generative Adversarial Network, and (ii) Near-IR LED: using a low-cost near-IR (NIR) LED attachment to the smartphone, where the NIR LED acts as a light source to illuminate the driver's face, which is not visible to the human eyes, but can be captured by standard smartphone cameras without any specialized hardware. We show that the proposed techniques can capture the driver's face accurately in low-lighting conditions to monitor driver's state. Further, since NIR and thermal imagery is significantly different than RGB images, we present a systematic approach to generate labelled data, which is used to train existing computer vision models. We present an extensive evaluation of both the approaches with data collected from 15 drivers in controlled basement area and on real roads in low-light conditions. The proposed NIR LED setup has an accuracy (Fl-score) of 85% and 93.8% in detecting driver fatigue and distraction, respectively in low-light.
Abstract 1007: Orphan nuclear receptor TLX regulates the antitumor immune response through transcriptional regulation of programmed death ligand 1 in glioma
Authors: Zhou Jiayi , Pei Xiaojuan , Wang Zhu , Gao Weijie , Chan Franky Leung , Li Xin , Mao Jie , Wu Dinglan 
Published: September 2020

Abstract
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis and novel treatment are urgently needed to improve patient outcomes. Clinical trials of immunotherapies for glioma including PD1/PD-L1 inhibition have performed but the outcome was not optimistic. In this study, we found that orphan nuclear recepter TLX and PD-L1 were both significantly upregulated in glioma lesions and the expression of TLX and PD-L1 in glioma was positively correlated. Moreover, the expression pattern of TLX also associated with a suppression microenvironment in glioma. Functional study revealed that suppression of TLX inhibited glioma cell growth and immune response, which accompanied with down-regulation of PD-L1. We also characterized that TLX could bind directly to PD-L1 promoter and activate PD-L1 gene transcription. Together, our present study shows, for the first time, that TLX can contribute to glioma immune escape via promoting the expression of PD-L1, targeting the druggable TLX may have a potential therapeutic significance in glioma immune therapy.
Citation Format: Jiayi Zhou, Xiaojuan Pei, Zhu Wang, Weijie Gao, Franky Leung Chan, Xin Li, Jie Mao, Dinglan Wu. Orphan nuclear receptor TLX regulates the antitumor immune response through transcriptional regulation of programmed death ligand 1 in glioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1007.
Abstract 1059: Targeting IDH1/2 mutant cancers with unique combinations of DNA repair inhibitors
Authors: Sule Amrita D. , Sundaram Ranjini , Bindra Ranjit 
Published: September 2020

Abstract
Mutations in the Isocitrate Dehydrogenase-1 and -2 (IDH1/2) genes occur in the vast majority of solid tumors including low-grade and secondary high-grade gliomas. These neomorphic mutations occur early on in gliomagenesis leading to the production of 2-Hydroxyglutarate (2HG). 2HG has been implicated in tumorigenesis via inhibiting α-ketoglutarate (αKG)-dependent dioxygenases. Our group recently demonstrated that the production of 2HG suppresses the high-fidelity homologous recombination (HR) DNA repair pathway, resulting in a state of “BRCAness”. We initially found that mutant IDH1/2-induced BRCAness confers exquisite sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, a finding which now has been replicated by multiple independent laboratories. Although IDH1/2 mutations were first identified in gliomas and acute myeloid leukemia (AML) cells, multiple other tumor types have subsequently been shown to harbor these mutations. Current clinical trials are testing the efficacy of PARP inhibitors as a monotherapy, as well as in combination with other DNA repair inhibitors. Here, we demonstrate that novel combinations of DNA repair inhibitors can be utilized to synergistically target IDH1/2-mutant glioma cells. In particular, we demonstrate potent synergy with ATRi and PARPis, a finding which was validated in multiple structurally unique drugs within these classes. We have shown that in an in vivo flank model bearing IDH1 R132H mutation, AZD6738 (ATRi) and Olaparib (PARPi) combination treatment reduces the tumor burden significantly relative to monotherapy and vehicle. As this combination is active in BRCA1/2-mutant cancers, in particular after the emergence of PARPi resistance, these data suggest are consistent with an underlying HR defect in IDH1/2-mutant gliomas. These preclinical investigations will provide a blueprint for future clinical trials combining PARP and ATR inhibitors in the treatment of IDH1/2 mutant cancers.
Citation Format: Amrita D. Sule, Ranjini Sundaram, Ranjit Bindra. Targeting IDH1/2 mutant cancers with unique combinations of DNA repair inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1059.
Abstract 1074: Programmable bacteria induce durable tumor regression and systemic antitumor immunity
Authors: Chowdhury Sreyan , Pu Kelly , Nimura Clare , Castro Samuel , Coker Courtney , Hinchliffe Taylor , Arpaia Nicholas , Danino Tal 
Published: September 2020

Abstract
Synthetic biology is driving a new era of medicine through the engineering of living cells. This transformative approach allows for the creation of systems that intelligently sense and respond to diverse environments, adding specificity and efficacy beyond the capabilities of molecular-based therapeutics. One particular area of focus has been the engineering of bacteria as therapeutic delivery systems to selectively release therapeutic payloads in vivo. We recently engineered a non-pathogenic Escherichia coli strain to specifically lyse within the tumor microenvironment and release an encoded nanobody antagonist of CD47 (CD47nb), an anti-phagocytic receptor that is commonly overexpressed in several human cancer types. We show that delivery of CD47nb by tumor-colonizing bacteria increases activation of tumor-infiltrating T cells, stimulates rapid tumor regression, prevents metastasis and leads to long-term survival in a syngeneic tumor model in mice. Moreover, we report that local injection of CD47nb-expressing bacteria stimulates systemic tumor-antigen-specific immune responses that reduce the growth of untreated tumors, providing proof-of-concept for an abscopal effect induced by an engineered bacterial immunotherapy. We have expanded this approach to include additional human and murine specific immunotherapeutic payloads and evaluate efficacy in multiple tumor model systems.
Citation Format: Sreyan Chowdhury, Kelly Pu, Clare Nimura, Samuel Castro, Courtney Coker, Taylor Hinchliffe, Nicholas Arpaia, Tal Danino. Programmable bacteria induce durable tumor regression and systemic antitumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1074.
Abstract 1079: Distinct DNA methylation targets by aging and chronic inflammation
Authors: Yamashita Satoshi , Nanjo Sohachi , Rehnberg Emil , Iida Naoko , Takeshima Hideyuki , Ando Takayuki , Maekita Takao , Sugiyama Toshiro , Ushijima Toshikazu 
Published: September 2020

Abstract
Aberrant DNA methylation is involved in many types of human cancers, and is induced by aging. In addition, it is known to be induced by chronic inflammation, and this inflammation-induced DNA methylation is considered as acceleration of age-related methylation. However, few studies addressed target genomic regions of age-related and inflammation-induced DNA methylation in a genome-wide manner. We previously demonstrated that Helicobacter pylori(HP) infection induces aberrant DNA methylation potently in human and gerbil gastric mucosa [Niwa, Cancer Res, 70:1430, 2010; Ushijima, Clin Cancer Res, 18:923, 2012]. Here, taking advantage of the potent methylation induction, we aimed to clarify the targets of methylation induction by aging and inflammation. We collected gastric mucosae from i) HP-never infected young individuals (under 40 years; n=4; G1), ii) HP-currently infected young individuals (n=4; G2), iii) HP-never-infected old individuals (above 60 years; n=4; G3), and vi) HP-currently-infected old individuals (n=4; G4). DNA methylation of 482,421 CpG probes was analyzed by Infinium Human Methylation 450K, and the probes were grouped into 270,249 genomic blocks. It was revealed that high levels of methylation were induced in 44,461 (16.5%) genomic blocks by current inflammation (G2/G1), even after correction of the influence of leucocyte infiltration. 61.8 % of the hypermethylation was acceleration of age-related methylation (G3/G1) while 21.6 % was specific to inflammation. Regions with H3K27me3 were frequently hypermethylated both by aging and inflammation. Basal methylation levels were essential for age-related hypermethylation while even regions with little basal methylation were hypermethylated by inflammation. When limited to promoter CpG islands, being a microRNA gene and high basal methylation levels strongly enhanced hypermethylation while H3K27me3 strongly enhanced inflammation-induced hypermethylation. Inflammation was capable of overriding active transcription. In young gastric mucosae (G2/G1), genes with high expression and frequent mutations in gastric cancers were more frequently methylated than in old ones (G4/G3).Methylation by inflammation was not simple acceleration of age-related methylation. Targets of aberrant DNA methylation were different between young and old gastric mucosae, and driver genes were preferentially methylated in young gastric mucosa [Yamashita, Clin Epigenet, in press].
Citation Format: Satoshi Yamashita, Sohachi Nanjo, Emil Rehnberg, Naoko Iida, Hideyuki Takeshima, Takayuki Ando, Takao Maekita, Toshiro Sugiyama, Toshikazu Ushijima. Distinct DNA methylation targets by aging and chronic inflammation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1079.