bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children’s Oncology Group
Authors:   for the Children’s Oncology Group, Kopp Lisa M. , Womer Richard B. , Schwartz Cindy L. , Ebb David H. , Franco Vivian I. , Hall David , Barkauskas Donald A. , Krailo Mark D. , Grier Holcombe E. , Meyers Paul A. , Wexler Leonard H. , Marina Neyssa M. , Janeway Katherine A. , Gorlick Richard , Bernstein Mark L. , Lipshultz Steven E. 
Published: October 2019

Abstract

Background
Dexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown.

Methods
We evaluated children with osteosarcoma (OS) on two Children’s Oncology Group trials with higher dose doxorubicin (375–600 mg/m2) preceded by dexrazoxane (10:1 dexrazoxane:doxorubicin dosing). They were evaluated after the minimum expected treatment time (METT), defined as 28 weeks. Cardiotoxicity was identified by echocardiography and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Second malignant neoplasm (SMN) data was collected.

Results
All children had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. The end-diastolic septal thickness Z-scores (P < 0.01) and LV mass Z-scores (P < 0.01) were significantly smaller than normal for body-surface area in both sexes. The average LV mass Z-scores were significantly smaller for girls (P < 0.01) and marginally smaller for boys (P = 0.06). Girls had significantly smaller LV end-diastolic dimension Z-scores normalized to BSA (P < 0.01) compared to healthy controls and had significant increases in NT-proBNP. Four children developed SMNs as first events, a rate similar to historical controls.

Conclusions
Dexrazoxane prevented LV dysfunction and heart failure in children with OS receiving higher dose doxorubicin. However, LV structural changes were not fully prevented, especially in girls. As a result, hearts become abnormally small for body size, resulting in higher LV stress. Dexrazoxane did not increase the risk of SMN. Dexrazoxane should be used in this population, particularly for girls, to mitigate anthracycline-induced cardiotoxicity.

Trial registrations
ClinicalTrials.gov: NCT00003937 (P9754) registered 1 Nov 1999, and NCT00023998 (AOST0121) registered 13 Sept 2001.
Synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions
Authors: Wu Wenzhao , Yenkie Kirti M , Maravelias Christos T. 
Published: October 2019

Abstract
Recent advances in metabolic engineering have enabled the production of chemicals via bio-conversion using microbes. However, downstream separation accounts for 60–80% of the total production cost in many cases. Previous work on microbial production of extracellular chemicals has been mainly restricted to microbiology, biochemistry, metabolomics, or techno-economic analysis for specific product examples such as succinic acid, xanthan gum, lycopene, etc. In these studies, microbial production and separation technologies were selected apriori without considering any competing alternatives. However, technology selection in downstream separation and purification processes can have a major impact on the overall costs, product recovery, and purity. To this end, we apply a superstructure optimization based framework that enables the identification of critical technologies and their associated parameters in the synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions. We divide extracellular chemicals into three categories based on their physical properties, such as water solubility, physical state, relative density, volatility, etc. We analyze three major extracellular product categories (insoluble light, insoluble heavy and soluble) in detail and provide suggestions for additional product categories through extension of our analysis framework. The proposed analysis and results provide significant insights for technology selection and enable streamlined decision making when faced with any microbial product that is released extracellularly. The parameter variability analysis for the product as well as the associated technologies and comparison with novel alternatives is a key feature which forms the basis for designing better bioseparation strategies that have potential for commercial scalability and can compete with traditional chemical production methods.
Biliptysis
Authors: Elbahr Osama 
Published: October 2019

Abstract

Background
Biliptysis means coughing of bile which is a presenting symptom of a rare condition called bronchobiliary fistula (BBF). BBF is a connection between the biliary tract and bronchial tree. BBF mostly occurs secondary to malignancy, liver abscess, and trauma. Surgical approach in BBF management was the main management strategy, then endoscopic approach.

Case presentation
We managed our first encountered case of biliptysis endoscopically by endoscopic retrograde cholangiopancreatography (ERCP).

Conclusion
ERCP management seems to be effective in management of biliptysis.
Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial
Authors: Sharma Priyanka , Barlow William E. , Godwin Andrew K. , Parkes Eileen E. , Knight Laura A. , Walker Steven M. , Kennedy Richard D. , Harkin Denis P. , Logan Gemma E. , Steele Christopher J. , Lambe Shauna M. , Badve Sunil , Gökmen-Polar Yesim , Pathak Harsh B. , Isakova Kamilla , Linden Hannah M. , Porter Peggy , Pusztai Lajos , Thompson Alastair M. , Tripathy Debu , Hortobagyi Gabriel N. , Hayes Daniel F. 
Published: October 2019

PURPOSE To independently validate two biomarkers, a 44-gene DNA damage immune response (DDIR) signature and stromal tumor-infiltrating lymphocytes (sTILs), as prognostic markers in patients with triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin (A) and cyclophosphamide (C) in SWOG 9313. METHODS Four hundred twenty-five centrally determined patient cases with TNBC from S9313 were identified. DDIR signature was performed on RNA isolated from formalin-fixed paraffin-embedded tumor tissue, and samples were classified as DDIR negative or positive using predefined cutoffs. Evaluation of sTILs was performed as described previously. Markers were tested for prognostic value for disease-free survival (DFS) and overall survival (OS) using Cox regression models adjusted for treatment assignment, nodal status, and tumor size. RESULTS Among 425 patients with TNBC, 33% were node positive. DDIR was tested successfully in 90% of patients (381 of 425), 62% of which were DDIR signature positive. DDIR signature positivity was associated with improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.92; P = .015) and OS (HR, 0.61; 95% CI, 0.43 to 0.89; P = .010). sTILs density assessment was available in 99% of patients and was associated with improved DFS (HR, 0.70; 95% CI, 0.51 to 0.96; P = .026 for sTILs density ≥ 20% v < 20%) and OS (HR, 0.59; 95% CI, 0.41 to 0.85; P = .004 for sTILs density ≥ 20% v < 20%). DDIR signature score and sTILs density were moderately correlated ( r = 0.60), which precluded statistical significance for DFS in a joint model. Three-year DFS and OS in a subgroup of patients with DDIR positivity and T1c/T2N0 disease were 88% and 94%, respectively. CONCLUSION The prognostic role of sTILs and DDIR in early-stage TNBC was confirmed. DDIR signature conferred improved prognosis in two thirds of patients with TNBC treated with adjuvant AC. DDIR signature has the potential to stratify outcome and to identify patients with less projected benefit after AC chemotherapy.
What factors indicate prognosis for adults with depression in primary care? A protocol for meta-analyses of individual patient data using the Dep-GP database
Authors: Buckman Joshua E.J. , Saunders Rob , Cohen Zachary D. , Clarke Katherine , Ambler Gareth , DeRubeis Robert J. , Gilbody Simon , Hollon Steven D. , Kendrick Tony , Watkins Edward , White Ian R. , Lewis Glyn , Pilling Stephen 
Published: October 2019

Background: Pre-treatment severity is a key indicator of prognosis for those with depression. Knowledge is limited on how best to encompass severity of disorders. A number of non-severity related factors such as social support and life events are also indicators of prognosis. It is not clear whether this holds true after adjusting for pre-treatment severity as a) a depressive symptom scale score, and b) a broader construct encompassing symptom severity and related indicators: “disorder severity”. In order to investigate this, data from the individual participants of clinical trials which have measured a breadth of “disorder severity” related factors are needed. Aims: 1) To assess the association between outcomes for adults seeking treatment for depression and the severity of depression pre-treatment, considered both as i) depressive symptom severity only and ii) “disorder severity” which includes depressive symptom severity and comorbid anxiety, chronicity, history of depression, history of previous treatment, functional impairment and health-related quality of life. 2) To determine whether i) social support, ii) life events, iii) alcohol misuse, and iv) demographic factors (sex, age, ethnicity, marital status, employment status, level of educational attainment, and financial wellbeing) are prognostic indicators of outcomes, independent of baseline “disorder severity” and the type of treatment received. Methods: Databases were searched for randomised clinical trials (RCTs) that recruited adults seeking treatment for depression from their general practitioners and used the same diagnostic and screening instrument to measure severity at baseline – the Revised Clinical Interview Schedule; outcome measures could differ between studies. Chief investigators of all studies meeting inclusion criteria were contacted and individual patient data (IPD) were requested. Conclusions: In total 15 RCTs met inclusion criteria. The Dep-GP database will include the 6271 participants from the 13 studies that provided IPD. This protocol outlines how these data will be analysed. Registration: PROSPERO CRD42019129512 (01/04/2019)
UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence
Authors: Bratcher Holly B. , Rodrigues Charlene M. C. , Finn Adam , Wootton Mandy , Cameron J. Claire , Smith Andrew , Heath Paul , Ladhani Shamez , Snape Matthew D. , Pollard Andrew J. , Cunningham Richard , Borrow Raymond , Trotter Caroline , Gray Stephen J. , Maiden Martin C. J. , MacLennan Jenny M. 
Published: October 2019

Carriage of Neisseria meningitidis, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the meningococcus, and it is carried asymptomatically in the nasopharynx of ~10% of the population. Rates of carriage are dependent on age of the host and social and behavioural factors. In the UK, meningococcal carriage has been studied through large, multi-centre carriage surveys of adolescents in 1999, 2000, and 2001, demonstrating carriage can be affected by immunisation with the capsular group C meningococcal conjugate vaccine, inducing population immunity against carriage. Fifteen years after these surveys were carried out, invasive meningococcal disease incidence had declined from a peak in 1999. The UKMenCar4 study was conducted in 2014/15 to investigate rates of carriage amongst the adolescent population during a period of low disease incidence. The protocols and methodology used to perform UKMenCar4, a large carriage survey, are described here.
Negligible heritability of language laterality assessed by functional transcranial Doppler ultrasound: a twin study
Authors: Bishop Dorothy V.M. , Bates Timothy C. 
Published: October 2019

Background: It is widely assumed that individual differences in language lateralisation have a strong genetic basis, yet prior studies show low heritability (around 0.25) for the related trait of handedness, and two twin studies of structural brain asymmetry obtained similarly low estimates. This report describes heritability estimates from a twin study of language laterality and handedness phenotypes. Methods: The total sample consisted of 194 twin pairs (49% monozygotic) aged from 6 to 11 years. A language laterality index was obtained for 141 twin pairs, who completed a protocol where relative blood flow through left and right middle cerebral arteries was measured using functional transcranial Doppler ultrasound (fTCD) while the child described animation sequences. Handedness data was available from the Edinburgh Handedness Inventory (EHI) and Quantification of Hand Preference (QHP) for all 194 pairs. Heritability was assessed using conventional structural equation modeling, assuming no effect of shared environment (AE model). Results: For the two handedness measures, heritability estimates were consistent with prior research: 0.23 and 0.22 respectively for the EHI and QHP. For the language laterality index, however, the twin-cotwin correlations were very close to zero for both MZ and DZ twins, and the heritability estimate was zero. Conclusions: A single study showing negligible heritability for language laterality cannot rule out a genetic effect on language lateralisation. It is possible that the low twin-cotwin correlations were affected by noisy data: although the split-half reliability of the fTCD-based laterality index was high (0.85), we did not have information on test-retest reliability in children, which is likely to be lower. We cannot rule out the possibility that true heritability of differences in language lateralization is non-zero, but results indicate that the heritability of this trait is low at best. Stochastic variation in neurodevelopment appears to play a major role in determining cerebral lateralisation.
Delayed Gastric Emptying Associates With Diabetic Complications in Diabetic Patients With Symptoms of Gastroparesis
Authors: Parkman Henry P. , Wilson Laura A. , Farrugia Gianrico , Koch Kenneth L. , Hasler William L. , Nguyen Linda A. , Abell Thomas L. , Snape William , Clarke John , Kuo Braden , McCallum Richard W. , Sarosiek Irene , Grover Madhusudan , Miriel Laura , Tonascia James , Hamilton Frank A. , Pasricha Pankaj J. ,   for the NIDDK Gastroparesis Clinical Research Consortium (GpCRC)
Published: October 2019

OBJECTIVES:
Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE).

METHODS:
Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy.

RESULTS:
One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than in T2DM; however, triopathies (all 3 complications together) were seen in 10% of T1DM and 3% of T2DM (P = 0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36% vs 10%; P = 0.006) and number of diabetic complications (1.0 vs 0.5; P = 0.009); however, 39% of diabetic patients with delayed GE did not have any diabetic complications.

DISCUSSION:
In diabetic patients with symptoms of Gp, delayed GE was associated with the presence of retinopathy and the total number of diabetic complications. Only 10% of patients with T1DM and 3% of those with T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have any diabetic complications. Thus, the presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.
Left Ventricular Assist Device as Destination Therapy
Authors: Guglin Maya , Miller Leslie W. 
Published: October 2019

Mechanical circulatory support is the most rapidly evolving strategy in heart failure management. The growing number of patients who need better results than medical therapy can offer, the limited pool of donors for cardiac transplantation, and several technological breakthroughs have all made the option of implanting a left ventricular assist device (LVAD) as destination therapy more important.
In this review, we outline the indications and decision making process of considering a patient for a destination therapy LVAD, as well as outcomes, complications, and issues related to management of patients on currently approved devices. The future direction of the field will be determined by progress in technology and by further improvement in size, durability, pump dynamics, and most importantly, by solving the problem of supplying energy to the pump without a percutaneous driveline.
Pulmonary Congestion (White Lungs) on VA ECMO
Authors: Guglin Maya , Burchett Andrew , Tribble Thomas , Charnigo Richard 
Published: October 2019

Background
Veno-arterial extracorporeal membrane oxygenation therapy (VA ECMO) is used for short-term circulatory support in the setting of cardiogenic shock or cardiac arrest. While VA-ECMO improves hemodynamics and gas exchange, it may result in left ventricular distention and pulmonary congestion.

Methods
The records of all patients supported with VA ECMO for at least three consecutive days at our institution from 2012-2014 were retrospectively analyzed. All chest radiographs taken during VA ECMO support were graded on a scale of 1 to 4. A score of 1 was used when no pulmonary congestion was present. A score of 2 was used for congestion occupying less than half of both lungs. A score of 3 was used for diffuse congestion occupying over half of both lung fields. A score of 4 was used when complete opacification of both lungs was present. Grades 3 and 4 were considered “white lungs”. The presence of white lungs was examined as a categorical variable. The grade of congestion was examined as a continuous variable. Ordinal logistic regression was used for the analysis.

Results
The sample size analyzed included 46 events of VA ECMO support in 44 individual patients. In 34 (73.9%) patients the lungs became opacified and reached a score of 3 or 4 (the white lungs group), while in 12 (%) patients there were no white lungs. Overall, the percentage of patients that survived to weaning off VA ECMO was 60.9%. The percentage of patients that survived to hospital discharge was 37.0%. In patients who did not have white lungs the percentages of survival to weaning off VA ECMO and survival to hospital discharge were 91.7% and 66.7%, respectively. In those with white lungs, the percentages of survival to weaning off VA ECMO and survival to hospital discharge were 50.0% and 26.5%, respectively (p=0.019 for discharged alive). The duration of VA ECMO support, ECMO flow, daily fluid balance, sum net fluid balance for the length of stay, and use of hemodialysis predicted a higher degree of pulmonary congestion.

Conclusion
Severe pulmonary congestion, or white lungs, is common in patients on VA ECMO and is associated with very poor prognosis. Longer duration of support, greater positive fluid balance, higher ECMO flow, and use of hemodialysis are linked to development of white lungs.
Exploring Body Mass Index Changes in Left Ventricular Assist Device Patients
Authors: Thomas Raquel E. , Hanson Corrine , Woscyna Glenda , Lowes Brian D. 
Published: October 2019

Background: Current treatment options for end-stage heart failure, such as transplantation, can be limited by obesity guidelines. Mechanical devices such as Left Ventricular Assistive Devices (LVAD) can bridge heart failure patients to transplantation, however, after implantation; some patients may experience weight gain that precludes them from transplantation. Therefore, the objective of this study was to evaluate weight changes after the implantation of an LVAD.
Methods: A retrospective review of 130 patients receiving an LVAD were divided into two groups based on BMI at the time of implantation: obese (>30 kg/m2) and non-obese (/m2). Patients were evaluated at three time points post LVAD implantation: 3, 6, and 12 months for changes in weight and BMI.
Results: The mean BMI of the overall cohort at the time of LVAD implantation was 30.3 kg/m2. Patients who were not classified as obese at the time of LVAD implementation had a significant increase in BMI (2.1 kg/m2, p<0.001).
Conclusion: Weight gain after LVAD implementation is more likely in patients who are non-obese at the time of LVAD evaluation; however, obese subjects remained unlikely to lose weight one year post implantation.
Caregiver Burden is Low Nine to Twelve Months after Ventricular Assist Device Implantation
Authors: Ghashghaei Roxana , Tran Hao , Silva Jorge , Greenberg Barry H. , Barnard Denise , Adler Eric 
Published: October 2019

Background
Prior studies have found that caregivers of chronically ill patients, including those with heart failure, have significant stress and burden. Ventricular Assist Devices (VADs) are a promising therapeutic modality for end stage heart failure. However, caregiver burden has not previously been studied in the caregivers of VAD patients.
Methods
We studied 31 caregivers of VAD patients receiving care at University of California, San Diego. Validated instruments tools, such as the Bakas Caregiving Outcomes scale and Oberst Caregiving Demand and Difficulty sub-scales, were used to measure the caregivers’ psychological burden.
Results
Nearly half of the caregivers were the patient’s spouse or partner (55%) with a mean age of 57 years. When evaluating caregiver burden difficulty, 23/31 (74.2%) of the caregivers experienced little to no difficulty, 5/31 (16.1%) had mild difficulty, and 3/31 (9.6%) noted moderate difficulty. When assessing caregiver burden demand, 17/31 (54.8%) experienced little to no demand, 8/31 (25.8%) reported mild to moderate, 5/31 (16.1%) noted moderate to severe, and 1/31 (3.2%) had severe demand. Using the Baka’s scale, 27/31 (87.1%) reported that VADs were not disruptive to their lives.

Conclusions
In this single center study, we found that 80-90% of VAD caregivers had little caregiver burden difficulty or demand, which is significantly less than published studies of caregivers of patients with other chronic diseases. Further study will be required to validate these findings and compare them to other therapies for end stage heart failure, such as cardiac transplantation.