bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling US maternal mortality through critical discourse analysis
Authors: Allen Rebecca , Sovik Benedetti Mary 
Published: June 2019

Objectives: Given that pregnancy health information seeking is common and considered impactful on health outcomes, the potential lack of fair and clear information within media may be an impediment towards women developing their own agency and working towards the transformation and betterment of their own outcomes. Setting: The USA has the worst maternal mortality rate of any developed country. Women’s opinions are shaped and informed by public media and discourse; therefore, a critical look at how public media texts support women’s agency is of significance. Method: Reducing maternal mortality requires more than just effective health interventions. This paper uses critical discourse analysis to examine two samples of widely viewed public discourse around the issue of US maternal mortality and reveals the murky and polarised dialogue contained in each. Results: The two samples may be representative of a larger lack of clarity in US discourse about maternal mortality, a body of discourse which – to the detriment of women’s maternal morbidity and mortality outcomes – subtly but powerfully either declines to admit mistakes or uses polarising, overly simplified language. Conclusion: Recognising the polarised dialogue surrounding maternal mortality and working towards a more reasoned discussion of the issue at hand may promote women’s advocacy and provide potentially better outcomes.
Tamoxifen administration in pregnant mice can be deleterious to both mother and embryo
Authors: Ved Nikita , Curran Angela , Ashcroft Frances Mary , Sparrow Duncan Burnaby 
Published: June 2019

Since it was introduced 20 years ago, tamoxifen-inducible genetic recombination in vivo has become a standard tool in many fields. This technique has great utility, allowing precise temporal and spatial gene recombination mediated by expression of a Cre recombinase-oestrogen receptor hormone binding domain fusion protein. It is frequently used in developmental biology, either for accurate spatio-temporal gene deletion or for lineage-labelling. Administration of high doses of tamoxifen can rapidly induce abortion in pregnant mice but this can be partially overcome by progesterone co-administration. However, administration of tamoxifen to pregnant mice early in pregnancy may have potentially lethal effects on the mother independently of abortion, and can also severely perturb embryonic development. Despite this, only a few published studies mention this fact in passing, and standard parameters for successful or unsuccessful use of tamoxifen in pregnant mice have not been reported. Therefore, in the interests of providing a framework for more humane animal research, we describe our experiences of tamoxifen administration during early gestation in mice. These observations should assist the design of future studies in accordance with the principles of the three Rs (Replacement, Reduction and Refinement of Animals in Research).
Intraoperative changes in blood lactate levels are associated with worse short-term outcomes after cardiac surgery with cardiopulmonary bypass
Authors: Duval Benoit , Besnard Thibaud , Mion Stefano , Leuillet Sébastien , Jecker Olivier , Labrousse Louis , Rémy Alain , Zaouter Cedrick , Ouattara Alexandre 
Published: June 2019

Background: A high perioperative blood lactate level has been reported to be associated with poor outcomes after cardiac surgery. More than isolated peaks of lactate values, it should be more interesting to take into account changes in intraoperative blood lactate level (∆Lact). This large-scale retrospective study evaluated the relationship between ∆Lact and overall intensive care unit morbidity and 30-day all-cause mortality. Methods: Perioperative data from consecutive patients undergoing on-pump cardiac surgery between September 2010 and June 2016 were retrospectively analysed through our institutional database including clinical, transfusion and laboratory test results implemented prospectively by physicians. Blood lactate levels were initially measured after induction of anaesthesia (baseline) and periodically during the surgery. The ∆Lact was defined as the difference between the highest intraoperative blood lactate and the baseline lactate level and offered the opportunity to stratify patients into four subgroups: ⩽0, 0.1-0.9, 1-1.9 and ⩾2 mmol L−1. Results: From the 7,795 patients found eligible during the study period, 7,447 patients were analysed. The median ∆Lact of our patients was 0.6 (0.3-1) mmol L−1. Most of the studied patients (65.9%) exhibited a ∆Lact between 0.1 and 0.9 mmol L−1. A concentration-dependent relationship was observed between ∆Lact and intensive care unit morbidity and 30-day mortality. After adjustment for co-variables, all ∆Lact > 0 was associated with an increase in overall intensive care unit morbidity. An independent relationship was also found between ∆Lact and 30-day mortality as of a 1 mmol L−1 increase. Conclusion: Our results suggest that ∆Lact is associated with poor short-term outcomes in adult cardiac surgical patients.
LncRNA PAPAS may promote triple-negative breast cancer by downregulating miR-34a
Authors: Kong Yan , Geng Cuizhi , Dong Qian 
Published: June 2019

Objective To investigate the role of promoter and pre-rRNA antisense (PAPAS) long noncoding (Lnc) RNA in cancer biology. Methods Tumour and tumour-adjacent healthy tissue biopsies from patients with triple-negative breast cancer (TNBC), and plasma samples from these patients plus healthy controls, were assessed for PAPAS and microRNA (miR)-34a. Effects of PAPAS and miR-34a overexpression were also investigated in vitro. Results PAPAS was upregulated in tumour tissues of patients with TNBC versus tumour-adjacent healthy tissues. Plasma PAPAS levels were also upregulated in patients with TNBC versus healthy controls. Levels of PAPAS in tumour tissue was significantly positively correlated with PAPAS levels in plasma from patients with TNBC. MiR-34a was downregulated in tumour tissues versus adjacent healthy tissues, and was significantly correlated with PAPAS in tumour tissues. PAPAS overexpression in vitro was associated with miR-34a inhibition, while miR-34a failed to significantly affect PAPAS levels. PAPAS overexpression promoted in vitro migration and invasion of TNBC cells, while miR-34a overexpression was inhibitory. MiR-34a overexpression decreased the enhanced cell migration and invasion associated with PAPAS overexpression. PAPAS overexpression showed no significant effects on cancer-cell proliferation. Conclusion LncRNA PAPAS may promote TNBC by downregulating miR-34a.
Severe Bone Marrow Edema Among Patients Who Underwent Prior Marrow Stimulation Technique Is a Significant Predictor of Graft Failure After Autologous Chondrocyte Implantation
Authors: Merkely Gergo , Ogura Takahiro , Bryant Tim , Minas Tom 
Published: June 2019

Background: Autologous chondrocyte implantation (ACI) is a well-established cartilage repair procedure; however, numerous studies have shown higher ACI graft failure rates after prior marrow stimulation techniques (MSTs). Purpose: To identify which factors may predict decreased graft survival after ACI among patients who underwent a prior MST. A secondary aim was to investigate the specificity of these predictors. Study Design: Case-control study; Level of evidence, 3. Methods: In this review of prospectively collected data, the authors analyzed 38 patients who had failed prior MST surgery and subsequently underwent collagen-covered ACI (case group). The case group was divided into graft failure ACI (n = 8, 21%) and successful ACI (n = 30, 79%). Fourteen clinical variables were categorized and analyzed to determine predictors for failure of the ACI graft: age, body mass index, sex, defect characteristics (number, size, location, etiology, type), presence of kissing lesion, intraoperative presence of intralesional osteophyte, time between an MST and ACI, previous surgery, duration of the symptoms, and concomitant surgical procedure. Preoperative magnetic resonance imaging (MRI) was used to evaluate the severity of subchondral bone marrow edema (BME), graded I (absent) to IV (severe), and the presence of subchondral cyst, hypertrophic sclerosis, and intralesional osteophyte. The effects of these MRI findings on the graft survivor were also investigated. Concurrently, a control group without a prior MST was matched to investigate the specificity of the previously determined predictors. These patients were matched individually according to age, sex, body mass index, and outcome of the procedure (failure [n = 8] or successful [n = 30] per the case group). Results: In the case group, the presence of preoperative severe BME was significantly higher among patients with failed ACI as compared with patients with successful ACI ( P < .001). In the control group, the presence of severe BME was not significantly different between the failure and successful groups ( P = .747). The ACI graft failure rate among patients with a prior MST and preoperative grade IV BME was 83.7% at 5 years postoperatively, resulting in a significantly lower survival rate as compared with patients with a prior MST and without severe BME (5-year graft failure rate, 6.5%; P < .001). All the other parameters did not differ significantly. Conclusion: After a prior MST, the presence of grade IV BME by MRI was a predictive factor for graft failure among patients who then underwent second-generation ACI.
Borrelia lusitaniae Infection Mimicking Headache, Neurologic Deficits, and Cerebrospinal Fluid Lymphocytosis
Authors: Vieira José Pedro , Brito Maria João , de Carvalho Isabel Lopes 
Published: June 2019

Headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare headache syndrome included in the Classification of Headache of the International Headache Society as a “headache attributed to non-infectious inflammatory intracranial disease.” We report one 15-year-old patient with clinical history and cerebrospinal fluid findings compatible with the diagnosis of HaNDL in whom Borrelia lusitaniae was identified in cerebrospinal fluid by polymerase chain reaction.
Maximum Norepinephrine Dosage Within 24 Hours as an Indicator of Refractory Septic Shock: A Retrospective Study
Authors: Kasugai Daisuke , Hirakawa Akihiko , Ozaki Masuyuki , Nishida Kazuki , Ikeda Takao , Takahashi Kunihiko , Matsui Shigeyuki , Uenishi Norimichi 
Published: June 2019

Background: The management of refractory septic shock remains a major challenge in critical care and its early indicators are not fully understood. We hypothesized that the maximum norepinephrine dosage within 24 hours of intensive care unit (ICU) admission may be a useful indicator of early mortality in patients with septic shock. Methods: In this retrospective single-center observational study, patients with septic shock admitted to the emergency ICU of an academic medical center between April 2011 and March 2017 were included. Individuals with cardiac arrest and those with do-not-resuscitate orders before admission were excluded. We analyzed if the maximum norepinephrine dosage within 24 hours of ICU admission (MD24) was associated with 7-day mortality. Results: Among 152 patients with septic shock, 20 (15%) did not survive by day 7. The receiver operating characteristic curve analysis for predicting 7-day mortality revealed a cutoff of MD24 of 0.6 μg/kg/min (sensitivity 47%, specificity 93%). In the multivariable regression analysis, a higher MD24 was significantly associated with 7-day mortality (odds ratio: 7.20; 95% confidence interval [CI]: 2.02-25.7; P = .002) but not with 30-day mortality. Using the inverse probability of treatment weighting method in a propensity scoring analysis, a higher MD24 was significantly associated with 7-day (hazard ratio [HR]: 8.9; 95% CI: 3.2-25.0; P < .001) and 30-day mortality (HR: 2.7; 95% CI: 1.2-5.8; P = .012). Conclusions: An MD24 ≥0.6 μg/kg/min was significantly associated with 7-day mortality in patients with septic shock and may therefore be a useful indicator of refractory septic shock.
Gene Replacement Therapy: A Primer for the Health-system Pharmacist
Authors: Petrich John , Marchese Dominic , Jenkins Chris , Storey Michael , Blind Jill 
Published: June 2019

Purpose: Comprehensive review of gene replacement therapy with guidance and expert opinion on handling and administration for pharmacists. Summary: There are currently ∼2600 gene therapy clinical trials worldwide and 4 Food and Drug Administration (FDA)-approved gene therapy products available in the United States. Gene therapy and its handling are different from other drugs; however, there is a lack of guidance from the National Institutes of Health (NIH), FDA, Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and professional associations regarding their pharmaceutical application. Although the NIH stratifies the backbone biologicals of viral vectors in gene therapies into risk groups, incomplete information regarding minimization of exposure and reduction of risk exists. In the absence of defined guidance, individual institutions develop their own policies and procedures, which often differ and are often outdated. This review provides expert opinion on the role of pharmacists in institutional preparedness, as well as gene therapy handling and administration. A suggested infrastructural model for gene replacement therapy handling is described, including requisite equipment acquisition and standard operating procedure development. Personnel, patient, and caregiver education and training are discussed. Conclusion: Pharmacists have a key role in the proper handling and general management of gene replacement therapies, identifying risk level, establishing infrastructure, and developing adequate policies and protocols, particularly in the absence of consensus guidelines for the handling and transport of gene replacement therapies.
Statin-Associated Bilateral Foot Myopathy
Authors: Baggett Mary Caitlin , Nykamp Diane 
Published: June 2019

Objective: To report a case of statin-induced bilateral foot myopathy that resulted from 2 different statins. Case Summary: A 44-year-old Caucasian male with a history of ventricular fibrillation cardiac arrest, hyperlipidemia, and coronary artery disease experienced bilateral foot pain, weakness, and soreness while taking atorvastatin 20 mg daily. The pain subsided within weeks of discontinuing atorvastatin but returned years later after the initiation of rosuvastatin. The Naranjo probability scale indicates that this is a definite association between bilateral foot myopathy and statin use. Discussion: There is an association with statin use and lowering cardiovascular risk in patients with dyslipidemia and cardiovascular disease. However, statin metabolites can accumulate in the myocytes of muscle groups to cause a common side effect of myopathy. Statin myopathy typically occurs in large, bilateral, or proximal muscle groups, such as the thighs, back, calves, or buttocks. This patient was unusual in that his muscle symptoms only occurred in his feet and was severe enough to affect his ambulation. Conclusion: Stain-associated muscle symptoms have been reported to lessen medication adherence. There is also a risk with muscle symptoms that the patient could develop rhabdomyolysis, a rare but serious condition. Recognizing statin-associated muscle symptoms even in uncommon locations is important, so that alternative lipid-lowering strategies can be implemented to lower cardiovascular risk.
Effectiveness of Statins as Primary Prevention in People With Gout: A Population-Based Cohort Study
Authors: Garcia-Gil Maria , Comas-Cufí Marc , Ramos Rafel , Martí Ruth , Alves-Cabratosa Lia , Parramon Dídac , Prieto-Alhambra Daniel , Baena-Díez Jose Miguel , Salvador-González Betlem , Elosua Roberto , Dégano Irene R. , Marrugat Jaume , Grau María 
Published: June 2019

Background: Cardiovascular guidelines do not give firm recommendations on statin therapy in patients with gout because evidence is lacking. Aim: To analyze the effectiveness of statin therapy in primary prevention of coronary heart disease (CHD), ischemic stroke (IS), and all-cause mortality in a population with gout. Methods: A retrospective cohort study (July 2006 to December 2017) based on Information System for the Development of Research in Primary Care (SIDIAPQ), a research-quality database of electronic medical records, included primary care patients (aged 35-85 years) without previous cardiovascular disease (CVD). Participants were categorized as nonusers or new users of statins (defined as receiving statins for the first time during the study period). Index date was first statin invoicing for new users and randomly assigned to nonusers. The groups were compared for the incidence of CHD, IS, and all-cause mortality, using Cox proportional hazards modeling adjusted for propensity score. Results: Between July 2006 and December 2008, 8018 individuals were included; 736 (9.1%) were new users of statins. Median follow-up was 9.8 years. Crude incidence of CHD was 8.16 (95% confidence interval [CI]: 6.25-10.65) and 6.56 (95% CI: 5.85-7.36) events per 1000 person-years in new users and nonusers, respectively. Hazard ratios were 0.84 (95% CI: 0.60-1.19) for CHD, 0.68 (0.44-1.05) for IS, and 0.87 (0.67-1.12) for all-cause mortality. Hazard for diabetes was 1.27 (0.99-1.63). Conclusions: Statin therapy was not associated with a clinically significant decrease in CHD. Despite higher risk of CVD in gout populations compared to general population, patients with gout from a primary prevention population with a low-to-intermediate incidence of CHD should be evaluated according to their cardiovascular risk assessment, lifestyle recommendations, and preferences, in line with recent European League Against Rheumatism recommendations.
Dosimetric Effect of Intrafraction Tumor Motion in Lung Stereotactic Body Radiotherapy Using CyberKnife Static Tracking System
Authors: Chang Yu , Liu Hong-Yuan , Liang Zhi-Wen , Nie Xin , Yang Jing , Liu Gang , Li Qin , Yang Zhi-Yong 
Published: June 2019

Purpose: We investigated the dosimetric effect of intrafraction tumor motion in lung stereotactic body radiotherapy using the CyberKnife static tracking system. Methods: Four-dimensional computed tomography scans of a dynamic thorax phantom were acquired. Two motion ranges, 3 collimator sizes, and 4 treatment starting phases were investigated. Monte Carlo dose distributions were calculated on internal target volume with a treatment-specific setup margin for 6 Gy/1 fraction. Dosimetric effects of intrafractional tumor motion were assessed with Gafchromic films. γ (5%/3 mm), dose differences, and distance to agreement were analyzed. Results: With 30 mm collimator plans, the measured dose passed the criteria γ (5%/3 mm) in all tumor motion ranges. The γ passing rates of the plans using 20 mm or 20+35 mm collimators were much lower than that with 30 mm collimator, especially with the 30 mm tumor motion range. The measured dose of 10 mm tumor motion ranges all passed the 90% criteria of γ (5%/3 mm), the results being much better than those of 30 mm tumor motion ranges, which were below 80%. The results of same delivered plan but treated with different starting phases varies greatly. Conclusion: Xsight Lung Tracking technique should be used with caution in lung cancer stereotactic body radiation therapy because the temporal dose variations can be significant.
Number needed to treat: A primer for neurointerventionalists
Authors: Martinez-Gutierrez Juan Carlos , Leslie-Mazwi Thabele , Chandra Ronil V , Ong Kevin L , Nogueira Raul G , Goyal Mayank , Albuquerque Felipe C , Hirsch Joshua A 
Published: June 2019

Background The number needed to treat is a commonly used statistical term in modern neurointerventional practice. It represents the number of patients that need to be treated for one patient to benefit from an intervention. Given its growing popularity in reflecting study results, understanding the basics behind this statistic is of practical value to the neurointerventionalist. Methods Here, we review the basic theory and calculation of the number needed to treat, its application to stroke interventions, and its limitations. In addition, we demonstrate several simple methods of calculating the number needed to treat utilizing recent thrombectomy trial results. By presenting the number needed to treat as a universal metric, we provide a comprehensive comparative of the number needed to treat for key stroke therapies, including mechanical thrombectomy, tissue plasminogen activator, carotid endarterectomy, and prevention with antiplatelet and statin drugs. Conclusions In comparison with available stroke therapies, mechanical thrombectomy stands out as the most effective acute intervention in patients with emergent large-vessel occlusions. Understanding how the number needed to treat is derived and its implications helps provide perspective to clinical trial data, identify health-care resource priorities, and improve communication with patients, health-care providers, and additional key stakeholders.
ETV6-related thrombocytopenia and leukemia predisposition
Authors: Di Paola Jorge , Porter Christopher C. 
Published: June 2019

Abstract
Germ line mutations in ETV6 are responsible for a familial thrombocytopenia and leukemia predisposition syndrome. Thrombocytopenia is almost completely penetrant and is usually mild. Leukemia is reported in ∼30% of carriers and is most often B-cell acute lymphoblastic leukemia. The mechanisms by which ETV6 dysfunction promotes thrombocytopenia and leukemia remain unclear. Care for individuals with ETV6-related thrombocytopenia and leukemia predisposition includes genetic counseling, treatment or prevention of excessive bleeding and surveillance for the development of hematologic malignancy.
Locomotor patterns change over time when exposed to an uneven surface
Authors: Kent Jenny A. , Sommerfeld Joel H. , Mukherjee Mukul , Takahashi Kota Z. , Stergiou Nicholas 
Published: June 2019

During walking, uneven surfaces impose new demands for controlling balance and forward progression at each step. It is unknown the extent to which walking may be refined given a level of stride-to-stride unpredictability at distal level. Here, we explored the effects of an uneven terrain surface on whole-body locomotor dynamics on immediate exposure and after a familiarization period.
Eleven young, unimpaired adults walked for 12 minutes on flat and uneven terrain treadmills. The whole-body center of mass excursion range (COMEXC) and peak velocity (COMVEL), step length and width were estimated. On first exposure to uneven terrain, we saw significant increases in lateral COMEXC and COMVEL, and in the variability of COMEXC, COMVEL and foot placement in both anterior-posterior and medial-lateral directions. Increases in step width and decreases in step length supported the immediate adoption of a cautious, restrictive solution on uneven terrain. After familiarization, step length increased and the variability of anterior-posterior COMVEL and step length reduced, while in the medial-lateral direction step width and COMVEL reduced, alluding to a refinement of movement and a reduction of conservative strategies over time. The variability of medial-lateral COMEXC and COMVEL increased, however, consistent with a release of previously constrained degrees of freedom. Despite this increase in variability, a strong relationship between step width and medial-lateral COM movement was maintained.
Our results indicate that movement strategies of unimpaired adults when walking on uneven terrain can evolve over time with longer exposure to the surface.