bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Breast Tomosynthesis: What Have We Learned?
Authors: Butler Reni , Conant Emily F , Philpotts Liane 
Published: March 2019

Abstract
Digital breast tomosynthesis (DBT) is increasingly recognized as a superior breast imaging technology compared with 2D digital mammography (DM) alone. Accumulating data confirm increased sensitivity and specificity in the screening setting, resulting in higher cancer detection rates and lower abnormal interpretation (recall) rates. In the diagnostic environment, DBT simplifies the diagnostic work-up and improves diagnostic accuracy. Initial concern about increased radiation exposure resulting from the DBT acquisition added onto a 2D mammogram has been largely alleviated by the development of synthesized 2D mammography (SM). Continued research is underway to reduce artifacts associated with SM, and improve its comparability to DM. Breast cancers detected with DBT are most often small invasive carcinomas with a preponderance for grade 1 histology and luminal A molecular characteristics. Recent data suggest that higher-grade cancers are also more often node negative when detected with DBT. A meta-analysis of early single-institution studies of the effect of DBT on interval cancers has shown a modest decrease when multiple data sets are combined. Because of the greater conspicuity of lesions on DBT imaging, detection of subtle architectural distortion is increased. Such findings include both spiculated invasive carcinomas and benign etiologies such as radial scars. The diagnostic evaluation of architectural distortion seen only with DBT can pose a challenge. When no sonographic correlate can be identified, DBT-guided biopsy and/or localization capability is essential. Initial experience with DBT-guided procedures suggests that DBT biopsy equipment may improve the efficiency of percutaneous breast biopsy with less radiation.
Pearls and Pitfalls of Contrast-Enhanced Mammography
Authors: Phillips Jordana , Fein-Zachary Valerie J , Slanetz Priscilla J 
Published: March 2019

Abstract
Contrast-enhanced mammography (CEM) is a promising new imaging modality that uses a dual-energy acquisition to provide both morphologic and vascular assessment of breast lesions. Although no official BI-RADS lexicon exists, interpretation entails using the mammographic BI-RADS lexicon in combination with that for breast MRI. CEM has comparable performance to breast MRI, with sensitivity of 93–100% and specificity of 80–94%. Currently FDA approved for diagnostic imaging, this technology can be helpful in determining disease extent in patients with newly diagnosed breast malignancy, monitoring response to neoadjuvant therapy, identifying mammographically occult malignancies, and diagnostic problem-solving. Studies are ongoing about its role in screening, especially in women with dense breasts or at elevated risk. There are some challenges to successful implementation into practice, but overall, patients tolerate the study well, and exam times are less than the full breast MRI protocol.
Proof Paradoxes and Normic Support: Socializing or Relativizing?
Authors: Di Bello Marcello 
Published: March 2019

AbstractSmith (2018) argues that, unlike other forms of evidence, naked statistical evidence fails to satisfy normic support. This is his solution to the puzzles of statistical evidence in legal proof. This paper focuses on Smith’s claim that DNA evidence in cold-hit cases does not satisfy normic support. I argue that if this claim is correct, virtually no other form of evidence used at trial can satisfy normic support. This is troublesome. I discuss a few ways in which Smith can respond.
Hybrid symplectic integrators for planetary dynamics
Authors: Rein Hanno , Hernandez David M , Tamayo Daniel , Brown Garett , Eckels Emily , Holmes Emma , Lau Michelle , Leblanc Réjean , Silburt Ari 
Published: March 2019

Abstract
Hybrid symplectic integrators such as MERCURY are widely used to simulate complex dynamical phenomena in planetary dynamics that could otherwise not be investigated. A hybrid integrator achieves high accuracy during close encounters by using a high-order integration scheme for the duration of the encounter while otherwise using a standard second-order Wisdom–Holman scheme, thereby optimizing both speed and accuracy. In this paper we reassess the criteria for choosing the switching function that determines which parts of the Hamiltonian are integrated with the high-order integrator. We show that the original motivation for choosing a polynomial switching function in MERCURY is not correct. We explain the nevertheless excellent performance of the MERCURY integrator and then explore a wide range of different switching functions including an infinitely differentiable function and a Heaviside function. We find that using a Heaviside function leads to a significantly simpler scheme compared to MERCURY , while maintaining the same accuracy in short-term simulations.
Serotonin Receptor 1A Variation Is Associated with Anxiety and Agonistic Behavior in Chimpanzees
Authors: Staes Nicky , Sherwood Chet C , Freeman Hani , Brosnan Sarah F , Schapiro Steven J , Hopkins William D , Bradley Brenda J 
Published: March 2019

AbstractSerotonin is a neurotransmitter that plays an important role in regulating behavior and personality in humans and other mammals. Polymorphisms in genes coding for the serotonin receptor subtype 1A (HTR1A), the serotonin transporter (SLC6A4), and the serotonin degrading enzyme monoamine oxidase A (MAOA) are associated with anxiety, impulsivity, and neurotic personality in humans. In primates, previous research has largely focused on SLC6A4 and MAOA, with few studies investigating the role of HTR1A polymorphic variation on behavior. Here, we examined variation in the coding region of HTR1A across apes, and genotyped polymorphic coding variation in a sample of 214 chimpanzees with matched measures of personality and behavior. We found evidence for positive selection at three amino acid substitution sites, one in chimpanzees-bonobos (Thr26Ser), one in humans (Phe33Val), and one in orangutans (Ala274Gly). Investigation of the HTR1A coding region in chimpanzees revealed a polymorphic site, where a C/A single nucleotide polymorphism changes a proline to a glutamine in the amino acid sequence (Pro248Gln). The substitution is located in the third intracellular loop of the receptor, a region important for serotonin signal transduction. The derived variant is the major allele in this population (frequency 0.67), and is associated with a reduction in anxiety, decreased rates of male agonistic behavior, and an increase in socio-positive behavior. These results are the first evidence that the HTR1A gene may be involved in regulating social behavior in chimpanzees and encourage further systematic investigation of polymorphic variation in other primate populations with corresponding data on behavior.
Nonsteroidal anti-inflammatory drug use and risk of acute kidney injury and hyperkalemia in older adults: a population-based study
Authors: Nash Danielle M , Markle-Reid Maureen , Brimble Kenneth S , McArthur Eric , Roshanov Pavel S , Fink Jeffrey C , Weir Matthew A , Garg Amit X 
Published: March 2019

Abstract

Background
Clinical guidelines caution against nonsteroidal anti-inflammatory drug (NSAID) use in older adults. The study objective was to quantify the 30-day risk of acute kidney injury (AKI) and hyperkalemia in older adults after NSAID initiation and to develop a model to predict these outcomes.

Methods
We conducted a population-based retrospective cohort study in Ontario, Canada from 2007 to 2015 of patients ≥66 years. We matched 46 107 new NSAID users with 46 107 nonusers with similar baseline health. The primary outcome was 30-day risk of AKI and secondary outcomes were hyperkalemia and all-cause mortality.

Results
NSAID use versus nonuse was associated with a higher 30-day risk of AKI {380 [0.82%] versus 272 [0.59%]; odds ratio (OR) 1.41 [95% confidence interval (CI) 1.20–1.65]} and hyperkalemia [184 (0.40%) versus 123 (0.27%); OR 1.50 (95% CI 1.20–1.89); risk difference 0.23% (95% CI 0.13–0.34)]. There was no association between NSAID use and all-cause mortality. A prediction model incorporated six predictors of AKI or hyperkalemia: older age, male gender, lower baseline estimated glomerular filtration rate, higher baseline serum potassium, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use or diuretic use. This model had moderate discrimination [C-statistic 0.72 (95% CI 0.70–0.74)] and good calibration.

Conclusions
In older adults, new NSAID use compared with nonuse was associated with a higher 30-day risk of AKI and hyperkalemia but not all-cause mortality. Prescription NSAID use among many older adults may be safe, but providers should use caution and assess individual risk.
Quantitative easing in a monetary union
Authors: Saraceno Francesco , Tamborini Roberto 
Published: March 2019

Abstract
The long season of unconventional monetary policies in advanced economies seems to be coming to an end. How can quantitative easing (QE) be effective where conventional monetary policy fails? How does it work in the peculiar environment of a monetary union? We study this latter case modelling a monetary union as the aggregate of two countries characterized by New Keynesian output and inflation relationships, with a Tobinian money market equation. QE is operated by the single central bank by expanding money supply in exchange for risky assets throughout the union. We assess the stabilization capacity of QE under different types of symmetric and asymmetric shocks, in which case fiscal accommodation at the country level should also intervene.
A Matter of Life or Death: A Survey Experiment on the Perceived Legitimacy of Political Decision-Making on Euthanasia
Authors: Christensen Henrik Serup , Himmelroos Staffan , Setälä Maija 
Published: March 2019

AbstractMost representative democracies seem to experience dwindling levels of legitimacy in the eyes of citizens. Nevertheless, it remains unclear what people want from parliamentary decision-making. In this study, we test the impact of outcome favourability, actor involvement and justifications on the perceived legitimacy of a parliamentary decision-making process on euthanasia in Finland. We do so with the help of a survey experiment (n = 1243), where respondents were exposed to a vignette where the treatments varied randomly. The results suggest that outcome favourability is of primary importance, but the involvement of experts and citizens also boost legitimacy in the eyes of citizens. Justifications, or presenting arguments for the decisions, does not enhance legitimacy and may even cause a backfire mechanism where the difference between getting and not getting the preferred outcome is amplified.
Incidence, risk factors, and outcomes of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia
Authors: MacKenzie Katelyn , Cunningham Kathy , Thomas Sumesh , Mondal Tapas , el Helou Salhab , Shah Prakesh S , Mukerji Amit 
Published: March 2019

Abstract

Objectives
To determine the incidence and risk factors for pulmonary hypertension (PH) in preterm infants with moderate to severe bronchopulmonary dysplasia (BPD) and to compare short-term outcomes.

Methods
Preterm infants &lt;32 weeks gestation born August 2013 through July 2015 with moderate to severe BPD at 36 weeks postmenstrual age were categorized into BPD-PH (exposure) and BPD-noPH (control) groups.

Results
Of 92 infants with BPD, 87 had echocardiographic assessment, of whom 24 (28%) had PH. On multiple logistic regression after adjustment for gestational age and sex, no significant risk factors for PH were identified based on data from this cohort. There were no differences in resource utilization or clinical outcomes including survival to discharge.

Conclusion
Approximately one out of four patients with moderate to severe BPD were identified as having PH. No significant risk factors for PH were identified. No differences in outcomes were identified for those with and without PH.
Synergistic effect of immunotherapy and radiotherapy in non-small cell lung cancer: current clinical trials and prospective challenges
Authors: Yang Hui , Jin Tao , Li Mengqian , Xue Jianxin , Lu Bo 
Published: March 2019

Abstract
Lately, the success of ICIs has drastically changed the landscape of cancer treatment, and several immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration (FDA) for advanced non-small cell lung cancer (NSCLC). However, numerous patients are resistant to ICIs and require additional procedures for better efficacy results. Thus, combination therapy is urgently needed to strengthen the anti-tumor immunity. A variety of preclinical and clinical studies combining ICIs with radiotherapy (RT) have demonstrated that the combination could induce synergistic effects, as RT overcomes the resistance to ICIs. However, the underlying mechanism of the synergistic effect and the optimal arrangement of the combination therapy are indecisive now. Hence, this review was conducted to provide an update on the current clinical trial results and highlighted the ongoing trials. We also discussed the optimal parameters in clinical trials, including radiation dose, radiation fractionation, radiation target field, and sequencing of combination therapy. In this review, we found that combination therapy showed stronger anti-tumor immunity with tolerable toxicities in clinical trials. However, the best combination mode and potential biomarkers for the target patients in combination therapy are still unclear.
Global Epidemiology of Use of and Disparities in Caesarean Sections
Authors: Boerma Ties , Ronsmans Carine , Melesse Dessalegn Y. , Barros Aluisio J. D. , Barros Fernando C. , Juan Liang , Moller Ann-Beth , Say Lale , Hosseinpoor Ahmad Reza , Yi Mu , de Lyra Rabello Neto Dácio , Temmerman Marleen 
Published: March 2019

(Abstracted from Lancet 2018;392(10155):1341–1348)
Cesarean delivery can save women's and infants' lives and should be universally accessible. However, the large increase in cesarean delivery use, often for nonmedical indications, is of concern given the risks for both women and children.
Association of Prenatal Maternal Depression and Anxiety Symptoms With Infant White Matter Microstructure
Authors: Dean Douglas C. , Planalp Elizabeth M. , Wooten William , Kecskemeti Steven R. , Adluru Nagesh , Schmidt Cory K. , Frye Corrina , Birn Rasmus M. , Burghy Cory A. , Schmidt Nicole L. , Styner Martin A. , Short Sarah J. , Kalin Ned H. , Goldsmith H. Hill , Alexander Andrew L. , Davidson Richard J. 
Published: March 2019

(Abstracted from JAMA Pediatr 2018;172(10):973–981)
Depression and anxiety are common during pregnancy. These disorders are estimated to affect 7% to 20% of pregnant women; however, many women reach only a subclinical threshold and are not formally diagnosed.
Personalised Perioperative Care by E-Health After Intermediate-Grade Abdominal Surgery: A Multicentre, Single-Blind, Randomised, Placebo-Controlled Trial
Authors: van der Meij Eva , Anema Johannes R. , Leclercq Wouter K. G. , Bongers Marlies Y. , Consten Esther C. J. , Schraffordt Koops Steven E. , van de Ven Peter M. , Terwee Caroline B. , van Dongen Johanna M. , Schaafsma Frederieke G. , Meijerink Wilhelmus J. H. J. , Bonjer Hendrik J. , Huirne Judith A. F. 
Published: March 2019

(Abstracted from Lancet 2018;392:51–59)
Instructing and guiding patients are essential for successful recovery after surgery. Because of efficiency-driven, shortened hospital stays, the amount of time health care professionals spend, before and after surgery with their patients, has been reduced.
Donor Spermatogenesis in De Novo Formed Seminiferous Tubules From Transplanted Testicular Cells in Rhesus Monkey Testis
Authors: Shetty Gunapala , Mitchell Jennifer M. , Lam Truong Nguyen Anh , Wu Zhuang , Zhang Jie , Hill Lorraine , Tailor Ramesh C. , Peters Karen A. , Penedo Maria Cecilia , Orwig Kyle E. , Meistrich Marvin L. 
Published: March 2019

(Abstracted from Hum Reprod 2018;33:2249–2255)
Cytotoxic cancer treatments, including chemotherapy and radiotherapy, cause damage to spermatogenic stem cells (SSCs), jeopardizing the fertility of young men of reproductive age. One potential method for future production of sperm in this population is SSC transplantation.
Geographic Distribution of Regional Quota Program Graduates of Japanese Medical Schools: A Nationwide Cohort Study
Authors: Matsumoto Masatoshi , Kashima Saori , Owaki Tetsuhiro , Iguchi Seitaro , Inoue Kazuo , Tazuma Susumu , Maeda Takahiro 
Published: March 2019

Purpose
To show the practice location of graduates from two Japanese programs recruiting physicians to rural areas: a regional quota program of medical schools and a prefecture scholarship program (a prefecture is an administrative geographic division). Graduates of each program must work in a designated rural prefecture for a fixed period.

Method
A nationwide cohort study was conducted for three groups of participants graduating between 2014 and 2016: quota graduates without scholarship (quota alone), nonquota graduates with scholarship (scholarship alone), and quota graduates with scholarship. A questionnaire was sent via medical school or prefecture office to each potential subject to collect baseline individual data, including home prefecture and graduation year. Data were connected through physician identification number to the Physician Census 2016 of the Ministry of Health, Labour and Welfare to identify the subjects’ practice location and compared with data for other physicians in the census. Comparisons were conducted with Mann-Whitney and chi-square tests.

Results
The proportion of physicians working in nonmetropolitan municipalities for quota alone (185/244; 75.8%), scholarship alone (305/363; 84.0%), and quota with scholarship (341/384; 88.8%) was significantly higher than for other physicians (13,299/22,906; 58.1%). Median population density of the municipalities where subjects worked for quota alone (1,042.4 persons per square kilometer), scholarship alone (613.5), and quota with scholarship (547.4) was significantly lower than that for other physicians (3,214.0). These disparities increased with number of years since graduation.

Conclusions
The regional quota and prefecture scholarship programs succeeded in producing physicians who practiced in rural areas of Japan.
Cadaver Rounds: A Comprehensive Exercise That Integrates Clinical Context Into Medical Gross Anatomy
Authors: Meredith M. Alex , Clemo H. Ruth , McGinn Melissa J. , Santen Sally A. , DiGiovanni Susan R. 
Published: March 2019

Problem
The purpose of medical schools is to train students to care for patients; however, the temporal and conceptual gap between course work and patient care may induce students to undervalue preclinical course work, thereby decreasing learning and retention. Bringing clinical context into preclinical courses reduces this problem, and many preclinical programs incorporate “cameo” appearances of clinical material. In contrast, the authors describe a comprehensive program at Virginia Commonwealth University School of Medicine that uses the cadaver as the students’ first patient to embed clinical context within preclinical anatomy.

Approach
As the students’ first patient, cadavers undergo modified physical exams, whole-body computed tomography scans, and pathology sample analysis. Students log daily dissection observations onto a “patient chart.” Group findings are integrated, on a self-directed basis, into a final grand rounds–style presentation (“Cadaver Rounds”) requiring students to synthesize longitudinally collected observations into a plausible clinical condition likely experienced by the cadaver-patient when alive. The entire exercise uses few additional contact hours (about six) and runs concurrently with the existing medical curriculum.

Outcomes
According to course surveys used to assess students’ perceptions of the relevance and effectiveness of Cadaver Rounds (2015–2017), the students’ experience was highly positive. Participation by faculty and clinicians has been enthusiastic.

Next Steps
The authors hope both to identify additional authentic clinical tasks to import into the dissection lab and to partner with other programs to adopt and evaluate this clinically centered approach to anatomy.
School Absence Associated With Childhood Pain in the United States
Authors: Groenewald Cornelius B. , Giles Marian , Palermo Tonya M. 
Published: March 2019

Objective:
The objective of this study was to estimate the national burden of school absenteeism associated with pain among 6 to 17-year-old children in the United States.

Methods:
Data were analyzed from a large, nationally representative sample from the 2012 National Health Interview Survey. Associations between pain and school absence were analyzed using multivariate negative binomial models controlling for sociodemographic and clinical characteristics.

Results:
The sample contained 8641 participants, of whom 30.3% reported pain over the preceding 12 months. Mean number of parent-reported school days missed across the entire sample was 3 per child; however pain was associated with an additional 1.5 reported missed school days per child. Furthermore, pain was associated with higher rates of chronic absenteeism (missing >15 d of school): 6.1% of children with pain was chronically absent as compared with 1.3% of children without pain. Extrapolated to the nation, childhood pain in the United States was associated with 22.2 million additional days of missed school, whereas childhood asthma, in comparison, was associated with 8 million additional days of school missed.

Discussion:
Associations between pain and school absenteeism highlight the need for interventions aimed at improving school attendance among children with pain.
Does postoperative alignment affect union in distal femoral fractures?
Authors: Long Charles Wyatt , Seligson David , Douglas Lonnie Rhea 
Published: March 2019

Background:
Distal femoral shaft fractures can be hard to treat. Recently, a meta-analysis concluded that healing rates of distal femoral fractures are suboptimal, and further research is needed. The purpose of our study was to evaluate if postoperative alignment affected union rates of distal femoral fractures.

Methods:
Eighty-nine distal femoral fractures from the University of Louisville met inclusion and exclusion criteria. We used the Fracture and Dislocation Classification Compendium-2018 to classify fractures. Radiographs were evaluated for fracture location, alignment, and for healing. All statistical tests had a level of significance of 0.05. Statistical tests included a chi squared analysis, a t-test for two independent samples for proportions, and Fisher’s exact tests.

Results:
Chi squared analysis showed a statistically significant difference in healing of fractures with anatomic alignment versus those with nonanatomic alignment (χ2=18.241, P<0.001). The t-test of two independent samples for proportions showed that the 51% increase in healing of fractures with anatomic alignment was statistically significant (P<0.002, 95% CI 0.22, 0.80). Fisher’s exact test for specific fracture types also showed statistical significance (P<0.01).

Conclusions:
Proper anatomical alignment during surgical fixation of infraisthmal and supracondylar fractures is strongly associated with increased rates of fracture healing. Likewise, there is a strong association between nonanatomic alignment and nonunion. A prospective study examining the effect of alignment on union, regardless of fixation method, is reasonable and recommended.