bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of prior knowledge in machine learning of complex network systems
Authors: Ferranti Dana , Krane David , Craft David 
Published: July 2017

Abstract

Motivation
Our overall goal is to develop machine-learning approaches based on genomics and other relevant accessible information for use in predicting how a patient will respond to a given proposed drug or treatment. Given the complexity of this problem, we begin by developing, testing and analyzing learning methods using data from simulated systems, which allows us access to a known ground truth. We examine the benefits of using prior system knowledge and investigate how learning accuracy depends on various system parameters as well as the amount of training data available.

Results
The simulations are based on Boolean networks—directed graphs with 0/1 node states and logical node update rules—which are the simplest computational systems that can mimic the dynamic behavior of cellular systems. Boolean networks can be generated and simulated at scale, have complex yet cyclical dynamics and as such provide a useful framework for developing machine-learning algorithms for modular and hierarchical networks such as biological systems in general and cancer in particular. We demonstrate that utilizing prior knowledge (in the form of network connectivity information), without detailed state equations, greatly increases the power of machine-learning algorithms to predict network steady-state node values (‘phenotypes’) and perturbation responses (‘drug effects’).

Availability and implementation
Links to codes and datasets here: https://gray.mgh.harvard.edu/people-directory/71-david-craft-phd.

Supplementary information
Supplementary data are available at Bioinformatics online.
Prelude to Forgery: Baldwin of Bury meets Pope Alexander II
Authors: Savill Benjamin 
Published: July 2017

Abstract
This article argues that we can only understand Bury St Edmunds’ post-Conquest dossier of forged Anglo-Saxon royal diplomas by viewing it alongside that house’s earlier acquisition of an authentic papal privilege from Alexander II (Oct. 1071). That is, the hitherto overlooked failure of that the genuine papal document to find any acceptance in 1070s England necessitated Bury’s recourse to royal forgery. The implications of this go well beyond Bury. Abbot Baldwin’s initial optimism in eliciting papal support sprang from the renewed strength of Anglo-papal relations in the decades preceding the Norman Conquest. The genuine document’s failure, and the subsequent turn to forging royal texts, is mirrored by an almost total absence of evidence of petitions for papal support in the post-Conquest decades. In light of this, we must be wary of attempts to date any part of the wider corpus of forged papal documents for English beneficiaries within these same immediately post-Conquest years: the failed application of even genuine papal acta under the new Anglo-Norman regime suggests that attempts to forge similar specimens would have been highly unlikely in this period. The article’s appendix comprises the first full critical edition of the Alexander II privilege, together with an English translation.
The Use of the Delphi and Other Consensus Group Methods in Medical Education Research: A Review
Authors: Humphrey-Murto Susan , Varpio Lara , Wood Timothy J. , Gonsalves Carol , Ufholz Lee-Anne , Mascioli Kelly , Wang Carol , Foth Thomas 
Published: July 2017

PurposeConsensus group methods, such as the Delphi method and nominal group technique (NGT), are used to synthesize expert opinions when evidence is lacking. Despite their extensive use, these methods are inconsistently applied. Their use in medical education research has not been well studied. The authors set out to describe the use of consensus methods in medical education research and to assess the reporting quality of these methods and results.MethodUsing scoping review methods, the authors searched the Medline, Embase, PsycInfo, PubMed, Scopus, and ERIC databases for 2009–2016. Full-text articles that focused on medical education and the keywords Delphi, RAND, NGT, or other consensus group methods were included. A standardized extraction form was used to collect article demographic data and features reflecting methodological rigor.ResultsOf the articles reviewed, 257 met the inclusion criteria. The Modified Delphi (105/257; 40.8%), Delphi (91/257; 35.4%), and NGT (23/257; 8.9%) methods were most often used. The most common study purpose was curriculum development or reform (68/257; 26.5%), assessment tool development (55/257; 21.4%), and defining competencies (43/257; 16.7%). The reporting quality varied, with 70.0% (180/257) of articles reporting a literature review, 27.2% (70/257) reporting what background information was provided to participants, 66.1% (170/257) describing the number of participants, 40.1% (103/257) reporting if private decisions were collected, 37.7% (97/257) reporting if formal feedback of group ratings was shared, and 43.2% (111/257) defining consensus a priori.ConclusionsConsensus methods are poorly standardized and inconsistently used in medical education research. Improved criteria for reporting are needed.
The Effect of a Community-Based Medical School on the State and Local Physician Workforce
Authors: Phillips Julie P. , Wendling Andrea L. , Fahey Carolyn A. , Mavis Brian E. 
Published: July 2017

Purpose
To assess the effect of community-based medical education as implemented by Michigan State University College of Human Medicine (MSU-CHM), which has immersed students in diverse communities across Michigan since its founding, on the physician workforce in the six communities in which clinical campuses were initially established.

Method
The authors used American Medical Association Masterfile data from 2011 to obtain practice locations and specialty data for all MSU-CHM graduates from 1972 through 2006. They classified physicians as either practicing primary care or practicing in a high-need specialty. Using Geographic Information Systems software, the authors geocoded practice locations to the ZIP Code level, evaluated whether the practice was within a Health Professional Shortage Area, and determined rurality, using 2006 Rural–Urban Commuting Area Code data. They visually compared maps of the footprints of each campus to glean insights.

Results
The authors analyzed 3,107 of 3,309 graduates (94%). Of these, 635 (20%) practiced within 50 miles of their medical school campus. Saginaw and Flint graduates were more likely to practice in Detroit and its surrounding suburbs, reflecting these communities’ urban character. Grand Rapids, the community with the strongest tertiary medical care focus, had the lowest proportions of rural and high-need specialty graduates.

Conclusions
This case study suggests that distributed medical education campuses can have a significant effect on the long-term regional physician workforce. Students’ long-term practice choices may also reflect the patient populations and specialty patterns of the communities where they learn.
Using Complexity Theory to Guide Medical School Evaluations
Authors: Jorm Christine , Roberts Chris 
Published: July 2017

Contemporary medical school evaluations are narrow in focus and often do not consider the wider systems implications of the relationship between learning and teaching, research, clinical care, and community engagement. The result is graduates who lack the necessary knowledge and skills for the modern health care system and an educational system that is limited in its ability to learn and change.
To address this issue, the authors apply complexity theory to medical school evaluation, using four key factors—nesting, diversity, self-organization, and emergent outcomes. To help medical educators apply this evaluation approach in their own settings, the authors offer two tools—a modified program logic model and sensemaking. In sensemaking, they use the organic metaphor of the medical school as a neuron situated within a complex neural network to enable medical educators to reframe the way they think about program evaluation. The authors then offer practical guidance for applying this model, including describing the example of addressing graduates’ engagement in the health care system. The authors consider the input of teachers, the role of culture and curriculum, and the clinical care system in this example.
Medical school evaluation is reframed as an improvement science for complex social interventions (medical school is such an intervention) in this model. With complexity theory’s focus on emergent outcomes, evaluation takes on a new focus, reimagining medical students as reaching their future potential as change agents, who transform health systems and the lives of patients.
Pain in Children With Cancer
Authors: Tutelman Perri R. , Chambers Christine T. , Stinson Jennifer N. , Parker Jennifer A. , Fernandez Conrad V. , Witteman Holly O. , Nathan Paul C. , Barwick Melanie , Campbell Fiona , Jibb Lindsay A. , Irwin Karen 
Published: July 2017

Objectives:
Pain is a common and distressing symptom of pediatric cancer, as reported by both children and their parents. Increasingly, children with cancer are cared for as outpatients, yet little is known about how parents manage their cancer-related pain. The aim of the current study was to examine pain prevalence and characteristics, and the pharmacological, physical, and psychological pain management strategies used by parents to manage their child’s cancer pain.

Materials and Methods:
In total, 230 parents and caregivers (89% mothers) of children (mean age=8.93 y, SD=4.50) with cancer currently in treatment or who are survivors completed an online survey about their child’s pain in the preceding month.

Results:
Results indicated that children with cancer who were on active treatment and who were posttreatment experienced clinically significant levels of pain. Parents reported using more physical and psychological strategies than pharmacological strategies to manage their child’s pain. The most frequently used physical/psychological strategy was distraction and acetaminophen was the most frequently administered pain medication. Parents’ confidence in managing their child’s pain was inversely associated with both how much pain they perceived their child had, and also whether they had given any pain medication.

Discussion:
The results of this study suggest that despite parents’ use of pain management strategies, management of cancer-related pain continues to be a problem for children during treatment and into survivorship.
Peripheral Interventions for Painful Stump Neuromas of the Lower Limb
Authors: Poyntz Stephanie A. , Hacking Nicholas M. , Dalal Milind , Fowler Stephen 
Published: July 2017

Objectives:
Painful stump neuromas in lower limb amputees are a significant burden on a person’s quality of life due to interference with wearing prostheses and therefore the ability to walk. Treating painful stump neuromas is a challenge perhaps reflected by the lack of clinical guidelines.

Materials and Methods:
A systematic review was conducted to evaluate the efficacy of all treatments tried in the management of symptomatic neuromas in the lower limb amputation stump in order to establish whether one treatment is superior.

Results:
Twenty-two studies were included in the final review which examined 14 different treatments both surgical and nonsurgical. Results showed that no single treatment showed superiority.

Discussion:
The 4 treatments that showed most promise included targeted nerve implantation, traction neurectomy, nerve-to-nerve anastomosis, and perineurial gluing. The short follow-up times and small sample sizes of the studies highlighted the need for more robust clinical studies.
Responsiveness of the Electrically Stimulated Cochlear Nerve in Children With Cochlear Nerve Deficiency
Authors: He Shuman , Shahsavarani Bahar S. , McFayden Tyler C. , Wang Haibo , Gill Katherine E. , Xu Lei , Chao Xiuhua , Luo Jianfen , Wang Ruijie , He Nancy 
Published: July 2017

Objectives:
This study aimed to (1) investigate the responsiveness of the cochlear nerve (CN) to a single biphasic-electrical pulse in implanted children with cochlear nerve deficiency (CND) and (2) compare their results with those measured in implanted children with normal-size CNs.

Design:
Participants included 23 children with CND (CND1 to CND23) and 18 children with normal-size CNs (S1 to S18). All subjects except for CND1 used Cochlear Nucleus cochlear implants with contour electrode arrays in their test ears. CND1 was implanted with a Cochlear Nucleus Freedom cochlear implant with a straight electrode array in the test ear. For each subject, the CN input/output (I/O) function and the refractory recovery function were measured using electrophysiological measures of the electrically evoked compound action potential (eCAP) at multiple electrode sites across the electrode array. Dependent variables included eCAP threshold, the maximum eCAP amplitude, slope of the I/O function, and time-constants of the refractory recovery function. Slopes of I/O functions were estimated using statistical modeling with a sigmoidal function. Recovery time-constants, including measures of the absolute refractory period and the relative refractory period, were estimated using statistical modeling with an exponential decay function. Generalized linear mixed-effect models were used to evaluate the effects of electrode site on the dependent variables measured in children with CND and to compare results of these dependent variables between subject groups.

Results:
The eCAP was recorded at all test electrodes in children with normal-size CNs. In contrast, the eCAP could not be recorded at any electrode site in 4 children with CND. For all other children with CND, the percentage of electrodes with measurable eCAPs decreased as the stimulating site moved in a basal-to-apical direction. For children with CND, the stimulating site had a significant effect on the slope of the I/O functions and the relative refractory period but showed no significant effect on eCAP threshold and the maximum eCAP amplitude. Children with CND had significantly higher eCAP thresholds, smaller maximum eCAP amplitudes, flatter slopes of I/O functions, and longer absolute refractory periods than children with normal-size CNs. There was no significant difference in the relative refractory period measured in these two subject groups.

Conclusions:
In children with CND, the functional status of the CN varied along the length of the cochlea. Compared with children with normal-size CNs, children with CND showed reduced CN responsiveness to electrical stimuli. The prolonged CN absolute refractory period in children with CND might account for, at least partially, the observed benefit of using relatively slow pulse rate in these patients.
Prosthesis and Hybrid Strategy Consideration for Treating Two-level Cervical Disc Degeneration in Hybrid Surgery
Authors: Li Yang , Fogel Guy R. , Liao Zhenhua , Tyagi Rajnesh , Liu Weiqiang 
Published: July 2017

Study Design.
Biomechanical analysis using a validated nonlinear finite element (FE) model.

Objective.
The aim of this study was to combine the strategy of two-level hybrid surgery (HS) to explore how prostheses affect cervical biomechanics.

Summary of Background Data.
Few FE studies have explored differences in biomechanical behavior between combined and stand-alone structured prostheses with HS. No FE studies have considered whether the prosthesis type and hybrid strategy influence two-level HS.

Methods.
Three prostheses—Prodisc-C, PCM, and DCI—were analyzed in flexion and extension during HS at C4-C6. There were two HS constructs: anterior cervical discectomy and fusion (ACDF) conducted at the C4-C5 levels and anterior cervical disc replacement (ACDR) conducted at C5-C6 levels (ACDF/ACDR); ACDR/ACDF.

Results.
Flexion motion at adjacent levels was greater than that of intact spine. A maximum increase of 80% was observed with PCM in the ACDF/ACDR group. Extension motion at adjacent levels for both hybrid strategies with PCM, however, was similar to that of intact spine (<10% change), whereas it increased by 14% to 32% with DCI. The strain energy-storing capability with DCI tended to be similar to that of normal discs. Facet stress at the infra-adjacent level, however, significantly increased with DCI in both groups, whereas it increased with PCM and Prodisc-C only in the ACDR/ACDF group. All prostheses produced overloads on cartilage at the arthroplasty level. Prodisc-C and PCM cores showed stress above the yield stress of ultrahigh-molecular-weight polyethylene.

Conclusion.
Each prosthesis had advantages and disadvantages. In extension, DCI (vs. Prodisc-C and PCM) exhibited more compensation at adjacent levels in terms of motion, moments, and facet stress. The biomechanical performance of Prodisc-C was easily affected by the hybrid strategy. Thus, if only a combined-structure prosthesis is available for two-level HS (C4-C6 level), the hybrid strategy should be carefully evaluated and the ACDF/ACDR construct is recommended to avoid accelerating degeneration of adjacent segments.

Level of Evidence: 5
The Role of Minimally Invasive Vertebral Body Stent on Reduction of the Deflation Effect After Kyphoplasty
Authors: Wang Dalin , Zheng Shengnai , Liu An , Xu Jie , Du Xiaotao , Wang Yijin , Wang Liming 
Published: July 2017

Study Design.
Biomechanical investigation using cadaver spines.

Objective.
The aim of the present study was to assess the magnitude of the deflation effect after balloon kyphoplasty (BKP) or use of minimally invasive vertebral body stent (MIVBS) in in vitro biomechanical condition.

Summary of Background Data.
BKP is a well-established minimally invasive treatment option for osteoporotic vertebral compression fractures. However, this technique can lead to a secondary height loss—known as the “deflation effect”—causing intrasegmental kyphosis and an overall alignment failure.

Methods.
The study was conducted on 24 human cadaveric vertebral bodies (T12-L5). After creating a compression fracture model, the fractured vertebral bodies were reduced by BKP (n = 12) or by MIVBS (n = 12) and then augmented with polymethyl methacrylate bone cement. Each step of the procedure was performed under fluoroscopic guidance and the results were analyzed quantitatively. Finally, the strength and stiffness of augmented vertebral bodies were measured by biomechanical tests.

Results.
Complete initial reduction of the fractured vertebral body height was achieved by both systems. Secondary loss of reduction after balloon deflation was significantly greater in the BKP group (2.36 ± 0.63 mm vs. 0.34 ± 0.43 mm in the MIVBS group; P < 0.05). Height gain was significantly higher in the MIVBS group (77.68% ± 11.46% vs. 34.87% ± 13.16% in the BKP group; P < 0.05). Increase in the kyphotic angle gain (relative to the preoperative kyphotic angle) was significantly more in the MIVBS group (95.60% ± 6.12% vs. 77.0% ± 4.94% in the BKP group; P < 0.05). Failure load was significantly higher in the MIVBS group (189% ± 16% vs. 146% ± 14%; P < 0.05). However, stiffness was not significantly different between the two groups.

Conclusion.
The deflation effect after BKP can be significantly decreased with the use of the MIVBS technique.

Level of Evidence: N/A
Intervertebral Disc Degeneration During Postoperative Follow-up More Than 10 Years After Corrective Surgery in Idiopathic Scoliosis
Authors: Nohara Ayato , Kawakami Noriaki , Tsuji Taichi , Ohara Tetsuya , Saito Toshiki , Kawakami Kazuki 
Published: July 2017

Study Design.
A retrospective comparative study.

Objective.
The aim of this study was to evaluate the difference in trends of disc degeneration (DD) at lower unfused segments (LUS) for postoperative patients who have gone through spinal instrumentation at 10-year follow-up with the natural progression of idiopathic scoliosis.

Summary of Background Data.
Studies that used magnetic resonance imaging (MRI) state that DD rates at LUS are higher than in the normal population. However, current studies do not prove that surgery is the most effective clinical method to treat idiopathic scoliosis, as no existing report compares the rates of DD with the natural history of idiopathic scoliosis.

Methods.
Female patients diagnosed of scoliosis were divided into three groups: 1) surgical group: postoperative 10-year patients with severe scoliosis before operation; 2) mild scoliosis group: with comparatively equal scoliosis to postoperative patients of the same age at 10 years follow-up; 3) severe scoliosis group: without any record of corrective surgery under the assumption that the scoliosis of the surgical group have progressed according to natural history.

Results.
MRI findings of the surgical group show DD in 32 patients (62.7%) where the highest rate of DD occurred at L5/S. In the mild scoliosis group, 21 patients (47.7%) had DD, with higher rates at L4/5 and L5/S. DD was most common in L3/4 and L4/5 in the severe scoliosis group where 27 patients (81.8%) had DD. As such, DD rates were significantly higher in the severe scoliosis group than the surgical group at the same spinal level. The same was true for the existence of low back pain, where the severe scoliosis group had greater incidence of low back pain than the surgical group.

Conclusion.
Corrective surgeries were able to reduce the incidence of DD. Radiological analysis also suggests that surgical intervention is a clinically feasible treatment for idiopathic scoliosis patients.

Level of Evidence: 3
Therapeutic oncolytic viruses: clinical advances and future directions
Authors: Warner Susanne G. , O’Leary Michael P. , Fong Yuman 
Published: July 2017

Purpose of review
The present review will highlight recent advances in the clinical application of oncolytic viral therapy.

Recent findings
Until recently, oncolytic viral researchers saw the immune system as an enemy that would clear the virus from the bloodstream. However, researchers now understand that sustained responses are seen in those patients with more robust antitumor immune responses. Much of the current focus in oncolytic viral research is trained on manipulation of the immune system to affect cancer cell killing in the tumor microenvironment and to facilitate durable systemic antitumor immunity. Many investigators have demonstrated synergistic effects of checkpoint inhibition and other immune therapies with viral administration. At the same time, insertion of various markers enables noninvasive deep tissue imaging. Finally, following regulatory approval in the United States and Europe, unbridled clinical use of T-VEC for patients with metastatic melanoma is also generating large volumes of patient data that will help elucidate strengths and weaknesses of oncolytic viral therapy. Perhaps the most telling sign of the field's future is a seismic shift in clinical trials with more investigators combining virus and immunotherapies.

Summary
This article reviews the current state of therapeutic oncolytic viruses in clinical use, and explores future directions of the field.