bluuebunny/crossref_metadata_2025 huggingface dataset:
Indirect Decompression Failure After Lateral Lumbar Interbody Fusion—Reported Failures and Predictive Factors: Systematic Review
Authors: Kirnaz Sertac , Navarro-Ramirez Rodrigo , Gu Jiaao , Wipplinger Christoph , Hussain Ibrahim , Adjei Joshua , Kim Eliana , Schmidt Franziska Anna , Wong Taylor , Hernandez Robert Nick , Härtl Roger
Published: May 2020

Background:

In patients with symptomatic lumbar stenosis undergoing lateral transpsoas approach for lumbar interbody fusion (LLIF) surgery, it is not always clear when indirect decompression is sufficient in order to achieve symptom resolution. Indirect decompression failure (IDF), defined as “postoperative persistent symptoms of nerve compression with or without a second direct decompression surgery to reach adequate symptom resolution,” is not widely reported. This information, however, is critical to better understand the indications, the potential, and the limitations of indirect decompression.

Objective:

The purpose of this study was to systematically review the current literature on IDF after LLIF.

Methods:

A literature search was performed on PubMed. We included randomized controlled trials and prospective, retrospective, case-control studies, and case reports. Information on sample size, demographics, procedure, number and location of involved levels, follow-up time, and complications were extracted.

Results:

After applying the exclusion criteria, we included 9 of the 268 screened articles that reported failure. A total of 632 patients were screened in these articles and detailed information was provided. Average follow-up time was 21 months. Overall reported incidence of IDF was 9%.

Conclusion:

Failures of decompression via LLIF are inconsistently reported and the incidence is approximately 9%. IDF failure in LLIF may be underreported or misinterpreted as a complication. We propose to include the term “IDF” as described in this article to differentiate them from complications for future studies. A better understanding of why IDF occurs will allow surgeons to better plan surgical intervention and will avoid revision surgery.
A Quasi-Experimental Study of a Basics of Evidence-Based Practice Educational Intervention for Health and Social Care Professionals
Authors: Melender Hanna-Leena , Salmela Susanne , Pape Bernd
Published: May 2020

Education is one of the central interventions to promote evidence-based practice (EBP) in service organizations. An educational intervention to promote EBP among health and social care professionals was implemented in a Finnish hospital. The aim of this study was to explore the outcomes of an educational intervention, focusing on the basics of EBP for health and social care professionals, using a quasi-experimental study design. The data were collected with a questionnaire before, immediately after, and 6 months after the education ( n = 48). The data were analyzed with descriptive statistics and nonparametric tests. Immediately after the education, an increase was found in the EBP knowledge of participants, in participants’ confidence in their own ability to conduct database searches and read scientific articles, and in the number of participants using databases at work. Six months after the education, improvements were still found between the first and the third measurement in the participants’ knowledge and confidence in their own ability to conduct database searches and read scientific articles. The number of those who had made an initiative about a research topic regarding the development of their own work had increased from the first to the third measurement. The educational intervention produced a statistically significant improvement on most of the areas evaluated. Significant improvements were often found even 6 months after the education was finished. However, the low completion rate and a quasi-experimental before and after design limit the conclusions that can be derived from this study.
Architectural Models and Their Contexts in China’s 20th-Century Architectural Heritage: An Overview
Authors: Chang Qing
Published: May 2020

The article explores the morphological evolution of China’s 20th-century architecture chronologically. Chinese Neoclassicism has played a major role in forming the 20th-century heritage buildings surviving today. The phenomenon of Neoclassicism emerged because of the late arrival of China’s modernisation and industrialisation process compared with the West. In turn, in accepting and contesting Western culture, the Chinese elite have consciously relied upon architecture as a vehicle to uphold visible symbols of national Chinese identity and traditional Chinese culture. Meanwhile, in the foreign settlements of the treaty ports such as Shanghai, the Western Neoclassical style, along with other imported construction trends, also forms part of China’s 20th-century architectural heritage. Western Neoclassicism’s influence on China’s new architecture became even more evident in the mid-20th century, with the modern architectural heritage in Tiananmen Square as its exemplar. Nevertheless, the impact of Western modernist architecture on China’s architecture was minimal. It was not until the 1980s, as China reopened to the world, that various schools of thought from the post-industrial West flowed into China, which significantly enriched the types and sources of China’s 20th-century architectural heritage. Modern Classicism, late Modernism and Postmodernism all found their way into China’s contemporary architecture.
Vernacular Architecture: A Term Denoting and Transporting Diverse Content
Authors: Zwerger Klaus
Published: May 2020

A selective review of the literature demonstrates the difficulty in defining ‘vernacular architecture’. Recent studies have presented an overly narrow, single-sided, or even unacceptable image of the topic in comparison with many earlier definitions and discussions. However, those earlier analyses also had various shortfalls. The interdependence of vernacular architecture, economic interests, and emerging awareness of buildings’ interaction with the environment demand a rethinking of vernacular architecture, which the present study understands as signifying housing offered for most of the world’s population.
Defining Local Heritages in Preserving Modern Shanghai Architecture
Authors: Lu Yongyi , Li Yanning
Published: May 2020

The notion that local heritage can be defined by the ‘collective memory’ of a city may be considered as being simplistic nowadays. Heritage is increasingly recognised as knowledge, a cultural product or even a political resource set within specific social circumstances. The local heritage underpins various ways of relating our past with our present and future, which are often much more complicated than we can imagine. The evolution of the conservation of Shanghai’s modern heritage architecture shows this complexity. By tracing more than 50 years’ progress in historic preservation, this paper shows how historical buildings from Shanghai’s early modern period were selected as urban heritage in the changing socio-political contexts of different time periods. Starting with how the first modern buildings were listed in a new Chinese narrative in the 1950s, this paper focuses on the great ideological changes and progress Shanghai achieved after China’s reform and opening policy since the 1980s. Emphasising the great significance of the establishment of local legislation for historic preservation as an extension of the national system, examples of the great enrichment of Shanghai’s local heritage are presented through multiple narratives and interpretations of Shanghai’s modern history. In a deeper observation of various practices and complicated contradictions, the historic preservation of Shanghai’s modern heritage architecture is shown to be a process of continuing to reconstruct the relationships between city and the State, the city and the world, as well as the city’s past, present and future in a pluralist society.
Clinical implication of plasma exchange on life-threatening antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Park Pil Gyu , Yoo Byung-Woo , Song Jason Jungsik , Park Yong-Beom , Lee Sang-Won
Published: May 2020

Background

We assessed the rate of and predictors for all-cause mortality in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) receiving plasma exchange (PLEX) and evaluated the survival benefit of PLEX for diffuse alveolar haemorrhage (DAH) between AAV patients receiving PLEX and those not receiving PLEX.

Methods

We retrospectively reviewed the medical records of 212 patients with AAV. Demographic, clinical and laboratory data at the time of PLEX were collected from nine patients receiving PLEX, six of whom had DAH. The follow-up duration was defined as the period from the time of PLEX or DAH occurrence to death for the deceased patients and to the last visit for the survived patients.

Results

The median age of nine AAV patients receiving PLEX was 71.0 years, and five patients were men. Four of nine patients receiving PLEX died at a median follow-up duration of 92.0 days. Three patients died of sepsis and one died owing to a lack of response to PLEX. When patients with DAH receiving or not receiving PLEX were compared, there were no significant differences in variables between the two groups. The cumulative patients’ survival rate between patients with DAH receiving and not receiving PLEX were also compared using the Kaplan-Meier survival analysis; however, no survival-benefit of PLEX for DAH was observed.

Conclusion

The rate of all-cause mortality in nine AAV patients receiving PLEX was found to be 44.4% and the notion that PLEX is beneficial for the improvement in the prognosis of AAV-related DAH was deemed controversial.
A comparison of contiguous two-level anterior cervical discectomy and fusion using a structural allograft versus a Polyetheretherketone (PEEK) cage: the results of a three-year follow-up
Authors: Moo Ing How , Kam Carmen Jia Wen , Lai Maksim Wen Sheng , Yeo William , Soh Reuben Chee Cheong
Published: May 2020

Background

Allografts and polyetheretherketone (PEEK) cages are the two most commonly used materials in anterior cervical discectomy and fusion (ACDF). However, their effectiveness in two-level ACDF remains controversial. The primary aim of this retrospective study was to compare the clinical and radiological outcomes of two-level ACDF with plate fixation using either a structural allograft or a PEEK cage.

Methods

From 2010 to 2015, 88 consecutive patients underwent two-level ACDF, of whom 53 received an allograft and 35 patients received a PEEK cage. All PEEK cages were filled with local autografts. All clinical outcomes were prospectively collected before and six months and two years after surgery. Clinical efficacy was evaluated using a visual analogue scale for neck pain and limb pain, the Neck Pain and Disability Score, the Neck Disability Index, the Neurogenic Symptom Score, and the Japanese Orthopedic Association score. Radiological outcomes were assessed preoperatively, immediately after surgery, and at the final follow-up.

Results

A preoperative comparison revealed no difference between the two patient groups in terms of age, sex, body mass index, smoking status, preoperative symptoms, operation level, or follow-up (mean = 42.8 months). No differences in the improvements in clinical outcomes were observed between the two groups. Both groups showed significant improvement in mean disc height, segmental height, and segmental lordosis postoperatively. The fusion rate for the PEEK cage was 100% at both levels, while the fusion rate for the allograft group was 98.1% at the cephalad level and 94.2% at the caudad level (p > 0.05). Subsidence at the cephalad level occurred in 22.9% (8/35) of segments in the PEEK group and 7.7% (4/52) of segments in the allograft group (p = 0.057). At the caudal level, a higher incidence of cage subsidence was noted in the PEEK group than in the allograft group [37.1% (13/35) versus 15.4% (8/52)] (p = 0.02). Overall, subsidence was noted in 30% (21/70) of the PEEK group and in 11% (12/104) of the allograft group (p <  0.05).

Conclusion

The use of PEEK cages resulted in a higher rate of subsidence in two-level ACDF than the use of allografts. Two-level ACDF using either allografts or PEEK cages resulted in similar clinical outcomes, radiological improvements in alignment and fusion rates.
Association of IL-6 174G/C (rs1800795) and 572C/G (rs1800796) polymorphisms with risk of osteoporosis: a meta-analysis
Authors: Chen Bin , Li Hong-zhuo
Published: May 2020

Background

Several studies have been performed to investigate association between IL-6 174G/C (rs1800795) and 572C/G (rs1800796) gene polymorphisms and osteoporosis predisposition. However, the results were conflicting. So, we performed a meta-analysis designed to provide more reliable results for the association between IL-6 gene polymorphisms and osteoporosis.

Methods

Studies were searched using PubMed, EMBASE, the Cochrane Library and Wanfang electronic databases. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between IL-6 174G/C (rs1800795) and 572C/G (rs1800796) gene polymorphisms and osteoporosis risk. The false-positive report probabilities (FPRP) test and the venice criteria were used to assess the credibility of statistically significant associations.

Results

A total of 9 studies with 1891 osteoporosis patients and 2027 healthy controls were included in current meta-analysis. Overall, The IL-6 174G/C (rs1800795) gene polymorphism was insignificantly associated with osteoporosis vulnerability. For IL-6 572C/G (rs1800796), statistically significant elevated osteoporosis vulnerability was found in IL-6 572C/G additive model (OR = 2.25, 95% CI: 1.55–3.26), dominant model (OR = 1.42, 95% CI: 0.78–2.56) and recessive model (OR = 1.96, 95% CI: 1.36–2.83). However, the IL-6 572C/G C allele was found to be associated with reduced susceptibility to osteoporosis (OR = 0.76, 95% CI: 0.56–1.04). When excluding studies that did not conform to HWE, the results did not change significantly. Further, when we evaluated the credibility of the positive results of the current meta-analysis, we identified less credible positive results in IL-6 572C/G recessive and additive model.

Conclusion

In conclusion, IL-6 572C/G GG genotype may be associated with increased risk of osteoporosis.
Systematic symptom and problem assessment at admission to the palliative care ward – perspectives and prognostic impacts
Authors: Coym Anja , Ullrich Anneke , Hackspiel Lisa Kathrin , Ahrenholz Mareike , Bokemeyer Carsten , Oechsle Karin
Published: May 2020

Background

Symptom assessment is essential in palliative care, but holds challenges concerning implementation and relevance. This study aims to evaluate patients’ main symptoms and problems at admission to a specialist inpatient palliative care (SIPC) ward using physician proxy- and patient self-assessment, and aims to identify their prognostic impact as well as the agreement between both assessments.

Methods

Within 12 h after admission, palliative care specialists completed the Symptom and Problem Checklist of the German Hospice and Palliative Care Evaluation (HOPE-SP-CL). Patients either used the new version of the minimal documentation system for patients in palliative care (MIDOS) or the Integrated Palliative Care Outcome Scale (IPOS) plus the Distress Thermometer (DT).

Results

Between 01.01.2016–30.09.2018, 1206 patients were included (HOPE-SP-CL 98%; MIDOS 21%, IPOS 34%, DT 27%) whereof 59% died on the ward. Proxy-assessment showed a mean HOPE-SP-CL Total Score of 24.6 ± 5.9 of 45. Most frequent symptoms/problems of at least moderate intensity were weakness (95%), needs of assistance with activities of daily living (88%), overburdening of family caregivers (83%), and tiredness (75%). Factor analysis identified four symptom clusters (SCs): (1) Deteriorated Physical Condition/Decompensation of Home Care, (2) Emotional Problems, (3) Gastrointestinal Symptoms and (4) Other Symptoms. Self-assessment showed a mean MIDOS Total Score of 11.3 ± 5.3 of 30, a mean IPOS Total Score of 32.0 ± 9.0 of 68, and a mean distress of 6.6 ± 2.5 of 10. Agreement of self- and proxy-assessment was moderate for pain (ƙ = 0.438) and dyspnea (ƙ = 0.503), fair for other physical (ƙ = 0.297 to 0.394) and poor for psychological symptoms (ƙ = 0.101 to 0.202). Multivariate regression analyses for single symptoms and SCs revealed that predictors for dying on the SIPC ward included impaired ECOG performance status, moderate/severe dyspnea, appetite loss, tiredness, disorientation/confusion, and the SC Deteriorated Physical Condition/Decompensation of Home Care.

Conclusion

Admissions to a SIPC ward are mainly caused by problems impairing mobility and autonomy. Results demonstrate that implementation of self- and reliability of proxy- and self-assessment is challenging, especially concerning non-physical symptoms/problems. We identified, specific symptoms and problems that might provide information needed for treatment discussions regarding the medical prognosis.
Clutter suppression in ultrasound: performance evaluation and review of low-rank and sparse matrix decomposition methods
Authors: Zhang Naiyuan , Ashikuzzaman Md , Rivaz Hassan
Published: May 2020

Vessel diseases are often accompanied by abnormalities related to vascular shape and size. Therefore, a clear visualization of vasculature is of high clinical significance. Ultrasound color flow imaging (CFI) is one of the prominent techniques for flow visualization. However, clutter signals originating from slow-moving tissue are one of the main obstacles to obtain a clear view of the vascular network. Enhancement of the vasculature by suppressing the clutters is a significant and irreplaceable step for many applications of ultrasound CFI. Currently, this task is often performed by singular value decomposition (SVD) of the data matrix. This approach exhibits two well-known limitations. First, the performance of SVD is sensitive to the proper manual selection of the ranks corresponding to clutter and blood subspaces. Second, SVD is prone to failure in the presence of large random noise in the dataset. A potential solution to these issues is using decomposition into low-rank and sparse matrices (DLSM) framework. SVD is one of the algorithms for solving the minimization problem under the DLSM framework. Many other algorithms under DLSM avoid full SVD and use approximated SVD or SVD-free ideas which may have better performance with higher robustness and less computing time. In practice, these models separate blood from clutter based on the assumption that steady clutter represents a low-rank structure and that the moving blood component is sparse. In this paper, we present a comprehensive review of ultrasound clutter suppression techniques and exploit the feasibility of low-rank and sparse decomposition schemes in ultrasound clutter suppression. We conduct this review study by adapting 106 DLSM algorithms and validating them against simulation, phantom, and in vivo rat datasets. Two conventional quality metrics, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), are used for performance evaluation. In addition, computation times required by different algorithms for generating clutter suppressed images are reported. Our extensive analysis shows that the DLSM framework can be successfully applied to ultrasound clutter suppression.
A multi-center analysis of single-fraction versus hypofractionated stereotactic radiosurgery for the treatment of brain metastasis
Authors: Remick Jill S. , Kowalski Emily , Khairnar Rahul , Sun Kai , Morse Emily , Cherng Hua-Ren R. , Poirier Yannick , Lamichhane Narottam , Becker Stewart J. , Chen Shifeng , Patel Akshar N. , Kwok Young , Nichols Elizabeth , Mohindra Pranshu , Woodworth Graeme F. , Regine William F. , Mishra Mark V.
Published: May 2020

Background

Hypofractionated-SRS (HF-SRS) may allow for improved local control and a reduced risk of radiation necrosis compared to single-fraction-SRS (SF-SRS). However, data comparing these two treatment approaches are limited. The purpose of this study was to compare clinical outcomes between SF-SRS versus HF-SRS across our multi-center academic network.

Methods

Patients treated with SF-SRS or HF-SRS for brain metastasis from 2013 to 2018 across 5 radiation oncology centers were retrospectively reviewed. SF-SRS dosing was standardized, whereas HF-SRS dosing regimens were variable. The co-primary endpoints of local control and radiation necrosis were estimated using the Kaplan Meier method. Multivariate analysis using Cox proportional hazards modeling was performed to evaluate the impact of select independent variables on the outcomes of interest. Propensity score adjustments were used to reduce the effects confounding variables. To assess dose response for HF-SRS, Biologic Effective Dose (BED) assuming an α/β of 10 (BED10) was used as a surrogate for total dose.

Results

One-hundred and fifty six patients with 335 brain metastasis treated with SF-SRS (n = 222 lesions) or HF-SRS (n = 113 lesions) were included. Prior whole brain radiation was given in 33% (n = 74) and 34% (n = 38) of lesions treated with SF-SRS and HF-SRS, respectively (p = 0.30). After a median follow up time of 12 months in each cohort, the adjusted 1-year rate of local control and incidence of radiation necrosis was 91% (95% CI 86–96%) and 85% (95% CI 75–95%) (p = 0.26) and 10% (95% CI 5–15%) and 7% (95% CI 0.1–14%) (p = 0.73) for SF-SRS and HF-SRS, respectively. For lesions > 2 cm, the adjusted 1 year local control was 97% (95% CI 84–100%) for SF-SRS and 64% (95% CI 43–85%) for HF-SRS (p = 0.06). On multivariate analysis, SRS fractionation was not associated with local control and only size ≤2 cm was associated with a decreased risk of developing radiation necrosis (HR 0.21; 95% CI 0.07–0.58, p < 0.01). For HF-SRS, 1 year local control was 100% for lesions treated with a BED10 ≥ 50 compared to 77% (95% CI 65–88%) for lesions that received a BED10 < 50 (p = 0.09).

Conclusions

In this comparison study of dose fractionation for the treatment of brain metastases, there was no difference in local control or radiation necrosis between HF-SRS and SF-SRS. For HF-SRS, a BED10 ≥ 50 may improve local control.
Artesunate: could be an alternative drug to chloroquine in COVID-19 treatment?
Authors: Uzun Tuğçenur , Toptas Orcun
Published: May 2020

SARS (Severe Acute Respiratory Syndrome Coronavirus)-CV-2 (2019-nCov), which showed up in China in December 2019 and spread all over the world, has becomed a serious health problem. An effective, safe and proven treatment has not yet been found. Chloroquine has been recommended by some authors to be used for the treatment of patients infected with this virus however chloroquine may have side effects and drug resistance problems. Artesunate is a semisynthetic derivative of artemisinin, an antimalarial drug. Artesunate was thought to be an effective treatment for covid-19 because of its anti-inflammatory activity, NF-κB (nuclear Factor kappa B)-coronavirus effect and chloroquine-like endocytosis inhibition mechanism.
A machine learning model that classifies breast cancer pathologic complete response on MRI post-neoadjuvant chemotherapy
Authors: Sutton Elizabeth J. , Onishi Natsuko , Fehr Duc A. , Dashevsky Brittany Z. , Sadinski Meredith , Pinker Katja , Martinez Danny F. , Brogi Edi , Braunstein Lior , Razavi Pedram , El-Tamer Mahmoud , Sacchini Virgilio , Deasy Joseph O. , Morris Elizabeth A. , Veeraraghavan Harini
Published: May 2020

Background

For breast cancer patients undergoing neoadjuvant chemotherapy (NAC), pathologic complete response (pCR; no invasive or in situ) cannot be assessed non-invasively so all patients undergo surgery. The aim of our study was to develop and validate a radiomics classifier that classifies breast cancer pCR post-NAC on MRI prior to surgery.

Methods

This retrospective study included women treated with NAC for breast cancer from 2014 to 2016 with (1) pre- and post-NAC breast MRI and (2) post-NAC surgical pathology report assessing response. Automated radiomics analysis of pre- and post-NAC breast MRI involved image segmentation, radiomics feature extraction, feature pre-filtering, and classifier building through recursive feature elimination random forest (RFE-RF) machine learning. The RFE-RF classifier was trained with nested five-fold cross-validation using (a) radiomics only (model 1) and (b) radiomics and molecular subtype (model 2). Class imbalance was addressed using the synthetic minority oversampling technique.

Results

Two hundred seventy-three women with 278 invasive breast cancers were included; the training set consisted of 222 cancers (61 pCR, 161 no-pCR; mean age 51.8 years, SD 11.8), and the independent test set consisted of 56 cancers (13 pCR, 43 no-pCR; mean age 51.3 years, SD 11.8). There was no significant difference in pCR or molecular subtype between the training and test sets. Model 1 achieved a cross-validation AUROC of 0.72 (95% CI 0.64, 0.79) and a similarly accurate (P = 0.1) AUROC of 0.83 (95% CI 0.71, 0.94) in both the training and test sets. Model 2 achieved a cross-validation AUROC of 0.80 (95% CI 0.72, 0.87) and a similar (P = 0.9) AUROC of 0.78 (95% CI 0.62, 0.94) in both the training and test sets.

Conclusions

This study validated a radiomics classifier combining radiomics with molecular subtypes that accurately classifies pCR on MRI post-NAC.
The medical transition of young adults with type 1 diabetes (T1D): a retrospective chart review identifies areas in need of improvement
Authors: Walch Abby M. , Cobb Carmen E. , Tsaih Shirng-Wern , Cabrera Susanne M.
Published: May 2020

Background

The transition process from pediatric to adult care in individuals with T1D has long-term ramifications on health outcomes. Recognition of differences in care delivery and changes made in management during this time may improve the process. We hypothesized that pediatric providers would be less likely to address T1D-related comorbidities than their adult counterparts, highlighting opportunities to strengthen care.

Methods

A retrospective chart review of patients aged 16–21 years diagnosed with T1D before age 18 was performed. Data on diagnosis, screening, and management of hypertension, dyslipidemia, microalbuminuria, retinopathy, and neuropathy were collected for 1 year before and 1 year after transition to adult care. The ‘ADA Standards of Medical Care in Diabetes’ were used to determine adherence to the above parameters. Data before and after transition was compared by Fischer’s Exact and Exact McNemar tests.

Results

Complete medical records for 54 subjects were reviewed before and after transition from pediatric to adult care providers within a single academic medical system (52% male; 78% Caucasian). Transition to adult care occurred at a mean age of 18 years. Mean length of transition was 7.8 months with no significant change in an individual’s HbA1c over that time. Over the transition period, there was no difference in diagnoses of hypertension or the use of anti-hypertensive. Adherence to lipid and retinopathy screening was similar across the transition period; however, adherence to microalbuminuria screening was higher after the transition to adult providers (p = 0.01). Neuropathy screening adherence was overall poor but also improved after transition (p < 0.001).

Conclusions

Overall, there were no significant changes in the diagnosis or management of several T1D-related comorbidities during the transition period in a small cohort of young adults with T1D. The transition length was longer than the recommended 3-months, highlighting an opportunity to improve the process. There was no deterioration of glycemic control over this time, although HbA1c values were above target. Adult providers had significantly higher rates of adherence to screening for microalbuminuria and neuropathy than their pediatric counterparts, but adherence for neuropathy was quite poor overall, indicating a need for practice improvement.
Correction to: Genetic and metabolic links between the murine microbiome and memory
Authors: Mao Jian-Hua , Kim Young-Mo , Zhou Yan-Xia , Hu Dehong , Zhong Chenhan , Chang Hang , Brislawn Colin J. , Fansler Sarah , Langley Sasha , Wang Yunshan , Peisl B. Y. Loulou , Celniker Susan E. , Threadgill David W. , Wilmes Paul , Orr Galya , Metz Thomas O. , Jansson Janet K. , Snijders Antoine M.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Molecular Profiling in Drug Development: Paving a Way Forward
Authors: Jones Suzanne F. , McKenzie Andrew J.
Published: May 2020

As researchers learn more about tumor biology and the molecular mechanisms involved in tumorigenesis, metastasis, and tumor evolution, clinical trials are growing more complex and patient selection for clinical trials is becoming more specific. Rather than exploit certain phenotypic characteristics of tumor cells (e.g., rapid cell division and uncontrolled cell growth), pharmaceuticals targeting the genotypic causes of tumorigenesis are emerging. The sequencing of the human genome, advances in chemical techniques, and increased efficiency in drug target identification have changed the way drugs are developed. Now, more precise drugs targeting specific mutations within individual genes are being used to treat narrow patient populations harboring these specific driver mutations, often with greater efficacy and lower toxicity than traditional chemotherapeutic agents. This precision in drug development relies not only on the ability to design exquisitely specific pharmaceuticals but also to identify (with the same level of precision) the patients who are most likely to respond to those therapies. Robust screening techniques and adequate molecular oncology education are required to match the appropriate patient to precision therapies, and these same screening techniques provide the data necessary to advance to the next generation of drug development.
Long-Term Incidence and Predictors of Significant Hearing Loss Requiring Hearing Assistive Devices Among Childhood Cancer Survivors: A Population-Based Study
Authors: Beyea Jason A. , Lau Cindy , Cooke Bonnie , Hall Stephen , Nathan Paul C. , Gupta Sumit
Published: May 2020

PURPOSE

Hearing loss is a significant late effect among childhood cancer survivors. Recent guidelines note insufficient evidence to quantify its natural history or risk associated with specific exposures. We examined the long-term incidence and predictors of hearing loss requiring hearing amplification devices (HADs) using population-based health care data.

METHODS

In Ontario, Canada, HAD costs are subsidized by the Assistive Devices Program (ADP). Ontario children < 18 years of age at cancer diagnosis between 1987 and 2016 were identified and linked to ADP claims. Cumulative HAD incidence was compared between cases and matched controls. Patient, disease, and treatment predictors of HAD were examined.

RESULTS

We identified 11,842 cases and 59,210 controls. Cases were at higher risk for HAD (hazard ratio [HR], 12.8; 95% CI, 9.8 to 16.7; P < .001). The cumulative incidence of HAD among survivors was 2.1% (95% CI, 1.7% to 2.5%) at 20 years and 6.4% (95% CI, 2.8% to 12.1%) at 30 years post-diagnosis. The 30-year incidence was highest in neuroblastoma (10.7%; 95% CI, 3.8% to 21.7%) and hepatoblastoma (16.2%; 95% CI, 8.6% to 26.0%) survivors. Predictors of HAD in multivariable analyses included age 0-4 years at diagnosis ( v 5-9 years; HR, 2.2; 95% CI, 1.4-3.3; P < .001). Relative to no cisplatin exposure, patients receiving < 200 mg/m2 were not at greater risk, unlike those receiving higher cumulative doses. Relative to no cranial or facial radiation, those who had received ≤ 32.00 Gy were at no higher risk, unlike those who had received > 32.00 Gy. Carboplatin exposure was not associated with HAD.

CONCLUSION

Childhood cancer survivors are at elevated risk for requiring HAD, which continues to increase between 20 and 30 years after diagnosis. Thresholds of cisplatin and radiation exposure exist, above which risk substantially increases. Prolonged monitoring and trials of otoprotective agents are warranted in high-risk populations.
Erratum: Local axisymmetry-breaking–induced transition of trapped-particle orbit and loss channels in quasi-axisymmetric stellarators
Authors: Yang Lang , Liu Haifeng , Shimizu Akihiro , Xu Yuhong , Wang Xianqu , Liu Hai , Tang Changjian , Li Yangbo , Liu Jinmao , Luo Yang , Xiong Guozhen , Su Chunyan , Kinoshita Shigeyoshi , Isobe Mitsutaka , Okamura Shoichi , Huang Jie , Zhang Xin , Yin Dapeng , Wan Yi ,   CFQS team
Published: May 2020

Original article:
EPL, 129 (2020) 35001.
Democracy, Capacity, and Coercion in Pandemic Response: COVID-19 in Comparative Political Perspective
Authors: Kavanagh Matthew M. , Singh Renu
Published: May 2020

The COVID-19 pandemic has challenged governments around the world. It also has challenged conventional wisdom and empirical understandings in the comparative politics and policy of health. Three major questions present themselves: First, some of the countries considered to be most prepared—having the greatest capacity for outbreak response—have failed to respond effectively to the pandemic. How should our understanding of capacity shift in light of COVID-19, and how can we incorporate political capacity into thinking about pandemic preparedness? Second, several of the mechanisms through which democracy has been shown to be beneficial for health have not traveled well to explain the performance of governments in this pandemic. Is there an authoritarian advantage in disease response? Third, after decades in which coercive public health measures have increasingly been considered counterproductive, COVID-19 has inspired widespread embrace of rigid lockdowns, isolation, and quarantine enforced by police. Will these measures prove effective in the long run and reshape public health thinking? This article explores some of these questions with emerging examples, even amid the pandemic, when it is too soon to draw conclusions.
Improving Quality as a Solution to the Health Care Cost Problem? Health Policy Experts and the Promotion of a Controversial Idea
Authors: Lepont Ulrike
Published: May 2020

Context: In the late 2000s, the contention that quality improvements achieved by reforms in the delivery of care would slow the growth of costs throughout the US health care system became the predominant strategy for cost containment in the discourses and programs of all the 2008 presidential candidates. The question that this paper addresses is why, despite all of the critiques of this idea (especially those of the Congressional Budget Office), what the author terms the quality solution has remained credible enough to be a possible argument in policy makers' discourses and programs. To answer this question, the article explores the role of health policy experts—who are expected to provide credibility and legitimacy to proposals defended by policy makers—in supporting and diffusing this quality solution.

Methods: The empirical research combines written sources with evidence from 78 interviews.

Findings: This article highlights the political factors that explain the rise and growing prominence of the quality solution in the community of policy analysts: the political support for delivery reform–oriented research since the 1980s and also the importance of political calculations for prominent health policy experts.

Conclusions: This policy history contributes to works that underscore the political dimension of policy analysis.
Transgelin-2 and phosphoregulation of the LIC2 subunit of dynein govern mitotic spindle orientation
Authors: Sharma Amit , Dagar Sunayana , Mylavarapu Sivaram V. S.
Published: May 2020

The molecular motor dynein is essential for mitotic spindle orientation, which defines the axis of cell division. The light intermediate chain subunits, LIC1 and LIC2, define biochemically and functionally distinct vertebrate dynein complexes, with LIC2-dynein playing a crucial role in ensuring spindle orientation. We reveal a novel, mitosis-specific interaction of LIC2-dynein with the cortical actin-bundling protein transgelin-2. Transgelin-2 is required for maintaining proper spindle length, equatorial metaphase chromosome alignment, spindle orientation and timely anaphase onset. We show that transgelin-2 stabilizes the cortical recruitment of LGN-NuMA, which together with dynein is required for spindle orientation. The opposing actions of transgelin-2 and LIC2-dynein maintain optimal cortical levels of LGN-NuMA. In addition, we show that the highly conserved serine 194 phosphorylation of LIC2 is required for proper spindle orientation, by maintaining mitotic centrosome integrity to ensure optimal astral microtubule nucleation. The work reveals two specific mechanisms through which LIC2-dynein regulates mitotic spindle orientation; namely, through a new interactor transgelin-2, which is required for engagement of LGN-NuMA with the actin cortex, and through mitotic phosphoregulation of LIC2 to control microtubule nucleation from the poles.

This article has an associated First Person interview with the first author of the paper.
A new pipeline for pathophysiological analysis of the mammary gland based on organoid transplantation and organ clearing
Authors: Lagoutte Emilie , Villeneuve Clémentine , Fraisier Vincent , Krndija Denis , Deugnier Marie-Ange , Chavrier Philippe , Rossé Carine
Published: May 2020

Recent developments in techniques for tissue clearing and size reduction have enabled optical imaging of whole organs and the study of rare tumorigenic events in vivo. The adult mammary gland provides a unique model for investigating physiological or pathological processes such as morphogenesis or epithelial cell dissemination. Here, we establish a new pipeline to study rare cellular events occurring in the mammary gland, by combining orthotopic transplantation of mammary organoids with the uDISCO organ size reduction and clearing method. This strategy allows us to analyze the behavior of individually labeled cells in regenerated mammary gland. As a proof of concept, we analyzed the localization of rare epithelial cells overexpressing atypical protein kinase C iota (also known as PRKCI, referred to here as aPKCι) with an N-terminal eGFP fusion (GFP-aPKCι+) in the normal mammary gland. Using this analytical pipeline, we were able to visualize epithelial aPKCι+ cells escaping from the normal mammary epithelium and disseminating into the surrounding stroma. This technical resource should benefit mammary development and tumor progression studies.
Social Ties and the Selection of China’s Political Elite
Authors: Fisman Raymond , Shi Jing , Wang Yongxiang , Wu Weixing
Published: May 2020

We study how sharing a hometown or college connection with an incumbent member of China’s Politburo affects a candidate’s likelihood of selection as a new member. In specifications that include fixed effects to absorb quality differences across cities and colleges, we find that hometown and college connections are each associated with 5–9 percentage point reductions in selection probability. This “connections penalty” is equally strong for retiring Politburo members, arguing against quota-based explanations, and it is much stronger for junior Politburo members, consistent with a role for intra-factional competition. Our findings differ from earlier work because of our emphasis on within-group variation, and our focus on shared hometown and college, rather than shared workplace, connections. (JEL D72, O17, P26, Z13)
Geographic Dispersion of Economic Shocks: Evidence from the Fracking Revolution: Comment
Authors: James Alexander G. , Smith Brock
Published: May 2020

Feyrer, Mansur, and Sacerdote (2017) estimates the spatial dispersion of the effects of the recent shale-energy boom by unconditionally regressing income and employment on energy production at various levels of geographic aggregation. However, producing counties tend to be located near each other and receive inward spillovers from neighboring production. This inflates the estimated effect of own-county production and spatial aggregation does not address this. We propose an alternative estimation strategy that accounts for these spillovers and identify reduced propagation effects. The proposed estimation strategy can be applied more generally to estimate the dispersion of multiple, simultaneously occurring economic shocks. (JEL E24, E32, J31, Q35, Q43, R11, R23)
Yeast pentatricopeptide protein Dmr1 (Ccm1) binds a repetitive AU-rich motif in the small subunit mitochondrial ribosomal RNA
Authors: Piątkowski Jakub , Golik Paweł
Published: May 2020

PPR proteins are a diverse family of RNA binding factors found in all Eukaryotic lineages. They perform multiple functions in the expression of organellar genes, mostly on the post-transcriptional level. PPR proteins are also significant determinants of evolutionary nucleo-organellar compatibility. Plant PPR proteins recognize their RNA substrates using a simple modular code. No target sequences recognized by animal or yeast PPR proteins were identified prior to the present study, making it impossible to assess whether this plant PPR code is conserved in other organisms. Dmr1p (Ccm1p, Ygr150cp) is a S. cerevisiae PPR protein essential for mitochondrial gene expression and involved in the stability of 15S ribosomal RNA. We demonstrate that in vitro Dmr1p specifically binds a motif composed of multiple AUA repeats occurring twice in the 15S rRNA sequence as the minimal 14 nt (AUA)4AU or longer (AUA)7 variant. Short RNA fragments containing this motif are protected by Dmr1p from exoribonucleolytic activity in vitro. Presence of the identified motif in mtDNA of different yeast species correlates with the compatibility between their Dmr1p orthologs and S. cerevisiae mtDNA. RNA recognition by Dmr1p is likely based on a rudimentary form of a PPR code specifying U at every third position, and depends on other factors, like RNA structure.
Bank Integration and the Market for Corporate Control: Evidence from Cross-State Acquisitions
Authors: John Kose , Qi Qianru , Wang Jing
Published: May 2020

Using the staggered and reciprocal passage of interstate bank deregulation as an exogenous variation in the degree of bank integration, we investigate how and why bank integration influences the market for corporate control for nonfinancial firms. We posit that bank integration affects acquisitions either through reducing the information asymmetry between acquirers and targets or through increasing credit supply. Our evidence is more consistent with the former channel. Specifically, we document that (1) cross-state acquisitions are more likely to occur between reciprocally deregulated states, and (2) firms are more likely taken over by out-of-state acquirers after deregulation; this effect is stronger for a target who borrows from an out-of-state bank, whose local bank is acquired by an out-of-state bank, and who is informationally more opaque. Announcement returns for acquirers of out-of-state (particularly private) targets increase after deregulation, consistent with better identification of higher-valued targets by acquirers after deregulation.

This paper was accepted by Tomasz Piskorski, finance.
The Financialization of Storable Commodities
Authors: Baker Steven D.
Published: May 2020

I solve a dynamic equilibrium model of commodity spot and futures prices, incorporating an active futures market, heterogeneous risk-averse participants, and storage. When calibrated to data from the crude oil market, the model implies that financialization reduces the futures risk premium and increases correlation between futures open interest and the spot price level. However, there is no long-run increase in the mean spot price, and speculative storage generally attenuates financialization’s effect on spot price volatility. Therefore, financialization’s effect on spot price dynamics through storage arbitrage is likely modest, even if futures positions and risk premia are substantially altered.

This paper was accepted by Gustavo Manso, finance.
Changing Educational Differentials in Female Sterilization
Authors: Hayford Sarah R. , Kissling Alexandra , Guzzo Karen Benjamin
Published: May 2020

CONTEXT

Female surgical sterilization is widely used in the United States. Educational differentials in sterilization are large, but poorly understood. Improved understanding of these differences is important to ensure that all women have access to the full range of contraceptive methods.

METHODS

Data from the National Survey of Family Growth (1973–2015) from 8,100 women aged 40–44 were used to describe trends in sterilization and other contraceptive methods by educational attainment. Demographic standardization was employed to examine how compositional changes in marital status and age at first birth contribute to aggregate changes in sterilization prevalence.

RESULTS

In 1982, women with a high school diploma and those with at least a bachelor's degree reported similar levels of sterilization use (38% and 32%, respectively), but by 2011–2015, prevalence had declined to 19% among college‐educated women and had increased to 44% among those with a diploma. The trend among college graduates was largely attributable to delayed fertility; all other things being equal, if their age at first birth had not increased, the prevalence of sterilization would have declined by approximately 3% instead of 14% between 1982 and 2002. Increased use of sterilization among women with a high school diploma was only weakly related to changes in birth timing and marital status.

CONCLUSIONS

Among women with a high school diploma, elements other than childbearing and marital status—such as contraceptive preferences and access—appeared to influence their contraceptive behavior. Sterilization differentials between high school and college graduates may reflect or exacerbate other socioeconomic disparities that affect women's health and well‐being.
Multi-focus image fusion using fractal dimension
Authors: Panigrahy Chinmaya , Seal Ayan , Kumar Mahato Nihar , Krejcar Ondrej , Herrera-Viedma Enrique
Published: May 2020

Multi-focus image fusion is defined as “the combination of a group of
partially focused images of a same scene with the objective of
producing a fully focused image.” Normally, transform-domain-based
image fusion methods preserve the textures and edges in the blend
image, but many are translation variant. The translation-invariant
transforms produce the same size approximation and detail images,
which are more convenient to devise the fusion rules. In this work, a
translation-invariant multi-focus image fusion approach using the
à-trous wavelet transform is introduced, which uses fractal dimension
as a clarity measure for the approximation coefficients and Otsu’s
threshold to fuse the detail coefficients. The subjective assessment
of the proposed method is carried out using the fusion results of nine
state-of-the-art methods. On the other hand, eight fusion quality
metrics are considered for the objective assessment. The results of
subjective and objective assessment on grayscale and color multi-focus
image pairs illustrate that the proposed method is competitive and
even better than some of the existing methods.