bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abdominal Aortic Calcification Is a Significant Poor Prognostic Factor for Clinical Outcomes After Decompressive Laminotomy for Lumbar Spinal Canal Stenosis
Authors: Sakaura Hironobu , Ikegami Daisuke , Fujimori Takahito , Sugiura Tsuyoshi , Owaki Hajime , Fuji Takeshi 
Published: February 2019

Study Design: Retrospective study. Objective: To examine whether the presence of chronic kidney disease (CKD) or advanced abdominal aortic calcification (AAC) negatively affects clinical outcomes after decompression surgery for lumbar spinal canal stenosis (LSCS). Methods: The subjects comprised 143 patients who underwent decompressive laminotomy for LSCS and were followed for ≥2 years. Fifty-five patients had CKD (Stage 3-4). Clinical outcome was assessed using the Japanese Orthopaedic Association (JOA) score before surgery and at 2-year postoperatively. According to the scoring system by Kauppila et al, the AAC score (a surrogate marker of systemic atherosclerosis) was assessed using preoperative lateral radiographs of the lumbar spine. Results: Patient age had weak but significantly negative correlations with both the preoperative JOA score and the JOA score at 2 years after surgery, but did not have a significant correlation with the recovery rate of the JOA score at 2 years postoperatively. The JOA score before surgery, the JOA score at 2-year follow-up, and the recovery rate of the JOA score were slightly lower in the CKD patients than in those without CKD, although there were no significant differences between the 2 groups. On the contrary, the AAC score had a weak but significantly negative correlation with the preoperative JOA score, and had relatively strong and significantly negative correlations with both the JOA score at 2 years after surgery and the recovery rate of the JOA score. Conclusions: At 2 years after surgery, advanced AAC was a significant poor prognostic factor for clinical outcomes of decompression surgery for LSCS.
Online Medical Education for Doctors: Identifying Potential Gaps to the Traditional, Face-to-Face Modality
Authors: Ifediora Chris O 
Published: February 2019

Background: Online education options increasingly complement traditional face-to-face (F2F) approaches. Few studies have compared both formats on doctors, and little evidence exists to prove that the online approach is universally effective. This gap needs to be addressed to ensure that the quality of education and health care delivery is not compromised. Methods: A quantitative survey targeting 881 doctors that required online and F2F teaching sessions offers identical contents over a 12-month period. The surveyed doctors work in the Australian after-hours house-call (AHHC) industry, and the teachings were parts of their continuing professional development activities. Results: In all, 89 responses were received; 10 (11.2%) participated exclusively online, while 23 (25.8%) did so by F2F; 52 (58.4%) engaged through both modalities. No statistical differences existed based on sex, specialty, and post-graduate fellowship status, as well as on the perceptions with teaching structure, contents, and duration of the education programmes. However, F2F-only doctors were likely to be junior and younger than 40 years (odds ratio [OR]: 3.85; P = .01). They also admit easy access to effective teaching environment (OR: 4.07; P = .01) and receive better feedbacks (OR: 3.75; P = .01). Conversely, online-only participants were more likely to combine AHHC duties with regular-hours general practice (OR: 0.15; P = .02) and are generally more satisfied with the programme frequency (OR: 6.90; P = .01). Conclusions: On multiple areas, no differences exist in the medical education delivered by online and the F2F methods to doctors and both should be encouraged. However, younger and junior practitioners, who tend to need feedbacks on their jobs, should participate more in the F2F sessions.
Genetic deletion of genes in the cerebellar rhombic lip lineage can stimulate compensation through adaptive reprogramming of ventricular zone-derived progenitors
Authors: Wojcinski Alexandre , Morabito Morgane , Lawton Andrew K. , Stephen Daniel N. , Joyner Alexandra L. 
Published: February 2019

Abstract
Background
The cerebellum is a foliated posterior brain structure involved in coordination of motor movements and cognition. The cerebellum undergoes rapid growth postnataly due to Sonic Hedgehog (SHH) signaling-dependent proliferation of ATOH1+ granule cell precursors (GCPs) in the external granule cell layer (EGL), a key step for generating cerebellar foliation and the correct number of granule cells. Due to its late development, the cerebellum is particularly vulnerable to injury from preterm birth and stress around birth. We recently uncovered an intrinsic capacity of the developing cerebellum to replenish ablated GCPs via adaptive reprogramming of Nestin-expressing progenitors (NEPs). However, whether this compensation mechanism occurs in mouse mutants affecting the developing cerebellum and could lead to mis-interpretation of phenotypes was not known.

Methods
We used two different approaches to remove the main SHH signaling activator GLI2 in GCPs: 1) Our mosaic mutant analysis with spatial and temporal control of recombination (MASTR) technique to delete Gli2 in a small subset of GCPs; 2) An Atoh1-Cre transgene to delete Gli2 in most of the EGL. Genetic Inducible Fate Mapping (GIFM) and live imaging were used to analyze the behavior of NEPs after Gli2 deletion.

Results
Mosaic analysis demonstrated that SHH-GLI2 signaling is critical for generating the correct pool of granule cells by maintaining GCPs in an undifferentiated proliferative state and promoting their survival. Despite this, inactivation of GLI2 in a large proportion of GCPs in the embryo did not lead to the expected dramatic reduction in the size of the adult cerebellum. GIFM uncovered that NEPs do indeed replenish GCPs in Gli2 conditional mutants, and then expand and partially restore the production of granule cells. Furthermore, the SHH signaling-dependent NEP compensation requires Gli2, demonstrating that the activator side of the pathway is involved.

Conclusion
We demonstrate that a mouse conditional mutation that results in loss of SHH signaling in GCPs is not sufficient to induce long term severe cerebellum hypoplasia. The ability of the neonatal cerebellum to regenerate after loss of cells via a response by NEPs must therefore be considered when interpreting the phenotypes of Atoh1-Cre conditional mutants affecting GCPs.
Efficacy of Internet-Based Cognitive Behavioral Therapy for Treatment-Induced Menopausal Symptoms in Breast Cancer Survivors: Results of a Randomized Controlled Trial
Authors: Atema Vera , van Leeuwen Marieke , Kieffer Jacobien M. , Oldenburg Hester S.A. , van Beurden Marc , Gerritsma Miranda A. , Kuenen Marianne A. , Plaisier Peter W. , Lopes Cardozo Alexander M.F. , van Riet Yvonne E.A. , Heuff Gijsbert , Rijna Herman , van der Meij Suzan , Noorda Eva M. , Timmers Gert-Jan , Vrouenraets Bart C. , Bollen Matthé , van der Veen Henk , Bijker Nina , Hunter Myra S. , Aaronson Neil K. 
Published: February 2019

PURPOSE We evaluated the effect of Internet-based cognitive behavioral therapy (iCBT), with or without therapist support, on the perceived impact of hot flushes and night sweats (HF/NS) and overall levels of menopausal symptoms (primary outcomes), sleep quality, HF/NS frequency, sexual functioning, psychological distress, and health-related quality of life in breast cancer survivors with treatment-induced menopausal symptoms. PATIENTS AND METHODS We randomly assigned 254 breast cancer survivors to a therapist-guided or a self-managed iCBT group or to a waiting list control group. The 6-week iCBT program included psycho-education, behavior monitoring, and cognitive restructuring. Questionnaires were administered at baseline and at 10 weeks and 24 weeks postrandomization. We used mixed-effects models to compare the intervention groups with the control group over time. Significance was set at P < .01. An effect size (ES) of .20 was considered small, .50 moderate and clinically significant, and .80 large. RESULTS Compared with the control group, the guided and self-managed iCBT groups reported a significant decrease in the perceived impact of HF/NS (ES, .63 and .56, respectively; both P < .001) and improvement in sleep quality (ES, .57 and .41; both P < .001). The guided group also reported significant improvement in overall levels of menopausal symptoms (ES, .33; P = .003), and NS frequency (ES, .64; P < .001). At longer-term follow-up (24 weeks), the effects remained significant, with a smaller ES for the guided group on perceived impact of HF/NS and sleep quality and for the self-managed group on overall levels of menopausal symptoms. Additional longer-term effects for both intervention groups were found for hot flush frequency. CONCLUSION iCBT, with or without therapist support, has clinically significant, salutary effects on the perceived impact and frequency of HF/NS, overall levels of menopausal symptoms, and sleep quality.
In Vivo Ablation of the Conserved GATA-Binding Motif in the Amh Promoter Impairs Amh Expression in the Male Mouse
Authors: Bouchard Marie France , Bergeron Francis , Grenier Delaney Jasmine , Harvey Louis-Mathieu , Viger Robert S 
Published: February 2019

AbstractGATA4 is an essential transcriptional regulator required for gonadal development, differentiation, and function. In the developing testis, proposed GATA4-regulated genes include steroidogenic factor 1 (Nr5a1), SRY-related HMG box 9 (Sox9), and anti-Müllerian hormone (Amh). Although some of these genes have been validated as genuine GATA4 targets, it remains unclear whether GATA4 is a direct regulator of endogenous Amh transcription. We used a CRISPR/Cas9-based approach to specifically inactivate or delete the sole GATA-binding motif of the proximal mouse Amh promoter. AMH mRNA and protein levels were assessed at developmental time points corresponding to elevated AMH levels: fetal and neonate testes in males and adult ovaries in females. In males, loss of GATA binding to the Amh promoter significantly reduced Amh expression. Although the loss of GATA binding did not block the initiation of Amh transcription, AMH mRNA and protein levels failed to upregulate in the developing fetal and neonate testis. Interestingly, adult male mice presented no anatomical anomalies and had no evidence of retained Müllerian duct structures, suggesting that AMH levels, although markedly reduced, were sufficient to masculinize the male embryo. In contrast to males, GATA binding to the Amh promoter was dispensable for Amh expression in the adult ovary. These results provide conclusive evidence that in males, GATA4 is a positive modulator of Amh expression that works in concert with other key transcription factors to ensure that the Amh gene is sufficiently expressed in a correct spatiotemporal manner during fetal and prepubertal testis development.
Reverse genetic screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the brain
Authors: Kuil Laura E. , Oosterhof Nynke , Geurts Samuël N. , van der Linde Herma C. , Meijering Erik , van Ham Tjakko J. 
Published: February 2019

Microglia are brain resident macrophages, which have specialized functions important in brain development and in disease. They colonize the brain in early embryonic stages, but few factors that drive the migration of yolk sac macrophages (YSMs) into the embryonic brain , or regulate their acquisition of specialized properties are currently known.Here, we present a CRISPR/Cas9-based in vivo reverse genetic screening pipeline to identify new microglia regulators using zebrafish. Zebrafish larvae are particularly suitable due to their external development, transparency and conserved microglia features. We targeted putative microglia regulators, by Cas9/gRNA-complex injections, followed by neutral red-based visualization of microglia. Microglia were quantified automatically in 3-day-old larvae using a software tool we called SpotNGlia. We identified that loss of the zebrafish colony stimulating factor 1 receptor (CSF1R) ligand IL34, caused reduced microglia numbers. Previous studies on the role of the IL34 on microglia development in vivo were ambiguous. Our data, and a concurrent paper, show that in zebrafish, il34 is required during the earliest seeding of the brain by microglia. Our data also indicate that Il34 is required for YSM distribution to other organs. Disruption of the other CSF1R ligand, Csf1, did not reduce microglia numbers in mutants, whereas overexpression increased the number of microglia. This shows Csf1 can influence microglia numbers, but might not be essential for the early seeding of the brain. In all, we identified il34 as a modifier of microglia colonization, by affecting distribution of YSMs to target organs, validating our reverse genetic screening pipeline in zebrafish.
Cancer cells in the tumor core exhibit spatially coordinated migration patterns
Authors: Staneva Ralitza , El Marjou Fatima , Barbazan Jorge , Krndija Denis , Richon Sophie , Clark Andrew G. , Vignjevic Danijela Matic 
Published: February 2019

ABSTRACT
In the early stages of metastasis, cancer cells exit the primary tumor and enter the vasculature. Although most studies have focused on the tumor invasive front, cancer cells from the tumor core can also potentially metastasize. To address cell motility in the tumor core, we imaged tumor explants from spontaneously forming tumors in mice in real time using long-term two-photon microscopy. Cancer cells in the tumor core are remarkably dynamic and exhibit correlated migration patterns, giving rise to local ‘currents’ and large-scale tissue dynamics. Although cells exhibit stop-and-start migration with intermittent pauses, pausing does not appear to be required during division. Use of pharmacological inhibitors indicates that migration patterns in tumors are actively driven by the actin cytoskeleton. Under these conditions, we also observed a relationship between migration speed and correlation length, suggesting that cells in tumors are near a jamming transition. Our study provides new insight into the dynamics of cancer cells in the tumor core, opening new avenues of research in understanding the migratory properties of cancer cells and later metastasis.
This article has an associated First Person interview with the first author of the paper.
Polyubiquitylation of α-tubulin at K304 is required for flagellar disassembly in Chlamydomonas
Authors: Wang Qiyu , Peng Zhao , Long Huan , Deng Xuan , Huang Kaiyao 
Published: February 2019

ABSTRACT
Cilia/flagella are structurally conserved and dynamic organelles; their assembly and disassembly are coordinated with the cell cycle and cell differentiation. Several post-translational modifications, including acetylation, methylation, phosphorylation and ubiquitylation, participate in ciliary disassembly. However, the detailed mechanism and the role of ubiquitylation in ciliary disassembly are unclear. This study identified 20 proteins that were ubiquitylated in shortening flagella of Chlamydomonas. α-Tubulin was the most abundant ubiquitylated protein and it was labeled with K63 polyubiquitin chains primarily at K304. Expression of an α-tubulin mutant (K304R), which could not be ubiquitylated, decreased the rate of flagellar disassembly and resulted in an enrichment of the mutant form in the axoneme, suggesting that ubiquitylation of α-tubulin is required for the normal kinetics of axonemal disassembly. Immunoprecipitation and glutathione-S-transferase pulldown assays demonstrated that the retrograde intraflagellar transport (IFT) protein, IFT139, interacted with a variety of ubiquitylated proteins, including α-tubulin, suggesting that IFT-A was responsible for transporting ubiquitylated proteins out of the flagella. Our data suggest an important role for ubiquitylation and retrograde IFT in ciliary disassembly.
This article has an associated First Person interview with the first author of the paper.
Quantitative diagnosis of osteoporosis using lumbar spine signal intensity in magnetic resonance imaging
Authors: Shayganfar Azin , Khodayi Maede , Ebrahimian Shadi , Tabrizi Zhale 
Published: February 2019

Objective:
Osteoporosis is the most common metabolic bone disease that is not recognized in many elderly people. To determine the cause of low back pain, lumbosacral MRI is done for a large population who may not have gone under dual energy X-ray absorptiometry (DXA). The aim of this study was to predict bone density using lumbar spine signals in lumbosacral MRI in high risk patients for osteoporosis including post-menopausal females and calculate a threshold for a new quantitative MRI-based score to be used in estimation of lumbar spine bone mass density.

Methods:
82 menopaused females, who had undergone DXA before, were selected and MRI was done within 6 months after DXA. 69 healthy females aged 20–29 years who had undergone lumbar MRI were selected as reference group. Results were analyzed and threshold and diagnostic performance of MRI-based score (M-score) on the method of T-score was calculated.

Results:
Negative correlation between M-score and T-score was detected. Cut off point of 2.05 was found for M-score with near sensitivity of 90% and specificity of 87% for detecting osteoporotic patients from non-osteoporotic individuals.

Conclusion:
M-score is a MRI-based method which can identify patients at risk of osteoporosis. Early diagnosis of osteoporosis can reduce morbidity and mortality caused by it.

Advances in knowledge:
The research introduced cut of points for M-score as a new MRI quantitative method to be used as an opportunistic technique for detecting osteoporotic patients.
How ‘smart’ is smart dentistry?
Authors: Kokol Peter , Blažun Vošner Helena , Završnik Jernej , Turčin Marko 
Published: February 2019

Background:Latest advances in information and health technologies enabled dentistry to follow the paradigm shift occurring in medicine – the transition to so called smart medicine. Consequently, the aim of this paper is to assess how ‘smart’ is smart dentistry as of the end of 2018.Methods:We analysed the state of the art in smart dentistry, performing bibliometric mapping on a corpus of smart dentistry papers found in the Scopus bibliographical database.Results:The search resulted in a corpus of 3451 papers, revealing that smart dentistry research is following the progress in smart medicine; however, there are some gaps in some specific areas like gamification and use of holistic smart dentistry systems.Conclusions:Smart dentistry is smart; however, it must become smarter.
Case Report: Rare comorbidity of celiac disease and Evans syndrome
Authors: Uddin Syed Mohammad Mazhar , Haq Aatera , Haq Zara , Yaqoob Uzair 
Published: February 2019

Background: Celiac disease is an immune-mediated enteropathy due to permanent sensitivity to gluten in genetically predisposed individuals. Evans syndrome is an autoimmune disorder designated with simultaneous or successive development of autoimmune hemolytic anemia and immune thrombocytopenia and/or immune neutropenia in the absence of any cause. Case Report: We report a rare case of Celiac disease and Evans syndrome in a 20-year-old female who presented to us with generalized weakness and shortness of breath. Her examination finding included anemia, jaundice, and raised jugular venous pulse. Her abdominal exam revealed hepatosplenomegaly. Her laboratory values showed microcytic anemia, leukocytosis and thrombocytopenia. To rule out secondary causes of idiopathic thrombocytopenia purpura, we tested viral markers for Human immunodeficiency virus, Epstein bar virus, Cytomegalovirus and performed a Helicobacter pylori test, all of which were negative. We also ruled out idiopathic thrombocytopenia purpura associated with any thyroid disorder. For celiac disease, we took anti-tissue transgulataminase titers of IgA and IgG which confirmed the diagnosis of celiac disease. For the diagnosis of Evans syndrome, despite a negative serum coombs test initially, her bone marrow sample showed a positive Coombs test along with immune mediated hemolytic anemia and immune mediated thrombocytopenia. The patient was treated with prednisone which was tapered off and counseling was provided regarding a gluten free diet. Conclusion: Although rare, tests for Evans syndrome (and other coexisting autoimmune problems) should be performed in patients with celiac disease.
Separate and Concentrate: Accounting for Patient Complexity in General Hospitals
Authors: Kuntz Ludwig , Scholtes Stefan , Sülz Sandra 
Published: February 2019

Scholars have recently suggested the reorganization of general hospitals into organizationally separate divisions for routine and non-routine services to overcome operational misalignments between the two types of services. We provide empirical evidence for this proposal from a quality perspective, using over 250,000 patient discharge records from 60 German hospitals across 39 high-mortality disease segments, and focusing on in-hospital mortality as outcome. Disentangling the effects of high, absolute, and relative hospital volumes in a disease group, our analysis suggests that routine and complex patients would benefit from a hospital organization with a multi-specialty hub for emergency and non-routine elective services at its core, complemented by organizationally separate disease-focused hospitals-within-hospitals for routine services. We also provide evidence that the hub hospital can further improve service quality for complex patients by adopting a disease-based rather than medical specialty-based departmental routing strategy for newly arriving patients. A counterfactual analysis, based on a simultaneous equations probit model that simultaneously controls for endogeneity of volume, focus, and routing strategy, suggests that the proposed reorganization could have reduced mortality in the sample by 13.43% (95% CI [6.87%; 18.95%]) for routine patients and by 11.67% (95% CI [6.13%; 16.86%]) for the most complex patients. The supplementary material is available at https://doi.org/10.1287/mnsc.2018.3064 . This paper was accepted by Serguei Netessine, operations management.
Portfolio Manager Ownership and Mutual Fund Risk Taking
Authors: Ma Linlin , Tang Yuehua 
Published: February 2019

This paper studies the effect of portfolio manager ownership (i.e., “skin in the game”) on mutual fund risk taking. Using holdings-based risk change measures that capture managers’ ex ante risk choices, we find that portfolio manager ownership reduces both intrayear and across-year risk-taking activities. The relationship between ownership and risk reduction is particularly strong among managers with high agency issue–induced risk-taking incentives—for example, managers who face a more convex flow-performance relationship, have poor past performance, or are not compensated based on long-term fund performance. Funds with greater managerial ownership are also associated with lower levels of total risk and downside risk. Overall, portfolio manager ownership serves as an incentive alignment mechanism and has important implications for mutual fund investors. This paper was accepted by Amit Seru, finance.