bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision medicine validation: identifying the MYBPC3 A31P variant with whole-genome sequencing in two Maine Coon cats with hypertrophic cardiomyopathy
Authors: Ontiveros Eric S , Ueda Yu , Harris Samantha P , Stern Joshua A ,   99 Lives Consortium
Published: December 2018

Objectives The objective of this study was to perform a proof-of-concept experiment that validates a precision medicine approach to identify variants associated with hypertrophic cardiomyopathy (HCM). We hypothesized that whole-genome sequencing would identify variant(s) associated with HCM in two affected Maine Coon/Maine Coon cross cats when compared with 79 controls of various breeds. Methods Two affected and two control Maine Coon/Maine Coon cross cats had whole-genome sequencing performed at approximately × 30 coverage. Variants were called in these four cats and 77 cats of various breeds as part of the 99 Lives Cat Genome Sequencing Initiative ( http://felinegenetics.missouri.edu/99lives ) using Platypus v0.7.9.1, annotated with dbSNP ID, and variants’ effect predicted by SnpEff. Strict filtering criteria (alternate allele frequency >49%) were applied to identify homozygous-alternate or heterozygous variants in the two HCM-affected samples when compared with 79 controls of various breeds. Results A total of four variants were identified in the two Maine Coon/Maine Coon cross cats with HCM when compared with 79 controls after strict filtering. Three of the variants identified in genes MFSD12, BTN1A1 and SLITRK5 did not segregate with disease in a separate cohort of seven HCM-affected and five control Maine Coon/Maine Coon cross cats. The remaining variant MYBPC3 segregated with disease status. Furthermore, this gene was previously associated with heart disease and encodes for a protein with sarcomeric function. Conclusions and relevance This proof-of-concept experiment identified the previously reported MYBPC3 A31P Maine Coon variant in two HCM-affected cases. This result validates and highlights the power of whole-genome sequencing for feline precision medicine.
A national survey of telemedicine use by US emergency departments
Authors: Zachrison Kori S , Boggs Krislyn M , M Hayden Emily , Espinola Janice A , Camargo Carlos A 
Published: December 2018

Objective Telemedicine has the potential to improve the delivery of emergency medical care: however, the extent of its adoption in United States (US) emergency departments is not known. Our objective was to characterise the prevalence of telemedicine use among all US emergency departments, describe clinical applications for which it is most commonly used, and identify emergency department characteristics associated with its use. Methods As part of the National Emergency Department Inventory-USA survey, we queried all 5375 US emergency departments open in 2016. Multivariable logistic regression analyses identified characteristics associated with emergency department receipt of telemedicine services. Results Overall, 4507 emergency departments (84%) responded to our survey, with 4031 responding to both telemedicine questions (75%). Although 1694 emergency departments (42%) reported no telemedicine in 2016, most did: 1923 (48%) emergency departments received telemedicine services, 149 (4%) emergency departments received telemedicine services and were in hospitals that provided telemedicine, and 265 emergency departments (7%) did not receive telemedicine but were in hospitals that provided telemedicine services. Among emergency departments receiving telemedicine, the most common applications were stroke/neurology (76%), psychiatry (38%), and paediatrics (15%). In multivariable analysis, telemedicine-receiving emergency departments had higher annual total visit volume for adults and lower annual total visit volume by children; were less likely to be academic or freestanding; and varied by region. In multivariable analysis, emergency departments in telemedicine-providing hospitals had higher annual total visit volume for adults and children, were more likely to be academic and were less likely to be freestanding. Conclusion In 2016, telemedicine was used in most US emergency departments (58%), especially for stroke/neurology and psychiatry. Future research is needed to understand the value of telemedicine for different clinical applications, and the barriers to its implementation.
High Risk of Suicide in Behavioral Variant Frontotemporal Dementia
Authors: Zucca Milena , Rubino Elisa , Vacca Alessandro , Govone Flora , Gai Annalisa , De Martino Paola , Boschi Silvia , Gentile Salvatore , Giordana Maria Teresa , Rainero Innocenzo 
Published: December 2018

Aim: The purpose of the study was to determine the prevalence of suicidal ideation and attempts in patients with behavioral variant frontotemporal dementia (bvFTD), evaluating possible risk factors for suicidality. Methods: Risk of suicide was assessed using the Scale for Suicide Ideation (SSI) in 35 patients with bvFTD and 25 controls. Results: According to SSI, 40% of patients with bvFTD had suicidal ideation in comparison to 8% of controls ( P = .009). Four patients with bvFTD have attempted suicide versus none control ( P = .006). Patients with bvFTD with suicide risk showed higher levels of anxiety, depression, stress, and hopelessness than patients without suicide risk ( P < .001). Patients who attempted suicide were younger and had a longer disease duration than those with only suicide ideation. Intriguingly, 40% of patients with parkinsonism presented high level of suicide ideation. Conclusions: Our findings show that patients with bvFTD have a high risk of suicide. Additional studies in larger populations are needed to confirm our results.
Variability of apparent diffusion coefficient in the brain in women during follicular and luteal phases of the menstrual cycle
Authors: Şafak Kadihan Yalçin 
Published: December 2018

Purpose To investigate the variability of apparent diffusion coefficient (ADC) in the brain in women during follicular and luteal phases of the menstrual cycle. Methods The present study included 32 females of reproductive age with regular menstruation. The participants were divided into two groups as group 1: females in the follicular phase, and group 2: females in the luteal phase. The regions of interest were manually drawn on the structures of the T2-weighted images (frontal gray and white matter, parietal gray and white matter, temporal gray and white matter, occipital gray and white matter, cerebellar gray and white matter, caudate nucleus, putamen, thalamus, internal capsule, pons, cerebrospinal fluid (CSF) in the frontal and in the occipital horn of the lateral ventricle and CSF in the middle part of the lateral ventricle). ADC values were averaged for each patient. We used Kruskal–Wallis ANOVA for more than two groups but used Mann Whitney U test for comparison of ADC values between the group of 18 females in the follicular phase and the group of 14 females in the luteal phase. Results No statistically significant differences were observed among the groups in terms of the ADC value of each neuroanatomic structure that was evaluated. Conclusion We did not determine a significant difference among volunteers at the two different phases of the menstrual cycle in terms of ADC values measured from different regions of the brain. However, although not statistically significant, ADC values measured from almost all parts of the brain were higher at the luteal phase than at the follicular phase.
Explicit and implicit experience of own’s body in painful musculoskeletal disorders and rheumatic diseases: A scoping review protocol of available quantitative and qualitative evidence
Authors: Viceconti Antonello , Camerone Eleonora Maria , Luzzi Deborah , Pardini Matteo , Ristori Diego , Gallace Alberto , Testa Marco 
Published: December 2018

Introduction: Our body experience is organized at twofold levels: perceptual and cognitive-emotional. These higher-order processes are clearly different from the primary sensory processing of somatic stimuli (somatosensation). However, most of the available studies have mainly investigated the mechanisms of somatosensation. Moreover, disturbances of our body experience have been documented in some pathological conditions of interest for rehabilitative interventions, but their clinical role and relevance is yet to be clarified. Because in this field we have limited knowledge on perceptual and cognitive body experience, there emerges a need to better clarify this matter. The aim of the present scoping review is to systematically map this topic and to examine the magnitude and the nature of the available evidences. Materials and Methods: The scoping review will be performed following the six-stage methodology suggested by Arksey and O’Malley. Ten electronic databases will be investigated since their inception. The search strategy will be peer reviewed by PRESS 2015 Evidence-Based Checklist as a quality assurance step. All records retrieved will be screened by two independent reviewers. The Population, Concept, and Context method will be adopted for eligibility criteria and Preferred Reporting Items for Systematic Reviews and Meta-Analyses will be used for results reporting. Two reviewers with different background will perform the search process independently. One author will extract data, checked by a second reviewer checking the matching with the research questions and goals. Any disagreements will be solved by a third reviewer. Ethics and Dissemination: Ethical approval is not required for scoping reviews. Dissemination will include submission to peer-reviewed journal and presentations in conferences in the area of rehabilitation.
Anatomic Anterior Cruciate Ligament Reconstruction Using Hamstring Tendons Restores Quantitative Pivot Shift
Authors: Zaffagnini Stefano , Signorelli Cecilia , Grassi Alberto , Hoshino Yuichi , Kuroda Ryosuke , de SA Darren , Sundemo David , Samuelsson Kristian , Musahl Volker , Karlsson Jon , Sheean Andrew , Burnham Jeremy M. , Lian Jayson , Smith Clair , Popchak Adam , Herbst Elmar , Pfeiffer Thomas , Araujo Paulo , Oostdyk Alicia , Guenther Daniel , Ohashi Bruno , Irrgang James J. , Fu Freddie H. , Nagamune Kouki , Kurosaka Masahiro , Marcheggiani Muccioli Giulio Maria , Lopomo Nicola , Raggi Federico , Svantesson Eleonor , Hamrin Senorski Eric , Bjoernsson Haukur , Ahlden Mattias , Desai Neel 
Published: December 2018

Background: It is still uncertain how surgical reconstruction of the anterior cruciate ligament (ACL) is able to restore rotatory laxity of the involved joint. The desired amount of restraint applied by the ACL graft, as compared with the healthy knee, has not been fully clarified. Purpose: To quantify the ability of single-bundle anatomic ACL reconstruction using hamstring tendons in reducing the pivot-shift phenomenon immediately after surgery under anesthesia. Study Design: Case series; Level of evidence, 4. Methods: An inertial sensor and image analysis were used at 4 international centers to measure tibial acceleration and lateral compartment translation of the knee, respectively. The standardized pivot-shift test was quantified in terms of the side-to-side difference in laxity both preoperatively and postoperatively with the patient under anesthesia. The reduction in both tibial acceleration and lateral compartment translation after surgery and the side-to-side difference were evaluated using the Wilcoxon signed-rank test. Alpha was set at P < .05. Results: A total of 107 patients were recruited for the study, and data were available for 89 patients. There was a statistically significant reduction in quantitative rotatory knee laxity between preoperatively (inertial sensor, 2.55 ± 4.00 m/s2; image analysis, 2.04 ± 2.02 mm) and postoperatively (inertial sensor, –0.54 ± 1.25 m/s2; image analysis, –0.10 ± 1.04 mm) between the involved and healthy joints, as measured by the 2 devices ( P < .001 for both). Postoperatively, both devices detected a lower rotatory laxity value in the involved joint compared with the healthy joint (inertial sensor, 2.45 ± 0.89 vs 2.99 ± 1.10 m/s2, respectively [ P < .001]; image analysis, 0.99 ± 0.83 vs 1.09 ± 0.92 mm, respectively [ P = .38]). Conclusion: The data from this study indicated a significant reduction in the pivot shift when compared side to side. Both the inertial sensor and image analysis used for the quantitative assessment of the pivot-shift test could successfully detect restoration of the pivot shift after anatomic single-bundle ACL reconstruction. Future research will examine how pivot-shift control is maintained over time and correlation of the pivot shift with return to full activity in patients with an ACL injury.
New therapies using nonfactor products for patients with hemophilia and inhibitors
Authors: Nogami Keiji , Shima Midori 
Published: December 2018

AbstractRegular prophylaxis with factor VIII (FVIII) or FIX products to prevent bleeding in patients with severe hemophilia A (HA) and HB, respectively, results in marked suppression of the onset of arthropathy and contributes greatly to improvements in quality of life. Some issues remain with the use of clotting factor replacement therapy, however. The need for multiple IV infusions is associated with a substantial mental and physical burden, and the hemostatic effect of bypassing agents (BPAs) in patients with inhibitor is inconsistent. The development of subcutaneous products with prolonged hemostatic efficiency, irrespective of the presence of inhibitors, has been a longtime wish for patients. A new class of therapeutic agents that act by enhancing coagulation (emicizumab) and inhibiting anticoagulant pathways (fitusiran and concizumab) have been established, and clinical trials using these nonfactor products are ongoing. The current findings have demonstrated that prophylaxis by nonfactor products supports marked reductions of bleeding episodes in hemophilia patients with or without inhibitor. Emicizumab has already been approved for use internationally. Some concerns are evident, however. Thrombotic microangiopathy and thromboembolism have occurred in 5 emicizumab-treated patients receiving repeated infusions of activated prothrombin complex concentrates, and a sinus vein thrombosis has occurred in a fitusiran-treated patient receiving repeated infusions of FVIII product. Moreover, reliable techniques to monitor hemostatic function in patients receiving nonfactor products with concomitant BPA or FVIII/FIX therapies require further assessment. These novel therapeutic agents have promising hemostatic properties, although wider experience in hemophilia centers is warranted to establish appropriate therapeutic strategies.
New therapies for hemophilia
Authors: Weyand Angela C. , Pipe Steven W. 
Published: December 2018

AbstractHemophilia A (HA) and hemophilia B (HB) are the most common severe bleeding disorders. Replacement therapy, providing the missing coagulation factor, has been the mainstay of treatment both prophylactically and to treat bleeding. Despite widespread availability of safe and effective replacement therapy, patients with HA and HB continue to experience a tremendous burden of treatment, breakthrough bleeding, and progressive joint disease, as well as high rates of inhibitor development. These remaining challenges are now being addressed by incredible advances in bioengineering. Recombinant bioengineering has led to replacement therapies with easier modes of administration, decreased immunogenicity, increased efficacy, and extended half-lives. Emicizumab, a bispecific antibody that acts as a substitutive therapy for HA, has been approved for patients with and without inhibitors. Novel compounds are in development to exploit the natural balance of hemostasis by targeting the natural anticoagulants protein C, protein S, tissue factor pathway inhibitor, and antithrombin. The substitution and rebalancing therapies provide an opportunity for steady-state hemostatic control without exposure to immunogenic clotting factor proteins. As such, they may have broader applications outside those being investigated in the clinical trial programs.
Functional outcomes in early (T1/T2) supraglottic cancer: A systematic review
Authors: van der Woerd Benjamin , Patel Krupal B. , Nichols Anthony C. , Fung Kevin , Yoo John , MacNeil S. Danielle 
Published: December 2018

Objectives Organ preserving surgery (OPS) and radiotherapy (RT) are both accepted treatment options for early stage supraglottic cancer (SGC). Radiation has supplanted surgery in most cases, because of the perception that surgery results in poorer functional outcomes. However, evidence suggests that OPS with a neck dissection may be associated with improved survival. Our objective was to conduct a systematic review of the literature to compare functional outcomes of OPS and RT for early SGC. Methods We searched Medline, EMBASE and Cochrane Central Register of Controlled Trials to identify studies. Studies were included if they reported functional outcomes on 10 or more patients with early stage SGC treated with radiation or OPS, including open partial laryngectomy, transoral laser microsurgery (TLM) or transoral robotic surgery (TORS). Two reviewers independently screened articles for relevance using pre-determined criteria. Results From 7720 references, we included 10 articles ( n = 640 patients). 50% ( n = 320) of patients were treated with surgery. Three head-to-head RT versus OPS papers were included, however different outcome measures were used for each group. Intractable aspiration management (including total laryngectomy or permanent tracheostomy) following OPS was reported in five papers representing 186 patients; the definitive intractable aspiration management rate was 2.6% (95% CI 1.0–6.8%). Four papers reported permanent G-tube rate for the surgical group ( n = 198), calculating a rate of 5.3% (95% CI 2.6–10.5%), this was not reported for the RT group in any papers. One study reported quality of life. Two studies reported objective voice measures. Conclusions This systematic review revealed a paucity of objective measures and significant data heterogeneity, rendering the comparison of functional outcomes following OPS versus RT for early SGC limited. Future research should include objective measures of functional outcomes including laryngectomy rate, g-tube rate, tracheostomy dependence, quality of life, and voice quality measures.
Unite to divide – how models and biological experimentation have come together to reveal mechanisms of cytokinesis
Authors: Cortes Daniel B. , Dawes Adriana , Liu Jian , Nickaeen Masoud , Strychalski Wanda , Maddox Amy Shaub 
Published: December 2018

ABSTRACT
Cytokinesis is the fundamental and ancient cellular process by which one cell physically divides into two. Cytokinesis in animal and fungal cells is achieved by contraction of an actomyosin cytoskeletal ring assembled in the cell cortex, typically at the cell equator. Cytokinesis is essential for the development of fertilized eggs into multicellular organisms and for homeostatic replenishment of cells. Correct execution of cytokinesis is also necessary for genome stability and the evasion of diseases including cancer. Cytokinesis has fascinated scientists for well over a century, but its speed and dynamics make experiments challenging to perform and interpret. The presence of redundant mechanisms is also a challenge to understand cytokinesis, leaving many fundamental questions unresolved. For example, how does a disordered cytoskeletal network transform into a coherent ring? What are the long-distance effects of localized contractility? Here, we provide a general introduction to ‘modeling for biologists’, and review how agent-based modeling and continuum mechanics modeling have helped to address these questions.
Administração fiscal dialógica
Authors: Fernandes André Dias , Cavalcante Denise Lucena 
Published: December 2018

Dialogic fiscal administration O presente artigo analisa os atuais paradigmas da administração pública e seus reflexos no âmbito da administração fazendária. O contexto contemporâneo exige novos procedimentos dos agentes fazendários e dos cidadãos-contribuintes, com uma atuação mais célere, transparente, eficiente e colaborativa dos agentes envolvidos na relação tributária. Tanto o Fisco como o contribuinte têm de se esforçar na instauração do diálogo e, consequentemente, na redução dos litígios. Demonstra-se que a busca de acordo acerca do crédito tributário é, além de medida racional e eficaz na resolução dos conflitos tributários, uma exigência do mundo contemporâneo. The purpose of this article is to analyze the new paradigms of public administration and its repercussions within the scope of fiscal administration. The contemporary context requires new procedures for the taxpayer and taxpayer agents, with a faster, transparent, efficient and collaborative action of the players involved in the tax relation. Both the tax authorities and the taxpayers must strive to establish dialogue and, consequently, to reduce litigation. It will be demonstrated that the search for agreement of the tax credit is, besides a rational and effective measure in the resolution of the tax conflicts, a demand of the contemporary world.
O princípio do contraditório necessário aos processos administrativos e aos processos nos tribunais de contas
Authors: Salles Alexandre Aroeira 
Published: December 2018

The adversarial system (the principle of the right to a fair hearing) needed for proceedings before administratives and accounting courts in Brazil A CRFB/88 entregou às atividades de controle interno e de controle externo brasileiros importantes competências, incluindo a função de aplicar sanções a pessoas físicas e jurídicas, podendo-lhes ainda condenar à devolução de valores irregularmente dispendidos. Ao mesmo tempo, a CRFB/88 garantiu, por meio do artigo 5o, a todos os indivíduos que o Estado somente lhes possa privar de seus bens e direitos caso siga fielmente as normas-princípio do devido processo legal, do contraditório e da ampla defesa. Desrespeitando frontalmente tais princípios, a Lei no 8.443/1992 organizou seu aparato de forma a incluir nas atribuições de seus ministros o papel de fiscalizar, acusar, instaurar, instruir, gerir as provas e decidir seus processos acusatórios contra os indivíduos. Além disso, a referida lei estabeleceu um processo em que as partes não conseguem: produzir suas provas; acompanhar as provas produzidas pelos seus acusadores e ao mesmo tempo julgadores; serem ouvidas; e nem recorrerem para instância que não já as tenha fiscalizado e julgado. Portanto, é necessário modernizar tal lei para viabilizar tanto uma organização como um processo justo. The Brazilian Constitution of 1988 provided the administrative agencies with important competencies for the internal and external control of public activities, including the function of imposing sanctions and order the return of amounts spent improperly against citzens. At the same time, the 1988 Brazilian Constitution, through its Article 5, guarantees to all individuals that the State can only deprive them of their assets and rights if it faithfully follows certain specific principles (“normas-princípio”) of due legal process, adversarial system and full defense. Disrespecting directly such principles, the act Law 8.443/92 structured its bodies in such a way as to give to the officials the role of auditing, accusing, instituting, instructing, administering the evidence and deciding on its accusatory proceedings against individuals. Moreover, these Laws established a process in which the parties cannot: produce their evidence; analyse the evidence presented by their accusers/judges; be heard; or even appeal to a forum that has not already reviewed and decided on their case. Therefore, it is necessary to adapt this act to enable the creation of a structure and process that is fair.