bluuebunny/crossref_metadata_2025 huggingface dataset:
Parapred: antibody paratope prediction using convolutional and recurrent neural networks
Authors: Liberis Edgar , Veličković Petar , Sormanni Pietro , Vendruscolo Michele , Liò Pietro
Published: April 2018

Motivation

Antibodies play essential roles in the immune system of vertebrates and are powerful tools in research and diagnostics. While hypervariable regions of antibodies, which are responsible for binding, can be readily identified from their amino acid sequence, it remains challenging to accurately pinpoint which amino acids will be in contact with the antigen (the paratope).

Results

In this work, we present a sequence-based probabilistic machine learning algorithm for paratope prediction, named Parapred. Parapred uses a deep-learning architecture to leverage features from both local residue neighbourhoods and across the entire sequence. The method significantly improves on the current state-of-the-art methodology, and only requires a stretch of amino acid sequence corresponding to a hypervariable region as an input, without any information about the antigen. We further show that our predictions can be used to improve both speed and accuracy of a rigid docking algorithm.

Availability and implementation

The Parapred method is freely available as a webserver at http://www-mvsoftware.ch.cam.ac.uk/and for download at https://github.com/eliberis/parapred.

Supplementary information

Supplementary information is available at Bioinformatics online.
Initial Assessment of the Risk Assessment and Prediction Tool in a Heterogeneous Neurosurgical Patient Population
Authors: Piazza Matthew , Sharma Nikhil , Osiemo Benjamin , McClintock Scott , Missimer Emily , Gardiner Diana , Maloney Eileen , Callahan Danielle , Smith J Lachlan , Welch William , Schuster James , Grady M Sean , Malhotra Neil R
Published: April 2018

BACKGROUND

Bundled care payments are increasingly being explored for neurosurgical interventions. In this setting, skilled nursing facility (SNF) is less desirable from a cost perspective than discharge to home, underscoring the need for better preoperative prediction of postoperative disposition.

OBJECTIVE

To assess the capability of the Risk Assessment and Prediction Tool (RAPT) and other preoperative variables to determine expected disposition prior to surgery in a heterogeneous neurosurgical cohort, through observational study.

METHODS

Patients aged 50 yr or more undergoing elective neurosurgery were enrolled from June 2016 to February 2017 (n = 623). Logistic regression was used to identify preoperative characteristics predictive of discharge disposition. Results from multivariate analysis were used to create novel grading scales for the prediction of discharge disposition that were subsequently compared to the RAPT Score using Receiver Operating Characteristic analysis.

RESULTS

Higher RAPT Score significantly predicted home disposition (P < .001). Age 65 and greater, dichotomized RAPT walk score, and spinal surgery below L2 were independent predictors of SNF discharge in multivariate analysis. A grading scale utilizing these variables had superior discriminatory power between SNF and home/rehab discharge when compared with RAPT score alone (P = .004).

CONCLUSION

Our analysis identified age, lower lumbar/lumbosacral surgery, and RAPT walk score as independent predictors of discharge to SNF, and demonstrated superior predictive power compared with the total RAPT Score when combined in a novel grading scale. These tools may identify patients who may benefit from expedited discharge to subacute care facilities and decrease inpatient hospital resource utilization following surgery.
Impact of diet deprivation and subsequent overallowance during gestation on lactation performance of primiparous sows1
Authors: Farmer Chantal , Herkelman Kevin , James Brad , Lessard Pierre , Samson Arnaud , Cormier Isabelle
Published: April 2018

The impact of diet deprivation followed by overallowance during gestation on metabolic status of pregnant gilts and their lactation performance was determined. Gilts were fed a standard diet until day 27 of gestation and were subsequently reared under a control (CTL; n = 28) or an experimental (treatment, TRT; n = 26) dietary regimen. The experimental regimen provided 70% (restriction diet, RES) and 115% (overallowance diet, OVER) of the protein and NE contents provided by the CTL diet. The RES diet was given from days 28 to 74 of gestation followed by the OVER diet from day 75 until farrowing. Blood samples were obtained from all gilts on days 28, 75, and 110 of gestation, and on days 3 and 20 of lactation to measure concentrations of IGF-1, urea, FFA, and glucose. Milk samples were collected from 12 sows per treatment on day 19 of lactation and sow feed intake was recorded daily throughout lactation. Piglets were weighed at 24 h (after standardization of litter size), and on days 7, 14, and 21 (weaning). The TRT gilts gained less BW than CTL gilts (17.3 vs. 31.7 kg; P < 0.01) from days 28 to 75 of gestation and more BW (29.5 vs. 21.9 kg; P < 0.01) from days 75 to 110, but their overall gain from mating to day 110 was lower (61.4 vs. 67.2 kg; P < 0.05). Metabolic status during gestation was affected, with TRT gilts having less IGF-1 and urea, and more FFA than CTL gilts on day 75 (P < 0.01), and more urea on day 110 (P < 0.01). Growth rate of suckling piglets, sow lactation feed intake, and standard milk composition in late lactation (DM, fat, protein, lactose) were not affected by treatment (P > 0.10). In conclusion, diet deprivation of gilts as of day 28 of gestation followed by overfeeding from day 75 of gestation until farrowing did not improve lactation performance. It is likely that the compensatory growth that took place in late gestation was not adequate to illicit beneficial effects.
The Mycoheterotrophic Symbiosis Between Orchids and Mycorrhizal Fungi Possesses Major Components Shared with Mutualistic Plant-Mycorrhizal Symbioses
Authors: Miura Chihiro , Yamaguchi Katsushi , Miyahara Ryohei , Yamamoto Tatsuki , Fuji Masako , Yagame Takahiro , Imaizumi-Anraku Haruko , Yamato Masahide , Shigenobu Shuji , Kaminaka Hironori
Published: April 2018

Achlorophylous and early developmental stages of chorolophylous orchids are highly dependent on carbon and other nutrients provided by mycorrhizal fungi, in a nutritional mode termed mycoheterotrophy. Previous findings have implied that some common properties at least partially underlie the mycorrhizal symbioses of mycoheterotrophic orchids and that of autotrophic arbuscular mycorrhizal (AM) plants; however, information about the molecular mechanisms of the relationship between orchids and their mycorrhizal fungi is limited. In this study, we characterized the molecular basis of an orchid-mycorrhizal (OM) symbiosis by analyzing the transcriptome of Bletilla striata at an early developmental stage associated with the mycorrhizal fungus Tulasnella sp. The essential components required for the establishment of mutual symbioses with AM fungi or rhizobia in most terrestrial plants were identified from the B. striata gene set. A cross-species gene complementation analysis showed one of the component genes, calcium and calmodulin-dependent protein kinase gene CCaMK in B. striata, retains functional characteristics of that in AM plants. The expression analysis revealed the activation of homologs of AM-related genes during the OM symbiosis. Our results suggest that orchids possess, at least partly, the molecular mechanisms common to AM plants.
Is the Current Management of Patients Presenting With Spinal Trauma to District General Hospitals Fit for Purpose?
Authors: Hill Daniel S. , Marynissen Hans
Published: April 2018

Study Design.

A retrospective cross-sectional analysis.

Objective.

The aim of this study was to describe the provision of a spinal service using an electronic platform to direct management from an external spinal unit, and to quantify the time taken to obtain definitive management plans while under prescribed spinal immobilization.

Summary of Background Data.

Most attending district general hospitals following spinal trauma will have stable injuries and normal neurology, with only a small proportion requiring urgent transfer to a specialist center.

Methods.

A retrospective review of 104 patients admitted following vertebral trauma during a 12-month period. The British Orthopaedic Association Standards for Trauma consensus that “spinal immobilisation is not recommended for more than 48 hours” was the standard of care measured against.

Results.

One hundred patients occupied a total of 975 hospital inpatient bed days. One hundred and seventeen radiological investigations were requested after the point of external referral [47 computed tomography (CT)-scans, 37 magnetic resonance imaging (MRI)-scans, and 33 weight-bearing radiographs]. The period between initial referral to the regional spinal service and then receiving a definitive final management plan had a median value of 72 hours and a range of 0 and 33 days. Patients will have been under some form of prescribed spinal immobilization until the definitive management plan was communicated. Thirty-four patients (34% of the overall cohort) had a definitive management plan in place within 48 hours. Eighty patients had vertebral injuries (73 stable, six unstable), three patients had prolapsed intervertebral disks, one had metastatic disease, and 17 did not have evidence of an acute injury following evaluation.

Conclusion.

Patients are being placed under prescribed immobilization for longer than is recommended. Delays in obtaining radiological imaging were an important factor, together with the time taken to receive a definitive management plan. Limitations in social care provision and delays in arranging this were additional barriers to hospital discharge following the final management plan.

Level of Evidence: 4
Ontology Development for Patient Education Documents Using a Professional- and Patient-Oriented Delphi Method
Authors: Heimonen Juho , Danielsson-Ojala Riitta , Salakoski Tapio , Lundgrén-Laine Heljä , Salanterä Sanna
Published: April 2018

Written patient education materials are essential to motivate and help patients to participate in their own care, but the production and management of a large collection of high-quality and easily accessible patient education documents can be challenging. Ontologies can aid in these tasks, but the existing resources are not directly applicable to patient education. An ontology that models patient education documents and their readers was constructed. The Delphi method was used to identify a compact but sufficient set of entities with which the topics of documents may be described. The preferred terms of the entities were also considered to ensure their understandability. In the ontology, readers may be characterized by gender, age group, language, and role (patient or professional), whereas documents may be characterized by audience, topic(s), and content, as well as the time and place of use. The Delphi method yielded 265 unique document topics that are organized into seven hierarchies. Advantages and disadvantages of the ontology design, as well as possibilities for improvements, were identified. The patient education material ontology can enhance many applications, but further development is needed to reach its full potential.
Complexities and potential pitfalls of clinical study design and data analysis in assisted reproduction
Authors: Patounakis George , Hill Micah J.
Published: April 2018

Purpose of review

The purpose of the current review is to describe the common pitfalls in design and statistical analysis of reproductive medicine studies. It serves to guide both authors and reviewers toward reducing the incidence of spurious statistical results and erroneous conclusions.

Recent findings

The large amount of data gathered in IVF cycles leads to problems with multiplicity, multicollinearity, and over fitting of regression models. Furthermore, the use of the word ‘trend’ to describe nonsignificant results has increased in recent years. Finally, methods to accurately account for female age in infertility research models are becoming more common and necessary.

The pitfalls of study design and analysis reviewed provide a framework for authors and reviewers to approach clinical research in the field of reproductive medicine. By providing a more rigorous approach to study design and analysis, the literature in reproductive medicine will have more reliable conclusions that can stand the test of time.
VISUAL ACUITY IN PSEUDOXANTHOMA ELASTICUM
Authors: Risseeuw Sara , Ossewaarde-van Norel Jeannette , Klaver Caroline C. W. , Colijn Johanna M. , Imhof Saskia M. , van Leeuwen Redmer
Published: April 2018

Purpose:

To assess the age-specific proportion of visual impairment in patients with pseudoxanthoma elasticum (PXE) and to compare this with foveal abnormality and similar data of late age-related macular degeneration patients.

Methods:

Cross-sectional data of 195 patients with PXE were reviewed, including best-corrected visual acuity and imaging. The World Health Organisation criteria were used to categorize bilateral visual impairment. These results were compared with similar data of 131 patients with late age-related macular degeneration from the Rotterdam study.

Results:

Overall, 50 PXE patients (26.0%) were visually impaired, including 21 (11%) with legal blindness. Visual functioning declined with increasing age. In patients older than 50 years, 37% was visually impaired and 15% legally blind. Foveal choroidal neovascularization was found in 84% of eyes with a best-corrected visual acuity lower than 20/70 (0.30) and macular atrophy in the fovea in 16%. In late age-related macular degeneration patients, 40% were visually impaired and 13% legally blind. Visual impairment started approximately 20 years later as compared with PXE patients.

Conclusion:

Visual impairment and blindness are frequent in PXE, particularly in patients older than 50 years. Although choroidal neovascularization is associated with the majority of vision loss, macular atrophy is also common. The proportion of visual impairment in PXE is comparable with late age-related macular degeneration but manifests earlier in life.
ENDOPHTHALMITIS AFTER PARS PLANA VITRECTOMY
Authors: Weiss Stephanie J. , Adam Murtaza K. , Gao Xinxiao , Obeid Anthony , Sivalingam Arunan , Fineman Mitchell S. , Maguire Joseph I. , Garg Sunir J. , Haller Julia , Fischer David H. , Hsu Jason
Published: April 2018

Purpose:

To examine rates of acute infectious endophthalmitis after pars plana vitrectomy (PPV) in eyes that received intraoperative subconjunctival antibiotics versus eyes that did not.

Methods:

A retrospective, nonrandomized, comparative case series of 18,886 consecutive cases of transconjunctival 23-, 25-, and 27-gauge PPV over a 5-year period was performed. The impact of prophylactic intraoperative subconjunctival antibiotics on the development of acute infectious postoperative endophthalmitis was examined.

Results:

Of 18,886 cases of PPV, 14,068 (74.5%) received intraoperative subconjunctival antibiotics, whereas 4,818 (25.5%) did not. Sixteen cases (0.085%, 1/1,176) of post-PPV endophthalmitis were identified. The incidence of endophthalmitis in eyes that received subconjunctival antibiotics was 0.078% (11/14,068 cases, 1/1,282), whereas the incidence in those that did not receive subconjunctival antibiotics was 0.10% (5/4,818 cases, 1/1,000). No statistically significant difference was identified in the incidence of endophthalmitis between those that received subconjunctival antibiotics and those that did not (P = 0.598). Microbial culture was performed in 11 cases with 6 culture-positive cases (5/8 cases that received subconjunctival antibiotics and 1/3 cases that did not).

Conclusion:

Prophylactic subconjunctival antibiotics were not associated with a significantly reduced rate of post-PPV endophthalmitis. With consideration of emerging multidrug-resistant bacteria, routine prophylactic subconjunctival antibiotics may not be justified.
Safety and Efficacy of Oki Stenting Used to Treat Obstructions in the Right Mainstem Bronchus
Authors: Dalar Levent , Abul Yasin
Published: April 2018

Background:

Silicone stenting has been used to palliatively manage respiratory symptoms in patients with airway stenoses. Oki and Saka recently developed stents that can be used to manage stenoses around the carina between the bronchus to the right upper lobe and the bronchus intermedius (termed the primary right carina). The aim of this study was to assess the efficacy and safety of Oki stenting used to treat airway stenosis around the primary right carina.

Methods:

We included 5 patients with airway stenoses. All Oki stenting procedures were performed with the patients under general anesthesia using either rigid or flexible bronchoscopy.

Results:

Oki stents were successfully placed in all 5 patients, and the dyspnea index improved in all. Modified Oki stenting was performed at the anastomotic site of 1 patient who had undergone sleeve resection. Four patients had airway obstructions caused by malignant disease. No serious procedural or early complication was noted. One patient died of liver insufficiency, and another with a malignancy died from cranial metastasis of the primary tumor.

Conclusion:

Oki stenting of the primary right carina is safe, efficient, and acceptable when used for palliative management of airway obstruction, even after sleeve resection; in the latter case, some procedural modifications are required.
Bending of an Aspirated Pin During Rigid Bronchoscopy
Authors: Elsayed Abdelrahman A.A. , Mansour Albaraa A. , Amin Ahmed A.A. , Ahmed Mohsen S.M.
Published: April 2018

Background:

Pin aspiration is a common problem in Muslim countries, where many women wear veils (hijab). This condition is usually treated using either a rigid or a flexible bronchoscope, and yet occasionally requires surgical approach. Pin bending may be necessary to extract impacted pins during the therapeutic rigid bronchoscopy.

Methods:

Medical records of patients who had pins extracted with a bending technique during the period from January 2012 to December 2016 in 1 institution were analyzed. Information on intraoperative and postoperative complications was collected.

Results:

Between 2012 and 2016, 315 rigid bronchoscopies were performed for pin extraction; in 38 cases, bending of the pin was required for the extraction because they were in a position that did not allow simple extraction. The procedure was successful in cases and there were no major complications.

Conclusion:

The extraction of visible, distally located or impacted pins can be safely performed by experienced bronchoscopists using the bending technique. Some safeguards and pitfalls must be noted to ensure maximum safety.
Tenofovir Versus Entecavir for the Treatment of Acute-on-Chronic Liver Failure due to Reactivation of Chronic Hepatitis B With Genotypes B and C
Authors: Wan Yue-Meng , Li Yu-Hua , Xu Zhi-Yuan , Wu Hua-Mei , Xu Ying , Wu Xi-Nan , Yang Jin-Hui
Published: April 2018

Background and Aims:

Acute-on-chronic liver failure (ACLF) can be triggered by reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are now the most potent antiviral agents for CHB. This study aimed to compare the short-term safety and efficacy of TDF with ETV in the treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF].

Patients and Methods:

In total, 67 consecutive patients with HBV-ACLF were divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35) receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the primary endpoint was overall survival at 3 months.

Results:

At 2 weeks, the TDF group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte-Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients; CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were comparable between the 2 groups, but markedly lower than at baseline (P<0.01); the TDF group had significantly higher cumulative survival rate than the ETV group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95% confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors for mortality. Both drugs were well tolerated.

Conclusions:

The short-term efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for mortality at 3 months.
Transitioning Patients With Iron Overload From Exjade to Jadenu
Authors: Tinsley Sara M. , Hoehner-Cooper Christine M.
Published: April 2018

Iron overload is a concern for patients who require chronic transfusions as a result of inherited or acquired anemias, including sickle cell disease, thalassemia, and myelodysplastic syndromes. Iron chelation therapy (ICT) is the primary treatment for iron overload in these patients. The ICT deferasirox, which has been available as an oral dispersible tablet for liquid suspension, is now also available as a once-daily, film-coated tablet (FCT). Deferasirox FCT allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. Dose adjustment increments, determined by titration monitoring, are lower for the FCT because of greater bioavailability.
A Standard Push-Pull Protocol for Waste-Free Sampling in the Pediatric Intensive Care Unit
Authors: McBride Clare , Miller-Hoover Suzan , Proudfoot James A.
Published: April 2018

Blood sampling is a major source of blood loss in the pediatric intensive care unit (PICU). Blood-sparing sampling techniques such as the push-pull method can significantly reduce sampling-related blood loss and protect patients from anemia and blood transfusions. The push-pull method is supported by research evidence for central venous catheter (CVC) sampling, but research protocols differ and not all CVCs and laboratory tests have been studied. A standard push-pull protocol for the PICU was developed, implemented, and evaluated in this evidence-based practice project. Results show that the protocol can be used safely and reliably as a standard waste-free sampling method in the PICU.
Psychiatric Services and “the Homeless”
Authors: Glick Ira D. , Olfson Mark
Published: April 2018

Given the changes in our society and worldwide massive migrations across borders, this article argues that we need to change the paradigm of how we think about “the homeless,” that is, to rethink our approach to not only those who cannot afford housing, the “economically homeless,” but especially important also the larger group—those with chronic, serious medical-psychiatric-addictive disorders, the “medically/mentally ill homeless.” We must place a greater emphasis on providing mental health services along with housing, legal, general medical, employment, and other services. The first and most crucial step toward adequate care is to understand these individuals and their lives as well as how we react to them. Second, we must become more proactive in helping those who live on the streets to receive adequate and coordinated services. And finally, for those who are unable to live independently in the community, we need to reinvent long-term, structured, humane residential, and inpatient settings.
A Needs Assessment of Brain Death Education in Pediatric Critical Care Medicine Fellowships*
Authors: Ausmus Andrew M. , Simpson Pippa M. , Zhang Liyun , Petersen Tara L.
Published: April 2018

Objectives:

To assess the current training in brain death examination provided during pediatric critical care medicine fellowship.

Design:

Internet-based survey.

Setting:

United States pediatric critical care medicine fellowship programs.

Subjects:

Sixty-four pediatric critical care medicine fellowship program directors and 230 current pediatric critical care medicine fellows/recent graduates were invited to participate.

Interventions:

Participants were asked demographic questions related to their fellowship programs, training currently provided at their fellowship programs, previous experience with brain death examinations (fellows/graduates), and perceptions regarding the adequacy of current training.

Measurements and Main Results:

Twenty-nine program directors (45%) and 91 current fellows/graduates (40%) responded. Third-year fellows reported having performed a median of five examinations (interquartile range, 3–6). On a five-point Likert scale, 93% of program directors responded they “agree” or “strongly agree” that their fellows receive enough instruction on performing brain death examinations compared with 67% of fellows and graduates (p = 0.007). The responses were similar when asked about opportunity to practice brain death examinations (90% vs 54%; p < 0.001). In a regression tree analysis, number of brain death examinations performed was the strongest predictor of trainee satisfaction. Both fellows and program directors preferred bedside demonstration or simulation as educational modalities to add to the fellowship curriculum.

Conclusions:

Pediatric critical care medicine fellows overall perform relatively few brain death examinations during their training. Pediatric critical care medicine fellows and program directors disagree in their perceptions of the current training in brain death examination, with fellows perceiving a need for increased training. Both program directors and fellows prefer additional training using bedside demonstration or simulation. Since clinical exposure to brain death examinations is variable, adding simulated brain death examinations to the pediatric critical care medicine fellowship curriculum could help standardize the experience.
Sera From Children After Cardiopulmonary Bypass Reduces Permeability of Capillary Endothelial Cell Barriers
Authors: Pierce Richard W. , Zahr Riad Abou , Kandil Sarah , Faustino E. Vincent S. , Pober Jordan S.
Published: April 2018

Objectives:

Children undergoing cardiopulmonary bypass develop clinically impactful capillary leak of unclear etiology. A widely held hypothesis that exposure of circulating cells to the cardiopulmonary bypass circuit induces the release of inflammatory mediators that act to disrupt intercellular junctions of capillary endothelial cells inducing paracellular capillary leak either directly or through new gene expression.

Design:

Cohort study.

Setting:

Tertiary pediatric hospital.

Patients:

Twenty children undergoing surgery with cardiopulmonary bypass for congenital heart disease. Serum was collected before cardiopulmonary bypass, 2 hours after cardiopulmonary bypass, and 18 hours after cardiopulmonary bypass.

Interventions:

None.

Measurements and Main Results:

We analyzed the effects of 10% patient sera on the “function, structure, and gene expression” of cultured human dermal and pulmonary microvascular endothelial cells. Changes in barrier “function” were measured using transendothelial electrical resistance. Associations between changes in transendothelial electrical resistance and subject characteristics were analyzed using linear mixed effects model with area under the resistance curve as outcome. Changes in junctional “structure” were assessed by analyzing the organization of the endothelial cell junctional proteins claudin-5 and VE-cadherin using immunofluorescence microscopy. Changes in inflammatory “gene expression” were measured using real-time quantitative reverse transcription-polymerase chain reaction. All serum samples induced a transient, 120-minute increase in transendothelial electrical resistance followed by persistent loss of barrier function. Unexpectedly, sera collected postcardiopulmonary bypass–induced significantly less loss of barrier function in both dermal and pulmonary capillary endothelial cell compared with precardiopulmonary bypass sera. Consistent with the transendothelial electrical resistance results, claudin-5 and vascular endothelial-cadherin junctional staining showed less disruption in cultures treated with postcardiopulmonary bypass sera. Expression of genes commonly associated with inflammation was largely unaffected by patient sera.

Conclusions:

Contrary to the hypothesis, sera taken from children after cardiopulmonary bypass induces less capillary barrier disruption relative to sera taken from children before cardiopulmonary bypass, and none of the sera induced significant changes in expression of inflammatory genes.
Anti–nerve growth factor therapy attenuates cutaneous hypersensitivity and musculoskeletal discomfort in mice with osteoporosis
Authors: Suzuki Miyako , Millecamps Magali , Ohtori Seiji , Mori Chisato , Stone Laura S.
Published: April 2018

Introduction:

The prevalence of osteoporosis is increasing with the aging population and is associated with increased risk of fracture and chronic pain. Osteoporosis is currently treated with bisphosphonate therapy to attenuate bone loss. We previously reported that improvement in bone mineral density is not sufficient to reduce osteoporosis-related pain in an ovariectomy (OVX)-induced mouse model of osteoporosis, highlighting the need for new treatments. Targeting of nerve growth factor (NGF) with sequestering antibodies is a promising new direction for the treatment of musculoskeletal pain including back pain and arthritis. Its efficacy is currently unknown for osteoporotic pain.

Objective:

To investigate the efficacy of anti-NGF antibody therapy on osteoporotic pain in an OVX-induced mouse model.

Methods:

Ovariectomy- and sham-operated mice were injected with an anti-NGF antibody (10 mg/kg, intraperitoneally, administered 2×, 14 days apart), and the effect on behavioural indices of osteoporosis-related pain and on sensory neuron plasticity was evaluated.

Results:

Treatment with anti-NGF antibodies attenuated OVX-induced hypersensitivity to mechanical, cold, and heat stimuli on the plantar surface of the hind paw. The OVX-induced impairment in grip force strength, used here as a measure of axial discomfort, was partially reversed by anti-NGF therapy. No changes were observed in the rotarod or open-field tests for overall motor function and activity. Finally, anti-NGF treatment attenuated the increase in calcitonin gene-related peptide–immunoreactive dorsal root ganglia neurons observed in OVX mice.

Conclusion:

Taken together, these data suggest that anti-NGF antibodies may be useful in the treatment of prefracture hypersensitivity that is reported in 10% of patients with osteoporosis.
Preliminary Study on Molecular Subtypes of Breast Cancer Based on Magnetic Resonance Imaging Texture Analysis
Authors: Sun Xinru , He Bing , Luo Xin , Li Yuhua , Cao Jinfeng , Wang Jinlan , Dong Jun , Sun Xiaoyu , Zhang Guangxia
Published: April 2018

Objective

The aim of the study was to investigate the molecular subtypes of breast cancer based on the texture features derived from magnetic resonance images (MRIs).

Methods

One hundred seven patients with preoperative confirmed breast cancer were recruited. One hundred eight breast lesions were divided into 4 subtypes according to the status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor type 2, and Ki67. Fisher discriminant analysis was performed on the texture features that extracted from the enhanced high-resolution T1-weighted images and diffusion weighted images to establish the classification model of molecular subtypes.

Results

The differentiation accuracies of Fisher discriminant analysis on the enhanced high-resolution T1-weighted images were 82.8% and 86.4% for 1.5T and 3.0T imaging. Fisher discriminant analysis on diffusion weighted imaging texture features were achieved with a classification ability of 73.4% and 88.6%. The combined discriminant results for 2 kinds magnetic resonance images were 95.0%, 97.7% in 1.5T and 3.0T imaging, respectively.

Conclusions

The fine results indicated a promising approach to predict the molecular subtypes of breast cancer.
Dual-Energy Computed Tomography in Patients With Small Hepatocellular Carcinoma: Utility of Noise-Reduced Monoenergetic Images for the Evaluation of Washout and Image Quality in the Equilibrium Phase
Authors: Matsuda Megumi , Tsuda Takaharu , Kido Teruhito , Tanaka Hiroaki , Nishiyama Hikaru , Itoh Toshihide , Nakao Kenichi , Hirooka Masashi , Mochizuki Teruhito
Published: April 2018

Purpose

This study aimed to evaluate the utility of virtual monoenergetic images for detecting washout of small (≤2 cm) hepatocellular carcinoma (HCC) in the equilibrium phase.

Methods

We performed 120-kVp–equivalent linear-blended (M120) and monoenergetic reconstructions from 40 to 90 keV by standard (40, 50, 60, 70, 80, 90) and novel noise-reduced (nMERA: 40+, 50+, 60+, 70+, 80+, 90+) monoenergetic reconstruction algorithms. Image quality and tumor visibility of delayed washout of HCCs in the equilibrium phase were compared between standard monoenergetic reconstruction algorithm and nMERA by objective and subjective analyses.

Results

Contrast-to-noise ratio of the tumor at 40+ was the highest, whereas the score of tumor visibility peaked at 50+. The score of overall image quality at 40+ was significantly lower than those on all other image series, and the image quality among other image series were not significantly different.

Conclusions

Virtual monoenergetic image reconstructed with nMERA 50+ was most appropriate to detect washout of small HCCs.
Adult Living Donor Liver Transplantation for Patients With Portal Vein Thrombosis: A Single-center Experience
Authors: Miura Kohei , Sugawara Yasuhiko , Uchida Koushi , Kawabata Seiichi , Yoshii Daiki , Isono Kaori , Hayashida Shintaro , Ohya Yuki , Yamamoto Hidekazu , Kobayashi Takashi , Wakai Toshifumi , Inomata Yukihiro , Hibi Taizo
Published: April 2018

Background

Living donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) is associated with several technical challenges for its complicated procedures and poor outcomes. Some institutions still consider preexisting PVT as a relatively contraindication for LDLT.

Methods

Between April 2010 and May 2016, 129 adults underwent LDLT at our institution, and 28 (21.7%) of whom had preexisting PVT. Portal vein thrombosis was diagnosed using preoperative imaging techniques and intraoperative findings. The characteristics and outcomes of the cases were retrospectively evaluated.

Results

The type of PVT included Yerdel grade 1 in 21 (75.0%) cases, grade 2 in 3 (10.7%) cases, and grade 3 in 4 (14.3%) cases. There were no cases of Yerdel grade 4 PVT. After removing thrombus inside the vessel, we performed simple portal vein anastomosis in 25 (89.3%) cases, patch technique with vascular graft in 1 case (3.6%), and an interposition technique with vascular graft in 2 cases (7.1%). Compared with the non-PVT group, cold ischemic time was longer (P = 0.012) and the rate of postoperative PVT was higher (P = 0.001) in PVT group. In the comparison between the recipient without and with postoperative PVT, the existence of preoperative PVT was the independent risk factor in the multivariate analysis (hazard ratio, 7.511; 95% confidence interval 1.382-40.820; P = 0.020).

Conclusions

Although it had a technically complicated operation, LDLT could be safely performed in the patients with PVT in our institution.
What is a useful university? knowledge economies and higher education in late eighteenth-century Denmark and central Europe
Authors: Hünniger Dominik
Published: April 2018

Universities were an important site of Enlightenment improvement discourse and knowledge economies in the German-speaking lands and Scandinavia. Late eighteenth-century state building and scholars’ expectations of their own ‘usefulness’ regarding these processes were closely intertwined. The life and publications of the German-speaking Danish naturalist Johann Christian Fabricius (1745–1808) are used here to understand contemporary debates on the state of education, political economy and the development of the sciences in relation to ideas about economic and social progress. Fabricius was professor for ‘œconomics, cameral sciences and natural history’ at Kiel University for more than 30 years, from 1775 to 1808, and was one of the most outspoken writers on economic reform in Schleswig-Holstein and Denmark. Fabricius’ suggestions for improvement involved directly addressing social categories as well as the re-organization of universities in form and curricular content. Fabricius was engaged in debates on how to best achieve the specific knowledge and skills considered useful for the emerging nation-state. The essay analyses Fabricius’ interventions in these debates in the context of the contemporary development of the ‘research university’ around 1800.
Precise tracking of vaccine-responding T-cell clones reveals convergent and personalized response in identical twins
Authors: Pogorelyy Mikhail V. , Minervina Anastasia A. , Touzel Maximilian Puelma , Sycheva Anastasiia L. , Komech Ekaterina A. , Kovalenko Elena I. , Karganova Galina G. , Egorov Evgeniy S. , Komkov Alexander Yu. , Chudakov Dmitriy M. , Mamedov Ilgar Z. , Mora Thierry , Walczak Aleksandra M. , Lebedev Yuri B.
Published: April 2018

T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 500-1500 responding TCRs in each donor and validated them using three independent assays. While the responding TCRs were mostly private, albeit with higher overlap between twins, they could be well predicted using a classifier based on sequence similarity. Our method can also be applied to samples obtained post-infection, making it suitable for systematic discovery of new infection-specific TCRs in the clinic.
Biotic interactions limit the geographic range of an annual plant: herbivory and phenology mediate fitness beyond a range margin
Authors: Benning John W. , Eckhart Vincent M. , Geber Monica A. , Moeller David A.
Published: April 2018

Species’ range limits offer powerful opportunities to study environmental factors regulating distributions and probe the limits of adaptation. However, we rarely know what aspects of the environment are actually constraining range expansion, much less which traits are mediating the organisms’ response to these environmental gradients. Though most studies focus on climatic limits to species’ distributions, biotic interactions may be just as important. We used field experiments and simulations to estimate contributions of mammal herbivory to a range boundary in the annual plantClarkia xantianassp.xantiana.A steep gradient of increasing probability of herbivory occurs across the boundary, and herbivory drives several-fold declines in lifetime fitness at and beyond the boundary. By including in our analyses data from a sister taxon with more rapid phenology, we show that delayed phenology drivesC. xantianassp.xantiana’ssusceptibility to herbivory and low fitness beyond its border.
Catalysis of cataract-associated human γD crystallin aggregation via dynamic disulfide exchange
Authors: Serebryany Eugene , Yu Shuhuai , Trauger Sunia A. , Budnik Bogdan , Shakhnovich Eugene I.
Published: April 2018

Several mutations in human γD-crystallin (HγD), a long-lived eye lens protein, cause misfolding and aggregation, leading to cataract. Surprisingly, wild-type HγD catalyzes aggregation of its cataract related W42Q variant while itself remaining soluble – the inverse of the classical prion-like scenario whereby misfolded polypeptides catalyze aggregation of natively folded ones. The search for a biochemical mechanism of catalysis of W42Q aggregation by WT has revealed that WT HγD can transfer a disulfide bond to the W42Q variant. The transferred disulfide kinetically traps an aggregation-prone intermediate made accessible by the W42Q mutation, facilitating light-scattering aggregation of the W42Q variant. The aggregating variant thus becomes a disulfide sink, removing the disulfides from solution. Such redox “hot potato” competitions among wild-type and mutant or modified polypeptides may be relevant for many long-lived proteins that function in oxidizing environments. In these cases aggregation may be forestalled by inhibiting disulfide flow toward damaged polypeptides.
Controlled cycling and quiescence enables homology directed repair in engraftment-enriched adult hematopoietic stem and progenitor cells
Authors: Shin Jiyung , Wyman Stacia K. , Dewitt Mark A. , Bray Nicolas L , Vu Jonathan , Corn Jacob E.
Published: April 2018

Hematopoietic stem cells (HSCs) are the source of all blood components, and genetic defects in these cells are causative of disorders ranging from severe combined immunodeficiency to sickle cell disease. However, genome editing of long-term repopulating HSCs to correct mutated alleles has been challenging. HSCs have the ability to either be quiescent or cycle, with the former linked to stemness and the latter involved in differentiation. Here we investigate the link between cell cycle status and genome editing outcomes at the causative codon for sickle cell disease in adult human CD34+ hematopoietic stem and progenitor cells (HSPCs). We show that quiescent HSPCs that are immunophenotypically enriched for engrafting stem cells predominantly repair Cas9-induced double strand breaks (DSBs) through an error-prone non-homologous end-joining (NHEJ) pathway and exhibit almost no homology directed repair (HDR). By contrast, non-quiescent cycling stem-enriched cells repair Cas9 DSBs through both error-prone NHEJ and fidelitous HDR. Pre-treating bulk CD34+ HSPCs with a combination of mTOR and GSK-3 inhibitors to induce quiescence results in complete loss of HDR in all cell subtypes. We used these compounds, which were initially developed to maintain HSCs in culture, to create a new strategy for editing adult human HSCs. CD34+ HSPCs are edited, allowed to briefly cycle to accumulate HDR alleles, and then placed back in quiescence to maintain stemness, resulting in 6-fold increase in HDR/NHEJ ratio in quiescent, stem-enriched cells. Our results reveal the fundamental tension between quiescence and editing in human HSPCs and suggests strategies to manipulate HSCs during therapeutic genome editing.
An enhanced framework for assessing the operational performance of public-private partnership school projects
Authors: Saeed Ali Mohammed , Duffield Colin , Hui Felix Kin Peng
Published: April 2018

Purpose

A study of the current practices for evaluating the ex-post performance of public-private partnership (PPP) school projects in Australia via literature review and qualitative case studies has found that no consistent approach exists for evaluating operational performance. A detailed critique of international PPP audits and practices has identified existing gaps in ex-post performance evaluation. Through a process of comparative analysis and industry confirmation, a performance analysis technique aligned with international practice has been developed that can be utilised by the educational departments across Australia to evaluate the ex-post performance of PPP projects (PPPs). The paper aims to discuss these issues.

Design/methodology/approach

This paper opted for qualitative archival analysis of case studies using pattern matching, explanation building, time series, and comparative analysis. The data used for document analysis included value reports, project summaries, and contract documents, as well as local and international audit guidelines.

Findings

This paper reviewed current practices, identified a range of processes, and reported the best practices. However, consideration of the approaches taken in the UK and Australia for evaluating operational performance indicates that current techniques lack consistency.

Research limitations/implications

The developed ex-post performance measurement framework is limited to Australian PPP school projects and, at this stage, cannot be generalised to other social PPP projects.

Practical implications

The paper includes implications for the development of better performance evaluation practices and audits.

Social implications

An enhanced framework for measuring operational performance will increase the accountability of taxpayers in the content of their utilisation by the government.

Originality/value

This paper presents an enhanced ex-post performance measurement framework for education departments across Australia.
Linking leadership practices to performance of the US federal agencies
Authors: Lee Hyung-Woo
Published: April 2018

Purpose

The mechanism by which leadership influences organizational performance has largely been unexplained. This study intends to fill this gap. This study identified the six specific leadership practices: promoting inter-unit collaboration, managing diversity, providing performance feedback, ensuring goal directedness, developing employees, and resource provision. This study also identified a number of generic functions of leadership, that is, promoting cooperation, clarifying employees’ roles, and improving skills in organization. Then the mediating effects of the three generic functions were tested in order to link the specific leadership practices to organizational performance. The paper aims to discuss these issues.

Design/methodology/approach

Structural equation modeling was used for analyzing the data from the 2014 Federal Employee Viewpoint Survey to investigate the mediating model.

Findings

The effects of the six specific leadership practices on organizational performance were mediated by the three generic leadership functions.

Originality/value

The result of this study delineated the linking paths between leadership practices and organizational performance which has largely remained as a black box. Moreover, since the specific leadership practices are categorized by the generic functions that are instrumental for organizational performance, it provides theoretical and empirical grounds for managerial prescriptions for improving organizational performance.