bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Application of the Pfirrmann Disc Degeneration Grading System to 9.4T MRI
Authors: Sher Idrees , Daly Chris , Oehme David , Chandra Ronil V. , Sher Mustafa , Ghosh Peter , Smith Julian , Goldschlager Tony 
Published: December 2018

Study Design.
Reliability study.

Objective.
To evaluate the applicability and reliability of 9.4T magnetic resonance imaging (MRI) in the assessment of degenerative disc disease compared with 3T MRI.

Summary of Background Data.
MRI is a reliable indicator of biochemical changes in the intervertebral disc (IVD) including hydration status, proteoglycan content, and disc degeneration compared with anatomical and histological studies. High-field 9.4T MRI has been shown to provide superior resolution and anatomical detail. However, it has not been tested against current standard MRI techniques.

Methods.
Disc degeneration was initiated in 36 skeletally mature ewes 6 months prior to necropsy via validated surgical IVD injury models using either scalpel injury or drill-bit injury techniques at lumbar spine levels L2/3 and L3/4 with L1/2, L4/5, and L5/6 serving as control discs. All ex vivo IVDs were examined with 9.4T MRI and 3T MRI. All scans were analyzed using the Pfirrmann grading system by four independent observers. Intra- and interobserver reliability was assessed using kappa statistics and Spearman correlation.

Results.
Inter- and intraobserver agreement for 9.4T MRI was excellent, both at κ 0.91 (P < 0.001). Comparatively, 3T interobserver reliability demonstrated substantial agreement at κ 0.61 (P < 0.001). Complete agreement was obtained in 92.7% to 100% of discs at 9.4T compared with 69.7% to 83.1% at 3T. A difference of one grade or more occurred in 6.7% at 9.4T and 39.3% at 3T. 9.4T MRI scored 97.3% of discs as grade 1 to 2 compared with 71.3% at 3T. 3T MRI tended to over-score the extent of disc degeneration with 28.6% of discs scored as grade 3 or higher compared with 2.7% at 9.4T MRI.

Conclusion.
9.4T MRI study of IVD degeneration using the Pfirrmann grading system demonstrated excellent inter- and intraobserver reliability. Comparatively, 3T MRI demonstrated a tendency to over score the extent of disc degeneration. This improved reliability of 9.4T MRI holds great potential for its clinical applications.

Level of Evidence: 3
OPTIC DISK ASTROCYTOMA UNASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX MANAGED WITH SURGICAL EXCISION AND A 7-YEAR FOLLOW-UP
Authors: Lu Yao , Xu Yimin 
Published: December 2018

Purpose:
Optic disk astrocytoma is a rare variant of congenital hamartoma, which is usually associated with tuberous sclerosis complex. Generally, it is stationary but in rare cases, it can show progressive growth and cause severe local complications.

Methods:
Clinical–pathologic correlation.

Results:
A 10-year-old boy presented a unilateral optic disk mass with vitreous hemorrhage that eventually necessitated vitrectomy of the affected eye. Visual acuity was hand movements at presentation. Pars plana vitrectomy was performed because of sudden loss of vision. At the time of vitrectomy, a yellow tumor that measured 1.5 mm in basal diameter and 6 mm in thickness was surgically removed. Cytological analysis revealed benign giant cells. The cells were negative for HMB-45 but stained positively for glial fibrillary acidic protein and neuron-specific enolase compatible with an astrocytic lesion. At the follow-up of 7 years, his vision was 20/80 and there has been no recurrence of the tumor.

Conclusion:
Optic disk astrocytoma can be managed with local surgical excision and vision can be preserved if treated timely. Histopathologic features can help evaluate the degree of nuclear pleomorphism and cell morphology. Special immunohistochemical studies of the tumor's coexpressed neuronal markers will help differentiate astrocytoma from other neoplasms.
Antiemetic Drug Use in Children
Authors: Romano Claudio , Dipasquale Valeria , Scarpignato Carmelo 
Published: December 2018

ABSTRACTVomiting is not only unpleasant for both children and families, but can lead to frequent hospital admission. The persistent vomiting hampers oral intake and increases the risk of dehydration, so the proper use of antiemetic drugs can be useful. The pharmacological treatment of vomiting in children remains a challenge for the pediatrician because several antiemetics are prescribed as “off‐label,” outside their authorized drug label. Domperidone and ondansetron are the most commonly known antiemetic drugs. A single oral dose of ondansetron has been shown to reduce the risk of recurrent vomiting, the need for intravenous fluids, and hospital admissions in children with acute gastroenteritis. There is enough evidence to support ondansetron administration in children, so the clinical use can be defined as “off‐label/on evidence.” This review aims to provide an overview of therapeutic use, safety, and main pharmacological properties of antiemetic drugs in children. A comprehensive search of published literature using the PubMed MEDLINE database was carried out to identify all articles published in English from 1998 to February 2018. At present time, the “off‐label/on‐evidence” use of some antiemetics could improve the success rate of oral rehydration therapy in pediatric emergency settings and to change the management of vomiting with the prevention of the complications.
A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients
Authors: Tracy Mary Fran , Chlan Linda , Savik Kay , Skaar Debra J. , Weinert Craig 
Published: December 2018

Background
Although potent sedative and opioid drugs are some of the most commonly used medications to manage pain, anxiety, and discomfort in critically ill patients, conducting clinical trials where sedative and opioid medications are outcome variables within a longitudinal research design can be a methodological challenge.

Objectives
The purpose of this article is to provide in detail a conceptual discussion of the concept and analysis of sedative exposure: A novel research analysis method for aggregating sedative and opioid medication doses from disparate drug classes commonly administered to critically ill patients and used by our team in several clinical research studies.

Methods
Comparing the dose of each sedative and opioid administered to an individual patient (within a defined time interval) to all other patients in a research study receiving the same medications allows for ranking of dosages for each medication by quartiles. Rank values for all sedatives and opioids received can be summed to a single value resulting in a Sedation Intensity Score. In addition, a simple count of how many hours at least one dose of a sedative or opioid medication has been administered can determine sedation frequency.

Results
This method can allow for comparison of sedative exposure with medications from disparate drug classes and for analysis of estimates of change in medication use over time.

Discussion
This novel research analysis method can overcome the challenges and limitations of determining changes in sedative and opioid medication regimens in cohort and clinical trial study designs.
Use of Assistive Devices to Lift, Transfer, and Reposition Hospital Patients
Authors: Schoenfisch Ashley L. , Kucera Kristen L. , Lipscomb Hester J. , McIlvaine Jennifer , Becherer Lori , James Tamara , Avent Susan 
Published: December 2018

BackgroundDevices to lift, transfer, and reposition patients are recommended for healthcare workers' and patients' safety, but their intended use has yet to be fully realized.ObjectiveThe aim of this study was to describe hospital nursing staff use of lift/transfer devices and the presence of factors at the time of lifts/transfers with potential to influence whether devices are used.MethodsParticipants were 108 US nursing staff in a university-based medical center and two community hospitals. A self-completed questionnaire was used to collect demographic and work characteristics, typical frequency of patient lifts/transfers, training in and typical use of lift equipment, and specific factors that could influence use. Proportional distributions of lifting/transferring and repositioning frequencies in a typical shift, amount of equipment use, and factors present were examined overall and across worker and work-related characteristics.ResultsAlthough trained in equipment use, only 40% used equipment for at least half of lifts/transfers. During lifts/transfers, factors often present included patient unable to help with lift/transfer (91.3%) or of a size/weight where participant needed assistance to help lift/transfer (87.5%); availability of others who could assist with manual lift (86.3%) or use of lift equipment (82.4%); and equipment functioning properly (86.4%), having supplies available (82.5%), and being easy to retrieve from storage (81.6%). During repositioning tasks, physical assistance was “always/almost always” provided from coworkers (83.3%) and often perceived as “very helpful” (92.6%) in reducing physical demands. Physical assistance from patients was less common (14.0% “always/almost always”) yet perceived as “very helpful” by 66.3%. One fifth always used friction-reducing devices.DiscussionDespite training in their use, nursing staff use of available lift equipment and assistive devices is limited. Factors present at the time of lifts/transfers that may influence equipment/device use reflect a complex mix of patient, worker, equipment, and situational characteristics.
Choice of Catheter Size for Infants in Continuous Renal Replacement Therapy: Bigger Is Not Always Better*
Authors: Garzotto Francesco , Zaccaria Marta , Vidal Enrico , Ricci Zaccaria , Lorenzin Anna , Neri Mauro , Murer Luisa , Nalesso Federico , Ruggeri Alfredo , Ronco Claudio 
Published: December 2018

Objectives:Renal replacement therapy in infants and small children is the treatment of choice for severe oligoanuric renal dysfunction, with an increasing consensus that early initiation might contribute to preventing acute kidney injury complications. Safer renal replacement therapy devices specifically designed for neonates may contribute to ameliorating outcomes and increasing chances of survival. One of the crucial factors to achieve an effective renal replacement therapy in small infants is adequate vascular access. The interaction of small size central vascular catheters with renal replacement therapy devices has never been investigated. The aim of this study was to characterize both the operating conditions and performance of three different central vascular catheters sizes (4F, 5F, and 7F) connected to two different extracorporeal blood circulation models (adult and pediatric). The rheologic performance of each vascular access size in combination with the adult and pediatric renal replacement therapy models was described.Design:Series of experimental extracorporeal circulation circuit tests were conducted with different setups. A two-roller pump was used to simulate a standard adult dialysis machine, whereas a small three-roller pump served as pediatric renal replacement therapy device.Setting:A pressure-flow setup aimed to collect pressure and flow values under different test conditions. A second experiment focused on hemolysis estimation induced by the extracorporeal system. Hemolysis exclusively induced by the 4F catheter was also evaluated. Finally, our data were applied to estimate the optimal catheter size theoretically capable of delivering adequate doses basing on anthropometric data (patient weight and cannulation site) in absence of direct ultrasound vessel measurement.Subjects:In vitro tests conducted on simulated extracorporeal circuit models of continuous pediatric and neonatal renal replacement therapy.Interventions:None.Measurements and Main Results:When 4F and 5F catheters are used, maximal blood flows within safe circuit pressures can be set at the values of 13 and 29 mL/min, respectively, when a small pump is used. Differently, when using adult roller pumps, only maximal flows of 10 and 20 mL/min are reached. However, hemolysis is higher when using a three-roller pump compared with the two-roller. The clinical impact of this increased hemolytic burden is likely not relevant.Conclusions:Small size central vascular catheters display optimal rheologic performances in terms of pressures and flows particularly when the renal replacement therapy device is equipped with pumps proportional to central vascular catheters sizes, and even when relatively high blood flows are set. This is achieved at the risk of a higher hemolysis rate.
Nonvascularized Bone Graft Reconstruction of the Irradiated Murine Mandible: An Analogue of Clinical Head and Neck Cancer Treatment
Authors: Urlaub Kevin M. , Ettinger Russell E. , Nelson Noah S. , Hoxie Jessie M. , Snider Alicia E. , Perosky Joseph E. , Polyatskaya Yekaterina , Donneys Alexis , Buchman Steven R. 
Published: December 2018

Abstract
Nonvascularized bone grafts (NBGs) represent a practical method of mandibular reconstruction that is precluded in head and neck cancer patients by the destructive effects of radiotherapy. Advances in tissue-engineering may restore NBGs as a viable surgical technique, but expeditious translation demands a small-animal model that approximates clinical practice. This study establishes a murine model of irradiated mandibular reconstruction using a segmental iliac crest NBG for the investigation of imperative bone healing strategies. Twenty-seven male isogenic Lewis rats were divided into 2 groups; control bone graft and irradiated bone graft (XBG). Additional Lewis rats served as graft donors. The XBG group was administered a fractionated dose of 35Gy. All rats underwent reconstruction of a segmental, critical-sized defect of the left hemi-mandible with a 5 mm NBG from the iliac crest, secured by a custom radiolucent plate. Following a 60-day recovery period, hemi-mandibles were evaluated for bony union, bone mineralization, and biomechanical strength (P < 0.05). Bony union rates were significantly reduced in the XBG group (42%) compared with controls (80%). Mandibles in the XBG group further demonstrated substantial radiation injury through significant reductions in all metrics of bone mineralization and biomechanical strength. These observations are consistent with the clinical sequelae of radiotherapy that limit NBGs to nonirradiated patients. This investigation provides a clinically relevant, quantitative model in which innovations in tissue engineering may be evaluated in the setting of radiotherapy to ultimately provide the advantages of NBGs to head and neck cancer patients and reconstructive surgeons.
High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine
Authors: Steinberg Asher Preska , Datta Sujit S. , Naragon Thomas , Rolando Justin C. , Bogatyrev Said R. , Ismagilov Rustem F. 
Published: December 2018

AbstractThe lumen of the small intestine (SI) is filled with particulates: microbes, therapeutic particles, and food granules. The structure of this particulate suspension could impact uptake of drugs and nutrients and the function of microorganisms; however, little is understood about how this suspension is re-structured as it transits the gut. Here, we demonstrate that particles spontaneously aggregate in SI luminal fluidex vivo. We find that mucins and immunoglobulins are not required for aggregation. Instead, aggregation can be controlled using polymers from dietary fiber in a manner that is qualitatively consistent with polymer-induced depletion interactions, which do not require specific chemical interactions. Furthermore, we find that aggregation is tunable; by feeding mice dietary fibers of different molecular weights, we can control aggregation in SI luminal fluid. This work suggests that the molecular weight and concentration of dietary polymers play an underappreciated role in shaping the physicochemical environment of the gut.
A probabilistic model to identify the core microbial community
Authors: Gumiere Thiago , Meyer Kyle M. , Burns Adam R. , Gumiere Silvio J. , Bohannan Brendan J. M. , Andreote Fernando D. 
Published: December 2018

ABSTRACTThe core microbial community has been hypothesized to have essential functions ranging from maintaining health in animals to protection against plant disease. However, the identification of the core microbial community is frequently based on arbitrary thresholds, selecting only the most abundant microorganisms. Here, we developed and tested an approach to identify the core community based on a probabilistic model. The Poisson distribution was used to identify OTUs with a probable occurrence in every sample of a given dataset. We identified the core communities of four extensive microbial datasets, and compared the results with conventional, but arbitrary, methods. The datasets were composed of the microbiomes of humans (tongue, gut, and skin), mice (gut), plant (grapevine) tissue, and the maize rhizosphere. Our proposed method revealed core microbial communities with higher richness and diversity than those previously described. This method also includes a greater number of rare taxa in the core, which are often neglected by arbitrary threshold methods. We demonstrated that our proposed method revels a probable core microbial community for each different habitat, which extend our knowledge about shared microbial communities. Our proposed method may help the next steps proving the essential functions of core microbial communities.Originality-Signifìcance StatementMore rigorous and less arbitrary statistical methods could increase knowledge regarding the role of microorganisms and their interactions. Here, we suggest a probabilistic method to identify the microbial core community across systems. Our method identifies a large proportion of the rare community that likely belongs to the microbial core community, which was not identified by conventional methods. Our probabilistic model is a non-arbitrary approach to defining the microbial core community, which may help in the next step of the microbial core community studies.
Structural Basis for Stereoselective Dehydration and Hydrogen-Bonding Catalysis by the SAM-Dependent Pericyclase LepI
Authors: Cai Yujuan , Hai Yang , Ohashi Masao , Jamieson Cooper S. , Garcia-Borras Marc , Houk K. N. , Zhou Jiahai , Tang Yi 
Published: December 2018

ABSTRACTLepI is an S-adenosylmethionine (SAM)-dependent pericyclase that catalyzes the formation of 2-pyridone natural product leporin C. Biochemical characterization showed LepI can catalyze the stereoselective dehydration to yield a reactive (E)-quinone methide which can undergo a bifurcating intramolecular Diels-Alder (IMDA) and hetero-Diels-Alder (HDA) cyclization from an ambimodal transition state, and a [3,3]-retro-Claisen rearrangement to recycle the IMDA product into leporin C. Here we solved the X-ray crystal structures of SAM-bound LepI, and in complex with a substrate analog, the product leporin C, and a retro-Claisen reaction transition-state analog to understand the structural basis for the multitude of reactions. Structural and mutational analysis revealed how Nature evolves a classic methyltransferase active site into one that can serve as a dehydratase and a multifunctional pericyclase. Catalysis of both sets of reactions employ His133 and Arg295, two active site residues that are not found in canonical methyltransferases. An alternative role of SAM, which is not found to be in direct contact of the substrate, is also proposed.
Virus-like vesicles expressing multiple antigens for immunotherapy of chronic hepatitis B
Authors: Yarovinsky Timur O. , Mason Stephen W. , Menon Manisha , Krady Marie M. , Haslip Maria , Madina Bhaskara R. , Ma Xianyong , Moshkani Safiehkhatoon , Chiale Carolina , Pal Anasuya Chattopadhyay , Almassian Bijan , Rose John K. , Robek Michael D. , Nakaar Valerian 
Published: December 2018

ABSTRACTInfection with hepatitis B virus (HBV) can initiate chronic hepatitis and liver injury, eventually progressing to liver fibrosis or cancer and causing more than 600,000 deaths each year worldwide. Current treatments for chronic hepatitis B, relying on nucleoside antivirals and interferon, are inadequate and leave an unmet need for immunotherapeutic approaches. This report describes virus-like vesicles (VLV), a form of self-amplifying RNA replicons, which express multiple HBV antigens (polymerase, core, and middle surface) from a single vector (HBV-VLV). The HBV-VLV induces HBV-specific T cell responses to all three HBV antigens. Immunization of naive mice with the multiantigen HBV-VLV renders them resistant to acute challenge with HBV delivered by adeno-associated virus (AAV). Using a chronic model of HBV infection by AAV delivery of HBV, we demonstrate immunotherapeutic potential of the multiantigen HBV-VLV in combination with DNA booster immunization, as 40% of the HBV-VLV-treated mice showed a decline of the serum HBV surface antigen below the detection limit and marked reduction in liver HBV RNA accompanied by induction of HBsAg-specific CD8 T cells. These results warrant further evaluation of multiantigen HBV-VLV for immunotherapy of chronic hepatitis B.IMPORTANCEMore than 240 million people worldwide are chronically infected with hepatitis B virus. Current therapies are not sufficiently effective and are often beyond reach in the developing world. We describe a virus-like vesicle-based immunotherapeutic vaccine that expresses three major antigens of hepatitis B virus as a self-amplifying RNA replicon. By incorporating three HBV antigens in a single vaccine, we ensure broad T cell responses. We demonstrate that immunization with this vaccine protects mice from hepatitis B virus in a model of acute challenge. Importantly, treatment with this vaccine shows 40% efficacy in a mouse model of chronic hepatitis B. Thus, this study paves the way for evaluation of the multi-antigen virus-like vesicles as a tool for immunotherapy of chronic hepatitis B.
Cortical excitation:inhibition imbalance causes abnormal brain network dynamics as observed in neurodevelopmental disorders
Authors: Markicevic Marija , Fulcher Ben D. , Lewis Christopher , Helmchen Fritjof , Rudin Markus , Zerbi Valerio , Wenderoth Nicole 
Published: December 2018

AbstractAbnormal brain development manifests itself at different spatial scales. However, whether abnormalities at the cellular level can be diagnosed from network activity measured withfunctional magnetic resonance imaging (fMRI) is largely unknown, yet of high clinical relevance. Here we applied fMRI while using chemogenetics to increase the excitation-to-inhibition ratio (E:I) within cortical microcircuits of the mouse brain, thereby mimicking a putative mechanism of neurodevelopmental disorders including autism. Increased E:I caused a significant reduction of long-range connectivity, irrespective of whether excitatory neurons were facilitated or inhibitory Parvalbumin interneurons were suppressed. Training a classifier on fMRI signals, we were able to accurately classify cortical areas exhibiting increased E:I. This classifier was validated in an independent cohort ofFmr1y/-knock-out mice, a model for autism with well-documented loss of Parvalbumin neurons and chronic alterations of E:I. Our findings demonstrate a promising novel approach towards inferring microcircuit abnormalities from macroscopic fMRI measurements.