bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Pyriform Space: Anatomical Clarifications and Clinical Implications
Authors: Surek Christopher K. , Vargo James , Lamb Jerome 
Published: June 2016

Background:
The purpose of this study was to define the anatomical boundaries, transformation in the aging face, and clinical implications of the Ristow space. The authors propose a title of deep pyriform space for anatomical continuity.

Methods:
The deep pyriform space was dissected in 12 hemifacial fresh cadaver dissections. Specimens were divided into three separate groups. For group 1, dimensions were measured and plaster molds were fashioned to evaluate shape and contour. For group 2, the space was injected percutaneously with dyed hyaluronic acid to examine proximity relationships to adjacent structures. For group 3, the space was pneumatized to evaluate its cephalic extension.

Results:
The average dimensions of the deep pyriform space are 1.1 × 0.9 cm. It is bounded medially by the depressor septi nasi and cradled laterally and superficially in a “half-moon” shape by the deep medial cheek fat and lip elevators. The angular artery courses on the roof of the space within a septum between the space and deep medial cheek fat. Pneumatization of the space traverses cephalic to the level of the tear trough ligament in a plane deep to the premaxillary space.

Conclusions:
The deep pyriform space is a midface cavity cradled by the pyriform aperture and deep medial cheek compartment. Bony recession of the maxilla with age predisposes this space for use as a potential area of deep volumization to support overlying cheek fat and draping lip elevators. The position of the angular artery in the roof of the space allows safe injection on the bone without concern for vascular injury.
Separation of Craniopagus Twins over the Past 20 Years: A Systematic Review of the Variables That Lead to Successful Separation
Authors: Harvey Donald J. , Totonchi Ali , Gosain Arun K. 
Published: June 2016

Background:
Attempted separation of craniopagus twins has continued to be associated with devastating results since the first partially successful separation with one surviving twin in 1952. To understand the factors that contribute to successful separation in the modern era of neuroimaging and modern surgical techniques, the authors reviewed and analyzed cases reported since 1995.

Methods:
All reported cases of craniopagus twin separation attempts from 1995 to 2015 were identified using PubMed (n = 19). In addition, the Internet was searched for additional unreported separation attempts (n = 5). The peer-reviewed cases were used to build a categorical database containing information on each twin pair, including sex; date of birth; date of surgery; multiple- versus single-stage surgery; angular versus vertical conjoining; nature of shared cerebral venous system; and the presence of other comorbidities identified as cardiovascular, genitourinary, and craniofacial. The data were analyzed to find factors associated with successful separation (survival of both twins at postoperative day 30).

Results:
Vertical craniopagus is associated with successful separation (p < 0.001). No statistical significance was attributed to the nature of the shared cerebral venous drainage or the other variables examined. Multiple-stage operations and surgery before 12 months of age are associated with a trend toward statistical significance for successful separation.

Conclusions:
The authors’ analysis indicates that vertical craniopagus twins have the highest likelihood of successful separation. Additional factors possibly associated with successful separation include the nature of the shared sinus system, surgery at a young age, and the use of staged separations.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Appropriate and Effective Dosage of BMP-2 for the Ideal Regeneration of Calvarial Bone Defects in Beagles
Authors: Choi Jong Woo , Jeong Woo Shik , Yang Sung Jun , Park Eun Jung , Oh Tae Suk , Koh Kyung S. 
Published: June 2016

Background:
Although bone morphogenetic protein-2 (BMP-2) is a potent growth factor, the appropriate and effective dosages for ideal bone formation according to defect size and type remain to be established. This study was designed to measure the effects of BMP-2 on calvarial defects in the beagle dog, by means of three-dimensional computed tomographic imaging.

Methods:
Eight beagles of equal age and weight were divided into one control and three experimental groups. After creating four circular 20-mm diameter defects, a BMP-2/tricalcium phosphate scaffolding mixture with concentrations of BMP-2 was introduced. The defect filling response was assessed until 16 weeks by three-dimensional computed tomograpy for the thickness, area, and density of the regenerating bone.

Results:
Statistically significant responses to BMP-2 were observed. The mean thicknesses of the regenerated bone were 1.6 mm for the control group and 1.6, 2.1, and 2.8 mm for 10, 50, and 200 µg/ml, respectively. As the original mean thickness of the calvarial bone in the beagles was 2.0 mm, a 50-µg quantity of BMP-2 proved to be ideal for 2-cm calvarial defects. The original surface area of the defect created was 314 mm2. The mean surface areas of the regenerated bone were 181.94 mm2 for the control group, and 237, 276, and 288 mm2 for 10, 50, and 200 µg/ml.

Conclusions:
BMP-2 promotes anatomically significant bone regeneration in critical-size cranial defects in this model, with an optimal dose-response at 50 µg/ml and without hyperosteogenesis or hypo-osteogenesis.
Can the Babysitter Procedure Improve Nerve Regeneration and Denervated Muscle Atrophy in the Treatment of Peripheral Nerve Injury?
Authors: Liu Hai-Fei , Chen Zeng-Gan , Lineaweaver William C. , Zhang Feng 
Published: June 2016

Background:
The authors evaluated the long-term efficacy of the “babysitter” procedure in improving nerve regeneration and denervated muscle atrophy for peripheral nerve repair.

Methods:
Eighty Lewis rats were allocated equally into four groups. The peroneal nerves of all animals were divided. In group A, the peroneal nerve stumps were anchored into adjacent muscles. Rats in group B underwent end-to-end neurorrhaphy. Rats in group C underwent end-to-side neurorrhaphy of the distal peroneal nerve stump to an epineurial window on the tibial nerve. Rats in group D underwent end-to-side neurorrhaphy of the distal stump to the tibial nerve with 40 percent neurectomy. After 8 weeks, end-to-end neurorrhaphy of the peroneal nerve stumps was performed in group A, C, and D during a second-stage procedure. Electrophysiology, myelinated fiber counts, muscle force and weight, and muscle histomorphometry were analyzed at 4, 8, 12, and 24 weeks postoperatively.

Results:
At 4 weeks, the end-to-end group showed predominant advantages in nerve regeneration and muscle preservation. No differences were observed in the latency delaying rate, tetanic tension, myelinated fiber number, or muscle weight between groups B and D by 24 weeks (p > 0.05). At 24 weeks, the results revealed superior latency delaying rate, myelinated axon regeneration, and size of muscle fibers in group D as compared with group C.

Conclusions:
Peripheral nerve repair with an initial motor nerve babysitter with 40 percent neurectomy of the donor nerve can achieve high efficacy in functional and structural recovery of the recipient system. Nerve babysitter by motor nerve with an epineural window was less effective.
Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant: A Reconstructive Solution for the Full Face and Total Scalp Burn
Authors: Sosin Michael , Ceradini Daniel J. , Levine Jamie P. , Hazen Alexes , Staffenberg David A. , Saadeh Pierre B. , Flores Roberto L. , Sweeney Nicole G. , Bernstein G. Leslie , Rodriguez Eduardo D. 
Published: June 2016

Background:
Reconstruction of extensive facial and scalp burns can be increasingly challenging, especially in patients that have undergone multiple procedures with less than ideal outcomes resulting in restricting neck and oral contractures, eyelid dysfunction, and suboptimal aesthetic appearance.

Methods:
To establish a reconstructive solution for this challenging deformity, a multidisciplinary team was assembled to develop the foundation to a facial vascularized composite allotransplantation program. The strategy of developing and executing a clinical transplant was derived on the basis of fostering a cohesive and supportive institutional clinical environment, implementing computer software and advanced technology, establishing a cadaveric transplant model, performing a research facial procurement, and selecting an optimal candidate with the aforementioned burn defect who was well informed and had the desire to undergo face transplantation.

Results:
Approval from the institutional review board and organ procurement organization enabled our face transplant team to successfully perform a total face, eyelids, ears, scalp, and skeletal subunit transplant in a 41-year-old man with a full face and total scalp burn.

Conclusions:
The culmination of knowledge attained from previous experiences continues to influence the progression of facial vascularized composite allotransplantation. This surgical endeavor methodically and effectively synchronized the fundamental principles of aesthetic, craniofacial, and microvascular surgery to restore appearance and function to a patient suffering from failed conventional surgery for full face and total scalp burns. This procedure represents the most extensive soft-tissue clinical face transplant performed to date.

CLINICAL QUESTION/LEVEL OF EVIDEMCE:
Therapeutic, V.
Looking Beyond the Cascade of HIV Care to End the AIDS Epidemic: Estimation of the Time Interval From HIV Infection to Viral Suppression
Authors: Supervie Virginie , Marty Lise , Lacombe Jean-Marc , Dray-Spira Rosemary , Costagliola Dominique ,   the FHDH-ANRS CO4 study group
Published: June 2016

Background:
Ensuring early universal access to HIV treatment is critical to reach the end of AIDS. The cascade of HIV care has become a critical metric to assess the coverage of treatment and viral suppression, but it does not provide any information on the elapsed times between becoming HIV-infected and reaching viral suppression.

Methods:
We estimated the cascade of care, the distribution of times between steps of the care continuum, in France, in 2010, at the national level, overall and by HIV exposure groups, using statistical modelling and large datasets: the national HIV surveillance system, the general social insurance scheme, and the French Hospital Database on HIV.

Results:
We found that the overall rate of viral suppression was high, with an estimated value of 52% (95% confidence interval: 49 to 54). However, the time intervals from HIV infection to viral suppression were long; overall, the median value was 6.1 years (inter quartile range: 3.6–9.2), and it ranged from ∼5.6 years among men who have sex with men and heterosexual women to 9.6 years among injection drug users. Time lost in achieving viral suppression was mainly due to delays in HIV testing (overall median of 3.4 years), except for injection drug users where it was also due to delayed care entry once diagnosed (∼1 year in median versus <1 month for other groups).

Conclusions:
High viral suppression rate can hide large gaps between time of HIV infection and time of viral suppression. Estimates of the flow-time between steps of the care continuum should become priority indicators to identify these gaps and monitor whether interventions are successful in closing them.
Superhydrophobicity of the gecko toe pad: biological optimization versus laboratory maximization
Authors: Stark Alyssa Y. , Subarajan Shairani , Jain Dharamdeep , Niewiarowski Peter H. , Dhinojwala Ali 
Published: June 2016

While many gecko-inspired hierarchically structured surfaces perform as well as or better than the natural adhesive system, these designs often fail to function across a variety of contexts. For example, the gecko can adhere to rough, wet and dirty surfaces; however, most synthetic mimics cannot maintain function when faced with a similar situation. The solution to this problem lies in a more thorough investigation of the natural system. Here, we review the adhesive system of the gecko toe pad, as well as the far less-well-studied anti-adhesive system that results from the chemistry and structure of the toe pad (superhydrophobicity). This paradoxical relationship serves as motivation to study functional optimization at the system level. As an example, we experimentally investigate the role of surface lipids in adhesion and anti-adhesion, and find a clear performance trade-off related to shear adhesion in air on a hydrophilic surface. This represents the first direct investigation of the role of surface lipids in gecko adhesion and anti-adhesion, and supports the argument that a system-level approach is necessary to elucidate optimization in biological systems. Without such an approach, bioinspired designs will be limited in functionality and context, especially compared to the natural systems they mimic.
This article is part of the themed issue ‘Bioinspired hierarchically structured surfaces for green science’.
Bioinspired surfaces for turbulent drag reduction
Authors: Golovin Kevin B. , Gose James W. , Perlin Marc , Ceccio Steven L. , Tuteja Anish 
Published: June 2016

In this review, we discuss how superhydrophobic surfaces (SHSs) can provide friction drag reduction in turbulent flow. Whereas biomimetic SHSs are known to reduce drag in laminar flow, turbulence adds many new challenges. We first provide an overview on designing SHSs, and how these surfaces can cause slip in the laminar regime. We then discuss recent studies evaluating drag on SHSs in turbulent flow, both computationally and experimentally. The effects of streamwise and spanwise slip for canonical, structured surfaces are well characterized by direct numerical simulations, and several experimental studies have validated these results. However, the complex and hierarchical textures of scalable SHSs that can be applied over large areas generate additional complications. Many studies on such surfaces have measured no drag reduction, or even a drag increase in turbulent flow. We discuss how surface wettability, roughness effects and some newly found scaling laws can help explain these varied results. Overall, we discuss how, to effectively reduce drag in turbulent flow, an SHS should have: preferentially streamwise-aligned features to enhance favourable slip, a capillary resistance of the order of megapascals, and a roughness no larger than 0.5, when non-dimensionalized by the viscous length scale.
This article is part of the themed issue ‘Bioinspired hierarchically structured surfaces for green science’.
Heterogeneity of cognitive decline in dementia: a failed attempt to take into account variable time-zero severity
Authors: J Kiddle Steven , Parodi Alice , Johnston Caroline , Wallace Chris , JB Dobson Richard ,   for the Alzheimer’s Disease Neuroimaging Initiative (ADNI),   for the Australian Imaging Biomarkers and Lifestyle flagship study of ageing (AIBL),   and for the Coalition Against Major Diseases (CAMD)
Published: June 2016

AbstractNOTEThe biases seen in simulations of Temporal Clustering appear to be even worse in real applications. While this was a novel and interesting approach, ultimately this work has been discontinued. I feel the biases are due to propagated error in estimating individual level offsets based on a single noisy measure, amplified by the fact that high MMSE scores change very slowly and therefore many estimates are from near an asymptote on the left hand of the model. We continue to work in this area, with other approaches showing significantly more promise.Understanding heterogeneity in Alzheimer’s disease (AD) progression is critically important for the optimal design of trials, allowing participants to be recruited who are correctly diagnosed and who are likely to undergo cognitive decline. Current knowledge about heterogeneity is limited by the paucity of long-term follow-up data and methodological challenges. Of the latter, a key problem is how to choose the most appropriate ‘time zero’ to use in longitudinal models, a choice which affects results. Rather than a pre-specified ‘time zero’ we propose a novel methodology – Temporal Clustering – that defines a new ‘time zero’ using individual offsets inferred from the data. We applied this to longitudinal Mini-Mental State Examination (MMSE), where this approach ensures that individuals have similar estimated MMSE scores at this new ‘time zero’. Simulations showed that it could accurately predict cluster membership after the application of a filter. Next we applied it to a cohort of 2412 individuals, with large variability in MMSE score at first visit. Temporal Clustering was used to split individuals into two clusters. The group showing faster decline had higher average levels of AD risk factors: cerebrospinal fluid tau andAPOE ∊4. Cluster membership predicted by Temporal Clustering was less affected by individuals’ cognitive ability at first visit than was the case for clusters found using Latent Class Mixture Models. Further application and development of this method will help researchers to identify risk factors affecting cognitive decline.
Two-Dimensional Hermite Filters Simplify the Description of High-Order Statistics of Natural Images
Authors: Hu Qin , Victor Jonathan 
Published: June 2016

AbstractNatural image statistics play a crucial role in shaping biological visual systems, understanding their function and design principles, and designing effective computer-vision algorithms. High-order statistics are critical for conveying local features, but they are challenging to study – largely because their number and variety is large. Here, via the use of two-dimensional Hermite (TDH) functions, we identify a covert symmetry in high-order statistics of natural images that simplifies this task. This emerges from the structure of TDH functions, which are an orthogonal set of functions that are organized into a hierarchy of ranks. Specifically, we find that the shape (skewness and kurtosis) of the distribution of filter coefficients depends only on the projection of the function onto a 1-dimensional subspace specific to each rank. The characterization of natural image statistics provided by TDH filter coefficients reflects both their phase and amplitude structure, and we suggest an intuitive interpretation for the special subspace within each rank.
A genetically encoded inhibitor of 53BP1 to stimulate homology-based gene editing
Authors: Canny Marella D. , Wan Leo C.K. , Fradet-Turcotte Amélie , Orthwein Alexandre , Moatti Nathalie , Juang Yu-Chi , Zhang Wei , Noordermeer Sylvie M. , Wilson Marcus D. , Vorobyov Andrew , Munro Meagan , Ernst Andreas , Zimmermann Michal , Ng Timothy F. , Sidhu Sachdev S. , Sicheri Frank , Durocher Daniel 
Published: June 2016

AbstractThe expanding repertoire of programmable nucleases such as Cas9 brings new opportunities in genetic medicine1–3. In many cases, these nucleases are engineered to induce a DNA double-strand break (DSB) to stimulate precise genome editing by homologous recombination (HR). However, HR efficiency is nearly always hindered by competing DSB repair pathways such as non-homologous end-joining (NHEJ). HR is also profoundly suppressed in non-replicating cells, thus precluding the use of homology-based genome engineering in a wide variety4of cell types. Here, we report the development of a genetically encoded inhibitor of 53BP1 (known as TP53BP1), a regulator of DSB repair pathway choice5. 53BP1 promotes NHEJ over HR by suppressing end resection, the formation of 3-prime single-stranded DNA tails, which is the rate-limiting step in HR initiation. 53BP1 also blocks the recruitment of the HR factor BRCA1 to DSB sites in G1 cells4,6. The inhibitor of 53BP1 (or i53) was identified through the screening of a massive combinatorial library of engineered ubiquitin variants by phage display7. i53 binds and occludes the ligand binding site of the 53BP1 Tudor domain with high affinity and selectivity, blocking its ability to accumulate at sites of DNA damage. i53 is a potent selective inhibitor of 53BP1 and enhances gene targeting and chromosomal gene conversion, two HR-dependent reactions. Finally, i53 can also activate HR in G1 cells when combined with the activation of end-resection and KEAP1 inhibition. We conclude that 53BP1 inhibition is a robust tool to enhance precise genome editing by canonical HR pathways.
Elucidating Combinatorial Chromatin States by Co-ImmunoPrecipitation (comb-ChIP)
Authors: Sadeh Ronen , Launer-Wachs Roee , Wandel Hava , Rahat Ayelet , Friedman Nir 
Published: June 2016

AbstractChromatin ImmunoPrecipitation followed by massively parallel sequencing (ChIP-Seq) has been instrumental to our current view of chromatin structure and function, and identifies correlating histone marks, which together demarcate biologically-relevant domains. However, as with most genome-wide assays, ChIP-seq is an ensemble measurement that reports on the average occupancy of individual modifications in a population of cells. Consequently, our understanding of the combinatorial nature of chromatin states relies almost exclusively on spatial correlations. Here, we report the development of a novel protocol, called indexed Combinatorial ChIP (comb-ChIP), which has the power to determine the genome-wide co-occurrence of histone marks at single nucleosome resolution. We show that at regions of overlapping ChIP signals, certain combinations of marks (H3K36me3 and H3K79me3) tend to co-occur on the same nucleosome, while other combinations (H3K4me3 and H3K36me3) do not, reflecting differences in the underlying chromatin pathways. We further use comb-ChIP to detect changes in histone mark co-occurrence upon genetic perturbation, illuminating new aspects of the Set2-RPD3S pathway. Overall, comb-ChIP promises to greatly improve our understanding of the structural and functional complexity of chromatin.
Assessment of carbon dioxide, carbon dioxide/oxygen, isoflurane and pentobarbital killing methods in rats
Authors: Chisholm Jessica M , Pang Daniel SJ 
Published: June 2016

AbstractBackground:Exposure to carbon dioxide (CO2) gas as a killing method is aversive and exposure to high concentrations likely to be painful. Bradycardia during exposure to CO2is associated with nociception and pain. However, it is unclear if bradycardia occurs before loss of consciousness as this is variably defined in the literature. The objectives of this study were to explore the relationship between recumbency, loss of righting reflex (LORR) and a quiescent electromyograph as measures of loss of consciousness, and identify the onset of bradycardia in relation to these measures.Methods:Thirty-two adult, female Sprague-Dawley rats were instrumented with a telemetry device and randomly assigned to one of four killing methods (100% CO2, CO2(70%)/O2(30%), isoflurane (5%) and intraperitoneal pentobarbital (200 mg/kg). Time to achieve recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph, heart rate and apnea were recorded.Results:The general order of progression was recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph and apnea. Recumbency preceded LORR in the majority of animals (CO2; 7/8, CO2/O2; 8/8, isoflurane; 5/8, pentobarbital; 4/8). Bradycardia occurred before recumbency in the CO2(p = 0.0002) and CO2/O2(p = 0.005) groups, with a 50% reduction in heart rate compared to baseline. The slowest (time to apnea) and least consistent killing methods were CO2/O2(1180 ± 658.1s) and pentobarbital (875 [239 to 4680]s).Conclusion:Bradycardia, and consequently nociception and pain, occurs before loss of consciousness during CO2exposure. Pentobarbital displayed an unexpected lack of consistency, questioning its classification as an acceptable euthanasia method in rats.