bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous Breast Radiation-associated Angiosarcoma: Anterior Chest Wall Reconstruction Options Following Extra-radical Resection
Authors: Mella Juan R. , Ross Kimberly M. , Li George Z. , Pomahac Bohdan , Raut Chandrajit P. , Orgill Dennis P. 
Published: September 2018

Background:
Radiation-associated angiosarcoma (RAAS) of the breast is a rare complication following breast irradiation with high rates of recurrence and death. To improve survival, we have advocated for an extra-radical resection where the entire irradiated skin and subcutaneous tissue is excised. This results in very large chest defects for which we describe our reconstructive experience.

Methods:
We performed a retrospective review of patients diagnosed with RAAS and treated with extra-radical resection followed by immediate reconstruction between 1999 and 2017. We analyzed reconstructive options, complications rates, length of stay, and operative times.

Results:
Extra-radical resections were performed in 35 patients. We reconstructed these large defects with abdominal advancement flaps with split-thickness skin grafting in 25 patients and added a pedicled latissimus dorsi or omental flap in the 10 other patients. Skin grafts took well over the irradiated pectoralis major muscle with a median take rate of over 90%. Average operative times were 150 minutes for those treated with an abdominal advancement flap and skin grafting with a median length of stay of 5 days for all patients.

Conclusion:
Large anterior chest soft-tissue defects caused by extra-radical resections leaves defects too large to be covered by traditional breast reconstruction flaps. Abdominal advancement, latissimus dorsi muscle, and omental flaps along with skin grafts can be safely performed while leaving other traditional options open for future breast reconstruction.
Early Experience With Nonporous Polyethylene Barrier Sheet in Orbital Fracture Repair
Authors: Compton Christopher J. , Melson Andrew T. , Sokol Jason A. , Nunery William R. , Ochoa Manuel , Ziaie Babak , Lee H.B. Harold 
Published: September 2018

Purpose:
The aim of this study was to evaluate the efficacy of the nonporous polyethylene barrier sheet as an alternative for nylon foil (SupraFOIL) implants in repair of orbital fractures.

Methods:
This is a prospective, case series using the Stryker 0.4-mm-thick nonporous polyethylene barrier sheet in all patients over the age of 18 years presenting with orbital fractures from December 2014 to June 2015. Patient’s age, location of fracture, etiology of injury, presence of preoperative restriction and diplopia, and postoperative diplopia and/or enophthalmos was recorded. Institutional review board approval was received, and consent was obtained from all participants. Patients were followed for at least 6 months when possible. Scanning electron microscopy was used to compare the thickness, surface characteristics, and porosity of the nonporous polyethylene barrier and nylon foil implants. Beam deflection testing was also performed to compare the biomechanical properties of each implant.

Results:
Forty-six patients who underwent repair of orbital fractures with the nonporous polyethylene barrier sheet were included in this series. Average age was 43.3 years (range: 18–84 years). Twenty-six of 46 patients (56.5%) were males, and 20 (43.4%) were females. The most common causes of injuries were assault (38.3%), falls (25.5%), motor vehicle accident (14.9%), and sports related (10.5%). Twenty of 46 patients (43.4%) had isolated orbital floor, and 2 patients (4.3%) had isolated medial wall fractures. Fifteen patients (32.6%) had combined floor and medial wall fractures involving the inferomedial orbital strut, and 9 (19.6%) had floor fractures associated with zygomaticomaxillary complex or lateral wall fractures. Twenty-eight patients (60.9%) had preoperative diplopia. Timing of surgery was between 3 and 55 days, with the median of 11.5 days. Five of 46 patients (10.8%) had residual diplopia at their 1-week postoperative visit, 4 of those patients’ diplopia had resolved at 2 months postoperatively. One patient had residual diplopia at 6-month follow up. Electron microscopy showed that the 0.4-mm nonporous polyethylene barrier implant was thinner (0.33 mm) than expected and thinner than 0.4-mm SupraFOIL (0.38 mm). Scanning electron microscopy exhibited that the surface of the nonporous polyethylene barrier was smooth and nonporous. Beam deflection testing showed that for small forces (<100 mN), the 2 materials behaved nearly identically, but at higher forces, the nonporous polyethylene implant exhibited less stiffness.

Conclusions:
The use of nonporous polyethylene barrier sheet implant for orbital fracture repair is a safe and effective alternative to nonporous nylon foil implants. There were no complications and one case of residual diplopia (2.1%) in this case series.
Mealtime Assistance ... From Chaos to Calm
Authors: Sykes Pamela , Norris Ian , Cook Megan , Woods Aaron , Boughton Rachel , Chilcott Kylie , Walsh Kenneth 
Published: September 2018

Background:
Providing appropriate and timely mealtime assistance to hospitalized patients should be part of a multifaceted and multidisciplinary approach to optimizing a patient's nutritional care plan.

Problem:
There was anecdotal evidence at the study hospital that patients did not receive adequate and/or timely assistance at mealtimes.

Approach:
A best practice implementation project, using a proven strategy of audit, feedback, and reaudit, was used to effect practice change on an acute general medical ward.

Outcomes:
The combined interventions of staff engagement, redesigning the model of care to reprioritize activities at mealtimes, clarifying nutritional care roles and responsibilities, introducing a protected mealtime and a novel 2-tiered colored tray system, and implementing an awareness and education program have resulted in significant improvements in mealtime assistance.

Conclusions:
Success of the project is considered to be replicable and sustainable hospitalwide and more broadly.
Using Lean Six Sigma to Improve Controlled Drug Processes and Release Nursing Time
Authors: Creed Maria , McGuirk Michelle , Buckley Ruth , De Brún Aoife , Kilduff Marie 
Published: September 2018

Background:
Hospital controlled drug processes are established to adhere to legislation, with little consideration of efficiency of processes.

Local Problem:
A controlled drug process existed, where nurses requested a porter to collect a hand-written order; however, only 19% of drug orders were processed this way. Instead, an unscheduled, ad hoc process led to an average of 17 nurse journeys to pharmacy daily. We aimed to reduce nurse journeys to the pharmacy by 25% to release nursing time.

Methods:
A pre-/postintervention design was used with Lean Six Sigma methods.

Interventions:
A multifaceted intervention involved process redesign, increasing the frequency of a porter-led delivery service, amending delivery times to reflect times of greatest need, and streamlining checking requirements.

Results:
Following implementation, there was a statistically significant 44% decrease in nurse journeys to pharmacy for drug collections, which was maintained after 18 months.

Conclusions:
Interprofessional collaboration improving hospital-wide processes can have significant benefits for the release of nursing time.
Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma
Authors: Palamidessi Andrea , Malinverno Chiara , Frittoli Emanuela , Corallino Salvatore , Barbieri Elisa , Sigismund Sara , Di Fiore Pier Paolo , Beznoussenko Galina V. , Martini Emanuele , Garre Massimiliano , Parazzoli Dario , Ferrara Ines , Tripodo Claudio , Giavazzi Fabio , Cerbino Roberto , Scita Giorgio 
Published: September 2018

AbstractDuring wound repair, branching morphogenesis and carcinoma dissemination, cellular rearrangements are fostered by a solid-to-liquid transition known as unjamming. The biomolecular machinery behind unjamming, its physiological and clinical relevance remain, however, a mystery. Here, we combine biophysical and biochemical analysis to study unjamming in a variety of epithelial 2D and 3D collectives: monolayers, differentiated normal mammary cysts, spheroid models of breast ductal carcinoma in situ (DCIS), andex vivoslices of orthotopically-implanted DCIS. In all cases, elevation of the small GTPase RAB5A sparks unjamming by promoting non-clathrin-dependent internalization of epidermal growth factor receptor that leads to hyper-activation of endosomally-confined ERK1/2 and phosphorylation of the actin nucleator WAVE2. Physically, activation of this pathway causes highly coordinated flocking of the cells, with striking rotational motion in 3D that eventually leads to matrix remodelling and collective invasiveness of otherwise jammed carcinoma. The identified endo-ERK1/2 pathway provides an effective switch for unjamming through flocking to promote epithelial tissues morphogenesis and carcinoma invasion and dissemination.
Repression of Transcription Factor AP-2 Alpha by Peroxisome Proliferator Activated Receptor Gamma Reveals a Novel Transcriptional Circuit in basal-squamous Bladder Cancer
Authors: Yamashita Hironobu , Kawasawa Yuka Imamura , Shuman Lauren , Zheng Zongyu , Tran Truc , Walter Vonn , Warrick Joshua I. , Al-Ahmadie Hikmat , Kaag Matthew , Wong Pak Kin , Raman Jay D. , DeGraff David J. 
Published: September 2018

AbstractThe discovery of bladder cancer transcriptional subtypes provides an opportunity to identify high risk patients, and tailor disease management. Recent studies suggest tumor heterogeneity contributes to “plasticity” of molecular subtype during progression and following treatment. Nonetheless, the transcriptional drivers of the aggressive basal-squamous subtype remain unidentified. As PPARγ has been repeatedly implicated in the luminal subtype of bladder cancer, we hypothesized inactivation of this transcriptional master regulator during progression results in increased expression of basal-squamous specific transcription factors (TFs) which act to drive aggressive behavior. We initiated a pharmacologic and RNA-seq-based screen to identify PPARγ-repressed, basal-squamous specific TFs. Hierarchical clustering of RNA-seq data following treatment of a panel of human bladder cancer cell lines with a PPARγ agonist identified a number of TFs regulated by PPARγ activation, several of which are implicated in urothelial and squamous differentiation. One PPARγ-repressed TF implicated in squamous differentiation identified is Transcription Factor Activating Protein 2 alpha (TFAP2A). We show TFAP2A and its paralog TFAP2C are overexpressed in basal-squamous bladder cancer and in squamous areas of cystectomy samples, and that overexpression is associated with increased lymph node metastasis and distant recurrence, respectively. Biochemical analysis confirmed the ability of PPARγ activation to repress TFAP2A, while PPARγ antagonist studies indicate the requirement of a functional receptor. In vivo tissue recombination studies show TFAP2A and TFAP2C promote tumor growth in line with the aggressive nature of basal-squamous bladder cancer. Our findings suggest PPARγ inactivation, as well as TFAP2A and TFAP2C overexpression cooperate with other TFs to promote the basal-squamous transition.
Improved high-quality genome assembly and annotation of Tibetan hulless barley
Authors: Zeng Xingquan , Li Xiangfeng , Bai Lijun , Wang Yulin , Xu Tong , Yuan Hongjun , Xu Qijun , Zha Sang , Wei Zexiu , Qimei Wangmu , Basang Yuzhen , Dunzhu Jiabu , Yu Mingzai , Nyima Tashi 
Published: September 2018

AbstractBackgroundThe Tibetan hulless barley (Hordeum vulgare L. var. nudum), also called “Qingke” in Chinese and “Ne” in Tibetan, is the staple food for Tibetans and an important livestock feed in the Tibetan Plateau. The Tibetan hulless barley in China has about 3500 years of cultivation history, mainly produced in Tibet, Qinghai, Sichuan, Yunnan and other areas. In addition, Tibetan hulless barley has rich nutritional value and outstanding health effects, including the beta glucan, dietary fiber, amylopectin, the contents of trace elements, which are higher than any other cereal crops.FindingsHere, we reported an improved high-quality assembly of Tibetan hulless barley genome with 4.0 Gb in size. We employed the falcon assembly package, scaffolding and error correction tools to finish improvement using PacBio long reads sequencing technology, with contig and scaffold N50 lengths of 1.563Mb and 4.006Mb, respectively, representing more continuous than the original Tibetan hulless barley genome nearly two orders of magnitude. We also re-annotated the new assembly, and reported 61,303 stringent confident putative protein-coding genes, of which 40,457 is HC genes. We have developed a new Tibetan hulless barley genome database (THBGD) to download and use friendly, as well as to better manage the information of the Tibetan hulless barley genetic resources.ConclusionsThe availability of new Tibetan hulless barley genome and annotations will take the genetics of Tibetan hulless barley to a new level and will greatly simplify the breeders effort. It will also enrich the granary of the Tibetan people.
RUNX3 regulates cell cycle-dependent chromatin dynamics by functioning as a pioneer factor of the restriction point
Authors: Lee Jung-Won , Kim Da-Mi , Jang Ju-Won , Park Tae-Geun , Lee You-Soub , Chi Xin-Zi , Park Il Yeong , Hyun Jin-Won , Ito Yoshiaki , Bae Suk-Chul 
Published: September 2018

AbstractThe cellular decision regarding whether to undergo proliferation or death is made at the restriction (R)-point, which is disrupted in nearly all tumors. The identity of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in cell biology. We found that early after mitogenic stimulation, RUNX3 bound to its target loci, where it opened chromatin structure by sequential recruitment of Trithorax group proteins and cell-cycle regulators to drive cells to the R-point. Soon after, RUNX3 closed these loci by recruiting Polycomb repressor complexes, causing the cell to pass through the R-point toward S phase. If the RAS signal was constitutively activated, RUNX3 inhibited cell cycle progression by maintaining R-point-associated genes in an open structure. Our results identify RUNX3 as a pioneer factor for the R-point and reveal the molecular mechanisms by which appropriate chromatin modifiers are selectively recruited to target loci for appropriate R-point decisions.
Relative Principal Components Analysis: Application to Analyzing Biomolecular Conformational Changes
Authors: Ahmad Mazen , Helms Volkhard , Kalinina Olga V. , Lengauer Thomas 
Published: September 2018

AbstractA new method termed “Relative Principal Components analysis” (RPCA) is introduced that extracts optimal relevant principal components to describe the change between two data samples representing two macroscopic states. The method is widely applicable in data-driven science. Calculating the components is based on a unified physical framework which introduces the objective function, namely the Kullback-Leibler divergence, appropriate for quantifying the change of the macroscopic state as it is effected by the microscopic features. To demonstrate the applicability of RPCA, we analyze the thermodynamically relevant conformational changes of the protein HIV-1 protease upon binding to different drug molecules. In this case, the RPCA method provides a sound thermodynamic foundation for the analysis of the binding process. The relevant collective (global) conformational changes can be reconstructed from the informative latent variables to exhibit both the enhanced and the restricted conformational fluctuations upon ligand association. Moreover, RPCA characterizes the locally relevant conformational changes which can be presented on the structure of the protein.
Cross-sectional and longitudinal research approaches: running pace and step characteristics of elite athletes in the 400-m hurdles
Authors: Otsuka Mitsuo , Isaka Tadao 
Published: September 2018

AbstractThe aim of this study was to clarify the running pace and step characteristics among various competitive-level 400-m hurdlers through cross-sectional and longitudinal research approaches. We analysed spatiotemporal data for 13 male world-class and 14 male national-level 400-m hurdlers. We analysed 16.8 ± 4.2 races for each world-class hurdler and 20.0 ± 6.0 races for each national-level hurdler (the total number of analysed runs was 499) using publicly available television and internet broadcasts. Cross-sectional approach showed that positive relationships of finish time were highly obtained between both first- (r = 0.901) and latter-half split times (r = 0.914). In contrast, the first- and latter-half split times were not significantly correlated to SL and SF. A multiple single-subject approach showed that 14/27 hurdlers were identified as being latter-half speed reliant. In contrast, no hurdlers demonstrated first-half reliance. In the latter half of the race, 12/27 hurdlers were identified as being SF reliant; no hurdlers demonstrated SL reliance. In conclusions, important findings regarding high performance in a cross-sectional research approach do not always corresponded with those in a longitudinal research approach. Athletes and coaches should carefully improve performance in the first half of the race based on an individualization principle for training.
Maternally-regulated gastrulation as a source of variation contributing to cavefish forebrain evolution
Authors: Torres-Paz Jorge , Leclercq Julien , Rétaux Sylvie 
Published: September 2018

AbstractSequential developmental events, starting from the moment of fertilization, are crucial for the acquisition of animal body plan. Subtle modifications in such early events are likely to have a major impact in later morphogenesis, bringing along morphological diversification. Here, comparing the blind cave and the surface morphotypes ofAstyanax mexicanusfish, we found heterochronies during gastrulation, producing organizer and axial mesoderm tissues with different properties, including differences in expression ofdkk1b, that may have contributed to cavefish brain evolution. These variations observed during gastrulation depend fully on maternal factors, whereas later phenotypic differences in neural development became progressively hidden when zygotic genes take the control over development. Transcriptomic analysis of fertilized eggs from both morphotypes and reciprocal F1 hybrids showed a strong and specific maternal signature. Our work strongly suggests that maternal effect genes and developmental heterochronies occurring during gastrulation have impacted morphological brain change during cavefish evolution.
Adaptive Encoding of Coordinating Information in the Crayfish Central Nervous System
Authors: Schneider Anna C. , Blumenthal Felix , Smarandache-Wellmann Carmen R. 
Published: September 2018

AbstractLocomotion is essential for an animal’s survival. This behavior can range from directional changes to adapting the motor force to the conditions of its surroundings. Even if speed and force of movement are changing, the relative coordination between the limbs or body segments has to stay stable in order to provide the necessary thrust. The coordinating information necessary for this task is not always conveyed by sensory pathways. Adaptation is well studied in sensory neurons, but only few studies have addressed if and how coordinating information changes in cases where a local circuit within the central nervous system is responsible for the coordination between body segments at different locomotor activity states.One system that does not depend on sensory information to coordinate a chain of coupled oscillators is the swimmeret system of crayfish. Here, the coordination of four coupled CPGs is controlled by central Coordinating Neurons. Cycle by cycle, the Coordinating Neurons encode information about the activity state of their home ganglion as burst of spikes, and send it as corollary discharge to the neighboring ganglia. Activity states, or excitation levels, are variable in both the living animal and isolated nervous system; yet the amount of coordinating spikes per burst is limited.Here, we demonstrate that the system’s excitation level tunes the encoding properties of the Coordinating Neurons. Their ability to adapt to excitation level, and thus encode relative changes in their home ganglion’s activity states, is mediated by a balancing mechanism. Manipulation of cholinergic pathways directly affected the coordinating neurons’ electrophysiological properties. Yet, these changes were counteracted by the network’s influence. This balancing may be one feature to adapt the limited spike range to the system’s current activity state.
Synaptic proteins expressed by oligodendrocytes mediate CNS myelination
Authors: Hughes Alexandria N. , Appel Bruce 
Published: September 2018

ABSTRACTOligodendrocytes ensheath neuronal axons with myelin, a proteolipid-rich membrane that increases conduction velocity and provides trophic support. Our lab and others have provided evidence that vesicular release from neurons promotes myelin sheath growth. Complementarily, transcriptomic and proteomic approaches have revealed that oligodendrocytes express many proteins that allow dendrites to sense and respond to vesicular release at synapses. Do axon-myelin contacts use similar communication mechanisms as nascent synapses to form myelin sheaths on axons? To test this, we used fusion proteins to track synaptic vesicle localization and membrane fusion within spinal cord axons of zebrafish larvae during developmental myelination. Additionally, we used a CRISPR/Cas9-mediated GAL4 enhancer trap and genetically-encoded intrabody to detect expression and localization of PSD-95, a component of dendritic postsynaptic complexes, within oligodendrocytes. We found that synaptic vesicles accumulate at ensheathment sites over time and are exocytosed with variable patterning underneath myelin sheaths. Accordingly, we also found that most, but not all sheaths localized PSD-95 with patterning similar to exocytosis site location within the axon. By querying published transcriptome databases, we found that oligodendrocytes express numerous transsynaptic adhesion molecules that function across synapses to promote synapse formation and maturation. Disruption of candidate PDZ-binding transsynaptic adhesion proteins in oligodendrocytes revealed that these proteins have variable effects on sheath length and number. We focused on one candidate, Cadm1b (SynCAM1), and demonstrated that it localized to myelin sheaths where both its PDZ binding and extracellular adhesion to axons are required for myelin sheath growth. Our work reveals shared mechanisms of synaptic and myelin plasticity and provides new targets for mechanistic unraveling of activity-regulated myelination.
Asymmetric adaptation reveals functional lateralization for graded versus discrete stimuli
Authors: Desrochers Melanie , Lang Marianne , Hendricks Michael 
Published: September 2018

Abstract 150 wordsAnimal navigation strategies depend on the nature of the environmental cues used. In the nematode Caenorhabditis elegans, navigation has been studied in the context of gradients of attractive or repellent stimuli as well is in response to acute aversive stimuli. We wanted to better understand how sensory responses to the same stimulus vary between graded and acute stimuli, and how this variation relates to behavioral responses. C. elegans has two salt-sensing neurons, ASEL and ASER, that show opposite responses to stepped changes in stimulus levels, however only ASER has been shown to play a prominent role in salt chemotaxis. We used pre-exposure to natural stimuli to manipulate the responsiveness of these neurons and tested their separate contributions to behavior. Our results suggest ASEL is specialized for responses to acute stimulus changes. We also found that ASER remains responsive to graded stimuli under conditions where it is unresponsive to large steps.