bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfusion Zones of Extended Transverse Skin Paddles in Muscle-Sparing Latissimus Dorsi Myocutaneous Flaps for Breast Reconstruction
Authors: Koonce Stephanie L. , Barnavon Yoav , Newman Martin I. , Hwee Yin Kan 
Published: April 2019

Background:
The authors report their experience using extended transversely oriented skin paddles in muscle-sparing latissimus dorsi pedicled flaps for breast reconstruction as an alternative to thoracodorsal artery perforator flaps.

Methods:
A retrospective review was conducted of patients who underwent muscle-sparing latissimus dorsi flap pedicled breast reconstruction from January of 2009 to July of 2014 with at least 3-month follow-up. Surgical outcomes and complications were analyzed.

Results:
Fifty-three patients underwent a total of 81 muscle-sparing latissimus dorsi pedicled flaps for breast reconstruction. Extended transversely oriented skin paddles ranged from 7 to 9 cm vertically by 25 to 35 cm horizontally and were perfused by a strip of latissimus dorsi muscle that was approximately 25 percent of the total muscular volume. Twenty patients had indocyanine green angiography revealing three distinct zones of perfusion in the extended transversely oriented skin paddles. The area of earliest perfusion (designated zone 1) was directly over the muscle containing the perforators. The second best area of perfusion (zone 2) was lateral to the muscle (toward the axilla). The last and relatively least well-perfused area (zone 3) was medial to the muscle (toward the spine). Zone 3 still had adequate viability. There were no flap losses. Minor complications included wound infection [six of 81 (7.4 percent)], fat necrosis [three of 81 (3.7 percent)], and seroma [four of 81 (4.9 percent)].

Conclusions:
Muscle-sparing latissimus dorsi pedicled flaps with extended transversely oriented skin paddles are reliable alternatives to thoracodorsal artery perforator flaps for breast reconstruction. Three zones of perfusion were delineated in the extended transversely oriented skin paddles on indocyanine green imaging, and all three zones were viable.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
The Latissimus Dorsi Myocutaneous Flap Is a Safe and Effective Method of Partial Breast Reconstruction in the Setting of Breast-Conserving Therapy
Authors: Mericli Alexander F. , Szpalski Caroline , Schaverien Mark V. , Selber Jesse C. , Adelman David M. , Garvey Patrick B. , Villa Mark T. , Robb Geoffrey , Baumann Donald P. 
Published: April 2019

Background:
Reconstruction of partial breast defects in low-volume, nonptotic breasts can be challenging. The authors hypothesized that use of the latissimus dorsi flap in partial breast reconstruction is safe and associated with low complication and high patient satisfaction rates.

Methods:
All patients who underwent breast-conserving therapy and latissimus dorsi flap reconstruction from January 1, 2006, to December 31, 2016, were identified in a prospectively maintained database. Patient demographics, tumor characteristics, and complications were recorded. Patient-reported outcomes were assessed with the BREAST-Q breast-conserving therapy module. A group of plastic surgeons and laypersons used a five-point Likert scale to evaluate aesthetic outcomes in representative patients.

Results:
Forty-seven patients met the inclusion criteria. Median follow-up was 5.4 years. Most patients (93.6 percent) underwent immediate reconstruction. The mean resection volume was 219.5 cc (range, 70 to 877 cc). The overall complication rate was 8.5 percent. Grade 2 or 3 ptosis (OR, 1.21; 95 percent CI, 1.0 to 1.46; p = 0.03), smoking (OR, 13.1; 95 percent CI, 1.2 to 143.2; p = 0.03), and multicentric tumor (OR, 1.23; 95 percent CI, 1.04 to 1.64; p = 0.02) were associated with a higher complication rate. Ductal carcinoma in situ was associated with reoperation for positive margins (OR, 14.4; 95 percent CI, 2.1 to 100; p = 0.009). Of particular interest, patient-reported outcomes were favorable, with the highest rated domains being Satisfaction with Breasts (61; interquartile range, 37 to 77), Psychosocial Well-being (87; interquartile range, 63 to 100), and Physical Well-being (87; interquartile range, 81 to 100). The median aesthetic score was 4 (of 5).

Conclusions:
This is the first study to date using the BREAST-Q to assess patient-reported outcomes associated with the latissimus dorsi flap for partial breast reconstruction. The flap is safe and effective for reconstruction in the setting of breast-conserving therapy, providing aesthetically pleasing results with high patient satisfaction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Laue diffraction and time-resolved crystallography: a personal history
Authors: Moffat Keith 
Published: April 2019

A personal, historical view is presented of Laue X-ray diffraction and its application to time-resolved studies of dynamic processes, largely in light-sensitive biological systems. In Laue diffraction, a stationary crystal is illuminated by a polychromatic X-ray source. Laue diffraction has inherent complications largely absent in monochromatic diffraction, and consequently fell into disuse for quantitative structure determination. However, the advent of naturally polychromatic, intense, pulsed storage ring X-ray sources in the 1970s led to re-examination at Daresbury and elsewhere of its underlying principles. Laue diffraction has been successfully applied at storage ring sources to time-resolved, pump–probe crystallographic studies, whose exposure time and time resolution were progressively reduced from minutes to seconds, milliseconds, nanoseconds and 100 ps. Most recently, hard X-ray free electron laser sources have been used to generate narrow bandpass Laue diffraction patterns. The femtosecond X-ray pulses from such sources are completely destructive, generate only one diffraction pattern per tiny crystal and have unusual properties. However, they too are being applied to time-resolved crystallography to explore, for example, isomerization and rapid tertiary structural changes on the chemical, femtosecond timescale.
This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
New nitrides: from high pressure–high temperature synthesis to layered nanomaterials and energy applications
Authors: McMillan Paul F. 
Published: April 2019

We describe work carried out within our group to explore new transition metal and main group nitride phases synthesized using high pressure–high temperature techniques using X-ray diffraction and spectroscopy at synchrotron sources in the USA, UK and France to establish their structures and physical properties. Along with previously published data, we also highlight additional results that have not been presented elsewhere and that represent new areas for further exploration. We also describe new work being carried out to explore the properties of carbon nitride materials being developed for energy applications and the nature of few-layered carbon nitride nanomaterials with atomically ordered structures that form solutions in polar liquids via thermodynamically driven exfoliation.This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
CoolBox: a interactive genomic data explorer for Jupyter Notebook
Authors: Xu Weize , Lin Da , Hong Ping , Yi Liang , Tyagi Rohit , Li Guoliang , Cao Gang 
Published: April 2019

AbstractSummaryCoolBox is a Python package for interactive genomic data exploration based on Jupyter notebook. It provides a ggplot2-like Application Programming Interface (API) for genomic data visualization, and a Jupyter/ipywidgets based Graphical User Interface (GUI) for interactive data exploration. CoolBox is a versatile multi-omics explorer supporting most types of data formats generated by various sequencing technologies like RNA-Seq, ChIP-Seq, ChIA-PET and Hi-C.Availability and implementationCoolBox is purely implemented with Python, and the GUI widget in Jupyter notebook is based on the ipywidgets package. It is open-source and available under GPLv3 license at https://github.com/GangCaoLab/CoolBox.
FIREcaller: Detecting Frequently Interacting Regions from Hi-C Data
Authors: Crowley Cheynna , Yang Yuchen , Qiu Yunjiang , Hu Benxia , Abnousi Armen , Lipiński Jakub , Plewczyński Dariusz , Wu Di , Won Hyejung , Ren Bing , Hu Ming , Li Yun 
Published: April 2019

AbstractHi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https://yunliweb.its.unc.edu/FIREcaller.Highlights– Frequently Interacting Regions (FIREs) can be used to identify tissue and cell-type-specific cis-regulatory regions.– An R software, FIREcaller, has been developed to identify FIREs and clustered FIREs into super-FIREs.
The guanine nucleotide exchange factor GBF1 participates in rotavirus replication
Authors: Martínez José L. , Arnoldi Francesca , Schraner Elisabeth M. , Eichwald Catherine , Silva-Ayala Daniela , Lee Eunjoo , Sztul Elizabeth , Burrone Óscar R. , López Susana , Arias Carlos F. 
Published: April 2019

ABSTRACTCellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference, or inhibiting its activity by treatment with Brefeldin A (BFA) or Golgicide A (GCA) significantly reduce the yield of infectious viral progeny. This reduction in virus yield was related to a block in virus assembly since in the presence of either BFA or GCA the assembly of infectious mature triple-layered virions was significantly prevented and only doubled layered-particles were detected. We report that the catalytic activity of GBF1, but not the activation of Arf1, is essential for the assembly of the outer capsid of rotavirus. We show that both BFA and GCA, as well as interfering with the synthesis of GBF1, alter the electrophoretic mobility of glycoproteins VP7 and NSP4 and block the trimerization of the virus surface VP7, a step required for its incorporation into virus particles. Although a post-translational modification of VP7 (other than glycosylation) could be related to the lack of trimerization, we found that NSP4 might also be involved in this process, since knocking-down its expression reduces VP7 trimerizarion. In support, recombinant VP7 protein overexpressed in transfected cells formed trimers only when co-transfected with NSP4.IMPORTANCERotavirus, a member of the family Reoviridae, is the major cause of severe diarrhea in children and young animals worldwide. Despite the significant advances in the characterization of the biology of this virus, the mechanisms involved in morphogenesis of the virus particle are still poorly understood. In this work, we show that the guanine nucleotide exchange factor GBF1, relevant for the COPI/Arf1-mediated cellular vesicular transport, participates in the replication cycle of the virus, influencing the correct processing of viral glycoproteins VP7 and NSP4, and the assembly of the virus surface proteins VP7 and VP4.
Functional effects of variation in transcription factor binding highlight long-range gene regulation by epromoters
Authors: Mitchelmore Joanna , Grinberg Nastasiya , Wallace Chris , Spivakov Mikhail 
Published: April 2019

AbstractIdentifying DNA cis-regulatory modules (CRMs) that control the expression of specific genes is crucial for deciphering the logic of transcriptional control. Natural genetic variation can point to the possible gene regulatory function of specific sequences through their allelic associations with gene expression. However, comprehensive identification of causal regulatory sequences in brute-force association testing without incorporating prior knowledge is challenging due to limited statistical power and effects of linkage disequilibrium. Sequence variants affecting transcription factor (TF) binding at CRMs have a strong potential to influence gene regulatory function, which provides a motivation for prioritising such variants in association testing. Here, we generate an atlas of CRMs showing predicted allelic variation in TF binding affinity in human lymphoblastoid cell lines (LCLs) and test their association with the expression of their putative target genes inferred from Promoter Capture Hi-C and immediate linear proximity. We reveal over 1300 CRM TF-binding variants associated with target gene expression, the majority of them undetected with standard association testing. A large proportion of CRMs showing associations with the expression of genes they contact in 3D localise to the promoter regions of other genes, supporting the notion of ‘epromoters’: dual-action CRMs with promoter and distal enhancer activity.
Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age
Authors: Willis Kent A. , Purvis John H. , Myers Erin D. , Aziz Michael M. , Karabayir Ibrahim , Gomes Charles K. , Peters Brian M. , Akbilgic Oguz , Talati Ajay J. , Pierre Joseph F. 
Published: April 2019

AbstractFungal and bacterial commensal organisms play a complex role in the health of the human host. Expansion of commensal ecology after birth is a critical period in human immune development. However, the initial fungal colonization of the primordial gut remains undescribed. To investigate primordial fungal ecology, we performed amplicon sequencing and culture-based techniques of first-pass meconium, which forms in the fetal intestine prior to birth, from a prospective observational cohort of term-born and preterm newborns. Here, we describe fungal ecologies in the primordial gut that develop complexity with advancing gestational age at birth. Our findings suggest homeostasis of fungal commensals may represent an important aspect of human biology present even before birth. Unlike bacterial communities which gradually develop complexity, the domination of the fungal communities of some preterm infants by Saccromycetes, specificallyCandida, may suggest a pathologic association with preterm birth.
Hairless as a novel component of the Notch signaling pathway
Authors: Miller Steven W , Movsesyan Artem , Zhang Sui , Fernández Rosa , Posakony James W 
Published: April 2019

AbstractSuppressor of Hairless [Su(H)], the transcription factor at the end of the Notch pathway in Drosophila, utilizes the Hairless protein to recruit two co-repressors, Groucho (Gro) and C-terminal Binding Protein (CtBP), indirectly. Hairless is present only in the Pancrustacea, raising the question of how Su(H) in other protostomes gains repressive function. We show that Su(H) from a wide array of arthropods, molluscs, and annelids includes motifs that directly bind Gro and CtBP; thus, direct co-repressor recruitment is ancestral in the protostomes. How did Hairless come to replace this ancestral paradigm? Our discovery of a protein (S-CAP) in Myriapods and Chelicerates that contains a motif similar to the Su(H)-binding domain in Hairless has revealed a likely evolutionary connection between Hairless and Metastasis-associated (MTA) protein, a component of the NuRD complex. Sequence comparison and widely conserved microsynteny suggest that S–CAP and Hairless arose from a tandem duplication of an ancestral MTA gene.
Pollen tube-triggered accumulation of NORTIA at the filiform apparatus facilitates fertilization inArabidopsis thaliana
Authors: Yuan Jing , Ju Yan , Jones Daniel S. , Zhang Weiwei , Lucca Noel , Staiger Christopher J. , Kessler Sharon A. 
Published: April 2019

AbstractDuring gamete delivery inArabidopsis thaliana, intercellular communication between the attracted pollen tube and the receptive synergid cell leads to subcellular events in both cells culminating in the rupture of the tip-growing pollen tube and release of the sperm cells to achieve double fertilization. Live imaging of pollen tube reception revealed dynamic subcellular changes that occur in the female synergid cells. Pollen tube arrival triggers the trafficking of NORTIA (NTA) MLO protein from Golgi-associated compartments and the accumulation of endosomes at or near the synergid filiform apparatus, a membrane-rich region that acts as the site of communication between the pollen tube and synergids. Domain swaps and site-directed mutagenesis reveal that NTA’s C-terminal cytoplasmic tail with its calmodulin-binding domain influences the subcellular localization and function of NTA in pollen tube reception and that accumulation of NTA at the filiform apparatus is necessary and sufficient for MLO function in pollen tube reception.
Dysmorphic neuron density underlies intrinsic epileptogenicity of the centre of cortical tubers
Authors: Stephenson Sarah EM. , Owens Harley G. , Richards Kay L. , Lee Wei Shern , D’Arcy Colleen , Barton Sarah , Mandelstam Simone A. , Maixner Wirginia J. , MacGregor Duncan , Petrou Steven , Lockhart Paul J. , Harvey A. Simon , Leventer Richard J. 
Published: April 2019

AbstractCortical tubers are benign lesions that develop in patients with tuberous sclerosis complex (TSC), often resulting in drug-resistant epilepsy. Surgical resection may be required for seizure control, but the extent of the resection required is unclear. Many centres include resection of perituberal cortex, which may be associated with neurological deficits. Also, patients with tubers in eloquent cortex may be excluded from epilepsy surgery.Our electrophysiological and MRI studies indicate that the tuber centre is the source of seizures, suggesting that smaller resections may be sufficient for seizure control. Here we report five epilepsy surgeries in four children with TSC and focal motor seizures from solitary epileptogenic tubers in the sensorimotor cortex in whom the resection was limited to the tuber centre, leaving the tuber rim and surrounding perituberal cortex intact. Seizures were eliminated in all cases, and no functional deficits were observed. On routine histopathology we observed an apparent increase in density of dysmorphic neurons at the tuber centre, which we confirmed using unbiased stereology which demonstrated a significantly greater density of dysmorphic neurons within the resected tuber centre (1951 ± 215 cells/mm3) compared to the biopsied tuber rim (531 ± 189 cells/mm3, n = 4, p = 0.008).Taken together with our previous electrophysiological and MRI studies implicating the tuber centre as the focus of epileptic activity, and other electrophysiological studies of dysmorphic neurons in focal cortical dysplasia, this study supports the hypothesis that dysmorphic neurons concentrated at the tuber centre are the seizure generators in TSC. Furthermore, our results support limiting resection to the tuber centre, decreasing the risk of neurological deficits when tubers are located within eloquent cortex.
Automated quantification of small vessel disease brain changes on MRI predicts cognitive and functional decline
Authors: Jokinen Hanna , Koikkalainen Juha , Laakso Hanna M. , Melkas Susanna , Nieminen Tuomas , Brander Antti , Korvenoja Antti , Rueckert Daniel , Barkhof Frederik , Scheltens Philip , Schmidt Reinhold , Fazekas Franz , Madureira Sofia , Verdelho Ana , Wallin Anders , Wahlund Lars-Olof , Waldemar Gunhild , Chabriat Hugues , Hennerici Michael , O’Brien John , Inzitari Domenico , Lötjönen Jyrki , Pantoni Leonardo , Erkinjuntti Timo 
Published: April 2019

ABSTRACTBackground and purposeCerebral small vessel disease (SVD) is characterized by a wide range of focal and global brain changes. We used automated MRI segmentation to quantify multiple types of SVD brain changes and examined their individual and combined predictive value on cognitive and functional abilities.MethodsMRI scans of 560 subjects of the Leukoaraiosis and Disability Study (LADIS) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities (WMH), lacunes, cortical infarcts, enlarged perivascular spaces and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years.ResultsThe strongest predictors of cognitive performance and functional outcome over time were total volumes of WMH, grey matter (GM) and hippocampi (p<0.001 for global cognitive function, processing speed, executive functions and memory; and p<0.001 for poor functional outcome). Volumes of lacunes, cortical infarcts and EVPS were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of WMH, lacunes, GM and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on z-scores strongly predicted cognitive and functional outcomes (p<0.001) even above the contribution of the individual brain changes.ConclusionsGlobal burden of SVD-related brain changes as quantified by automated image segmentation is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of WMH, lacunar, GM and hippocampal volumes could be used as an imaging identification model of vascular cognitive impairment.
Visualizing movements inE. coliF1FoATP synthase indicates how the F1and Fomotors are coupled
Authors: Sobti Meghna , Walshe James L. , Ishmukhametov Robert , Stewart Alastair G. 
Published: April 2019

AbstractF1FoATP synthase functions as a biological rotary generator and makes a major contribution to cellular energy production. It is comprised of two motors that are coupled together by a central “rotor” and peripheral “stator” stalk. Proton flow through the Fomotor generates rotation of the central stalk that induces conformation changes that catalyze production of ATP in the F1motor. Here we provide 3-4 Å resolution cryo-EM structures ofE. coliF1FoATP synthase in 10 mM MgADP. In addition to generating a comprehensive structural model ofE. coliF1FoATP synthase to provide a framework to interpret mutagenesis studies, we describe a rotational sub-step of the Fomotorc-ring associated with long-range conformational changes that suggests an elegant mechanism by which the F1and Fomotors can be coupled with minimal energy loss.