bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insight into the Pathophysiologic Mechanisms behind Cognitive Dysfunction in Trigonocephaly
Authors: van der Vlugt Joris J. B. , van der Meulen Jacques J. M. N. , van den Braak Robert R. J. Coebergh , Vermeij-Keers Christl , Horstman Edwin G. C. , Hovius Steven E. R. , Verhulst Frank C. , Wierdsma André I. , Lequin Maarten H. , Okkerse Jolanda M. E. 
Published: March 2017

Background:
The relationship between trigonocephaly and cognitive problems might be explained by: secondary mechanical factors related to growth restriction of the skull, and primary structural defects caused by a shared mechanism related to brain developmental disorder(s) and skull malformation. However, because the exact pathophysiology remains unknown, we examined the pathophysiologic mechanisms behind cognitive dysfunction in patients with trigonocephaly, with an aim of providing a model for cognitive dysfunction based on routinely available variables.

Methods:
Included were 72 patients with trigonocephaly who were operated on. Postoperatively, intelligence was assessed prospectively. The two independent variables, secondary mechanical and primary brain developmental mechanisms, were evaluated retrospectively. Computed tomographic imaging was used to assess skull volume and severity of the frontal stenosis (secondary mechanical factors), width of the central part of the lateral ventricles, and other structural brain anomalies (primary brain developmental factors). Extracranial congenital anomalies were also taken into account.

Results:
No association was found between secondary mechanical factors and postoperative IQ score. Width of the central part of the lateral ventricles, and an interaction effect between this width and additional extracranial anomalies, showed a significant negative association with postoperative IQ.

Conclusions:
Primary brain developmental disorders seem to play an important role in the development of cognitive problems in trigonocephaly. Assessment of width of the central part of the lateral ventricle scores and additional extracranial congenital anomalies for the early prediction of cognitive problems in patients with trigonocephaly could be clinically valuable and can be performed using routinely available tools.
First Female-to-Male Facial Confirmation Surgery with Description of a New Procedure for Masculinization of the Thyroid Cartilage (Adam’s Apple)
Authors: Deschamps-Braly Jordan C. , Sacher Caitlin L. , Fick Jennifer , Ousterhout Douglas K. 
Published: March 2017

Summary:
Although male-to-female transgender patients commonly seek facial feminization surgery, facial masculinization surgery in the female-to-male transgender population is unreported in the literature. This report documents the first known female-to-male facial masculinization surgery, including a new technique for creating an “Adam’s apple” to enhance the facial masculine appearance of a natal female. The authors “reversed” the methods typically used to feminize male facial features, and modified the forehead, nose, and chin to masculinize the patient’s natal female facial features. The authors devised a novel technique to augment the thyroid cartilage using autologous rib cartilage to create a visible Adam’s apple. Initially, masculinization of the chin was accomplished with a multisegment chin osteotomy with grafts to vertically expand and widen the chin along with correcting pronounced microgenia. Subsequently, a second facial masculinization procedure was performed to masculinize the forehead, nose, and thyroid cartilage. Rib cartilage was harvested and carved into an appropriately shaped thyroid cartilage onlay graft and then attached and integrated with the native thyroid cartilage, creating a fully mobile cartilage that translocates up and down with swallowing and a visible Adam’s apple. Previously described techniques to masculinize the facial features of natal male patients were adapted to masculinize the female-to-male patient. Those procedures were combined with the novel technique to create a visually perceptible and naturally mobile Adam’s apple in the female-to-male transsexual patient. Collectively, these described procedures can now provide most female-to-male transsexual patients with a satisfying transformation of their facial features.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation
Authors: Shammas Ronnie L. , Fales Andrew M. , Crawford Bridget M. , Wisdom Amy J. , Devi Gayathri R. , Brown David A. , Vo-Dinh Tuan , Hollenbeck Scott T. 
Published: March 2017

Background:
Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics.

Methods:
To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy. The effects of gold nanostars on cell phenotype, proliferation, and viability were assessed with flow cytometry, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide metabolic assay, and trypan blue, respectively. Trilineage differentiation of gold nanostar–labeled adipose-derived stem cells was induced with the appropriate media. Photothermolysis was performed on adipose-derived stem cells cultured alone or in co-culture with SKBR3 cancer cells.

Results:
Efficient uptake of gold nanostars occurred in adipose-derived stem cells, with persistence of the luminescent signal over 4 days. Labeling efficiency and signal quality were greater than with Qtracker. Gold nanostars did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the gold nanostar–labeled adipose-derived stem cells were observed following photothermolysis in both monoculture and co-culture models.

Conclusions:
Gold nanostars effectively label adipose-derived stem cells without altering cell phenotype. Once labeled, photoactivation of gold nanostar–labeled adipose-derived stem cells ablates neighboring cancer cells, demonstrating the potential of adipose-derived stem cells as a vehicle for the delivery of site-specific cancer therapy.
Moderate-Intensity Intermittent External Volume Expansion Optimizes the Soft-Tissue Response in a Murine Model
Authors: Giatsidis Giorgio , Cheng Liying , Facchin Federico , Haddad Anthony , Lujan-Hernandez Jorge , Lancerotto Luca , Nabzdyk Christoph Gunther , Matsumine Hajime , Orgill Dennis P. 
Published: March 2017

Background:
Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential.

Methods:
Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i.e., single-application control, low-intensity, moderate-intensity, and two groups of high-intensity). Five days after the final stimulation, skin biopsy specimens were obtained from stimulated and contralateral nonstimulated areas. Microscopic sections were analyzed for angiogenesis, skin remodeling, and adipogenesis.

Results:
Moderate-intensity intermittent stimulation (0.5 hour, 6 times/day for 5 days at −25 mmHg suction) almost doubled cutaneous vascular density (1.9-fold increase), induced skin thickening (1.9-fold increase), and expanded the subcutaneous tissue (2.3-fold increase) compared with control. External volume expansion kinetics did not affect tissue inflammation at 5 days after treatment. High-intensity intermittent stimulations also increased the density of blood vessels (1.6-fold increase compared with controls) but caused tissue damage, whereas low-intensity external volume expansion did not induce significant changes.

Conclusion:
Application of moderate-intensity intermittent external volume expansion optimizes induction of angiogenesis and adipogenesis in soft tissues without tissue damage, holding potential for time-effective recipient-site preconditioning before fat grafting.
Acellular Hypothermic Extracorporeal Perfusion Extends Allowable Ischemia Time in a Porcine Whole Limb Replantation Model
Authors: Kueckelhaus Maximilian , Dermietzel Alexander , Alhefzi Muayyad , Aycart Mario A. , Fischer Sebastian , Krezdorn Nicco , Wo Luccie , Maarouf Omar H. , Riella Leonardo V. , Abdi Reza , Bueno Ericka M. , Pomahac Bohdan 
Published: March 2017

Background:
One of the major challenges in traumatic amputation is the need to keep ischemia time brief (4 to 6 hours) to avoid ischemic damage and enable successful replantation. The current inability to meet this challenge often leads to traumatic limb loss, which has a considerable detrimental impact on the quality of life of patients.

Methods:
The authors’ team built a portable extracorporeal membrane oxygenator device for the perfusion of amputated extremities with oxygenated acellular solution under controlled parameters. The authors amputated forelimbs of Yorkshire pigs, perfused them ex vivo with acellular Perfadex solution for 12 hours at 10°C in their device, and subsequently replanted them into the host animal. The authors used limbs stored on ice slurry for 4 hours before replantation as their control group.

Results:
Clinical observation and histopathologic evaluation both demonstrated that there was less morbidity and less tissue damage to the cells during preservation and after replantation in the perfusion group compared with the standard of care. Significant differences in blood markers of muscle damage and tissue cytokine levels underscored these findings.

Conclusions:
The authors demonstrated the feasibility and superiority of ex vivo hypothermic oxygenated machine perfusion for preservation of amputated limbs over conventional static cold storage and herewith a substantial extension of the allowable ischemia time for replantation after traumatic amputation. This approach could also be applied to the field of transplantation, expanding the potential pool of viable donor vascularized composite allografts.
The Combination of Tissue Dissection and External Volume Expansion Generates Large Volumes of Adipose Tissue
Authors: He Yunfan , Dong Ziqing , Xie Gan , Zhou Tao , Lu Feng 
Published: March 2017

Background:
Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue.

Method:
In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control.

Results:
In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation.

Conclusions:
Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.
Current Concepts in the Surgical Management of Lymphedema
Authors: Kung Theodore A. , Champaneria Manish C. , Maki Jeffrey H. , Neligan Peter C. 
Published: March 2017

Learning Objectives:After studying this article, the participant should be able to: 1. Discuss the key points in diagnosing lymphedema. 2. Understand the imaging modalities that facilitate diagnosis and surgical planning. 3. Appreciate the indications for both physiologic and ablative procedures. 4. Recognize the potential role of lymphaticovenular anastomosis and vascularized lymph node transfer in the treatment of patients with lymphedema.Summary:Lymphedema is an incurable disease caused by insufficient lymphatic drainage leading to abnormal accumulation of interstitial fluid within the soft tissues. Although this condition may result from a primary structural defect of the lymphatic system, most cases in developed countries are secondary to iatrogenic causes. The diagnosis of lymphedema can be made readily by performing a clinical history and physical examination and may be confirmed by imaging studies such as lymphoscintigraphy, magnetic resonance lymphangiography, or indocyanine green lymphangiography. Nonsurgical treatment continues to be the mainstay of lymphedema management. However, advances in microsurgical techniques have revolutionized surgical options for treating lymphedema, and emerging evidence suggests that reconstructive methods may be performed to restore lymphatic flow. Procedures such as lymphaticovenular anastomosis and vascularized lymph node transfer can potentially offer a more permanent solution to chronic lymphedema, and initial studies have demonstrated promising results.
Direct-to-Implant Breast Reconstruction without the Use of an Acellular Dermal Matrix Is Cost Effective and Oncologically Safe
Authors: Serrurier L. Charles. J. , Rayne Sarah , Venter Marisse , Benn Carol-Ann 
Published: March 2017

Background:
Direct-to-implant breast reconstruction is a predictable, reliable, and cost-effective reconstruction. Most units performing direct-to-implant reconstructions recommend the use of an acellular dermal matrix or a mesh to reinforce the lower pole of the breast reconstruction.

Methods:
Two hundred seventy-two consecutive patients with 488 immediate direct-to-implant breast reconstructions performed in a 34-month period are included in this group. Mean follow-up of this group is 35 months.

Results:
Four hundred eight reconstructions were performed through a lazy-S mastectomy, and 80 were performed through a Wise pattern mastectomy. Two local recurrences occurred. Minor complications accounted for 5.5 percent (n = 27): seromas, 3.4 percent (n = 17); wound healing problems, 0.6 percent (n = 3); and grade 2 capsular contracture, 1.4 percent (n = 7). Major complications accounted for 4.3 percent (n = 21): infection, 0.8 percent (n = 4); prosthetic loss, 0.4 percent (n = 2); hematoma, 0.4 percent (n = 2); and wounds requiring débridement, 2 percent (n = 10). The additional cost of acellular dermal matrix is dependent on manufacturer and size, but increases the cost of the procedure by 35.5 to 47.7 percent.

Conclusions:
This reconstruction method compares very favorably with published data from other units as far as early and late complications and cosmetic outcome are concerned. It has a complication rate similar to that of reconstructions using an acellular dermal matrix and is more cost effective.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Response of microbial community function to fluctuating geochemical conditions within a legacy radioactive waste trench environment
Authors: Vázquez-Campos Xabier , Kinsela Andrew S. , Bligh Mark W. , Harrison Jennifer J. , Payne Timothy E. , Waite T. David 
Published: March 2017

AbstractDuring the 1960s, small quantities of radioactive materials were co-disposed with chemical waste at the Little Forest Legacy Site (Sydney, Australia) in three-metre-deep, unlined trenches. Chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a six-week period immediately after a prolonged rainfall event to assess how changing water levels impact upon the microbial ecology and contaminant mobility. Collectively, results demonstrated that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solid-iron-associated species immediately after the initial rainwater pulse, to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the potentially important role that the taxonomically-diverse microbial community played in this transition. In particular, aerobes dominated in the first day followed by an increase of facultative anaerobes/denitrifiers at day four. Towards the mid-end of the sampling period, the functional and taxonomic profiles depicted an anaerobic community distinguished by a higher representation of dissimilatory sulfate reduction and methanogenesis pathways. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs.ImportanceThe role of chemical and microbiological factors in mediating the biogeochemistry of groundwaters from trenches used to dispose of radioactive materials during the 1960s is examined in this study. Specifically, chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a six-week period immediately after a prolonged rainfall event to assess how changing water levels influence microbial ecology and contaminant mobility.Results demonstrate that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solidiron-associated species immediately after the initial rainwater pulse, to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the important role that the taxonomically-diverse microbial community played in this transition. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs.
Integrating patient and whole genome sequencing data to provide insights into the epidemiology of seasonal influenza A(H3N2) viruses
Authors: Goldstein Emily J. , Harvey William T. , Wilkie Gavin S. , Shepherd Samantha J. , MacLean Alasdair R. , Murcia Pablo R. , Gunson Rory N. 
Published: March 2017

AbstractGenetic surveillance of seasonal influenza is largely focused upon sequencing of the haemagglutinin gene. Consequently, our understanding of the contribution of the remaining seven gene segments to the evolution and epidemiological dynamics of seasonal influenza is relatively limited. The increased availability of next generation sequencing technologies allows rapid and economic whole genome sequencing (WGS). Here, 150 influenza A(H3N2) positive clinical specimens with linked epidemiological data, from the 2014/15 season in Scotland, were sequenced directly using both Sanger sequencing of the HA1 region and WGS using the Illumina MiSeq platform. Sequences generated by both methods were highly consistent and WGS provided on average >90% whole genome coverage. As reported in other European countries during 2014/15, all strains belonged to genetic group 3C, with subgroup 3C.2a predominating. Inter-subgroup reassortants were identified (9%), including three 3C.3 viruses descended from a single reassortment event, which had persisted in the population. Significant phylogenetic associations with cases of severe acute respiratory illness observed herein warrant further investigation. Severe cases were also more likely to be associated with reassortant viruses (odds ratio: 4.4 (1.3-15.5)) and occur later in the season. These results suggest that increased levels of WGS, linked to clinical and epidemiological data, could improve influenza surveillance.
Transient network synchrony of the developing medial entorhinal cortex
Authors: Dawitz Julia , Hjorth J.J. Johannes , Kroon Tim , Ruiperez-Alonso Marta , Chandrasekhar Nandakumar , Hartung Henrike , Hanganu-Opatz Ileana L. , Mansvelder Huibert D. , Meredith Rhiannon M. 
Published: March 2017

AbstractThe medial entorhinal cortex (MEC) contains a variety of specialized spatially-tuned neurons whose properties emerge during the third postnatal week onwards in rodents. How neuronal networks underlying the spatial firing patterns are formed is largely unknown but they are hypothesized to develop from topographic modules of synchronized neurons in superficial MEC. Here, we show that developing MEC neuronal networks in the second postnatal week are synchronously active in spatially-grouped modules. Network synchrony is intrinsic to MEC and desynchronized just prior to the emergence of spatially-tuned firing properties. The MEC network is modulated but not driven by the immature hippocampus and is tightly-coupled to neighboring neocortical networks. Unlike hippocampal networks, developing modules are dominated by glutamatergic excitation rather than GABAergic inhibition. Our results demonstrate that intrinsically synchronous modules exist in immature MEC: these may play a key role in establishing and organizing circuitry necessary for spatially-tuned firing properties of MEC neurons.
DNA methylation as a marker for prenatal smoke exposure in adults
Authors: Richmond R.C. , Suderman M. , Langdon R. , Relton C.L. , Davey Smith G. 
Published: March 2017

AbstractPrenatal cigarette smoke is an environmental stressor that has a profound effect on DNA methylation in the exposed offspring. We have previously shown that some of these effects persist throughout childhood and into adolescence. Of interest is whether these signals persist into adulthood.We conducted an analysis to investigate associations between reported maternal smoking in pregnancy and DNA methylation in peripheral blood of women in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=754; mean age 30 years). We observed associations at 15 CpG sites in 11 gene regions,MYO1G, FRMD4A, CYP1A1, CNTNAP2, ARL4C, AHRR, TIFAB, MDM4, AX748264, DRD1, FTO(FDR < 5%). All but two of these CpG sites have previously been identified in relation to prenatal smoke exposure in the offspring at birth and the majority showed persistent hypermethylation among the offspring of smokers.We confirmed that most of these associations were not driven by own smoking and that they were still present 18 years later (N = 656; mean age 48 years). In addition, we replicated findings of a persistent methylation signal related to prenatal smoke exposure in peripheral blood among men in the ALSPAC cohort (N = 230; mean age 53 years). For both participant groups, there was a strong signal of association above that expected by chance at CpG sites previously associated with prenatal smoke exposure in newborns (Wilcoxon rank sum p-value < 2.2 × 10−4). Furthermore, we found that a prenatal smoking score, derived by combining methylation values at these CpG sites, could predict whether the mothers of the ALSPAC women smoked during pregnancy with an AUC 0.69 (95% 0.67, 0.73).