Suction assisted liposuction does not impair the regenerative potential of adipose derived stem cells
JOURNAL OF TRANSLATIONAL MEDICINE
Adipose-derived stem cells (ASCs) have been identified as a population of multipotent cells with promising applications in tissue engineering and regenerative medicine. ASCs are abundant in fat tissue, which can be safely harvested through the minimally invasive procedure of liposuction. However, there exist a variety of different harvesting methods, with unclear impact on ASC regenerative potential. The aim of this study was thus to compare the functionality of ASCs derived from the common technique of suction-assisted lipoaspiration (SAL) versus resection.Human adipose tissue was obtained from paired abdominoplasty and SAL samples from three female donors, and was processed to isolate the stromal vascular fraction. Fluorescence-activated cell sorting was used to determine ASC yield, and cell viability was assayed. Adipogenic and osteogenic differentiation capacity were assessed in vitro using phenotypic staining and quantification of gene expression. Finally, ASCs were applied in an in vivo model of tissue repair to evaluate their regenerative potential.SAL specimens provided significantly fewer ASCs when compared to excised fat tissue, however, with equivalent viability. SAL-derived ASCs demonstrated greater expression of the adipogenic markers FABP-4 and LPL, although this did not result in a difference in adipogenic differentiation. There were no differences detected in osteogenic differentiation capacity as measured by alkaline phosphatase, mineralization or osteogenic gene expression. Both SAL- and resection-derived ASCs enhanced significantly cutaneous healing and vascularization in vivo, with no significant difference between the two groups.SAL provides viable ASCs with full capacity for multi-lineage differentiation and tissue regeneration, and is an effective method of obtaining ASCs for cell-based therapies.
View details for DOI 10.1186/s12967-016-0881-1
View details for Web of Science ID 000375475200004
View details for PubMedID 27153799
View details for PubMedCentralID PMC4859988
Effects of A Novel Decision Aid for Breast Reconstruction: A Randomized Prospective Trial.
Annals of plastic surgery
2016; 76: S249-54
The choice to undergo mastectomy and breast reconstruction is a highly personal decision with profound psychosocial effects, and ultimately, the decision between implant- and autologous tissue-based reconstruction should be made based on a combination of factual information and the patient's personal values and preferences. Unfortunately, patients undergoing breast reconstruction surgery may experience decision regret. Decision aids promote patient involvement in decision making by not only providing standard information about options, but also emphasizing comparative risks, benefits, and alternatives, and most importantly by providing clarification exercises regarding personal values to guide patients toward an individualized decision.We developed a novel decision aid to provide decision support and structured guidance for prosthetic, autologous, and combined prosthetic-autologous breast reconstruction surgery. New breast reconstruction patients of one surgeon at our institution were randomized by week to either receive the decision aid or standard preconsultation material. Immediately preceding their new patient consultation clinic visit, patients were asked to complete the validated Decisional Conflict Scale and the BREAST-Q Preoperative survey. After 3 to 5 months following breast mound reconstruction, patients were asked to complete the Decision Regret Scale, BREAST-Q Postoperative survey, and the Hospital Anxiety and Depression Scale.Patients who received the decision aid demonstrated a trend toward decreased preoperative decisional conflict (mean of 13.3 ± 5.5, compared to 26.2 ± 4.2; n = 8 per group, P = 0.069), with similar preoperative BREAST-Q scores. Most patients desired to know "everything" regarding their reconstruction surgery (75%), and to be "very involved" in the decisions in their care (81%), with remaining patients wanting to know "as much as I need to be prepared" and to be "somewhat involved." Postoperatively, patients who received the decision aid demonstrated significantly less decision regret (P < 0.001), although there was no significant difference in anxiety, depression, or quality of life-related outcomes as measured by the BREAST-Q.The use of decision aids in breast reconstruction surgery may help decrease decisional conflict and regret through promoting improved information sharing and shared decision making, which are highly important in this particular setting, patient population, and in our move toward greater patient-centered care.
View details for DOI 10.1097/SAP.0000000000000722
View details for PubMedID 27070681
Superior Gluteal Artery Perforator Flap: The Beauty of the Buttock.
Annals of plastic surgery
2016; 76: S191-5
The superior gluteal artery perforator (SGAP) flap is a useful technique for breast reconstruction. This perforator flap allows for the transfer of the patient's own skin and subcutaneous tissue with minimal donor-site morbidity. Despite its usefulness, the SGAP flap is not widely used among reconstructive surgeons. The challenging perforator dissection and need for microsurgery may contribute to the reluctant use of the flap by many reconstructive surgeons. The ability to perform a single-stage breast reconstruction with buttock tissue when abdominal or thigh tissue are unavailable provides a significant service to the patient desiring an autologous breast reconstruction.The authors performed a retrospective review and outcomes analysis of a single surgeon's surgical technique and experience. Consecutive patients, who underwent SGAP flaps for breast reconstruction during a 7-year period from 2007 to 2014, were compared to a matched cohort of consecutive patients undergoing deep inferior epigastric perforator (DIEP) flaps and clinical outcomes were analyzed.Thirteen patients underwent SGAP flap breast reconstruction for a total of 16 flaps during the study period compared to 34 consecutive DIEP flaps for breast reconstruction. There was no significant difference in flap or donor-site complications between the 2 groups. There was no statistically significant difference between the average operative time for unilateral breast reconstruction in the SGAP and DIEP flap groups. In 4 patients, a bipedicled SGAP flap was used due to perforator anatomy. All SGAP patients returned to full activity. Average follow-up time was 1 year.Although utilization of buttock tissue for breast reconstruction can be challenging and requires microsurgical expertise, in the hands of experienced microsurgeons the SGAP flap is a safe and reliable option for autologous breast reconstruction with minimal donor-site morbidity and excellent aesthetic results.
View details for DOI 10.1097/SAP.0000000000000723
View details for PubMedID 26808742
Cell-Assisted Lipotransfer Improves Volume Retention in Irradiated Recipient Sites and Rescues Radiation-Induced Skin Changes
2016; 34 (3): 668-673
Radiation therapy is not only a mainstay in the treatment of many malignancies but also results in collateral obliteration of microvasculature and dermal/subcutaneous fibrosis. Soft tissue reconstruction of hypovascular, irradiated recipient sites through fat grafting remains challenging; however, a coincident improvement in surrounding skin quality has been noted. Cell-assisted lipotransfer (CAL), the enrichment of fat with additional adipose-derived stem cells (ASCs) from the stromal vascular fraction, has been shown to improve fat volume retention, and enhanced outcomes may also be achieved with CAL at irradiated sites. Supplementing fat grafts with additional ASCs may also augment the regenerative effect on radiation-damaged skin. In this study, we demonstrate the ability for CAL to enhance fat graft volume retention when placed beneath the irradiated scalps of immunocompromised mice. Histologic metrics of fat graft survival were also appreciated, with improved structural qualities and vascularity. Finally, rehabilitation of radiation-induced soft tissue changes were also noted, as enhanced amelioration of dermal thickness, collagen content, skin vascularity, and biomechanical measures were all observed with CAL compared to unsupplemented fat grafts. Supplementation of fat grafts with ASCs therefore shows promise for reconstruction of complex soft tissue defects following adjuvant radiotherapy. Stem Cells 2016;34:668-673.
View details for DOI 10.1002/stem.2256
View details for Web of Science ID 000372552600013
Enrichment of Adipose-Derived Stromal Cells for BMPR1A Facilitates Enhanced Adipogenesis
TISSUE ENGINEERING PART A
2016; 22 (3-4): 214-221
Reconstruction of soft tissue defects has traditionally relied on the use of grafts and flaps, which may be associated with variable resorption and/or significant donor site morbidity. Cell-based strategies employing adipose-derived stromal cells (ASCs), found within the stromal vascular fraction (SVF) of adipose tissue, may offer an alternative strategy for soft tissue reconstruction. In this study, we investigated the potential of a bone morphogenetic protein receptor type 1A (BMPR1A)(+) subpopulation of ASCs to enhance de novo adipogenesis.Human lipoaspirate was enzymatically digested to isolate SVF and magnetic-activated cell separation was utilized to obtain BMPR1A(+) and BMPR1A(-) cells. These cells, along with unenriched cells, were expanded in culture and evaluated for adipogenic gene expression and in vitro adipocyte formation. Cells from each group were also labeled with a green fluorescent protein (GFP) lentivirus and transplanted into the inguinal fat pads, an adipogenic niche, of immunocompromised mice to determine their potential for de novo adipogenesis. Confocal microscopy along with staining of lipid droplets and vasculature was performed to evaluate the formation of mature adipocytes by transplanted cells.In comparison to BMPR1A(-) and unenriched ASCs, BMPR1A(+) cells demonstrated significantly enhanced adipogenesis when cultured in an adipogenic differentiation medium, as evidenced by increased staining with Oil Red O and increased expression of peroxisome proliferator-activating receptor gamma (PPAR-γ) and fatty acid-binding protein 4 (FABP4). BMPR1A(+) cells also formed significantly more adipocytes in vivo, as demonstrated by quantification of GFP+ adipocytes. Minimal formation of mature adipocytes was appreciated by BMPR1A(-) cells.BMPR1A(+) ASCs show an enhanced ability for adipogenesis in vitro, as shown by gene expression and histological staining. Furthermore, within an adipogenic niche, BMPR1A(+) cells possessed an increased capacity to generate de novo fat compared to BMPR1A(-) and unenriched cells. This suggests utility for the BMPR1A(+) subpopulation in cell-based strategies for soft tissue reconstruction.
View details for DOI 10.1089/ten.tea.2015.0278
View details for PubMedID 26585335
Ultrasound-Assisted Liposuction Does Not Compromise the Regenerative Potential of Adipose-Derived Stem Cells.
Stem cells translational medicine
2016; 5 (2): 248-257
Human mesenchymal stem cells (MSCs) have recently become a focus of regenerative medicine, both for their multilineage differentiation capacity and their excretion of proregenerative cytokines. Adipose-derived mesenchymal stem cells (ASCs) are of particular interest because of their abundance in fat tissue and the ease of harvest via liposuction. However, little is known about the impact of different liposuction methods on the functionality of ASCs. Here we evaluate the regenerative abilities of ASCs harvested via a third-generation ultrasound-assisted liposuction (UAL) device versus ASCs obtained via standard suction-assisted lipoaspiration (SAL). Lipoaspirates were sorted using fluorescent assisted cell sorting based on an established surface-marker profile (CD34+/CD31-/CD45-), to obtain viable ASCs. Yield and viability were compared and the differentiation capacities of the ASCs were assessed. Finally, the regenerative potential of ASCs was examined using an in vivo model of tissue regeneration. UAL- and SAL-derived samples demonstrated equivalent ASC yield and viability, and UAL ASCs were not impaired in their osteogenic, adipogenic, or chondrogenic differentiation capacity. Equally, quantitative real-time polymerase chain reaction showed comparable expression of most osteogenic, adipogenic, and key regenerative genes between both ASC groups. Cutaneous regeneration and neovascularization were significantly enhanced in mice treated with ASCs obtained by either UAL or SAL compared with controls, but there were no significant differences in healing between cell-therapy groups. We conclude that UAL is a successful method of obtaining fully functional ASCs for regenerative medicine purposes. Cells harvested with this alternative approach to liposuction are suitable for cell therapy and tissue engineering applications. Significance: Adipose-derived mesenchymal stem cells (ASCs) are an appealing source of therapeutic progenitor cells because of their multipotency, diverse cytokine profile, and ease of harvest via liposuction. Alternative approaches to classical suction-assisted liposuction are gaining popularity; however, little evidence exists regarding the impact of different liposuction methods on the regenerative functionality of ASCs. Human ASC characteristics and regenerative capacity were assessed when harvested via ultrasound-assisted (UAL) versus standard suction-assisted liposuction. ASCs obtained via UAL were of equal quality when directly compared with the current gold standard harvest method. UAL is an adjunctive source of fully functional mesenchymal stem cells for applications in basic research and clinical therapy.
View details for DOI 10.5966/sctm.2015-0064
View details for PubMedID 26702129
View details for PubMedCentralID PMC4729547
Flow-through omental flap to free anterolateral thigh flap for complex chest wall reconstruction: Case report and review of the literature.
2016; 36 (1): 70-76
Despite the options currently available for chest wall reconstruction, patients with complex composite defects may still pose a significant challenge for the reconstructive surgeon when only using conventional methods. In particular, prior radiotherapy and/or large en bloc resection may leave inadequate regional flaps and recipient vessels for free tissue transfer. Here, we describe a case in which we reconstruct a 14 cm × 18 cm complex chest wall defect, secondary to tumor resection and infected sternum debridement, with a pedicled flow-through omental flap to a 14 cm × 22 cm free anterolateral thigh flap using the omental gastroepiploic vessels as recipient vessels. Reconstruction was successful with excellent flap viability, and no complications at recipient or donor sites. We review the literature on complex chest wall reconstruction and introduce this valuable option of utilizing a pedicled omental flap as a flow-through flap to a free flap for patients without viable recipient vessels or local flaps.
View details for DOI 10.1002/micr.22444
View details for PubMedID 26140609
RNA Sequencing for Identification of Differentially Expressed Noncoding Transcripts during Adipogenic Differentiation of Adipose-Derived Stromal Cells.
Plastic and reconstructive surgery
2015; 136 (4): 752-763
Adipose-derived stromal cells represent a relatively abundant source of multipotent cells, with many potential applications in regenerative medicine. The present study sought to demonstrate the use of RNA sequencing in identifying differentially expressed transcripts, particularly long noncoding RNAs, associated with adipogenic differentiation to gain a clearer picture of the mechanisms responsible for directing adipose-derived stromal cell fate toward the adipogenic lineage.Human adipose-derived stromal cells were cultured in adipogenic differentiation media, and RNA was harvested at days 0, 1, 3, 5, and 7. Directional RNA sequencing libraries were prepared and sequenced. Paired-end reads were mapped to the human genome reference sequence hg19. Transcriptome assembly was performed and significantly differentially expressed transcripts were identified. Gene ontology term analysis was then performed to identify coding and noncoding transcripts of interest. Differential expression was verified by quantitative real-time polymerase chain reaction.Of 2868 significantly differentially expressed transcripts identified, 207 were noncoding. Enriched gene ontology terms among up-regulated coding transcripts notably reflected differentiation toward the adipogenic lineage. Enriched gene ontology terms among down-regulated coding transcripts reflected growth arrest. Guilt-by-association analysis revealed noncoding RNA candidates with potential roles in the process of adipogenic differentiation.The precise mechanisms that guide lineage-specific differentiation in multipotent cells are not yet fully understood. Defining long noncoding RNAs associated with adipogenic differentiation allows for potential manipulation of regulatory pathways in novel ways. The authors present RNA sequencing as a powerful tool for expanding the understanding of adipose-derived stromal cells and developing novel applications within regenerative medicine.
View details for DOI 10.1097/PRS.0000000000001582
View details for PubMedID 26090763
What Makes a Plastic Surgery Residency Program Attractive? An Applicant's Perspective
PLASTIC AND RECONSTRUCTIVE SURGERY
2015; 136 (1): 189-196
Plastic surgery is among the most competitive specialties in medicine, but little is known about the attributes of programs that are most attractive to successful applicants. This study aimed to understand and provide insights regarding program characteristics that are most influential to students when ranking plastic surgery programs.An anonymous online survey was conducted with newly matched plastic surgery residents for the integrated and combined Match in 2012 and 2013. Subjects were queried regarding their demographics, qualifications, application experiences, and motivations for residency program selection.A total of 92 of 245 matched plastic surgery residents (38 percent) responded to the survey. The perception of resident happiness was the most positive factor influencing program ranking, followed by high operative volume, faculty mentorship, and strong research infrastructure. Perception of a program as "malignant" was the most negative attribute. Applicants with Step 1 scores greater than 245 received significantly more interviews (p =0.001) and considered resident benefits less important (p < 0.05), but geographic location more important (p =0.005). Applicants who published more than two articles also received more interviews (p =0.001) and ranked a strong research infrastructure and program reputation as significantly more important (p < 0.05). Forty-two percent of applicants completed an away rotation at the program with which they matched, and these applicants were more likely to match at their number one ranked program (p = 0.001).Plastic surgery applicants have differing preferences regarding the ideal training program, but some attributes resonate. These trends can guide programs for improvement in attracting the best applicants.
View details for DOI 10.1097/PRS.0000000000001365
View details for Web of Science ID 000357097900001
View details for PubMedID 26111321
Studies in Fat Grafting: Part V. Cell-Assisted Lipotransfer to Enhance Fat Graft Retention Is Dose Dependent
PLASTIC AND RECONSTRUCTIVE SURGERY
2015; 136 (1): 67-75
Cell-assisted lipotransfer has shown much promise as a technique for improving fat graft take. However, the concentration of stromal vascular fraction cells required to optimally enhance fat graft retention remains unknown.Human lipoaspirate was processed for both fat transfer and harvest of stromal vascular fraction cells. Cells were then mixed back with fat at varying concentrations ranging from 10,000 to 10 million cells per 200 μl of fat. Fat graft volume retention was assessed by means of computed tomographic scanning over 8 weeks, and then fat grafts were explanted and compared histologically for overall architecture and vascularity.Maximum fat graft retention was seen at a concentration of 10,000 cells per 200 μl of fat. The addition of higher number of cells negatively impacted fat graft retention, with supplementation of 10 million cells producing the lowest final volumes, lower than fat alone. Interestingly, fat grafts supplemented with 10,000 cells showed significantly increased vascularity and decreased inflammation, whereas fat grafts supplemented with 10 million cells showed significant lipodegeneration compared with fat alone: The authors' study demonstrates dose dependence in the number of stromal vascular fraction cells that can be added to a fat graft to enhance retention. Although cell-assisted lipotransfer may help promote graft survival, this effect may need to be balanced with the increased metabolic load of added cells that may compete with adipocytes for nutrients during the postgraft period.
View details for DOI 10.1097/PRS.0000000000001367
View details for Web of Science ID 000357096300002
View details for PubMedID 25829158
View details for PubMedCentralID PMC4483157
Emerging drugs for the treatment of wound healing
EXPERT OPINION ON EMERGING DRUGS
2015; 20 (2): 235-246
Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process.A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed.The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.
View details for DOI 10.1517/14728214.2015.1018176
View details for Web of Science ID 000356118400007
View details for PubMedID 25704608
Therapeutic Applications of Human Adipose-Derived Stromal Cells for Soft Tissue Reconstruction
2015; 105: 245-253
Adipose derived stromal cells (ASCs) are a multipotent cell population derived from the stromal vascular fraction of lipoaspirate. Given their relatively broad differentiation potential and paracrine capabilities, ASCs represent a readily accessible, endogenous resource for novel reconstructive strategies. In particular, augmentation of autologous fat grafts with ASCs has already been employed clinically for restoration of soft tissue defects. While fat grafting alone remains highly unpredictable, enrichment of fat with supplemental ASCs, also known as cell-assisted lipotransfer (CAL), has been shown to significantly enhance volume retention. How addition of these cells to fat grafts results in improved outcomes, however, remains poorly understood. Furthermore, the safety of CAL in the setting of prior malignancy and post-radiation wound beds has yet to be fully determined, an important consideration for its use in cancer reconstruction. Thus, further studies to determine the how and why behind the efficacy of CAL are necessary before it can be widely adopted as a safe and reliable surgical technique.
View details for Web of Science ID 000356922200001
- Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis. Journal of visualized experiments : JoVE 2015
Cloud-Based Applications for Organizing and Reviewing Plastic Surgery Content.
Cloud-based applications including Box, Dropbox, Google Drive, Evernote, Notability, and Zotero are available for smartphones, tablets, and laptops and have revolutionized the manner in which medical students and surgeons read and utilize plastic surgery literature. Here we provide an overview of the use of Cloud computing in practice and propose an algorithm for organizing the vast amount of plastic surgery literature. Given the incredible amount of data being produced in plastic surgery and other surgical subspecialties, it is prudent for plastic surgeons to lead the process of providing solutions for the efficient organization and effective integration of the ever-increasing data into clinical practice.
View details for PubMedID 26576208
Design and Focus Test of a Preconsultation Decision Aid for Breast Cancer Reconstruction Patients: A Quality Improvement Initiative.
To design, develop, and evaluate via focus group a preconsultation decision aid to improve patient satisfaction for breast reconstruction.The design of the decision aid was based on perceived patient needs, literature, existing decision aids, and current standard of breast cancer reconstruction treatment and consultation at Stanford. Our decision aid was designed to (1) reducing fear of the unknown in patients via providing a knowledge base that they can rely on, (2) helping patients identify their key breast reconstruction concerns, (3) addressing common patient concerns, (4) providing a framework to help patients identify the treatment option that may be right for them, and (5) promoting shared decision making. Physicians were consulted on the decision aid, following which a focus group was conducted for patient feedback.Interviewed patients (n = 12) were supportive of the decision aid initiative. Participants were especially pleased with the side-by-side comparison of surgical options and the parsimonious way information was represented. All patients before undergoing reconstruction (n = 3) requested the decision guide to reference at home. All interviewed patients believed information level was "about right."Decision aid was well received by patients in the focus group. As the initiative is for quality improvement, we saw no need to further delay the distribution of the decision aid. A pilot study will be conducted to evaluate whether our decision aid has an effect on patients' decision regret, stress, and anxiety.
View details for PubMedID 26171096
Cost-effectiveness of preoperative imaging for appendicitis after indeterminate ultrasonography in the second or third trimester of pregnancy.
Obstetrics and gynecology
2013; 122 (4): 821-829
To assess the cost-effectiveness of diagnostic laparoscopy, computed tomography (CT), and magnetic resonance imaging (MRI) after indeterminate ultrasonography in pregnant women with suspected appendicitis.A decision-analytic model was developed to simulate appendicitis during pregnancy taking into consideration the health outcomes for both the pregnant women and developing fetuses. Strategies included diagnostic laparoscopy, CT, and MRI. Outcomes included positive appendectomy, negative appendectomy, maternal perioperative complications, preterm delivery, fetal loss, childhood cancer, lifetime costs, discounted life expectancy, and incremental cost-effectiveness ratios.Magnetic resonance imaging is the most cost-effective strategy, costing $6,767 per quality-adjusted life-year gained relative to CT, well below the generally accepted $50,000 per quality-adjusted life-year threshold. In a setting where MRI is unavailable, CT is cost-effective even when considering the increased risk of radiation-associated childhood cancer ($560 per quality-adjusted life-year gained relative to diagnostic laparoscopy). Unless the negative appendectomy rate is less than 1%, imaging of any type is more cost-effective than proceeding directly to diagnostic laparoscopy.Depending on imaging costs and resource availability, both CT and MRI are potentially cost-effective. The risk of radiation-associated childhood cancer from CT has little effect on population-level outcomes or cost-effectiveness but is a concern for individual patients. For pregnant women with suspected appendicitis, an extremely high level of clinical diagnostic certainty must be reached before proceeding to operation without preoperative imaging.
View details for DOI 10.1097/AOG.0b013e3182a4a085
View details for PubMedID 24084540
Small Increases To Employer Premiums Could Shift Millions Of People To The Exchanges And Add Billions To Federal Outlays
2013; 32 (9): 1531-1537
The Affordable Care Act will expand insurance coverage to more than twenty-five million Americans, partly through subsidized private insurance available from newly created health insurance exchanges for people with incomes of 133-400 percent of the federal poverty level. The act will alter the financial incentive structure for employers and influence their decisions on whether or not to offer their employees coverage. These decisions, in turn, will affect federal outlays and revenues through several mechanisms. We model the sensitivity of federal costs for the insurance exchange coverage provision of the Affordable Care Act using the nationally representative Medical Expenditure Panel Survey data set. We assess revenues and subsidy outlays for premiums and cost sharing for individuals purchasing private insurance through exchanges. Our findings show that changing theoretical premium contribution levels by just $100 could induce 2.25 million individuals to transition to exchanges and increase federal outlays by $6.7 billion. Policy makers and analysts should pay especially careful attention to participation rates as the act's implementation continues.
View details for DOI 10.1377/hlthaff.2013.0522
View details for Web of Science ID 000324681500004
View details for PubMedID 24019356