bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum n‐6 and n‐9 Fatty Acids Correlate With Serum IGF‐1 and Growth Up to 4 Months of Age in Healthy Infants
Authors: Kjellberg Emma , Roswall Josefine , Bergman Stefan , Strandvik Birgitta , Dahlgren Jovanna 
Published: July 2017

ABSTRACTObjective:The aim of this study was to study the relationship between insulin‐like growth factor‐1 (IGF‐1), serum phospholipid fatty acids, and growth in healthy full‐term newborns during infancy.Methods:Prospective observational study of a population‐based Swedish cohort comprising 126 healthy, term infants investigating cord blood and serum at 2 days and 4 months of age for IGF‐1 and phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4 months, compared with anthropometric measurements (standard deviation scores).Results:At all time‐points arachidonic acid (AA) was negatively associated with IGF‐1. IGF‐1 had positive associations with linoleic acid (LA) at 2 days and 4 months and mead acid (MA) showed positive associations in cord blood. Multiple regression analyses adjusted for maternal factors (body mass index, weight gain, smoking, education), sex, birth weight and feeding modality confirmed a negative association for the ratio AA/LA to IGF‐1. MA in cord blood correlated to birth size. Changes in the ratios of n‐6/n‐3 and AA/docosahexaenoic acid from day 2 to 4 months together with infants′ weight and feeding modality determined 55% of the variability of delta‐IGF‐1. Breast‐fed infants at 4 months had lower IGF‐1 correlating with lower LA and higher AA concentrations, which in girls correlated with lower weight gain from birth to 4 months of age.Conclusions:Our data showed interaction of n‐6 fatty acids with IGF‐1 during the first 4 months of life, and an association between MA and birth size when adjusted for confounding factors. Further follow‐up may indicate whether these correlations are associated with later body composition.
Early Onset of Wilson Disease
Authors: Wiernicka Anna , Dądalski Maciej , Jańczyk Wojciech , Kamińska Diana , Naorniakowska Magdalena , Hüsing‐Kabar Anna , Schmidt Hartmut , Socha Piotr 
Published: July 2017

ABSTRACTObjectives:The aim of the study was to analyze the clinical presentations, diagnosis, and treatment of patients ages ⩽5 years with early onset Wilson disease (WD).Methods:Data from 143 pediatric patients with WD treated at our center between January 1996 and November 2015 were retrospectively analyzed.Results:A review of the 143 pediatric patients with WD identified 21 (10 girls, 11 boys) with first symptoms or abnormal liver function test results at age ⩽5 years. The diagnosis of WD was confirmed in 8 patients younger than 5 years. At baseline the mean serum alanine aminotransferase level was 222 U/L and the mean serum aspartate aminotransferase level was 130 U/L. The mean serum ceruloplasmin concentration in 16 tested patients was <20 mg/dL. Of the 15 patients who underwent urinary copper excretion testing, 8 had levels between 40 and 100 μg/day, with only 4 having levels >100 μg/day. Liver copper quantification was >250 μg/g dry weight in 16 patients. The most common mutation was p.H1069Q, with compound heterozygosity in 5 patients and homozygosity in 9. Sixteen patients were treated with zinc salts and 5 with D‐penicillamine. Both treatments were effective, with no serious side effects observed after 3 to 24 months.Conclusions:WD can present as early as 2 years of age. Because biochemical tests may be less sensitive in very young children, diagnoses may require a combination of tests. If molecular tests are inconclusive, liver copper content should be measured.
Auricular Tissue Engineering Using Osteogenic Differentiation of Adipose Stem Cells with Small Intestine Submucosa
Authors: Lin Chih-Hsun , Yang I-Chen , Tsai Chi-Han , Fang Hsu-Wei , Ma Hsu 
Published: July 2017

Background:
Ear reconstruction remains a challenge for plastic surgeons. A tissue-engineering approach could provide another route for obtaining shape maintenance in neoauricular tissue.

Methods:
The authors designed a novel tissue-engineering auricular construct by culturing human adipose stem cells, which differentiated into osteocytes but not chondrocytes, in small intestine submucosa scaffolds. The authors evaluated cell growth potential and mechanical properties. An ear-shaped construct was created in vitro and then implanted in the backs of nude mice. The histology, cellularity, neovascularization, mechanical properties, and ear shape maintenance were investigated.

Results:
In vitro, human adipose stem cells could be successfully seeded in the small intestine submucosa and differentiated toward osteogenesis. The ear-shaped human adipose stem cell/small intestine submucosa construct could maintain its shape in vivo up to 1 year. Alizarin Red S staining confirmed osteogenic differentiation. CD31 stain showed prominent angiogenesis in the human adipose stem cell/small intestine submucosa construct at 6 months and persistence up to 1 year. h-MHC stain revealed the maintenance of cellularity at 6 months and persistence up to 1 year. The mechanical properties were similar to those of native ear cartilage.

Conclusion:
The authors’ study found that the combination of human adipose stem cells and small intestine submucosa could provide a more durable ear-shaped construct in vivo. The mechanical properties, shape, and cellularity were maintained in the constructs for up to 12 months.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Male-to-Female Sex Reassignment Surgery Using the Combined Technique Leads to Increased Quality of Life in a Prospective Study
Authors: Papadopulos Nikolaos A. , Zavlin Dmitry , Lellé Jean-Daniel , Herschbach Peter , Henrich Gerhard , Kovacs Laszlo , Ehrenberger Benjamin , Machens Hans-Günther , Schaff Jürgen 
Published: July 2017

Background:
The authors’ previous research showed that various plastic surgical procedures can increase a patient’s quality of life in its different aspects. In a prospective setting, they evaluated whether sex reassignment surgery has similar effects for male-to-female transgender patients compared to baseline data before sex reassignment surgery.

Methods:
All 39 patients who underwent their first-stage male-to-female sex reassignment surgery between October of 2012 and January of 2014 received one set of questionnaires preoperatively (time 0) and approximately 6 months after their final operation (time 1). Each set contained self-developed, indication-specific questions combined with the standardized validated Questions on Life Satisfaction, Modules (German version) questionnaire, the Freiburg Personality Inventory, the Rosenberg Self-Esteem Scale, and the Patient Health Questionnaire, which were compared to available norm data.

Results:
The mean patient age was 38.6 years. The majority of the patients were highly educated, childless, and single. Significant improvements were found in the Questions on Life Satisfaction, Modules (German version), especially for the items “partnership,” “ability to relax,” “energy,” “freedom from anxiety,” “hair,” “breast,” and “penis/vagina” (p < 0.01). Furthermore, the patients appeared more emotionally stable (p = 0.03), showed higher self-esteem (p = 0.01), and showed much lower depression/anxiety (p < 0.01).

Conclusions:
The positive study findings were confirmed with the results from prior retrospective studies. However, medical literature focuses largely on surgical and functional satisfaction and not overall quality of life. In addition, standardized questionnaires are used rarely and solely retrospectively, with the risk of recall bias. The increased quality of life of transgender women postoperatively endorses sex reassignment surgery as a valuable option for these patients.

CLINICAL QUESTON/LEVEL OF EVIDENCE:
Therapeutic, IV.
Facial Assessment and Injection Guide for Botulinum Toxin and Injectable Hyaluronic Acid Fillers: Focus on the Upper Face
Authors: de Maio Maurício , Swift Arthur , Signorini Massimo , Fagien Steven 
Published: July 2017

Summary:
Techniques for the administration of injectable fillers and neuromodulators for facial aesthetic rejuvenation and enhancement continue to evolve. As the number of physicians with limited experience in providing aesthetic treatments expands, the need for guidance and training from more experienced injectors has become apparent. The use of a slow, careful, and methodical injection technique is imperative in all treatment settings and for all facial areas. Constant attention to local anatomy, particularly arteries, veins, and nerve bundles, is critical for minimizing complications. This first article of a three-part series addresses techniques and recommendations for aesthetic treatment of the upper face. Traditionally, the upper face has been considered a basic area for treatment with neuromodulators but an advanced area for treatment with fillers. Injectable fillers may be used for temple volumization, eyebrow shaping, and forehead contouring. Neuromodulators are well suited for diminishing the appearance of dynamic facial lines such as forehead, glabellar, and crow’s feet lines, and eyebrow lifting and eye-aperture widening. These techniques may be used independently or together, sequentially or concurrently, to address rejuvenation of individual or multiple facial regions. Overall, this series provides a practical framework of techniques for physicians who desire to perform safe and effective aesthetic treatments using a multimodal approach.
101 Consecutive Profunda Artery Perforator Flaps in Breast Reconstruction: Lessons Learned with Our Early Experience
Authors: Haddock Nicholas T. , Gassman Andrew , Cho Min-Jeong , Teotia Sumeet S. 
Published: July 2017

Background:
Free and local flaps based on the profunda artery perforators were first used for reconstruction of pressure sores, burn contractures, and extremity wounds. Recently, a revised profunda artery perforator flap was introduced for breast reconstruction. However, despite increasing reports of the use of the flap, it remains a rarely used option. The authors present their early experience with the first 101 profunda artery perforator flaps used for breast reconstruction at their institution.

Methods:
The authors conducted a retrospective review of the first 101 profunda artery perforator flaps at their institution. Patient demographics, perioperative data, and postoperative complications were recorded and analyzed.

Results:
One hundred one consecutive profunda artery perforator flaps were used to reconstruct 96 breasts in 56 patients. In 42 breasts, the flap was used in conjunction with another flap—with a deep inferior epigastric perforator flap (n = 36), a superior gluteal artery perforator flap (n = 1), or as stacked profunda artery perforator flaps (n = 5). Mean flap weight was 425 g (range, 170 to 815 g), and mean patient body mass index was 26.8 kg/m2 (range, 18.2 to 42.3 kg/m2). Complications included total flap loss (2 percent), donor-site cellulitis (5.9 percent), and donor-site wound dehiscence (10.9 percent).

Conclusions:
The profunda artery perforator flap is a safe and reliable option for breast reconstruction. Flap size is adequate for breast reconstruction in appropriately selected patients. Furthermore, it can be combined with other flaps when additional volume or skin requirements are present. Flap and donor-site complications are comparable to those of other free tissue breast reconstruction options. It is a clear second option to the deep inferior epigastric perforator flap for autologous tissue reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Rates of Primary and Secondary Syphilis Among White and Black Non-Hispanic Men Who Have Sex With Men, United States, 2014
Authors: Grey Jeremy A. , Bernstein Kyle T. , Sullivan Patrick S. , Kidd Sarah E. , Gift Thomas L. , Hall Eric W. , Hankin-Wei Abigail , Weinstock Hillard S. , Rosenberg Eli S. 
Published: July 2017

Background:
Men who have sex with men (MSM) in the United States experience an approximately 100-fold greater rate of primary and secondary (P&S) syphilis diagnoses compared with men who have sex with women only. As in the general population, racial/ethnic disparities in P&S syphilis diagnosis rates may exist among MSM, but MSM-specific P&S syphilis rates by race/ethnicity are unavailable. We enhanced a published modeling approach to estimate area-level MSM populations by race/ethnicity and provide the first estimates of P&S syphilis among black and white non-Hispanic MSM.

Methods:
We used data from the American Community Survey (ACS), published findings from the National Health and Nutrition Examination Survey (NHANES), and national syphilis surveillance data to estimate state-level rates of P&S syphilis diagnoses among MSM, overall and for black and white non-Hispanic MSM. We also used variability around ACS and NHANES estimates to calculate 95% confidence intervals for each rate.

Results:
Among 11,359 cases of P&S syphilis among MSM with known race/ethnicity in 2014, 72.5% were among white (40.3%) or black (32.2%) MSM. The national rate of P&S syphilis diagnosis was 168.4/100,000 for white MSM and 583.9/100,000 for black MSM. Regional rates for black MSM ranged from 602.0/100,000 (South) to 521.5/100,000 (Midwest) and were consistently higher than those for white MSM.

Conclusions:
Although white MSM accounted for more P&S syphilis diagnoses than black MSM in 2014, when evaluating diagnoses based on rate per 100,000, black MSM had consistently and markedly higher rates than white MSM, with the highest impacted states located in the US South.
Missed Opportunities: Adapting the HIV Care Continuum to Reduce HIV-Related Deaths
Authors: Braunstein Sarah L. , Robbins Rebekkah S. , Daskalakis Demetre C. 
Published: July 2017

Introduction:
With advances in HIV care, persons with HIV/AIDS (PWHA) can lead healthy lives, but avoidable HIV-related deaths continue to occur in New York City (NYC).

Methods:
We selected PWHA from our surveillance registry who died between 2007 and 2013, resided in NYC, and survived ≥15 months after diagnosis to generate an HIV Mortality Reduction Continuum of Care (HMRCC) describing predeath care patterns among PWHA. We used HIV laboratory test reports to measure care outcomes during an “intervenable period” during which deaths may have been avoided. The continuum was stratified by the underlying cause of death (HIV-related vs. other), and the HIV-related HMRCC was stratified by demographic characteristics.

Results:
Eleven thousand one hundred eighty-seven analysis-eligible PWHA died during 2007–2013. Ninety-eight percent linked to care; 80% were retained in care during the intervenable period; 66% were prescribed antiretroviral therapy; 47% had viral load ≤1500 copies/mL; and 40% achieved viral suppression (VS). Half (47%) of the deaths were HIV-related. Retention was higher among HIV-related cause of death (83% vs. 78%) but VS was lower (34% vs. 46%). The HIV-related HMRCC revealed disparities in VS. Despite comparable retention rates, whites had the highest VS (42%, vs. 32% blacks and 33% Latinos/Hispanics). In addition, retention and VS increased with increasing age. People with a history of injection drug use had relatively high rates of retention (88%) and VS (37%).

Discussion:
The HMRCC is a novel framework for evaluating predeath care patterns among PWHA and identifying opportunities to reduce preventable deaths. In NYC, reducing mortality will require increasing VS among those already in care, particularly for blacks and Latinos/Hispanics.
P53 toxicity is a hurdle to CRISPR/CAS9 screening and engineering in human pluripotent stem cells
Authors: Ihry Robert J. , Worringer Kathleen A. , Salick Max R. , Frias Elizabeth , Ho Daniel , Theriault Kraig , Kommineni Sravya , Chen Julie , Sondey Marie , Ye Chaoyang , Randhawa Ranjit , Kulkarni Tripti , Yang Zinger , McAllister Gregory , Russ Carsten , Reece-Hoyes John , Forrester William , Hoffman Gregory R. , Dolmetsch Ricardo , Kaykas Ajamete 
Published: July 2017

SUMMARYCRISPR/Cas9 has revolutionized our ability to engineer genomes and to conduct genome-wide screens in human cells. While some cell types are easily modified with Cas9, human pluripotent stem cells (hPSCs) poorly tolerate Cas9 and are difficult to engineer. Using a stable Cas9 cell line or transient delivery of ribonucleoproteins (RNPs) we achieved an average insertion or deletion efficiency greater than 80%. This high efficiency made it apparent that double strand breaks (DSBs) induced by Cas9 are toxic and kill most treated hPSCs. Cas9 toxicity creates an obstacle to the high-throughput use CRISPR/Cas9 for genome-engineering and screening in hPSCs. We demonstrated the toxic response istp53-dependent and the toxic effect oftp53severely reduces the efficiency of precise genome-engineering in hPSCs. Our results highlight that CRISPR-based therapies derived from hPSCs should proceed with caution. Following engineering, it is critical to monitor fortp53function, especially in hPSCs which spontaneously acquiretp53mutations.
A GAL80 collection to inhibit GAL4 transgenes inDrosophilaolfactory sensory neurons
Authors: Eliason Jessica , Afify Ali , Potter Christopher , Matsumura Ichiro 
Published: July 2017

ABSTRACTFruit flies recognize hundreds of ecologically relevant odors and respond appropriately to them. The complexity, redundancy and interconnectedness of the olfactory machinery complicate efforts to pinpoint the functional contributions of any component neuron or receptor to behavior. Some contributions can only be elucidated in flies that carry multiple mutations and transgenes, but the production of such flies is currently labor-intensive and time-consuming. Here, we describe a set of transgenic flies that express theSaccharomyces cerevisiaeGAL80 in specific olfactory sensory neurons (OrX-GAL80s). The GAL80s effectively and specifically subtract the activities of GAL4-driven transgenes that impart anatomical and physiological phenotypes.OrX-GAL80scan allow researchers to efficiently activate only one or a few types of functional neurons in an otherwise nonfunctional olfactory background. Such experiments will improve our understanding of the mechanistic connections between odorant inputs and behavioral outputs at the resolution of only a few functional neurons.
Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth
Authors: Benzekry Sebastien , Lamont Clare , Barbolosi Dominique , Hlatky Lynn , Hahnfeldt Philip 
Published: July 2017

AbstractInteractions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, p<0.05). The competition model had to be rejected while the angiogenesis inhibition and proliferation inhibition models were able to describe the data. Additional models including a theory based on distant cytotoxic log-kill effects were unable to fit the data. The proliferation inhibition model was identifiable and minimal (4 parameters), and its descriptive power was validated against the data, including consistency in predictions of single tumor growth when no secondary tumor was present. This theory may also shed new light on single cancer growth insofar as it offers a biologically translatable picture of how local and global action may combine to control local tumor growth, and in particular, the role of tumor-tumor inhibition. This model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post-surgery metastatic acceleration.
Trade-off and flexibility in the dynamic regulation of the cullin-RING ubiquitin ligase repertoire
Authors: Straube Ronny , Flockerzi Dietrich , Wolf Dieter A. 
Published: July 2017

AbstractCullin-RING ubiquitin ligases (CRLs) catalyze the ubiquitylation of substrates many of which are degraded by the 26S proteasome. Their modular architecture enables recognition of numerous substrates via exchangeable substrate receptors that competitively bind to a cullin scaffold with high affinity. Due to the plasticity of these interactions there is ongoing uncertainty how cells maintain a flexible CRL repertoire in view of changing substrate loads. Based on a series of invivoandin vitrostudies, different groups proposed that the exchange of substrate receptors is mediated by a protein exchange factor named cullin-associated and neddylation-dissociated 1 (Cand1). Here, we have performed quantitative mathematical modeling to support this hypothesis. To this end we first show that the exchange activity of Cand1 necessarily leads to a trade-off between high ligase activity and fast receptor exchange. Supported by previousin vivostudies we argue that this trade-off yields an optimal Cand1 concentration where the time scale for substrate degradation becomes minimal. In a second step we show through simulations that (i) substrates bias the CRL repertoire leading to preferential assembly of ligases for which substrates are available and (ii) differences in binding affinities create a temporal hierarchy for the degradation of substrates. Together, our results provide general constraints for the operating regimes of molecular exchange systems and suggest that Cand1 endows the CRL network with the properties of an “on demand” system allowing cells to dynamically adjust their CRL repertoire to fluctuating substrate abundances.Author summaryCullin-RING ubiquitin ligases (CRLs) are multisubunit protein complexes where exchangeable substrate receptors (SRs) assemble on a cullin scaffold to mediate ubiquitylation and subsequent degradation of a large variety of substrates. In humans there are hundreds of different CRLs having potentially thousands of substrates. Due to the high affinity of cullin-SR interactions, it has long been a mystery how cells would maintain flexibility to sample the entire SR repertoire in order to match fluctuating substrate loads. Recent experiments indicate that the exchange of different SRs is mediated by a novel protein exchange factor (Cand1). However, the proposed biochemical function of Cand1 as a promoter of CRL activity remained difficult to reconcile with previous reports of Cand1 acting as an inhibitor of CRL activityin vitro. Here we show that these two findings are not contradictory, but that the exchange activity of Cand1 necessarily leads to a trade-off between high ligase activity and fast receptor exchange which leads us to predict an optimal Cand1 concentration and a temporal hierarchy for substrate degradation. Our results support the view that Cand1 endows the CRL network with the flexibility of an “on demand” system where relative CRL abundances are dictated by substrate availability.