bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Lumbopelvic Fixation Add Stability? A Cadaveric Biomechanical Analysis of an Unstable Pelvic Fracture Model
Authors: Jazini Ehsan , Klocke Noelle , Tannous Oliver , Johal Herman S. , Hao John , Salloum Kanaan , Gelb Daniel E. , Nascone Jason W. , Belin Eric , Hoshino C. Max , Hussain Mir , O'Toole Robert V. , Bucklen Brandon , Ludwig Steven C.
Published: December 2016

Objective:

We sought to determine the role of lumbopelvic fixation (LPF) in the treatment of zone II sacral fractures with varying levels of sacral comminution combined with anterior pelvic ring (PR) instability. We also sought to determine the proximal extent of LPF necessary for adequate stabilization and the role of LPF in complex sacral fractures when only 1 transiliac–transsacral (TI–TS) screw is feasible.

Materials and Methods:

Fifteen L4 to pelvis fresh-frozen cadaveric specimens were tested intact in flexion-extension (FE) and axial rotation (AR) in a bilateral stance gliding hip model. Two comminution severities were simulated through the sacral foramen using an oscillating saw, with either a single vertical fracture (small gap, 1 mm) or 2 vertical fractures 10 mm apart with the intermediary bone removed (large gap). We assessed sacral fracture zone (SZ), PR, and total lumbopelvic (TL) stability during FE and AR. The following variables were tested: (1) presence of transverse cross-connector, (2) presence of anterior plate, (3) extent of LPF (L4 vs. L5), (4) fracture gap size (small vs. large), (5) number of TI–TS screws (1 vs. 2).

Results:

The transverse cross-connector and anterior plate significantly increased PR stability during AR (P = 0.02 and P = 0.01, respectively). Increased sacral comminution significantly affected SZ stability during FE (P = 0.01). Two versus 1 TI–TS screw in a large-gap model significantly affected TL stability (P = 0.04) and trended toward increased SZ stabilization during FE (P = 0.08). Addition of LPF (L4 and L5) significantly improved SZ and TL stability during AR and FE (P < 0.05). LPF in combination with TI–TS screws resulted in the least amount of motion across all 3 zones (SZ, PR, and TL) compared with all other constructs in both small-gap and large-gap models.

Conclusions:

The role of LPF in the treatment of complex sacral fractures is supported, especially in the setting of sacral comminution. LPF with proximal fixation at L4 in a hybrid approach might be needed in highly comminuted cases and when only 1 TI–TS screw is feasible to obtain maximum biomechanical support across the fracture zone.
Functional Outcomes of Operative Management of Scapula Fractures in a Geriatric Cohort
Authors: Cole Peter A. , Gilbertson Jeffrey A. , Cole Peter A.
Published: December 2016

Objectives:

To analyze functional outcomes, motion, and strength in patients 65 years of age and older who underwent operative management of a scapula fracture.

Design:

Retrospective review of prospective database.

Setting:

A single level-1 teaching trauma center.

Patients/Participants:

Two hundred fifty patients with scapula fractures were operated between January 2002 and March 2014. A review identified 16 geriatric patients 65 years of age and older.

Intervention:

All patients underwent operative treatment of a scapular fracture.

Main Outcome Measurements:

Disabilities of the Arm, Shoulder, and Hand (DASH), Short-Form Health Survey versions 1 and 2 (SF-36), Range of Motion (ROM), and Strength assessment at final follow-up 1 year or greater.

Results:

Outcomes were attained on 15/16 patients at a mean follow-up of 40 months (range = 12–114). All fractures were united. Three patients experienced minor perioperative complications (temporary delirium in 2 patients, urinary tract infection in 1). One patient required subsequent removal of an intraarticular screw, and 1 patient required resection of heterotopic ossification and requested implant removal. The mean ROM expressed as a percent of contralateral ROM ranged from 78% to 96%. The mean strength expressed as a percent of contralateral strength ranged from 76% to 92%. The mean DASH score was 8.4. SF-36 scores were comparable with the normal population. All patients returned to activities.

Conclusions:

Operative treatment for displaced fractures in patients 65 years of age and older is safe and can yield good functional results and return to function.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Pilot Testing a Web-Based System for the Assessment and Management of Chemotherapy-Induced Peripheral Neuropathy
Authors: Knoerl Robert , Dudley William N. , Smith Gloria , Bridges Celia , Kanzawa-Lee Grace , Lavoie Smith Ellen M.
Published: December 2016

Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies.
BH4 improves postprandial endothelial function after a high-fat meal in men and postmenopausal women
Authors: Shah Yashesh , Bass Leon , Davison Gareth W. , Seigler Nichole , Pollock Jennifer S. , Thomas Jeff , Harris Ryan A.
Published: December 2016

Objective:

The timing and duration of menopause is important when evaluating the risk for cardiovascular disease in postmenopausal women, likely related in part to nitric oxide (NO) bioavailability. The flow-mediated dilation (FMD) test is a noninvasive assessment of NO bioavailability in humans, and tetrahydrobiopterin (BH4) is essential for NO synthesis. A high-fat meal (HFM) has been used to increase lipemia and reduce NO bioavailability. Thus, this study sought to determine if menopausal transition has any impact on the postprandial endothelial function response to a HFM, and evaluate the effect of BH4 on postprandial endothelial function in postmenopausal women and men.

Methods:

Utilizing a randomized, double-blind, placebo-controlled design, sex-steroid hormones and FMD were determined in 30 older adults (10 postmenopausal women aged below 3 y [W < 3], 10 postmenopausal women aged above 10 y [W > 10], and 10 men) at baseline and 4 hours after the ingestion of a HFM alone or a HFM with BH4 (HFM + BH4; 5 mg/kg).

Results:

Data are presented as mean ± SEM. Independent of treatment, postprandial testosterone was significantly (P < 0.05) decreased in men (−64 ± 11 ng/dL), whereas no changes were observed in W < 3 or W > 10 group. In addition, concentrations of progesterone were higher (P = 0.019) and the testosterone/estradiol ratio was lower (P = 0.026) in all groups after the ingestion of HFM + BH4 compared with the ingestion of HFM alone. Overall, an increase in FMD was observed after the ingestion of HFM + BH4 (Δ1.9% ± 0.6%), whereas no change in FMD was observed after the ingestion of HFM alone (Δ−0.7% ± 0.6%).

Conclusions:

Co-ingestion of BH4 with a HFM not only alters the sex-steroid hormone ratio, it improves postprandial FMD after a HFM regardless of postmenopause status or sex.
Impact of Contact Lens Material, Design, and Fitting on Discomfort
Authors: Stapleton Fiona , Tan Jacqueline
Published: December 2016

Objective:

To review the effect of contact lens (CL) material, design, and fitting characteristics on CL discomfort.

Methods:

A PubMed search identified publications describing subjective comfort and CL material, fitting, and design parameters. The review included clinical signs associated with discomfort that may be a consequence of these parameters.

Results:

Reduced lens movement or more CL tightness were associated with improved comfort. Increased lens-induced paralimbal conjunctival staining and indentation, considered as quasi-indicators of CL fitting or edge design, were also associated with better comfort. No recent studies have evaluated varying CL design parameters and subjective comfort. Silicone hydrogel CLs are no different in comfort compared with hydrogel CLs. Lower equilibrium water content is associated with improved comfort in hydrogel CL wear. Coefficient of friction shows promise as a material factor potentially associated with comfort. Lid wiper epitheliopathy and lid-parallel conjunctival folds have been linked with comfort in established wearers.

Conclusions:

Recent studies have confirmed the association between more mobile CLs and more discomfort, whereas closer conformity of the CL to the bulbar conjunctiva improved subjective comfort. There is no evidence to support the perceived comfort difference between silicone hydrogel and hydrogel CL. There has been limited progress in understanding the impact of varying specific CL design parameters. Although specific clinical signs may be predictive of discomfort, their role in the natural history of discomfort remains unclear. A better understanding of the relationship between coefficient of friction and comfort and strategies to improve lubricity may hold promise for limiting CL discomfort.
Vector Analysis of 1-Year Astigmatic Outcomes From a Randomized Fellow Eye Comparison of Photorefractive Keratectomy Using 2 Excimer Laser Platforms
Authors: Toy Brian C. , Manche Edward E.
Published: December 2016

Objective:

To compare the astigmatic outcomes of photorefractive keratectomy (PRK) with a wavefront-guided (WFG) and a wavefront-optimized (WFO) excimer laser performed on two different platforms.

Methods:

Setting: institutional.

Design:

Prospective, randomized, fellow eye comparison clinical trial.

Participants:

A total of 142 eyes of 71 patients with myopia of 12 diopters (D) or less and astigmatism of 3D or less were enrolled at the Byers Eye Institute at Stanford between April 2009 and March 2011.

Intervention:

One eye of each patient underwent WFG-PRK with the VISX CustomVue Star S4 IR (Abbott Medical Optics, Abbott Park, IL) and the contralateral eye underwent WFO-PRK with the Wavelight Allegretto Eye-Q 400-Hz laser platform (Alcon, Inc., Hüenberg, Switzerland). Alpins vector analysis of astigmatism was performed using manifest refraction measured preoperatively and 12 months postoperatively and vertexed to the corneal plane. Eyes were stratified for subgroup analysis based on preoperative manifest astigmatism.

Results:

WFG-PRK and WFO-PRK were similar regarding surgically induced astigmatism, difference vector, magnitude of error, correction index, flattening index, and index of success. The angle of error was 60% less in the WFG group compared with the WFO group (4.9±1.1° vs. 11.8±2.4°, P=0.01).

Conclusions:

WFG-PRK with the VISX CustomVue Star S4 IR and WFO-PRK with the Alcon WaveLight Allegretto Eye-Q 400-Hz excimer laser platform produce similar astigmatic results in myopic patients; however, the WFG mode may produce slightly more predictable astigmatic corrections.
Meibomian Gland Dysfunction and Contact Lens Discomfort
Authors: Arita Reiko , Fukuoka Shima , Morishige Naoyuki
Published: December 2016

Meibomian glands are located in the eyelids and secrete meibum, which gives rise to the lipid layer of the tear film. Changes to these glands can lead to the development of meibomian gland dysfunction (MGD), which is associated with various ocular symptoms such as fatigue, dryness, burning sensation, and heavy sensation. The diagnosis of MGD thus relies on evaluation of ocular symptoms, meibum condition, and lid margin abnormalities. The recent development of noninvasive meibography and tear interferometry has provided important insight into meibomian gland structure and function, respectively. Wearers of contact lenses complain of ocular symptoms that are thought to be attributable to a variety of causes, such as a diminished aqueous or mucin layer of the tear film, changes in tear protein concentration, and altered meibomian gland structure or function. Many studies have examined the relation between contact lens wear and meibomian gland changes. Such studies have found that lens wear is associated with adverse changes in meibomian gland morphology and in the condition of the lid margin and meibum, suggesting that contact lenses negatively affect meibomian glands. Meibomian gland dysfunction-like changes in meibomian glands induced by contact lens wear may thus be responsible for at least some of the ocular symptoms in lens wearers.
Early Reoperation Rate, Complication, and Outcomes in Resident-performed Glaucoma Surgery
Authors: Hsia Yen C. , Lee Jun Hui , Cui Qi N. , Stewart Jay M. , Naseri Ayman , Porco Travis , Stamper Robert L. , Han Ying
Published: December 2016

Purpose of the Study:

The purpose of the study was to examine reoperation rate and complications of resident-performed glaucoma surgeries within the first 90 postoperative days.

Materials and Methods:

A retrospective study of resident-performed glaucoma filtering surgeries at the San Francisco Veterans Affairs Medical Center between 2002 and 2014 was performed. Patients requiring reoperation within 90 days of the initial surgery were included in our study. Combined surgeries were excluded. Complications and the rates of reoperation within the first 90 days were evaluated. Clinical outcomes for those who needed reoperations were evaluated at the 1-year follow-up.

Results:

Total of 180 cases were reviewed [34 trabeculectomy, 85 Ex-PRESS shunt, and 61 Ahmed glaucoma valve (AGV)]. One hundred and four eyes developed complications, most commonly choroidal effusion (65.3%), followed by hypotony (45.2%) and wound leak (32.7%). Complications were comparable among the 3 groups, except that filtering surgery had significantly more wound leak than AGV (P<0.001). Seven (3.9%) cases required reoperation within first 90 days. There was no reoperation for trabeculectomy group. Reoperation rate was 4.7% for Ex-PRESS and 4.9% for AGV (P=0.74). Indications for reoperation were persistent wound leak (4 cases) and tube occlusion/revision (3 cases). For the 7 patients who required reoperations, their intraocular pressure at 1-year postreoperation was significantly decreased compared with intraocular pressure before the initial glaucoma surgery (P<0.001) with similar number of glaucoma medications and stable visual acuity.

Conclusions:

Glaucoma incisional surgeries performed by third-year ophthalmology residents had acceptable and comparable reoperation rates and complication rates for patients with trabeculectomy, Ex-PRESS, and AGV. Clinical outcomes for the patients requiring reoperation were favorable.
Orbital Cellulitis Following Uncomplicated Aqueous Shunt Surgery
Authors: Beck Daniel E.R. , El-Assal Karim S.L. , Doherty Mark D. , Wride Nicholas K.
Published: December 2016

Purpose:

To date, there have only been 5 reported cases of orbital cellulitis following implantation of an aqueous tube shunt for glaucoma. Previously reported cases have involved eyes with significant comorbidities and successful management has often required the removal of the device alongside systemic antibiotic therapy.

Patients and Methods:

We present a 53-year-old man with severe orbital cellulitis, 3 months after routine implantation of a Baerveldt tube shunt for primary open angle glaucoma. The patient was managed medically, with topical and systemic antibiotic therapy. The patient went on to make a full recovery with the tube in situ.

Results and Conclusions:

We report that a more conservative approach (without tube removal) to be successful in a case where there is no evidence of tube exposure. It is important to appreciate that in some cases of orbital cellulitis without clear signs of intraocular involvement, a tube can be left in situ.
The Lifestyle Change Experiences of Cancer Survivors
Authors: Tsay Shiow-Luan , Ko Wang-Sheng , Lin Kuan-Pin
Published: December 2016

Background:

Leading a healthy lifestyle not only alleviates the physical problems but also improves the quality of life of cancer survivors. Healthcare professionals should understand the benefits of altering lifestyle behaviors to provide effective intervention programs to assist cancer survivors to improve their health.

Purpose:

The aim of this study was to understand the experiences of cancer survivors in changing their lifestyle after a cancer diagnosis.

Methods:

A qualitative descriptive study was conducted on 13 cancer survivors who were sampled purposively from a regional teaching hospital in central Taiwan. Data were collected using in-depth interviews that were guided by semistructured, open-ended questions and analyzed using content analysis.

Results:

The analysis of interview data revealed four main themes: motivation of lifestyle change, exploring ways toward a healthy lifestyle, making adjustments in lifestyle, and feeling the benefits of lifestyle changes. In striving for survival, an unwillingness to bear the suffering from treatment and their acceptance of responsibility and gratitude to family members prompted most of the participants to change their lifestyle proactively. They had received inadequate lifestyle guidance and sought health lifestyle information on their own. After a period of research and self-contemplation, most of the participants adopted a consistently healthy lifestyle, changed their dietary consumption habits, abstained from tobacco and alcohol, and managed emotional problems that were caused by the disease. Participants who changed to a healthy lifestyle realized benefits in the physical, emotional, and life domains.

Conclusions/Implications for Practice:

It is hoped that these findings help healthcare professionals to better appreciate that a cancer diagnosis is a critical opportunity to link the disease to lifestyle choices in the minds of cancer survivors. Healthcare professionals should ask cancer survivors about their lifestyle and then provide appropriate advice and education on healthy lifestyles and related benefits.
Differences in Hospital Risk-standardized Mortality Rates for Acute Myocardial Infarction When Assessed Using Transferred and Nontransferred Patients
Authors: Barbash Ian J. , Zhang Hongwei , Angus Derek C. , Reis Steven E. , Chang Chung-Chou H. , Pike Francis R. , Kahn Jeremy M.
Published: December 2016

Background:

One in 5 patients with acute myocardial infarction (AMI) are transferred between hospitals. However, current hospital performance measures based on AMI mortality exclude these patients from the evaluation of referral hospitals.

Objective:

To determine the relationship between risk-standardized mortality for transferred and nontransferred patients at referral hospitals.

Research Design:

This is a retrospective cohort study.

Subjects:

Fee-for-service Medicare claims from 2011 for patients hospitalized with a primary diagnosis of AMI, at hospitals admitting at least 15 patients in transfer.

Measures:

Hospital-specific risk-standardized 30-day mortality rates (RSMRs) for 2 groups of patients: those admitted through transfer from another hospital, and those natively admitted without a preceding or subsequent interhospital transfer.

Results:

There were 304 hospitals admitting at least 15 patients in transfer. These hospitals cared for 77,711 natively admitted patients (median, 254; interquartile range, 162–321), and 11,829 patients admitted in transfer (median, 26; interquartile range, 19–46). Risk-standardized mortality rates were higher for natively admitted patients than for those admitted in transfer (mean, 11.5%±1.2% vs. 7.2%±1.1%). There was weak correlation between hospital performance as assessed by RSMR for patients natively admitted versus those admitted in transfer (Pearson r=0.24, P<0.001); when performance was arrayed by quartile, 102 hospitals (33.6%) differed at least 2 quartiles of performance across the 2 patient groups.

Conclusions:

For Medicare patients with AMI, hospital-specific RSMRs for natively admitted patients are only weakly associated with RSMRs for patients transferred in from another hospital. Current AMI performance metrics may fail to provide guidance about hospital quality for transferred patients.
Do Inactive Older Adults Who Increase Physical Activity Experience Less Disability
Authors: Song Jing , Gilbert Abigail L. , Chang Rowland W. , Pellegrini Christine A. , Ehrlich-Jones Linda S. , Lee Jungwha , Pinto Daniel , Semanik Pamela A. , Sharma Leena , Kwoh C. Kent , Jackson Rebecca D. , Dunlop Dorothy D.
Published: December 2016

Background

Physical inactivity is a leading risk factor for developing disability. Although randomized clinical trials have demonstrated improving physical activity can reduce this risk in older adults with arthritis, these studies did not specifically evaluate inactive adults.

Objectives

The aim of this study was to evaluate the relationship of changes in physical activity with disability changes among initially inactive adults with or at high risk of knee osteoarthritis from Osteoarthritis Initiative.

Methods

Inactive persons were identified at baseline based on the US Department of Health and Human Services classification (no [zero] 10-minute session of moderate-to-vigorous [MV] activity over 1 week) from objective accelerometer monitoring. Two years later, physical activity change status was classified as follows: (1) met Federal physical activity guidelines (≥150 MV minutes/week acquired in bouts ≥10 minutes), (2) insufficiently increased activity (some but <150 MV bout minutes/week), or (3) remained inactive. Disability at baseline and 2 years was assessed by Late Life Disability Instrument limitation and frequency scores. Multiple regression evaluated the relationship of physical activity change status with baseline–to–2-year changes in disability scores adjusting for socioeconomics, health factors, and baseline disability score.

Results

Increased physical activity showed a graded relationship with improved disability scores in Late Life Disability Instrument limitation (P < 0.001) and frequency scores (P = 0.027). While increasing MV activity to guideline levels showed the greatest reduction, even insufficiently increased physical activity was related to reduced disability.

Conclusions

Findings support advice to increase MV physical activity to reduce disability among inactive adults with or at high risk of knee osteoarthritis, even when guidelines are not met.
Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients
Authors: Bank Jonna R. , Heidt Sebastiaan , Moes Dirk Jan A. R. , Roelen Dave L. , Mallat Marko J. K. , van der Boog Paul J.M. , Vergunst Manon , Jol-van der Zijde Cornelia M. , Bredius Robbert G. M. , Braat Andries E. , Ringers Jan , van Tol Maarten J. D. , Claas Frans H. J. , Reinders Marlies E. J. , de Fijter Johannes W.
Published: December 2016

Background

The optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive.

Methods

This cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls. In addition, we provided mechanistic insights in AREs after alemtuzumab depletion, including composition and alloreactivity of lymphocytes (flow cytometry and mixed lymphocyte reaction) plasma alemtuzumab levels (enzyme-linked immunosorbent assay), and maintenance drug exposure.

Results

Overall number of AREs at 3 years was significantly lower with alemtuzumab versus ATG induction (26.0% vs 43.5%; adjusted hazard ratio, 0.38;P= 0.029). Most AREs (94.6%) with ATG occurred within the first month, whereas 84.2% of AREs with alemtuzumab occurred beyond 3 months. Patients with and without an ARE in the steroid-free alemtuzumab group showed no differences in composition of lymphocytes, or in alemtuzumab levels. Of note, more than two thirds of these AREs were preceded by empiric tacrolimus and/or mycophenolate mofetil dose adjustments due to viral infections, leukopenia, or gastrointestinal symptoms.

Conclusions

Alemtuzumab induction resulted in a significant lower incidence of AREs. Empiric dose adjustments beyond 3 months in the absence of steroids carry a significant risk for subsequent rejection in SPKT recipients.
Detection of long repeat expansions from PCR-free whole-genome sequence data
Authors: Dolzhenko Egor , van Vugt Joke J.F.A. , Shaw Richard J. , Bekritsky Mitchell A. , van Blitterswijk Marka , Narzisi Giuseppe , Ajay Subramanian S. , Rajan Vani , Kingsbury Zoya , Humphray Sean J. , Schellevis Raymond D. , Brands William J. , Baker Matt , Rademakers Rosa , Kooyman Maarten , Tazelaar Gijs H.P. , van Es Michael A. , McLaughlin Russell , Sproviero William , Shatunov Aleksey , Jones Ashley , Al Khleifat Ahmad , Pittman Alan , Morgan Sarah , Hardiman Orla , Al-Chalabi Ammar , Shaw Chris , Smith Bradley , Neo Edmund J. , Morrison Karen , Shaw Pamela J. , Reeves Catherine , Winterkorn Lara , Wexler Nancy S. ,   The US-Venezuela Collaborative Research Group, Housman David E. , Ng Christopher , Li Alina , Taft Ryan J. , van den Berg Leonard H. , Bentley David R. , Veldink Jan H. , Eberle Michael A.
Published: December 2016

Identifying large repeat expansions such as those that cause amyotrophic lateral sclerosis (ALS) and Fragile X syndrome is challenging for short-read (100-150 bp) whole genome sequencing (WGS) data. A solution to this problem is an important step towards integrating WGS into precision medicine. We have developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3,001 ALS patients who have been tested for the presence of theC9orf72repeat expansion with repeat-primed PCR (RP-PCR). Taking the RP-PCR calls as the ground truth, our WGS-based method identified pathogenic repeat expansions with 98.1% sensitivity and 99.7% specificity. Further inspection identified that all 11 conflicts were resolved as errors in the original RP-PCR results. Compared against this updated result, ExpansionHunter correctly classified all (212/212) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2,786/2,789) of the wild type samples were correctly classified as wild type by this method with the remaining two identified as possible expansions. We further applied our algorithm to a set of 144 samples where every sample had one of eight different pathogenic repeat expansions including examples associated with fragile X syndrome, Friedreich’s ataxia and Huntington’s disease and correctly flagged all of the known repeat expansions. Finally, we tested the accuracy of our method for short repeats by comparing our genotypes with results from 860 samples sized using fragment length analysis and determined that our calls were >95% accurate. ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.
Genome Wide Computational Prediction of miRNAs in Kyasanur Forest Disease Virus and their Targeted Genes in Human
Authors: Saini Sandeep , Jyoti Chander , Kumar Varinder
Published: December 2016

RNAs are versatile biomolecules and can be coding or non-coding. Among the non-coding RNAs, miRNAs are small endogenous molecules that play important role in posttranscriptional gene regulation. miRNAs are identified in viruses too and involved in down regulation of host genes. Flavivirus family members are classified in to two groups: mosquito-borne flaviviruses (MBFV) and tick-borne flaviviruses (TBFV). Kyasanur forest disease virus (KFDV) found in India in 1957 (Karnataka) relates to TBFV. Virus has been diffuse to new areas in India and needs attention as it can cause severe hemorrhagic fever. Here in this study, we scanned the virus genome for prediction of miRNAs that can inhibit host target genes. VMir, tool was used for extraction of pre-miRNAs. A total of four miRNAs were found and submitted to ViralMir for classification in to real or pseudo. Interestingly, all four pre-miRNAs were classified as real. Eight mature miRNAs were located in pre-miRNAs by Mature Bayes. A total of 539 human target genes has been identified by using miRDB but ANGPT1 (angiopoietin 1) and TFRC (transferrin receptor) genes were screened to play role in hemorrhagic fever and neurological problems. GO analysis of target genes also supported the evidences.
Silversword and lobeliad reintroduction linked to landscape restoration on Mauna Loa and Kīlauea, and its implications for plant adaptive radiation in Hawaiʻi
Authors: Robichaux Robert H. , Moriyasu Patrice Y. , Enoka Jaime H. , McDaniel Sierra , Loh Rhonda K. , Bio Kealiʻi F. , Bakutis Ane , Tunison J. Timothy , Bergfeld Steven T. , Perry J. Lyman , Warshauer Frederick R. , Wasser Mark , Cole T. Colleen , Agorastos Nicholas R. , Cole Ian W. , Camara J. Kualiʻi , Rubenstein Tanya , Whitehead A. Nāmaka , VanDeMark Joshua R. , Loo Reid , Bruegmann Marie M.
Published: December 2016

The endemic Hawaiian silversword and lobeliad lineages, which are two of the world’s premier examples of plant adaptive radiation, exemplify the severity of the threats confronting the Hawaiian flora, especially the threats posed by alien species. We have implemented collaborative reintroduction efforts with the endangered Kaʻū silversword (Argyroxiphium kauense) and Pele lobeliad (Clermontiapeleana)in Hawaiʻi Volcanoes National Park. The efforts with the Kaʻū silversword have involved rediscovery, helicopter assisted rescue of diminutive remnant founders, managed breeding, outplanting at two sites in the Park of more than 21,000 seedlings deriving from 169 founders, and facilitated achene dispersal following flowering. The efforts with the Pele lobeliad have involved rediscovery, air-layering of remnant founders while suspended on climbing ropes, managed breeding, and outplanting at two sites in the Park of more than 1,000 seedlings (to date) deriving from six of the seven known founders. We have linked the reintroduction efforts to landscape restoration at large scales in the Park and in adjacent State and private lands, thereby increasing the opportunities for substantial population growth and expansion of the Kaʻū silversword and Pele lobeliad in the future. Additionally, we have extended the reintroduction efforts, including the link to landscape restoration, to encompass all other endangered silversword and lobeliad taxa occurring historically on the eastern slopes of Mauna Loa or on Kīlauea. In so doing, we seek to restore the possibility of adaptive radiation of the silversword and lobeliad lineages going forward, especially on the youngest and most geologically active, and thus perhaps most evolutionarily dynamic, part of the Hawaiian archipelago.

Dedication

This paper celebrates the centennial of Hawaiʻi Volcanoes National Park, which was founded in August 1916.
Environmental exposure does not explain putative maladaptation in road-adjacent populations
Authors: Brady Steven P.
Published: December 2016

While the ecological consequences of roads are well described, little is known of their role as agents of natural selection, which can shape adaptive and maladaptive responses in populations influenced by roads. This is despite a growing appreciation for the influence of evolution in human-altered environments. There, insights indicate that natural selection typically results in local adaptation. Thus populations influenced by road-induced selection should evolve fitness advantages in their local environment. Contrary to this expectation, wood frog tadpoles from roadside populations show evidence of a fitness disadvantage, consistent with local maladaptation. Specifically, in reciprocal transplants, roadside populations survive at lower rates compared to populations away from roads. A key question remaining is whether roadside environmental conditions experienced by early-stage embryos induce this outcome. This represents an important missing piece in evaluating the evolutionary nature of this maladaptation pattern. Here, I address this gap using a reciprocal transplant experiment designed to test the hypothesis that embryonic exposure to roadside pond water induces a survival disadvantage. Contrary to this hypothesis, my results show that reduced survival persists when embryonic exposure is controlled. This indicates that the survival disadvantage is parentally mediated, either genetically and/or through inherited environmental effects. This result suggests that roadside populations are either truly maladapted or potentially locally adapted at later life stages. I discuss these interpretations, noting that regardless of mechanism, patterns consistent with maladaptation have important implications for conservation. In light of the pervasiveness of roads, further resolution explaining maladaptive responses remains a critical challenge in conservation.
Fetal therapy model of myelomeningocele with three-dimensional skin using amniotic fluid cell-derived induced pluripotent stem cells
Authors: Kajiwara Kazuhiro , Tanemoto Tomohiro , Wada Seiji , Karibe Jurii , Ihara Norimasa , Ikemoto Yu , Kawasaki Tomoyuki , Ohishi Yoshie , Samura Osamu , Okamura Kohji , Takada Shuji , Akutsu Hidenori , Sago Haruhiko , Okamoto Aikou , Umezawa Akihiro
Published: December 2016

Myelomeningocele (MMC) is a congenital disease without genetic abnormalities. Neurological symptoms are irreversibly impaired after birth. No effective treatment has been reported to date. Only surgical repairs have reported so far. In this study, we performed antenatal treatment of MMC with an artificial skin using induced pluripotent stem cells (iPSCs) generated from a patient with Down syndrome (AF-T21-iPSCs) and twin–twin transfusion syndrome (AF-TTTS-iPSCs) to a rat model. We manufactured three-dimensional skin with epidermis generated from keratinocytes derived from AF-T21-iPSCs and AF-TTTS-iPSCs and dermis of human fibroblasts and collagen type I. For generation of epidermis, we developed a novel protocol using Y-27632 and epidermal growth factor. The artificial skin was successfully covered over MMC defect sites during pregnancy, implying a possible antenatal surgical treatment with iPSC technology.
Blood flow-induced Notch activation and endothelial migration enable embryonic vascular remodeling
Authors: Weijts Bart , Gutierrez Edgar , Saikin Semion K , Ablooglu Ararat J , Traver David , Groisman Alex , Tkachenko Eugene
Published: December 2016

Arteries and veins are formed independently by different types of endothelial cells (ECs). In vascular remodeling, arteries and veins become connected and some arteries become veins. It is unclear how ECs in transforming vessels change their type and how fates of individual vessels are determined. In embryonic trunk, vascular remodeling transforms arterial intersegmental vessels (ISVs) into a functional network of arteries and veins. We found that, once an ISV is connected to venous circulation, venous blood flow promotes upstream migration of ECs that results in displacement of arterial ECs by venous ECs, completing the transformation of this ISV into a vein without trans-differentiation of ECs. Arterial blood flow initiated in two neighboring ISVs prevents their transformation into veins by activating Notch signaling in ECs. Together, different responses of ECs to arterial and venous blood flow lead to the formation of a balanced network with equal numbers of arteries and veins.
Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease
Authors: Baillie J. Kenneth , Bretherick Andrew , Haley Christopher S. , Clohisey Sara , Gray Alan , Barret Jeffrey , Stahl Eli A. , Tenesa Albert , Andersson Robin , Brown J. Ben , Faulkner Geoffrey J. , Lizio Marina , Schaefer Ulf , Daub Carsten , Itoh Masayoshi , Kondo Naoto , Lassmann Timo , Kawai Jun ,   IIBDGC Consortium,   FANTOM5 Consortium, Bajic Vladimir B. , Heutink Peter , Rehli Michael , Kawaji Hideya , Sandelin Albin , Suzuki Harukazu , Satsangi Jack , Wells Christine A. , Hacohen Nir , Freeman Thomas C , Hayashizaki Yoshihide , Carninci Piero , Forrest Alistair R.R. , Hume David A.
Published: December 2016

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share patterns of transcriptional regulation. Accordingly, shared transcriptional regulation (coexpression) may help prioritise loci associated with a given trait, and help to identify the biological processes underlying it. Using cap analysis of gene expression (CAGE) profiles of promoter and enhancer-derived RNAs across 1824 human samples, we have quantified coexpression of RNAs originating from trait-associated regulatory regions using a novel analytical method (network density analysis; NDA). For most traits studied, sequence variants in regulatory regions were linked to tightly coexpressed networks that are likely to share important functional characteristics. These networks implicate particular cell types and tissues in disease pathogenesis; for example, variants associated with ulcerative colitis are linked to expression in gut tissue, whereas Crohn’s disease variants are restricted to immune cells. We show that this coexpression signal provides additional independent information for fine mapping likely causative variants. This approach identifies additional genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. This approach enables a deeper biological understanding of the causal basis of complex traits.

ONE SENTENCE SUMMARY

We discover that variants associated with a specific disease share expression profiles across tissues and cell types, enabling fine mapping and identification of new disease-associated variants, illuminating key cell types involved in disease pathogenesis.
Incidental identification of maternal malignancies in two Asian women underwent noninvasive prenatal test
Authors: Ji Xing , Chen Fang , Zhou Yafeng , Li Jia , Yuan Yuying , Mo Yu , Liu Qiang , Tseng Jen-Yu , Lin Diego Shih-Chieh , Shen Shu-Huei , Liu Yu , Ye Weiping , Zhang Hongyun , Liu Na , Shen Li , Jin Xin , Sung Pi-Lin , Mao Mao
Published: December 2016

Noninvasive prenatal test (NIPT) has been widely used as a screening test for trisomy 13, 18 and 21 worldwide. Recently, coexistence of maternal malignancy and pregnancy has drawn increasing attention in NIPT studies. Malignancy in pregnant women potentially affected NIPT results, which may cause false positive results or failed tests. However, no such case has ever been reported in Asian population. In this study, for the first time, we reported a stage III dysgerminoma and advanced gastric cancer during pregnancy accidentally identified during NIPT tests. These two women showed aberrant chromosome aneuploidies in NIPT results and concordant pattern of genome disruption found in tumor samples. The findings in this study further validate the effect of maternal malignancy on NIPT results and strengthen the possibility of detecting malignant tumors through NIPT in the future.
Second Generation Drosophila Chemical Tags: Sensitivity, Versatility and Speed
Authors: Sutcliffe Ben , Ng Julian , Auer Thomas O. , Pasche Mathias , Benton Richard , Jefferis Gregory S. X. E. , Cachero Sebastian
Published: December 2016

Labeling and visualizing cells and sub-cellular structures within thick tissues, whole organs and even intact animals is key to studying biological processes. This is particularly true for studies of neural circuits where neurons form sub-micron synapses but have arbors that may span millimeters in length. Traditionally labeling is achieved by immunofluorescence; however diffusion of antibody molecules (>100 kDa) is slow and often results in uneven labeling with very poor penetration into the centre of thick specimens; these limitations can be partially addressed by extending staining protocols to over a week (Drosophilabrain) and months (mice). Recently we developed an alternative approach using genetically encoded chemical tags CLIP, SNAP, Halo and TMP for tissue labeling; this resulted in >100 fold increase in labeling speed in both mice andDrosophila, at the expense of a considerable drop in absolute sensitivity when compared to optimized immunofluorescence staining. We now present a second generation of UAS and LexA responsive CLIP, SNAPf and Halo chemical labeling reagents for flies. These multimerized tags with translational enhancers display up to 64 fold increase in sensitivity over first generation reagents. In addition we developed a suite of conditional reporters (4xSNAPf tag and CLIP-SNAP-Halo) that are activated by the DNA recombinase Bxb1. Our new reporters can be used with weak and strong GAL4 and LexA drivers and enable stochastic, intersectional and multicolor Brainbow labeling. These improvements in sensitivity and experimental versatility, while still retaining the substantial speed advantage that is a signature of chemical labeling, should significantly increase the scope of this technology.
In situestimates of iron-oxidation and accretion rates for iron-oxidizing bacterial mats at Lō’ihi Seamount
Authors: Emerson David , Scott Jarrod J. , Leavitt Anna , Fleming Emily , Moyer Craig
Published: December 2016

It is increasingly recognized that diffuse, hydrothermal venting is an important source of iron to the deep-sea that can influence oceanic iron dynamics and abundance. Lithotrophic Fe-oxidizing bacteria (FeOB) are dominant at diffuse hydrothermal vent sites, producing microbial iron mats that are often centimeters or more thick. At present, little is known aboutin situFe-oxidation rates, or accretion rates for iron mats. Anin situproductivity chamber was developed that took advantage of the unique mineral morphotypes produced by FeOB to estimate rates of Fe-oxidation and accretion. Chambers were placed at two diffuse vents (1179 and 1300 mbsl) at Lō’ihi Seamount where they were colonized by FeOB for different amounts of time. From this analysis, it was estimated that Fe-oxidation rates could range from 8.2–51.9 × 10−6mol · hr−1, and that iron mats could accrete at around 2.2 cm · yr−1. Molecular analysis indicated that the relative abundance of Zetaproteobacteria, a group of known FeOB, accounted for 80–90% of the bacteria colonizing the chambers. There was a distinct difference between populations at the 1179m site (Pohaku), and the 1300m site (North Hiolo Ridge). Microscope slides placed within the productivity chambers were colonized by different morphotypes of FeOB. The cells responsible for one common morphotype that produces a Y-shaped filament were identified as Zetaproteobacteria by use of a small subunit rRNA probe. This work confirms the importance of FeOB in the formation of chemosynthetic iron mats, and provides the first estimates forin situFe-oxidation rates and mat accretion rates.

Highlights

Anin-situproductivity chamber was developed to estimate rates of Fe-oxidation and understand colonization patterns at chemosynthetic iron mats at Lō’ihi Seamount.

Fe-oxidation rates ranged from 8.2–51.9 × 10−6mol ˙ hr−1, and it was estimated that the iron mats could accrete at around 2.2 cm ˙ yr−1.

The iron mat community was dominated by Zetaproteobacteria, whose relative abundance accounted for up to 89% of the microbial community.

The community membership that grew during short-term incubations reflected the community composition of nearby microbial mats.
Malate-dependent Fe accumulation is a critical checkpoint in the root developmental response to low phosphate
Authors: Mora-Macías Javier , Ojeda-Rivera Jonathan Odilón , Gutiérrez-Alanís Dolores , Yong-Villalobos Lenin , Oropeza-Aburto Araceli , Raya González Javier , Jiménez-Domínguez Gabriel , Chávez-Calvillo Gabriela , Rellán-Álvarez Rubén , Herrera-Estrella Luis
Published: December 2016

Low phosphate (Pi) availability constrains plant development and crop production in both natural and agricultural ecosystems. When Pi is scarce, modifications of root system architecture (RSA) enhance soil exploration ability and can lead to an increase in Pi uptake. InArabidopsis, an iron-dependent determinate developmental program that induces premature differentiation in the root apical meristem (RAM) begins when the root tip contacts low Pi media, resulting in a short-root phenotype. However, the mechanisms that enable the regulation of root growth in response to Pi-limiting conditions remain largely unknown. Cellular, genomic and transcriptomic analysis of low-Pi insensitive mutants revealed that the malate-exudation related genesSENSITIVE TO PROTON RHIZOTOXICITY(STOP1) andALUMINUM ACTIVATED MALATE TRANSPORTER 1(ALMT1) represent a critical checkpoint in the root developmental response to Pi starvation inArabidopsis thaliana.
Hardy Weinberg Exact Test In Large Scale Variant Calling Quality Control
Authors: Huang Zhuoyi , Rustagi Navin , Zhi Degui , Cupples L. Adrienne , Gibbs Richard , Boerwinkle Eric , Yu Fuli
Published: December 2016

Hardy Weinberg Equilibrium (HWE) test is widely used as a quality control measure to detect sequencing artifacts like mismapping, allelic dropout and biases. However, in the high throughput sequencing era, where the sample size is beyond a thousand scale, the utility of HWE test in reducing the false positive rate remains unclear. In this paper, we demonstrate that HWE test has limited power in identifying sequencing artifacts when the variant allele frequency is lower than 1% in a variant call set produced from more than five thousand whole genome sequenced samples from two homogeneous populations. We develop a novel strategy of implementing HWE filtering in which we incorporate site frequency spectrum information and determine the p-value cutoff which optimizes the tradeoff between sensitivity and specificity. The novel strategy is shown to outperform the exact test of HWE with an empirical constant p-value cutoff regardless of the sequencing sample size. We also present best practice recommendations for identifying possible sources of false positives from large sequencing datasets based on an analysis of intrinsic biases in the variant calling process. Our novel strategy of determining the HWE test p-value cutoff and applying the test to the common variants provides a practical approach for the variant level quality controls in the upcoming sequencing projects with tens to hundreds of thousand of samples.
(E)-4-Methoxy-3,5-dimethyl-2-[(3-nitrophenyl)ethenyl]pyridine
Authors: El Bakri Youness , Ramli Youssef , Harmaoui Abdallah , Sebhaoui Jihad , Essassi El Mokhtar , Mague Joel T.
Published: December 2016

In the crystal of the title compound, C16H16N2O3, weak C—H...O hydrogen bonds involving the nitro group as acceptor form chains extending in theb-axis direction. The chains are arranged into layers by π–π stacking interactions along thec-axis direction between the substituted pyridine rings, separated by 3.624 (1) Å.