bluuebunny/crossref_metadata_2025 huggingface dataset:
The Surgical Management of Tibial Spine Fractures in Children: A Survey of the Pediatric Orthopaedic Society of North America (POSNA)
Authors: Jackson Taylor J. , Storey Eileen P. , Ganley Theodore J.
Published: September 2017

Background:

Tibial spine fractures are rare, complex injuries. Management remains varied given a lack of consensus about the optimal approach. Thus, the purpose of this study is to determine prevailing strategies among pediatric orthopaedists and establish areas of agreement and ongoing controversy in the management of tibial spine fractures.

Methods:

An electronic survey was distributed to the Pediatric Orthopaedic Society of North America (POSNA) membership. Surgeon demographics, experience, and responses to clinical vignettes were collected. Surgeons were grouped according to how frequently they treat tibial spine fractures and responses were compared.

Results:

Of the 180 POSNA members who completed the survey, all were attending surgeons and nearly all (90.4%) had academic affiliations, treated mostly skeletally immature patients (88.5%), and 3 or fewer fractures per year (62.4%). In younger patients, respondents were more likely to treat type II fractures closed and less likely to cross the physis. Arthrofibrosis was the most commonly reported complication and postoperative duration of immobilization was identified as a risk factor by most. However, high-frequency surgeons identified this risk factor more often (P=0.015) and recommended immobilization for <2 weeks more frequently (P=0.018). There was, however, considerable discrepancy regarding the duration of immobilization. Although there were areas of agreement on general principles, there continues to be disagreement regarding specific treatment strategies.

Conclusions:

Surgeons within POSNA agree on general principles of treatment for tibial spine fractures. Members, regardless of high-volume or low-volume caseload, are all less likely to pursue surgical options when treating younger patients and treating arthrofibrosis during the first 2 postoperative months. The most commonly reported adverse outcome after treatment was arthrofibrosis, for which high-frequency surgeons identified length of immobilization as a significant risk factor more often and thus, recommended shorter periods of immobilization. Although surgeons may agree on general principles in some cases, there continues to be disagreement regarding specific strategies suggesting that a prospective multicenter study of this topic is warranted.

Level of Evidence:

Level V.
10 Years Later: Lessons Learned from an Academic Multidisciplinary Cosmetic Center
Authors: Chen Jenny T. , Nayar Harry S. , Rao Venkat K
Published: September 2017

Background:

In 2006, a Centers for Medicare and Medicaid Services-accredited multidisciplinary academic ambulatory surgery center was established with the goal of delivering high-quality, efficient reconstructive, and cosmetic services in an academic setting. We review our decade-long experience since its establishment.

Methods:

Clinical and financial data from 2006 to 2016 are reviewed. All cosmetic procedures, including both minimally invasive and operative cases, are included. Data are compared to nationally published reports.

Results:

Nearly 3,500 cosmetic surgeries and 10,000 minimally invasive procedures were performed. Compared with national averages, surgical volume in abdominoplasty is high, whereas rhinoplasty and breast augmentation is low. Regarding trend data, breast augmentation volume has decreased by 25%, whereas minimally invasive procedural volume continues to grow and is comparable with national reports. Similarly, where surgical revenue remains steady, minimally invasive revenue has increased significantly. The majority of surgical cases (70%) are reconstructive in nature and insurance-based. Payer mix is 71% private insurance, 18% Medicare and Medicaid, and 11% self-pay. Despite year-over-year revenue increases, net profit in 2015 was $6,120. Rent and anesthesia costs exceed national averages, and employee salary and wages are the highest expenditure.

Conclusion:

Although the creation of our academic cosmetic ambulatory surgery center has greatly increased the overall volume of cosmetic surgery performed at the University of Wisconsin, the majority of surgical volume and revenue is reconstructive. As is seen nationwide, minimally invasive cosmetic procedures represent our most rapidly expanding revenue stream.
Hair Transplantation in Migraine Headache Patients
Authors: Ors Safvet
Published: September 2017

Background:

Migraine headache is a primary neurologic disease affecting millions of people worldwide. As a consequence, quality of life is diminished, productivity suffers (through loss of work force), and treatment costs are substantial. The occurrence rate in the general population is quite high, with women accounting for 3 of every 4 cases.

Methods:

Between January 2011 and May 2012, a total of 221 patients received hair transplants. Another 590 patients underwent hair transplantation between June 2012 and December 2016. Initially (first interval), patients were not questioned on migraine headaches in preoperative visits, but questioning was regularly done thereafter. Overall, 150 patients given transplants in the first period were surveyed by phone regarding preoperative migraine headaches. Aside from the 1 incidental discovery, no other instances of migraine emerged. Headache origins were occipital-frontal in 2 patients, occipital-temporal in 2 patients, and occipital-temporal-frontal in the 2 others. Donor/receiver areas in hair transplantation and migraine trigger zones shared locations. Headache frequencies ranged from 4 to 8 days per month (average, 6 days), and pain scores were 5–8 (10 being highest). Duration of pain was 3–5 hours (average, 4 hours). All six patients had used various medications, such as triptans, ergot, and nonsteroidal anti-inflammatory drugs, before hair transplantation. The 1 female patient was a 32-year-old seeking treatment for alopecia, with a 6-year history of migraine headaches. The male patients presenting with androgenetic alopecia (grade 4–5 by Norwood classification) had 6- to 20-year migrainous histories.

Results:

After hair transplantation, each migraine sufferer was checked once in the first month and then once every 3 months. Those who could not appear in person after the first year were evaluated by phone every 3 months. Migraine headaches had ceased in all 6 patients, none of whom used medical treatments for migraines thereafter. The postoperative improvement each patient experienced was dramatic (P < 0.001). Overall, the mean intensity of headaches declined from 6.6 ± 1.47 to 0, on an analog scale of 1–10 (P < 0.001); and mean headache frequency was reduced from 5.83 ± 1.03/month to 0/month (P < 0.001). Likewise, the migraine pain index fell from a mean of 149.33 ± 19.21/month to mean of 0/month (P < 0.001).

Conclusions:

This report details 6 patients who experienced abatement of migraine headache symptoms following hair transplantation. The positive effects of hair transplantation on migraine headache and potential mechanisms of action are also discussed.
Reconstruction of Near-Total Loss of the Upper and Lower Lips due to Purpura Fulminans with Local Tissue and a Dual-Skin Paddled Anterolateral Thigh Flap
Authors: Kuwahara Masamitsu , Yurugi Satoshi , Yamanaka Yuji , Sasaki Chikako , Nakanishi Takashi
Published: September 2017

It is difficult to totally reconstruct the lip, achieving good functional and aesthetic results. There have been few reports of reconstructing complete lip defects. Moreover, upper and lower lip necrosis by purpura fulminans has not been reported. We present a case of a 60-year-old male purpura fulminans patient with upper and lower lip necrosis. Fortunately, our patient had retained his oral commissure function. We reconstructed this defect with an orbicularis oris muscle-skin-mucosal pedicled flap derived from the region between the nasolabial folds for upper lip; a similar bipedicled flap for the lower lip and the donor site was closed with a dual-skin paddled anterolateral thigh flap. Postoperative results were satisfactory, that is, no lip tightness or aperture restriction was seen, and symmetry had been achieved. The new lips exhibited complete sensory recovery. Drooling was minimal during rest and feeding. We could select a method that combined the advantages of local and free flaps. We consider our method for this defect is superior to those described in previous studies, in that the restoration of lip sensation and oral sphincter function can be achieved to some extent in 1 stage while preserving the oral commissure function.
Simulation Training in Obstetrics
Authors: GAVIN NICOLE R. , SATIN ANDREW J.
Published: September 2017

Simulation now permeates all levels of training in obstetrics and maternal-fetal medicine. We will review the role of obstetric simulation through the continuum of training and practice. Simulation allows learners to acquire skills in a nonthreatening environment while avoiding harm to patients. Simulation in obstetrics evolved from a learning tool for students and residents, to a method for experienced physicians to learn new procedures and reenter the full breadth and depth of practice. Specialty boards and credentialing organizations recognize simulation training as an innovative approach to assess and assure technical, clinical, and teamwork skills.
Long-Term Stability of Keratometry, Scheimpflug-Derived True Net Power, and Total Corneal Refractive Power After Primary Pterygium Excision
Authors: Kam Ka Wai , Kuan Timothy A. , Belin Michael W. , Young Alvin L.
Published: September 2017

Purpose:

To evaluate long-term changes in mean keratometry, astigmatism, true net power (TNP), and total corneal refractive power (TCRP) of corneas after primary pterygium excision.

Methods:

This is a prospective observational series conducted at a tertiary teaching hospital eye center in Hong Kong. A total of 31 eyes of 31 patients with primary pterygium excision were included. Patients with recurrent or double-headed pterygia or a history of corneal scars from previous trauma, infection, or surgery were excluded. Data were collected prospectively at postoperative weeks 1, 4, 12, and month 18.

Results:

Mean keratometry of the anterior cornea was 44.3 diopters (D) [95% confidence interval (CI): 43.6–44.9 D] at week 1, 44.3 D (95% CI: 43.6–44.9 D, standard error = 0.3) at week 4, 44.3 D (95% CI: 43.7–44.9 D) at week 12, and 44.1 D (95% CI: 43.5–44.7 D) at month 18. Mean astigmatism of the anterior cornea was 1.1 D (95% CI: 0.7–1.4 D), 1.0 D (95% CI: 0.7–1.3 D), 0.9 D (95% CI: 0.6–1.1 D), and 1.0 D (95% CI: 0.7–1.3 D) at postoperative 1, 4, 12 weeks, and 18 months, respectively. Mean keratometry, astigmatism of the anterior and posterior cornea, TNP and TCRP at 2.0-mm, 3.0-mm, 4.0-mm rings and zones remained unchanged on all follow-up visits (P = 1 for all comparisons).

Conclusions:

Keratometric values including TNP and TCRP were stable as soon as 1 week after pterygium excision. This information might help clinicians in planning subsequent intraocular surgery that requires biometric assessment for intraocular lens implantation.
Bacterial Keratitis in Toronto: A 16-Year Review of the Microorganisms Isolated and the Resistance Patterns Observed
Authors: Tam Alex L. C. , Côté Elie , Saldanha Mario , Lichtinger Alejandro , Slomovic Allan R.
Published: September 2017

Purpose:

To review the incidence, distribution, current trends, and resistance patterns of bacterial keratitis isolates in Toronto over the past 16 years.

Methods:

Microbiology records of suspected bacterial keratitis that underwent a diagnostic corneal scraping and cultures from January 1, 2000, through December 31, 2015, were retrospectively reviewed. The distribution of the main isolated pathogens and in vitro laboratory minimum inhibitory concentration testing results were used to identify resistance patterns.

Results:

A total of 2330 corneal scrapings were taken over 16 years. A pathogen was recovered in 1335 samples (57.3%), with bacterial keratitis accounting for 1189 of the positive cultures (86.0% of all isolates). The total number of gram-positive and gram-negative isolates was 963 and 324, respectively. Coagulase-negative Staphylococcus and Pseudomonas aeruginosa were the most common gram-positive and gram-negative bacteria isolates, respectively. A decreasing trend in the number of isolates in gram-positive bacteria (P = 0.01), specifically among Staphylococcus aureus (P < 0.0001) and Streptococcus species (P = 0.005), was identified. When analyzing the susceptibilities of gram-positive and gram-negative isolates, an increasing trend in antibiotic resistance was observed in erythromycin (P = 0.018), ceftazidime (P = 0.046), and piperacillin/tazobactam (P = 0.005). The susceptibility of tested gram-positive microorganisms to vancomycin was 99.6%.

Conclusions:

There has been a decreasing trend in the number of isolates in gram-positive microorganisms over the past 16 years. An increasing trend in resistance for various antibiotics against gram-negative and gram-positive isolates was identified. High susceptibility to vancomycin reinforced the empirical use of fortified tobramycin and vancomycin in the initial management of severe bacterial keratitis.
Verruconis Gallopava
Authors: Grewal Harkiran K. , Kumar Princy N. , Shah Namrata , Timpone Joseph G.
Published: September 2017

Verruconis gallopava is a neurotropic dematiaceous mold that causes a wide range of infections in immunocompromised and occasionally immunocompetent individuals. This mold has unique pathogenic characteristics. We describe a case of recurrent/relapsing V. gallopava infection in a renal transplant patient, which occurred years after transplantation. To the best of our knowledge, this is the second case of recurrent V. gallopava infection reported in the literature. We also discuss the unique clinical characteristics of this organism in solid organ transplant recipients and review current literature describing the potential treatment options for this organism.
Design and Development of a Miniaturized Percutaneously Deployable Wireless Left Ventricular Assist Device: Early Prototypes and Feasibility Testing
Authors: Letzen Brian , Park Jiheum , Tuzun Zeynep , Bonde Pramod
Published: September 2017

The current left ventricular assist devices (LVADs) are limited by a highly invasive implantation procedure in a severely unstable group of advanced heart failure patients. Additionally, the current transcutaneous power drive line acts as a nidus for infection resulting in significant morbidity and mortality. In an effort to decrease this invasiveness and eliminate drive line complications, we have conceived a wireless miniaturized percutaneous LVAD, capable of being delivered endovascularly with a tether-free operation. The system obviates the need for a transcutaneous fluid purge line required in existing temporary devices by utilizing an incorporated magnetically coupled impeller for a complete seal. The objective of this article was to demonstrate early development and proof-of-concept feasibility testing to serve as the groundwork for future formalized device development. Five early prototypes were designed and constructed to iteratively minimize the pump size and improve fluid dynamic performance. Various magnetic coupling configurations were tested. Using SolidWorks and ANSYS software for modeling and simulation, several geometric parameters were varied. HQ curves were constructed from preliminary in vitro testing to characterize the pump performance. Bench top tests showed no-slip magnetic coupling of the impeller to the driveshaft up to the current limit of the motor. The pump power requirements were tested in vitro and were within the appropriate range for powering via a wireless energy transfer system. Our results demonstrate the proof-of-concept feasibility of a novel endovascular cardiac assist device with the potential to eventually offer patients an untethered, minimally invasive support.
Sensor-Based Physiologic Control Strategy for Biventricular Support with Rotary Blood Pumps
Authors: Wang Yu , Koenig Steven C. , Wu Zhongjun , Slaughter Mark S. , Giridharan Guruprasad A.
Published: September 2017

Rotary biventricular assist devices (BiVAD) are becoming a clinically accepted treatment option for end-stage biventricular failure. To improve BiVAD efficacy and safety, we propose a control algorithm to achieve the clinical objectives of maintaining left-right–sided balance, restoring physiologic flows, and preventing ventricular suction. The control algorithm consists of two proportional-integral (PI) controllers for left and right ventricular assist devices (LVAD and RVAD) to maintain differential pump pressure across LVAD (ΔP

L
) and RVAD (ΔP

R
) to provide left-right balance and physiologic flow. To prevent ventricular suction, LVAD and RVAD pump speed differentials (ΔRPM

L
, ΔRPM

R
) were maintained above user-defined thresholds. Efficacy and robustness of the proposed algorithm were tested in silico for axial and centrifugal flow BiVAD using 1) normal and excessive ΔP

L
and/or ΔP

R
setpoints, 2) rapid threefold increase in pulmonary vascular or vena caval resistances, 3) transient responses from exercise to rest, and 4) ventricular fibrillation. The study successfully demonstrated that the proposed BiVAD algorithm achieved the clinical objectives but required pressure sensors to continuously measure ΔP

L
and ΔP

R
. The proposed control algorithm is device independent, should not require any modifications to the pump or inflow/outflow cannulae/grafts, and may be directly applied to current rotary blood pumps for biventricular support.
A Useful Device to Measure Kinetics of Platelet Contraction
Authors: George Mitchell J. , Aroom Kevin R. , Skibber Max A. , Sharma Tushar , Wade Charles E. , Cox Charles S. , Gill Brijesh S.
Published: September 2017

Platelet contraction provides a minimally invasive source for physiologic information. In this article, we describe a device that directly measures the kinetics of platelet contraction. Whole blood is injected between acrylic plates and an adherent clot forms. The bottom plate is fixed, and the top plate is attached to a wire cantilever. Platelet contraction drives deflection of the wire cantilever which is captured by a camera. Force generated by the clot with time is derived using beam equations. Force derivations were verified using a microelectromechanical (MEMS) force sensor. Kinetics of clot contraction were defined, including maximum contraction force (FMAX), lift-off time (TLIFTOFF), and contraction rate (CR). Metrics were compared with optical aggregometry and thromboelastography. FMAX correlates with optical aggregometry maximal amplitude with a Spearman’s rho of 0.7904 and p = 0.0195 and thromboelastography maximal amplitude with a Spearman’s rho of 0.8857 and p = 0.0188. Lift-off time correlates with optical aggregometry lag time with a Spearman’s rho of 0.9048 and p = 0.002. This preliminary study demonstrates the repeatability of a useful platelet contraction device and its correlation with thromboelastography and optical aggregometry, the gold standard platelet function test.
Incidence and Outcome of Pericardial Effusion in Pediatric Patients After Hematopoietic Stem Cell Transplant: A Single-institution Experience
Authors: Diamond Melissa , Ruiz-Mesa Catalina , Corrales-Medina Fernando F. , Tamariz Leonardo J. , Ziga Edward , Swaminathan Sethuraman
Published: September 2017

Background:

Pericardial effusion (PE) is a known complication after hematopoietic stem cell transplant (HSCT). Limited data is currently available regarding the incidence and outcomes of PE in pediatric HSCT.

Methods:

We conducted a retrospective study on a cohort of patients who underwent HSCT between 2004 and 2015. Risk factors associated with development of PE were evaluated.

Results:

In 111 HSCT, stem cell source was bone marrow in 37 (33.3%), peripheral blood—42 (37.8%) and cord blood—32 (28.8%). Incidence of PE after HSCT was 37.8%. Insignificant effusion (trivial or small) was noted in 30 (27.0%) transplants, and significant (moderate or large) PE in 12 (10.8%). There were no associations between incidence of effusion and stem cell source, graft versus host disease or CMV infection. Risk factors associated with development of PE included systemic hypertension (P<0.05), total body irradiation (P<0.05), and sinusoidal obstruction syndrome formerly known as venoocclusive disease (P=0.03). Overall mortality was 22.5% after HSCT, but 38.1% among those with effusion (P<0.05). None of these deaths were attributed to primary cardiac etiologies.

Conclusions:

The incidence of PE in this cohort of pediatric HSCT recipients is high and associated with higher morbidity and mortality.
Best practice guidelines for the measurement of physical activity levels in stroke survivors: a secondary analysis of an observational study
Authors: Tinlin Louise , Fini Natalie , Bernhardt Julie , Lewis Lucy K. , Olds Tim , English Coralie
Published: September 2017

The aim of this study was to investigate the phenomenon of activity (increased activity in response to monitor wear) and determine the minimum wear time of accelerometers when objectively measuring habitual physical activity levels of community dwelling stroke survivors. Exploratory, secondary analyses of cross-sectional data were carried out. Physical activity variables [sitting, standing and stepping time, step count, light physical activity and moderate-to-vigorous physical activity (MVPA)] were measured with two activity monitors for 7 days. Repeated-measures analysis of variance was used to assess reactivity. Minimum wear time was assessed using regression analyses and median absolute differences. Paired t-tests were used to assess differences between weekend and weekday activity levels. There was no evidence of reactivity. Minimum wear time was 3 days for all activity variables, with the exception of MVPA, for which 7 days of monitoring was required. There were no significant differences in weekend and weekday activity levels. To accurately measure activity levels of individuals with stroke, we recommend 3 days of monitoring for all activity variables, with the exception of MVPA, which requires 7 days.
Improvements to Phakometry Using Bessel Beams
Authors: Suheimat Marwan , Bhattarai Dipesh , Maher Hannah K. , Chandra Meera , Chelepy William , Halloran Sarah K. , Lambert Andrew J. , Atchison David A.
Published: September 2017

SIGNIFICANCE

The main problem with phakometry is the low visibility of the third Purkinje image. We built a phakometer using Bessel beams, which have properties of being resistant to diffraction and the potential for self-reconstruction. This instrument had lenticular images three times brighter than those of a conventional phakometer.

PURPOSE

To investigate Purkinje image brightness, accuracy, and repeatability of a “Bessel” phakometer compared with those of a conventional phakometer.

METHODS

Phakometers were developed with a telecentric imaging system focused at the pupil plane of the eye to capture anterior cornea, anterior lens (PIII), and posterior lens (PIV) Purkinje images. A Bessel beam was generated by a diode laser beam passing through a high-powered doublet with a central obstruction. Software was used to determine image sizes and estimate lens anterior and posterior surface radii of curvature (R
a, R
p), equivalent refractive index (RI), and equivalent power (F). The Bessel phakometer's accuracy was assessed using a model eye. Repeatability (interobserver and intraobserver) and Purkinje images brightnesses of Bessel and conventional phakometers were assessed with six participants.

RESULTS

The lens parameters of the model eye determined by the Bessel phakometer were similar to those provided by the model eye's manufacturer with differences (manufacturer − Bessel) in R
a and R
p, RI, and F of +1.18 mm, 0.18 mm, +0.0053, and −0.55 D, respectively. The intraobserver repeatabilities for the Bessel and conventional phakometers were similar. The interobserver repeatabilities of R
a, R
p, and RI for the Bessel phakometer were almost half those (i.e., two times better) for the conventional phakometer. Brightnesses of PIII and PIV were approximately three times higher with the Bessel phakometer than with the conventional phakometer.

CONCLUSIONS

The Bessel beam phakometer provided accurate estimates of lens parameters of a model eye and produced brighter Purkinje images and better interobserver repeatability than that of a conventional phakometer.
Camouflaging Cleft Lip Scar Using Follicular Unit Extraction Hair Transplantation Combined with Autologous Fat Grafting
Authors: Akdag Osman , Evin Nuh , Karamese Mehtap , Tosun Zekeriya
Published: September 2017

Background:

The scar that occurs after cleft lip surgery poses a serious cosmetic problem. One of the methods used to solve this problem in adult male patients is hair transplantation. However, satisfactory results with this method cannot always be achieved because of possible graft loss. The corrective feature of fat grafting has been reported in many studies. The authors’ aim with this report is to share their results with hair transplantation combined with fat grafting in patients with cleft lip.

Methods:

This study included 20 patients who had both a scar and alopecia in the cleft lip area. The patients underwent fat grafting from the periumbilical region by means of miniature liposuction harvesting cannulas. Three months after fat injection, hair transplantation was performed with hair from the submental area and scalp using the folliculate unit extraction technique. Patients were followed for 12 months. Survival rate of transplanted hair and patient satisfaction were analyzed after the procedures.

Results:

After this camouflaging technique with fat grafting and hair transplantation, the scar was hidden quite well. The graft survival rate was also better compared with results from similar studies. Patient and observer satisfaction results with the scar tissue were significantly improved, which was confirmed statistically.

Conclusions:

This study demonstrates that this combined camouflaging technique is a very effective treatment in male patients with cleft lip who have serious secondary upper lip scars. The authors present a series of patients treated with this technique, which resulted in a high level of patient satisfaction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Acute Pancreatitis: A Complication of Intragastric Balloon
Authors: Aljiffry Murad , Habib Razan , Kotbi Eman , Ageel Amro , Hassanain Mazen , Dahlan Yaser
Published: September 2017

Purpose:

This study was carried out because intragastric balloon (IGB) is a widely used method to combat obesity, and acute pancreatitis complicating IGB is rare and yet to be understood.

Method:

This study was a retrospective analysis of all patients with a history of IGB insertion, who developed acute pancreatitis before balloon removal.

Results:

A total of 4 cases were found, with a mean age of 27±2.9 years. The mean duration of IGB insertion was 2.25±1.25 months, with an average body mass index of 37.7±3.4 kg/m2. Abdominal computed tomography visualized signs of pancreatitis with the balloon compressing the pancreatic body. Pancreatitis resolved after endoscopic balloon extraction, with an average aspiration of 607.5±64.5 mL of the fluid used to fill the balloon.

Conclusion:

Our study demonstrates that acute pancreatitis can complicate IGB and recommends the need to measure amylase and lipase in patients who have a history of IGB insertion and present with a picture suggestive of pancreatitis.
Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans
Authors: O’Donnell Michael P. , Chao Pin-Hao , Kammenga Jan E. , Sengupta Piali
Published: September 2017

Animals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms that are not fully understood. The conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in response to cellular stressors and growth factors. Here we show that TORC2 coordinates larval development and adult behaviors in response to environmental cues and feeding state in the bacterivorous nematodeC. elegans. During development, pheromone, bacterial food, and temperature regulate expression of thedaf-7TGF-β anddaf-28insulin-like peptide in sensory neurons to promote a binary decision between reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 acts in the intestine to regulate neuronal expression of bothdaf-7anddaf-28,which together reflect bacterial-diet dependent feeding status, thus providing a mechanism for integration of food signals with external cues in the regulation of neuroendocrine gene expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated foraging behaviors via the PDFR-1 neuropeptide receptor. We also demonstrate that genetic variation affects food-dependent larval and adult phenotypes, and identify quantitative trait loci (QTL) associated with these traits.Together, these results suggest that TORC2 acts as a hub for communication of feeding state information from the gut to the brain, thereby contributing to modulation of neuronal function by internal state.

AUTHOR SUMMARY

Decision-making in all animals, including humans, involves weighing available information about the external environment as well as the animals’ internal conditions. Information about the environment is obtained via the sensory nervous system, whereas internal state can be assessed via cues such as levels of hormones or nutrients. How multiple external and internal inputs are processed in the nervous system to drive behavior or development is not fully understood. In this study, we examine how the nematodeC. elegansintegrates dietary information received by the gut with environmental signals to alter nervous system function. We have found that a signaling complex, called TORC2, acts in the gut to relay nutrition signals to alter hormonal signaling by the nervous system inC. elegans. Altered neuronal signaling in turn affects a food-dependent binary developmental decision in larvae, as well as food-dependent foraging behaviors in adults. Our results provide a mechanism by which animals prioritize specific signals such as feeding status to appropriately alter their development and/or behavior.
Subfunctionalization versus neofunctionalization after whole-genome duplication
Authors: Sandve Simen R. , Rohlfs Rori V. , Hvidsten Torgeir R.
Published: September 2017

The question of what is the predominant evolutionary fate of genes after duplication events has been hotly debated for decades1,2. Two recently published articles in Nature (Lienet al.3) and Nature Genetics (Braaschet al.4) investigated the regulatory fate of gene duplicates after the salmonid-specific (Ss4R) and teleost specific (Ts3R) whole genome duplication (WGD) events, respectively. Both studies relied on tissue expression atlases for estimating regulatory divergence and used closely related unduplicated sister taxa (i.e. Northern pike and the spotted gar, respectively) as proxies for the ancestral expression state. Surprisingly, the two studies reach very different conclusions about the evolutionary mechanisms impacting gene expression after WGD. Braaschet al.4concluded that the expression divergence was consistent with partitioning of tissue regulation between duplicates (subfunctionalization), while Lienet al.3concluded that most divergence in tissue regulation were consistent with one copy maintaining ancestral tissue regulation while the other having diverged (in line with neofunctionalization). Here we show that this striking discrepancy in the conclusions of the two studies is a consequence of the data analysis approaches used, and is not related to underlying differences in the data.
Grip force adjustments reflect prediction of dynamic consequences in varying gravitoinertial fields
Authors: White Olivier , Thonnard Jean-Louis , Lefèvre Philippe , Hermsdörfer Joachim
Published: September 2017

One remarkable capacity when we grasp and manipulate tools relies on the ability to predict the grip force required to handle them in relation to their mechanical properties and the surrounding environment. However, rapid changes in the dynamical context may constitute a substantial challenge. Here, we test how participants can switch between different and never experienced dynamical environments induced by centrifugation of the body. Seven subjects lifted an object four times in a row successively in 1, 1.5, 2, 2.5, 2, 1.5 and 1g. We continuously measured grip force, load force and the gravitoinertial acceleration that was aligned with body axis (perceived gravity). Participants adopted stereotyped grasping movements immediately upon entry in a new environment and needed only one trial to adapt grip forces to a stable performance in each new gravity environment. While participants predictively applied larger grip forces when they expected increasing gravity steps, they did not decrease grip force proportionally when they expected decreasing gravity steps, indicating imperfect anticipation in that condition. The subjects’ performance could rather be explained by a combination of successful scaling of grip force according to gravity changes and a separate safety factor. The data suggest that in highly unfamiliar dynamic environments, grip force regulation is characterized by a combination of a successful anticipation of the experienced environmental condition, a safety factor reflecting strategic response to uncertainties about the environment and rapid feedback mechanisms to optimize performance under constant conditions.
An Interpretable Framework for Clustering Single-Cell RNA-Seq Datasets
Authors: Zhang Jesse M. , Fan Jue , Fan H. Christina , Rosenfeld David , Tse David N.
Published: September 2017

Background

With the recent proliferation of single-cell RNA-Seq experiments, several methods have been developed for unsupervised analysis of the resulting datasets. These methods often rely on unintuitive hyperparameters and do not explicitly address the subjectivity associated with clustering.

Results

In this work, we present DendroSplit, an interpretable framework for analyzing single-cell RNA-Seq datasets that addresses both the clustering interpretability and clustering subjectivity issues. DendroSplit offers a novel perspective on the single-cell RNA-Seq clustering problem motivated by the definition of “cell type,” allowing us to cluster using feature selection to uncover multiple levels of biologically meaningful populations in the data. We analyze several landmark single-cell datasets, demonstrating both the method’s efficacy and computational efficiency.

Conclusion

DendroSplit offers a clustering framework that is comparable to existing methods in terms of accuracy and speed but is novel in its emphasis on interpretabilty. We provide the full DendroSplit software package athttps://github.com/jessemzhang/dendrosplit.
Spatial and temporal translocation of PKCα in single endothelial cell in response to focal mechanical stimulus
Authors: Aarai Masataka , Sera Toshihiro , Hasegawa Takumi , Kudo Susumu
Published: September 2017

We observed the kinetics of protein kinase Cα (PKCα) and the intracellular Ca2+wave in endothelial cells (ECs) in response to microscopic mechanical stress to investigate the effect of mechanical stress on PKCα translocation. The results show that a focal mechanical stimulus induced biphasic and directional PKCα translocation; PKCα initially translocated toward distinct spots near or at the membrane and then accumulated at the stimulus point. The low initial translocation occurred simultaneously in parallel with the increase in Ca2+. Initial translocation was inhibited in spite of Ca2+increase when the diacylglycerol (DAG) binding domain of PKCα was inhibited, suggesting that translocation requires intracellular Ca2+increase and DAG. On the other hand, high secondary translocation was delayed, occurring after the Ca2+wave; however, this secondary translocation occurred even when Ca2+release from the endoplasmic reticulum was inhibited, while it did not occur when the mechanosensitive (MS) channel was inhibited. These results indicated that at least Ca2+influx through MS channels is required. Our results support the implication of PKCα in the Ca2+signaling pathway in response to mechanical stress in ECs.

Summary statement

In response to a focal mechanical stimulus, PKCα in an endothelial cell was initially translocated toward distinct spots near or at the membrane and then accumulated at the stimulus point.
MARS-Net: Deep learning-based segmentation pipeline for profiling cellular morphodynamics from multiple types of live cell microscopy
Authors: Jang Junbong , Wang Chuangqi , Zhang Xitong , Choi Hee June , Pan Xiang , Lin Bolun , Yu Yudong , Whittle Carly , Ryan Madison , Chen Yenyu , Lee Kwonmoo
Published: September 2017

Quantitative studies of cellular morphodynamics rely on extracting leading-edge velocity time-series based on accurate cell segmentation from live cell imaging. However, live cell imaging has numerous challenging issues about accurate edge localization. Here, we develop a deep learning-based pipeline, termed MARS-Net (Multiple-microscopy- type-based Accurate and Robust Segmentation Network), that utilizes transfer learning and the datasets from multiple types of microscopy to localize cell edges with high accuracy, allowing quantitative profiling of cellular morphodynamics. For effective training with the datasets from multiple types of live cell microscopy, we integrated the pretrained VGG-19 encoder with U-Net decoder and added dropout layers. Using this structure, we were able to train one neural network model that can accurately segment various live cell movies from phase contrast, spinning disk confocal, and total internal reflection fluorescence microscopes. Intriguingly, MARS-Net produced more accurate edge localization than the neural network models trained with single microscopy type datasets, whereas the standard U-Net could not increase the overall accuracy. We expect that MARS-Net can accelerate the studies of cellular morphodynamics by providing accurate segmentation of challenging live cell images.
A space and time-efficient index for the compacted colored de Bruijn graph
Authors: Almodaresi Fatemeh , Sarkar Hirak , Patro Rob
Published: September 2017

We present a novel data structure for representing and indexing the compacted colored de Bruijn graph, which allows for efficient pattern matching and retrieval of the reference information associated with each k-mer. As the popularity of the de Bruijn graph as an index has increased over the past few years, so have the number of proposed representations of this structure. Existing structures typically fall into two categories; those that are hashing-based and provide very fast access to the underlying k-mer information, and those that are space-frugal and provide asymptotically efficient but practically slower pattern search.

Our representation achieves a compromise between these two extremes. By building upon minimum perfect hashing, carefully organizing our data structure, and making use of succinct representations where applicable, our data structure provides practically fast k-mer lookup while greatly reducing the space compared to traditional hashing-based implementations. Further, we describe a sampling scheme built on the same underlying representation, which provides the ability to trade off k-mer query speed for a reduction in the de Bruijn graph index size. We believe this representation strikes a desirable balance between speed and space usage, and it will allow for fast search on large reference sequences.

Pufferfish is developed in C++11, is open source (GPL v3), and is available athttps://github.com/COMBINE-lab/Pufferfish. The scripts used to generate the results in this manuscript are available athttps://github.com/COMBINE-lab/pufferfish_experiments.
Modeling the schizophrenias: subunit-specific NMDAR antagonism dissociates frontalδand hippocampalθmodulation of ~140 Hz oscillations
Authors: Pittman-Polletta Benjamin , Hu Kun , Kocsis Bernat
Published: September 2017

NMDAR antagonism alters mesolimbic, hippocampal, and cortical function, acutely reproducing the positive, cognitive, and negative symptoms of schizophrenia. These physiological and behavioral effects may depend differentially on NMDAR subtype-and region-specific effects. The dramatic electrophysiological signatures of NMDAR blockade in rodents include potentiated high frequency oscillations (HFOs, ~140 Hz), likely generated in mesolimbic structures, and increased HFO phase-amplitude coupling (PAC), a phenomenon related to goal-directed behavior and dopaminergic tone. This study examined the impact of subtype-specific NMDAR antagonism on HFOs and PAC. We found that positive-symptom-associated NR2A-preferring antagonism (NVP-AAM077), but not NR2B-specific antagonism (Ro25-6985) or saline control, replicated increases in HFO power seen with nonspecific antagonism (MK-801). However, PAC following NR2A-preferring antagonism was distinct from all other conditions. Whileθ-HFO PAC was prominent or potentiated in other conditions, NVP-AAM077 increasedδ-HFO PAC and decreasedθ-HFO PAC. Furthermore, active wake epochs exhibiting narrowband frontalδoscillations, and not broadband sleep-associatedδ, selectively exhibitedδ-HFO coupling, while paradoxical sleep epochs having a high CA1θto frontalδratio selectively exhibitedθ-HFO coupling. Our results suggest: (1) NR2A-preferring antagonism induces oscillopathies reﬂecting frontal hyperfunction and hippocampal hypofunction; and (2) HFO PAC indexes cortical vs. hippocampal control of mesolimbic circuits.
Prediction of residue-residue contacts in CASP12 targets from its predicted tertiary structures
Authors: Agrawal Piyush , Singh Sandeep , Nagpal Gandharva , Sethi Deepti , Raghava Gajendra P.S.
Published: September 2017

One of the challenges in the field of structural proteomics is to predict residue-residue contacts in a protein. It is an integral part of CASP competitions due to its importance in the field of structural biology. This manuscript describes RRCPred 2.0 a method participated in CASP12 and predicted residue-residue contact in targets with high precision. In this approach, firstly 150 predicted protein structures were obtained from CASP12 Stage 2 tarball and ranked using clustering-based quality assessment software. Secondly, residue-residue contacts were assigned in top 10 protein structures based on distance between residues. Finally, residue-residue contacts were predicted in target protein based on consensus/average in top 10 predicted structures. This simple approach performs better than most of CASP12 methods in the categories of TBM and TBM/FM. It ranked 1stin following categories; i) TBM domain on list size L/5, ii) TBM/FM domain on list size L/5 and iii) TBM/FM domain on Top 10. These observations indicate that predicted tertiary structure of a protein can be used for predicting residue-residue contacts in protein with high accuracy.
Updating the 97% identity threshold for 16S ribosomal RNA OTUs
Authors: Edgar Robert C.
Published: September 2017

The 16S ribosomal RNA (rRNA) gene is widely used to survey microbial communities. Sequences are often clustered into Operational Taxonomic Units (OTUs) as proxies for species. The canonical clustering threshold is 97% identity, which was proposed in 1994 when few 16S rRNA sequences were available, motivating a reassessment on current data. Using a large set of high-quality 16S rRNA sequences from finished genomes, I assessed the correspondence of OTUs to species for five representative clustering algorithms using four accuracy metrics. All algorithms had comparable accuracy when tuned to a given metric. Optimal identity thresholds that best approximated species were ∼99% for full-length sequences and ∼100% for the V4 hypervariable region.
Incorporating trait-based mechanisms, alternative interaction modes and forbidden links increases the minimum trait dimensionality of ecological networks
Authors: Kiziridis Diogenis A. , Boddy Lynne , Eastwood Daniel C. , Yuan Chenggui , Fowler Mike S.
Published: September 2017

Species’ traits mediate ecological interaction outcomes and community structure. It is important, therefore, to identify the minimum number of traits required to characterise observed networks, i.e. the ‘minimum dimensionality’. Existing methods for estimating minimum dimensionality often lack three features commonly associated with a higher numbers of traits: a mechanistic description of observed interactions, alternative interaction modes (e.g. different feeding strategies such as activevssit-and-wait feeding), and trait-mediated ‘forbidden links’. Omitting these features can lead to underestimation of the trait numbers involved, and therefore, minimum dimensionality. Here, we develop a ‘minimum mechanistic dimensionality’ measure, accounting for these three features.

The only input required by our method is the observed network of interaction outcomes. We then assume how traits are mechanistically involved in alternative interaction modes. These unidentified traits are contrasted using pairwise performance inequalities between the interacting species. E.g. if a predator feeds upon a prey species via a typical predation mode, in each step of the predation sequence the predator’s performance must be greater than the prey’s. We construct a system of inequalities from all observed outcomes, which we attempt to solve with mixed integer linear programming. The minimum number of traits required for a feasible system of inequalities provides our dimensionality estimate.

We applied our method to 658 published empirical ecological networks including animal dominance, predator–prey, primary consumption, pollination, parasitism and seed dispersal networks, to compare with minimum dimensionality estimates when the three focal features are missing. Minimum dimensionality was typically higher when including alternative interaction modes (54% of empirical networks), ‘forbidden interactions’ as trait-mediated interaction outcomes (92%), or a mechanistic perspective (81%), compared to network dimensionality estimates missing these features.

Our method can reduce the risk of omitting essential traits that are involved mechanistically, in different interaction modes, or in failure outcomes. More accurate estimates will allow us to parameterise models to generate theoretical networks with a more realistic structure at the interaction outcome level. Thus, we hope our method can improve predictions of community structure and structure-dependent dynamics.
hichipper: A preprocessing pipeline for assessing library quality and DNA loops from HiChIP data
Authors: Lareau Caleb , Aryee Martin
Published: September 2017

Mumbach et al. recently described HiChIP, a novel protein-mediated chromatin conformation assay that lowers cellular input requirements while simultaneously increasing the yield of informative reads compared to previous methods. To facilitate the dissemination and adoption of this assay, we introduce hichipper (http://aryeelab.org/hichipper), an open-source HiChIP data preprocessing tool, with features that include bias-corrected peak calling, library quality control, DNA loop calling, and output of processed data for downstream analysis and visualization.