bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining a New Variable That May Impact Long-term Postoperative Nasal Tip Support
Authors: Sezgin Billur , Guney Kirdar , Lazoglu Ismail , Tatar Sedat , Layegh Ehsan , Ozel Melis , Ozmen Selahattin , Yavuzer Reha
Published: September 2018

Background

Although columellar strut grafts (CSGs) are considered among the fundamental steps for providing nasal tip support, a downward rotation of the nasal tip in patients with strut grafts can still be encountered. Patient-related factors such as nasal skin thickness can allow the plastic surgeon to anticipate certain drawbacks that can be encountered in the healing phase, but patient-based differences of nasal cartilage and the resulting impact have yet to be investigated. The purpose of this study was to evaluate the effect of the biomechanical properties of CSGs on late postoperative nasal tip position and support.

Methods

The study was undertaken with the participation of 20 patients undergoing closed-technique primary rhinoplasty with CSGs. Each cartilage specimen was biomechanically analyzed to calculate the modulus of elasticity. Preoperative and postoperative images were obtained to determine nasal tip position and rotation with quantitative measurements. Postoperative 3- and 12-month measurements were evaluated according to their relationship with the elasticity modulus of the utilized cartilages.

Results

The evaluation demonstrated that the elasticity modulus can impact the long-term support of the nasolabial angle in which an increase in the coefficient of elasticity can result in a decrease in long-term nasal tip support.

Conclusion

The results of the study reveal a new objective variable that can impact nasal tip dynamics and patient-related differences following rhinoplasty. This study not only brings forth a different perspective in the evaluation of nasal tip dynamics but can also provide data for determining ideal values for cartilage prefabrication.
Two Cases of Radial Ray Deficiency With Absence of First Metacarpus and 2 Tiny Fingers
Authors: Hosomi Kento , Iwasawa Motonao , Kitazawa Takeshi , Nagai Fumio
Published: September 2018

We report 2 cases showing both radial ray deficiency and thumb duplication. The common features of these cases were absence of the first metacarpus and presence of 2 tiny fingers. The features of our cases may have been due to continuous abnormality of the mesenchymal cells before limb bud formation and apical ectodermal ridge at the established limb bud. In 1 case, we created a 5-finger hand using 2 tiny floating fingers. Two fingers as vascularized bones with growth potential were useful to make 1 thumb. Two tendon transfers at 2 years of age were effective to allow gripping and pinching of objects. At 6 years of age, the thumb was lengthened by an iliac bone graft and a reverse forearm flap. At 27 years of age, the patient showed grip power of 20 kg in the affected hand. The Quick-DASH (the Japanese Society for Surgery of the Hand version) score was 4.6. The patient was satisfied with the appearance and function of the hand, although size discrepancy between the thumbs remained.
Endoscopic Thyroidectomy Using the Unilateral Axillo-breast Approach Versus the Modified Anterior Chest Wall Approach: A Prospective Comparative Study
Authors: Elzahaby Islam A. , Fathi Adel , Abdelwahab Khaled , Eldamshiety Osama , Metwally Islam H. , Abdallah Ahmed , Ramadan Mohamed M. , Kotb Sherif , Abdel Aziz Mahmoud , Refky Basel , Abouzid Amr , Saleh Saleh , Gaballah Khaled
Published: September 2018

Introduction:

Endoscopic thyroidectomy (ET) has become a well-established surgical technique that is mainly performed for benign thyroid lesions. Several endoscopic approaches are available, such as transaxillary, unilateral axillo-breast approach (UABA), modified anterior chest wall approach (MACWA), bilateral axillo-breast approach, and most recently the transoral approach and the robotic-assisted techniques. There is no recommended approach, because each approach has its own positive and negative attributes. We, herein, compare between UABA and MACWA in terms of surgical and cosmetic outcomes.

Methods:

This prospective study was conducted from April 2016 to August 2017. Forty patients with unilateral benign thyroid lesions were selected. Of them, 20 patients underwent ET using UABA, and 20 patients underwent ET using MACWA. Gas insufflation was implemented for all patients. Clinicopathologic data, surgical outcomes, and cosmetic outcomes in both groups were analyzed.

Results:

There was no significant difference between both groups in the clinicopathologic characteristics. The mean surgical time was significantly longer in the UABA group compared with the chest wall group (147.3 vs. 124.3 min). The postoperative pain scores were relatively lower in the UABA group compared with the MACWA group. We reported a higher rate of persistent paresthesia, neck contracture with swallowing discomfort, and hypertrophic scars in the MACWA group. Cosmetic satisfaction scores for patients who underwent UABA were higher than for those who underwent MACWA.

Conclusions:

Both approaches were similar in terms of safety, feasibility, and operative complications. Even though the surgical time was longer, patients who underwent the UABA reported relatively less postoperative pain, superior cosmetic results, scar perception, and patient satisfaction compared with MACWA.
Postoperative Opioid Prescribing Following Gynecologic Surgery for Pelvic Organ Prolapse
Authors: Leach D. Allan , Habermann Elizabeth B. , Glasgow Amy E. , Occhino John A.
Published: September 2018

Objectives

The aim of this study was to evaluate postoperative pain scores, quantity of prescribed opioids at hospital discharge, and need for additional opioid prescriptions among women undergoing surgical treatment of pelvic organ prolapse.

Methods

Institutional billing data were used to identify all patients undergoing pelvic reconstructive surgery between January 1, 2012, and May 30, 2017. Inpatient records were utilized to obtain prescription data (reported in oral morphine equivalents for standardization) and pain scores. The cohort was organized by surgical approach (open, endoscopic, vaginal), number of concomitant procedures, and patient age stratified by decade. These factors were then matched to postoperative pain scores, amount of opioid prescribed at discharge, and number of subsequent opioid refills. Pain scores and opioid use were also compared for correlation.

Results

One thousand eight hundred thirty patients underwent surgical treatment of pelvic organ prolapse and met criteria for study participation. A significant decrease in pain scores, mean oral morphine equivalents prescribed, and opioid refill rates was seen with increasing patient age by decade regardless of surgical approach. Pain scores were significantly different only between patients undergoing vaginal surgery with 0 concomitant procedures versus 1 or more concomitant procedures. Finally, pain scores were directly correlated to the amount of opioid prescribed.

Conclusions

Pain scores, opioid prescription amounts, and refills varied by patient age and surgical approach but were unaffected by concomitant procedures. Further work in correlating pain scores to opioid utilization is needed to ensure appropriate prescribing patterns and reduce risks of opioid dependence and diversion.
A Hypothesis Generating the Mechanical Systems Underlying Posterior Vaginal Prolapse Based on Observed Displacements by Dynamic Magnetic Resonance Imaging
Authors: Qiu Zhongyuan , Song Yanfeng
Published: September 2018

Objective

The aim of this study was to analyze quantified displacements of the posterior vaginal wall (PVW) on dynamic magnetic resonance imaging (MRI), which may generate hypotheses for the detailed mechanisms that underlie the development of posterior vaginal prolapse.

Methods

Pelvic dynamic MRI scans were obtained for 12 women with normal vaginal structure (stage 0) and 62 women with 4 consecutive stages (1–4) of posterior vaginal prolapse. Structural locations (apex vagina, distal vagina, and mid–perineal body [PB]) and equidistant points along the PVW (points 4–6 were considered as midvagina) were identified, and PVW length, straight distance of PVW, levator ani parameters (levator hiatus length [LHL], levator hiatus width [LHW], levator plate angle, anorectal angle, and M line [ML]), urogenital hiatus, and prolapse diameter were measured at rest and maximal Valsalva, respectively. The displacement of these measurements was obtained.

Results

From stage 0 to 2, the variables LHL, LHW, levator plate angle, anorectal angle, and ML increased gradually, but midvagina, distal vagina, and mid-PB were the opposite. From stage 2 to 3, apex vagina, midvagina, distal vaginal, mid-PB, LHL, LHW, and ML raised rapidly and peaked at stage 3, then declined at stage 4. In addition, the correlation coefficients between each measurement from stage 2 to 3 were statistically higher than those from stage 0 to 2.

Conclusions

Quantified displacements of the PVW and its supporting structure were shown on dynamic MRI, and the mechanical mechanisms were hypothesized regarding the interaction between pressure and the support force contributing to the deformation of the PVW and the supporting structures.
Effects of a restrictive blood transfusion protocol on acute pediatric burn care: Transfusion threshold in pediatric burns
Authors: Voigt Charles D. , Hundeshagen Gabriel , Malagaris Ioannis , Watson Kaitlin , Obiarinze Ruth N. , Hasanpour Houman , Woodson Lee C. , Capek Karel D. , Lee Jong O. , Nunez Lopez Omar , Cambiaso-Daniel Janos , Branski Ludwik K. , Norbury William B. , Finnerty Celeste C. , Herndon David N.
Published: September 2018

BACKGROUND

Blood transfusion is costly and associated with various medical risks. Studies in critically ill adult and pediatric patients suggest that implementation of more restrictive transfusion protocols based on lower threshold hemoglobin concentrations can be medically and economically advantageous. The purpose of this study was to evaluate the implications of a hemoglobin threshold change in pediatric burn patients.

METHODS

We implemented a change in hemoglobin threshold from 10 g/dL to 7 g/dL and compared data from patients before and after this protocol change in a retrospective review. Primary endpoints were hemoglobin concentration at baseline, before transfusion, and after transfusion; amount of blood product administered; and mortality. Secondary endpoints were the incidence of sepsis based on the American Burn Association physiological criteria for sepsis and mean number of septic days per patient. All endpoint analyses were adjusted for relevant clinical covariates via generalized additive models or Cox proportional hazard model. Statistical significance was accepted at p less than 0.05.

RESULTS

Patient characteristics and baseline hemoglobin concentrations (pre, 13.5 g/dL; post, 13.3 g/dL; p > 0.05) were comparable between groups. The group transfused based on the more restrictive hemoglobin threshold had lower hemoglobin concentrations before and after transfusion throughout acute hospitalization, received lower volumes of blood during operations (pre, 1012 mL; post, 824 mL; p < 0.001) and on days without surgical procedures (pre, 602 mL; post, 353 mL; p < 0.001), and had a lower mortality (pre, 8.0%; post, 3.9%; mortality hazard decline, 0.55 [45%]; p < 0.05). Both groups had a comparable incidence of physiological sepsis, though the more restrictive threshold group had a lower number of sepsis days per patient.

CONCLUSION

More restrictive transfusion protocols are safe and efficacious in pediatric burn patients. The associated reduction of transfused blood may lessen medical risks of blood transfusion and lower economic burden.

LEVEL OF EVIDENCE

Therapeutic, level IV
Emergency response teams in and outside of medicine—structurally crafted to be worlds apart
Authors: Fernandez-Moure Joseph , Pascual Jose L. , Martin Niels D. , Rodgers Holly , Kaplan Lewis J.
Published: September 2018

Medical emergency response teams (MERTs) are widespread throughout inpatient hospital care facilities. Besides the rise of the ubiquitous rapid response team, current MERTs span trauma, stroke, myocardial infarction, and sepsis in many hospitals. Given the multiplicity of teams with widely varying membership, leadership, and functionality, the structure of MERTs is appropriate to review to determine opportunities for improvement. Since nonmedical ERTs predate MERT genesis and are similar across multiple disciplines, nonmedical ERTs provide a standard against which to compare and review MERT design and function.

Nonmedical ERTs are crafted to leverage team members who are fully trained and dedicated to that domain, whose skills are regularly updated, with leadership tied to unique skill sets rather than based on hierarchical rank; activity is immediately reviewed at the conclusion of each deployment and teams continue to work together between team deployments. Medical emergency response teams, in sharp contradistinction, often incorporate trainees into teams that do not train together, are not focused on the discipline required to be leveraged, are led based on arrival time or hierarchy, and are usually reviewed at a time remote from team action; teams rapidly disperse after each activity and generally do not continue to work together in between team activations. These differences between ERTs and MERTs may impede MERT success with regard to morbidity and mortality mitigation. Readily deployable approaches to bridge identified gaps include dedicated Advanced Practice Provider (APP) team leadership, reductions in trainee MERT leadership while preserving participation, discipline-dedicated rescue teams, and interteam integration training.

Emergency response teams in medical and nonmedical domains share parallels yet lack congruency in structure, function, membership, roles, and performance evaluation. Medical emergency response team structural redesign may be warranted to embrace the beneficial elements of nonmedical ERTs to improve patient outcome and reduce variation in rescue practices and team functionality.
Negative Focused Abdominal Sonography for Trauma examination predicts successful nonoperative management in pediatric solid organ injury: A prospective Arizona-Texas-Oklahoma-Memphis-Arkansas + Consortium study
Authors: McGaha Paul , Motghare Prasenjeet , Sarwar Zoona , Garcia Nilda M. , Lawson Karla A. , Bhatia Amina , Langlais Crystal S. , Linnaus Maria E. , Maxson R. Todd , Eubanks James W. , Alder Adam C. , Tuggle David , Ponsky Todd A. , Leys Charles W. , Ostlie Daniel J. , St. Peter Shawn D. , Notrica David M. , Letton Robert W.
Published: September 2018

BACKGROUND

Focused Abdominal Sonography for Trauma (FAST) examination has long been proven useful in the management of adult trauma patients, however, its utility in pediatric trauma patients is not as proven. Our goal was to evaluate the utility of a FAST examination in predicting the success or failure of nonoperative management (NOM) of blunt liver and/or spleen (BLSI) in the pediatric trauma population.

METHODS

A retrospective analysis of a prospective observational study of patients younger than 18 years presenting with BLSI to one of ten Level I pediatric trauma centers between April 2013 and January 2016. 1,008 patients were enrolled and 292 had a FAST examination recorded. We analyzed failure of NOM of BLSI in the pediatric trauma population. We then compared FAST examination alone or in combination with the pediatric age adjusted shock index (SIPA) as it relates to success of NOM of BLSI.

RESULTS

Focused Abdominal Sonography for Trauma examination had a negative predictive value (NPV) of 97% and positive predictive value (PPV) of 13%. The odds ratio of failing with a positive FAST examination was 4.9 and with a negative FAST was 0.20. When combined with SIPA, a positive FAST examination and SIPA had a PPV of 17%, and an odds ratio for failure of 4.9. The combination of negative FAST and SIPA had an NPV of 96%, and the odds ratio for failure was 0.20.

CONCLUSION

Negative FAST is predictive of successful NOM of BLSI. The addition of a positive or negative SIPA score did not affect the PPV or NPV significantly. Focused Abdominal Sonography for Trauma examination may be useful clinically in determining which patients are not at risk for failure of NOM of BLSI and do not require monitoring in an intensive care setting.

LEVEL OF EVIDENCE

Prognostic study, level IV; therapeutic/care management, level IV.
Development of a Predictive Model for Hyperglycemia in Nondiabetic Recipients After Liver Transplantation
Authors: Zelada Henry , VanWagner Lisa B. , Pollack Teresa , Higginbotham Devan , Zhao Lihui , Yang Amy , Molitch Mark E. , Wallia Amisha
Published: September 2018

Background

Posttransplant hyperglycemia has been associated with increased risks of transplant rejection, infections, length of stay, and mortality.

Methods

To establish a predictive model to identify nondiabetic recipients at risk for developing postliver transplant (LT) hyperglycemia, we performed this secondary, retrospective data analysis of a single-center, prospective, randomized, controlled trial of glycemic control among 107 adult LT recipients in the inpatient period. Hyperglycemia was defined as a posttransplant glucose level greater than 200 mg/dL after initial discharge up to 1 month following surgery. Candidate variables with P less than 0.10 in univariate analyses were used to build a multivariable logistic regression model using forward stepwise selection. The final model chosen was based on statistical significance and additive contribution to the model based on the Bayesian Information Criteria.

Results

Forty-three (40.2%) patients had at least 1 episode of hyperglycemia after transplant after the resolution of the initial postoperative hyperglycemia. Variables selected for inclusion in the model (using model optimization strategies) included length of hospital stay (odds ratio [OR], 0.83; P < 0.001), use of glucose-lowering medications at discharge (OR, 3.76; P = 0.03), donor female sex (OR, 3.18; P = 0.02) and donor white race (OR, 3.62; P = 0.01). The model had good calibration (Hosmer-Lemeshow goodness-of-fit test statistic = 9.74, P = 0.28) and discrimination (C-statistic = 0.78; 95% confidence interval, 0.65-0.81, bias-corrected C-statistic = 0.78).

Conclusions

Shorter hospital stay, use of glucose-lowering medications at discharge, donor female sex and donor white race are important determinants in predicting hyperglycemia in nondiabetic recipients after hospital discharge up to 1 month after liver transplantation.
Identifying Incidence of and Risk Factors for Fluoroscopy-Guided Lumbar Puncture and Subsequent Persistent Low-Pressure Syndrome in Patients With Idiopathic Intracranial Hypertension
Authors: Lu Patricia , Goyal Manu , Huecker Julia B. , Gordon Mae O. , Van Stavern Gregory P.
Published: September 2018

Background:

To explore the incidence of and potential risk factors for developing persistent low-pressure syndrome after lumbar puncture (LP) in patients with idiopathic intracranial hypertension (IIH), as measured by use of blood patches.

Methods:

A retrospective chart review was conducted of patients with definitively diagnosed IIH by clinical examination and LP, comparing them to patients with multiple sclerosis (MS) as controls who also received diagnostic LPs. Demographic, clinical, and radiological data were collected for each patient. The main outcome measure was the rate of post-LP blood patches in IIH patients compared with MS patients. Secondary outcome measures were the likelihood of undergoing an epidural blood patch related to age, body mass index, volume removed, opening pressure, the difference between opening and closing pressure, and the level of puncture within the IIH cohort.

Results:

One hundred four IIH patients and 149 MS patients were included in the study. Among IIH patients, 12/104 (11.5%) underwent an epidural blood patch after LP as compared to 8/149 (5.4%) of the MS control patients (P = 0.086). Within the IIH population, none of the clinical or LP parameters were significantly correlated with increased risk of needing a blood patch.

Conclusions:

The incidence of low-pressure syndrome, as measured by blood patches, is similar in IIH patients and MS controls. This suggests that having elevated intracranial pressure before an LP is not protective against developing postpuncture low-pressure syndrome, contrary to common assumptions.
Predictive Value of Midline Spikes on Pediatric EEG for Seizure and Developmental Outcome
Authors: Datta Anita N. , Wallbank Laura , Xu Qi , Wong Peter K. H.
Published: September 2018

Purpose:

Midline spikes are epileptiform discharges localized to the midsagittal regions of the brain. Isolated midline spikes are rare, but more common in children. Our objective was to determine whether midline spikes are predictive of seizure characteristics and neurodevelopment.

Methods:

EEGs and clinical information of 123 children with isolated midline spikes, and EEG follow-up within 12 to 24 months, were reviewed and compared with controls.

Results:

Most children with midline spikes had seizures (91%), with an equal predisposition to focal or generalized seizure semiology. There was no difference between the midline spike and control groups in terms of neonatal complications, seizure characteristics (type, frequency, and etiology), and neurologic examination findings. In patients with abnormal neuro-maging, deep gray or white matter abnormalities were more frequent in the midline group (41% vs. 13%, P = 0.02). The midline group had a higher risk of development delay (DD) than controls (43% vs. 29%, odds ratio: 1.8, 95% CI [1.1–3.2], P = 0.03). A higher risk of DD was also noted in the midline group in those aged less than 4 years (52% vs. 26%, odds ratio: 3.1, 95% CI [1.0–9.2], P = 0.04) and in those without seizures (40% vs. 17%, odds ratio: 3.16, 95% CI [1.1–8.8], P = 0.03).

Conclusions:

This is the largest reported group of patients with midline spikes. Midline spikes have a strong association with seizures and DD. Our data suggest that midline spikes result from heterogeneous etiologies, are more common in young children, and are not benign.
Needle EMG of Thenar Muscles in Less Severe Carpal Tunnel Syndrome
Authors: Rubin Devon I. , Dimberg Elliot L.
Published: September 2018

Introduction:

The value of needle electromyography (EMG) in thenar muscles in patients with less severe carpal tunnel syndrome is controversial.

Methods:

Patients referred for electrodiagnostic testing for carpal tunnel syndrome, in which nerve conduction study demonstrated median sensory nerve conduction study abnormalities and either normal median motor nerve conduction study or only prolonged median motor distal latencies (DLs) (with normal amplitudes) were prospectively studied. Patients with low-median compound muscle action potential amplitudes or any other EMG abnormality were excluded. Needle EMG of a thenar muscle was performed to assess for the presence and grade of fibrillation potentials and motor unit potential abnormalities. The frequency of abnormalities was recorded. Statistical comparison between patients with and without needle EMG abnormalities was performed.

Results:

One-hundred two patients were included (50 with normal median motor DLs and 52 with abnormal DLs). Minimal or equivocal thenar needle EMG abnormalities were found in 12% of subjects with normal DLs. In patients with abnormal DLs, 32.6% had abnormalities, 15.4% with a mild degree of fibrillation potentials, and 25.0% with mild motor unit potential abnormalities. Patients with abnormal DLs and needle EMG abnormalities had significantly lower compound muscle action potential amplitudes compared to those without needle EMG changes.

Conclusions:

Patients with carpal tunnel syndrome with no involvement of the median motor nerve conduction study are unlikely to demonstrate prominent abnormalities on needle EMG of thenar muscles, and needle EMG of the thenar muscles is not necessary. However, in patients with carpal tunnel syndrome in which the median motor DL is prolonged but compound muscle action potential amplitudes are absolutely normal, needle EMG should be considered, as it may provide value in indicating some axonal loss despite a normal median compound muscle action potential amplitude.
Diversification dynamics of mammalian clades during the K–Pg mass extinction
Authors: Pires Mathias M. , Rankin Brian D. , Silvestro Daniele , Quental Tiago B.
Published: September 2018

The Cretaceous/Palaeogene (K–Pg) episode is an iconic mass extinction, in which the diversity of numerous clades abruptly declined. However, the responses of individual clades to mass extinctions may be more idiosyncratic than previously understood. Here, we examine the diversification dynamics of the three major mammalian clades in North America across the K–Pg. Our results show that these clades responded in dramatically contrasting ways to the K–Pg event. Metatherians underwent a sudden rise in extinction rates shortly after the K–Pg, whereas declining origination rates first halted diversification and later drove the loss of diversity in multituberculates. Eutherians experienced high taxonomic turnover near the boundary, with peaks in both origination and extinction rates. These findings indicate that the effects of geological episodes on diversity are context dependent and that mass extinctions can affect the diversification of clades by independently altering the extinction regime, the origination regime or both.
Inferring locomotor behaviours in Miocene New World monkeys using finite element analysis, geometric morphometrics and machine-learning classification techniques applied to talar morphology
Authors: Püschel Thomas A. , Marcé-Nogué Jordi , Gladman Justin T. , Bobe René , Sellers William I.
Published: September 2018

The talus is one of the most commonly preserved post-cranial elements in the platyrrhine fossil record. Talar morphology can provide information about postural adaptations because it is the anatomical structure responsible for transmitting body mass forces from the leg to the foot. The aim of this study is to test whether the locomotor behaviour of fossil Miocene platyrrhines could be inferred from their talus morphology. The extant sample was classified into three different locomotor categories and then talar strength was compared using finite-element analysis. Geometric morphometrics were used to quantify talar shape and to assess its association with biomechanical strength. Finally, several machine-learning (ML) algorithms were trained using both the biomechanical and morphometric data from the extant taxa to infer the possible locomotor behaviour of the Miocene fossil sample. The obtained results show that the different locomotor categories are distinguishable using either biomechanical or morphometric data. The ML algorithms categorized most of the fossil sample as arboreal quadrupeds. This study has shown that a combined approach can contribute to the understanding of platyrrhine talar morphology and its relationship with locomotion. This approach is likely to be beneficial for determining the locomotor habits in other fossil taxa.
Evolution of the calcium feedback steps of vertebrate phototransduction
Authors: Lamb Trevor D. , Hunt David M.
Published: September 2018

We examined the genes encoding the proteins that mediate the Ca-feedback regulatory system in vertebrate rod and cone phototransduction. These proteins comprise four families: recoverin/visinin, the guanylyl cyclase activating proteins (GCAPs), the guanylyl cyclases (GCs) and the sodium/calcium-potassium exchangers (NCKXs). We identified a paralogon containing at least 36 phototransduction genes from at least fourteen families, including all four of the families involved in the Ca-feedback loop (recoverin/visinin, GCAPs, GCs and NCKXs). By combining analyses of gene synteny with analyses of the molecular phylogeny for each of these four families of genes for Ca-feedback regulation, we have established the likely pattern of gene duplications and losses underlying the expansion of isoforms, both before and during the two rounds of whole-genome duplication (2R WGD) that occurred in early vertebrate evolution. Furthermore, by combining our results with earlier evidence on the timing of duplication of the visual G-protein receptor kinase genes, we propose that specialization of proto-vertebrate photoreceptor cells for operation at high and low light intensities preceded the emergence of rhodopsin, which occurred during 2R WGD.
A spatio-temporal model reveals self-limiting FcɛRI cross-linking by multivalent antigens
Authors: Shahinuzzaman Md , Khetan Jawahar , Barua Dipak
Published: September 2018

Aggregation of cell surface receptor proteins by multivalent antigens is an essential early step for immune cell signalling. A number of experimental and modelling studies in the past have investigated multivalent ligand-mediated aggregation of IgE receptors (FcɛRI) in the plasma membrane of mast cells. However, understanding of the mechanisms of FcɛRI aggregation remains incomplete. Experimental reports indicate that FcɛRI forms relatively small and finite-sized clusters when stimulated by a multivalent ligand. By contrast, modelling studies have shown that receptor cross-linking by a trivalent ligand may lead to the formation of large receptor superaggregates that may potentially give rise to hyperactive cellular responses. In this work, we have developed a Brownian dynamics-based spatio-temporal model to analyse FcɛRI aggregation by a trivalent antigen. Unlike the existing models, which implemented non-spatial simulation approaches, our model explicitly accounts for the coarse-grained site-specific features of the multivalent species (molecules and complexes). The model incorporates membrane diffusion, steric collisions and sub-nanometre-scale site-specific interaction of the time-evolving species of arbitrary structures. Using the model, we investigated temporal evolution of the species and their diffusivities. Consistent with a recent experimental report, our model predicted sharp decay in species mobility in the plasma membrane in response receptor cross-linking by a multivalent antigen. We show that, due to such decay in the species mobility, post-stimulation receptor aggregation may become self-limiting. Our analysis reveals a potential regulatory mechanism suppressing hyperactivation of immune cells in response to multivalent antigens.
A mathematical and numerical framework for near-field optics
Authors: Ammari Habib , Sung Choi Doo , Yu Sanghyeon
Published: September 2018

This paper is concerned with the inverse problem of reconstructing small and local perturbations of a planar surface using the field interaction between a known plasmonic particle and the planar surface. The aim is to perform a super-resolved reconstruction of these perturbations from shifts in the plasmonic frequencies of the particle-surface system. In order to analyse the interaction between the plasmonic particle and the planar surface, a well-chosen conformal mapping, which transforms the particle-surface system into a coated structure, is used. Then the even Fourier coefficients of the transformed domain are related to the shifts in the plasmonic resonances of the particle-surface system. A direct reconstruction of the perturbations of the planar surface is proposed. Its viability and limitations are documented by numerical examples.
An innovative ovipositor for niche exploitation impacts genital coevolution between sexes in a fruit-damaging
Drosophila
Authors: Muto Leona , Kamimura Yoshitaka , Tanaka Kentaro M. , Takahashi Aya
Published: September 2018

Limited attention has been given to ecological factors influencing the coevolution of male and female genitalia. The innovative ovipositor of
Drosophila suzukii
, an invading fruit pest, represents an appealing case to document this phenomenon. The serrated saw-like ovipositor is used to pierce the hard skin of ripening fruits that are not used by other fruit flies that prefer soft decaying fruits. Here, we highlight another function of the ovipositor related to its involvement in genital coupling during copulation. We compared the morphology and coupling of male and female genitalia in this species to its sibling species,
Drosophila subpulchrella
, and to an outgroup species,
Drosophila biarmipes
. These comparisons and a surgical manipulation indicated that the shape of male genitalia in
D. suzukii
has had to be adjusted to ensure tight coupling, despite having to abandon the use of a hook-like structure, paramere, because of the more linearly elongated ovipositor. This phenomenon demonstrates that ecological niche exploitation can directly affect the mechanics of genital coupling and potentially cause incompatibility among divergent forms. This model case provides new insights towards elucidating the importance of the dual functions of ovipositors in other insect species that potentially induce genital coevolution and ecological speciation.
Control of seminal fluid protein expression via regulatory hubs in
Drosophila melanogaster
Authors: Mohorianu Irina , Fowler Emily K. , Dalmay Tamas , Chapman Tracey
Published: September 2018

Highly precise, yet flexible and responsive coordination of expression across groups of genes underpins the integrity of many vital functions. However, our understanding of gene regulatory networks (GRNs) is often hampered by the lack of experimentally tractable systems, by significant computational challenges derived from the large number of genes involved or from difficulties in the accurate identification and characterization of gene interactions. Here we used a tractable experimental system in which to study GRNs: the genes encoding the seminal fluid proteins that are transferred along with sperm (the ‘transferome’) in
Drosophila melanogaster
fruit flies. The products of transferome genes are core determinants of reproductive success and, to date, only transcription factors have been implicated in the modulation of their expression. Hence, as yet, we know nothing about the post-transcriptional mechanisms underlying the tight, responsive and precise regulation of this important gene set. We investigated this omission in the current study. We first used bioinformatics to identify potential regulatory motifs that linked the transferome genes in a putative interaction network. This predicted the presence of putative microRNA (miRNA) ‘hubs’. We then tested this prediction, that post-transcriptional regulation is important for the control of transferome genes, by knocking down miRNA expression in adult males. This abolished the ability of males to respond adaptively to the threat of sexual competition, indicating a regulatory role for miRNAs in the regulation of transferome function. Further bioinformatics analysis then identified candidate miRNAs as putative regulatory hubs and evidence for variation in the strength of miRNA regulation across the transferome gene set. The results revealed regulatory mechanisms that can underpin robust, precise and flexible regulation of multiple fitness-related genes. They also help to explain how males can adaptively modulate ejaculate composition.
Hyoliths with pedicles illuminate the origin of the brachiopod body plan
Authors: Sun Haijing , Smith Martin R. , Zeng Han , Zhao Fangchen , Li Guoxiang , Zhu Maoyan
Published: September 2018

Hyoliths are a taxonomically problematic group of Palaeozoic lophotrochozoans that are among the first shelly fossils to appear in the Cambrian period. On the basis of their distinctive exoskeleton, hyoliths have historically been classified as a separate phylum with possible affinities to the molluscs, sipunculans or lophophorates—but their precise phylogenetic position remains uncertain. Here, we describe a new orthothecide hyolith from the Chengjiang Lagerstätte (Cambrian Series 2 Stage 3),Pedunculotheca dianiaSun, Zhao et Zhu gen. et sp. nov., which exhibits a non-mineralized attachment structure that strikingly resembles the brachiopod pedicle—the first report of a peduncular organ in hyoliths. This organ establishes a sessile, suspension feeding ecology for these orthothecides and—together with other characteristics (e.g. bilaterally symmetrical bivalve shell enclosing a filtration chamber and the differentiation of cardinal areas)—identifies hyoliths as stem-group brachiopods. Our phylogenetic analysis indicates that both hyoliths and crown brachiopods derived from a tommotiid grade, and that the pedicle has a single origin within the brachiopod total group.
Chromosomal copy number variation analysis by next generation sequencing confirms ploidy stability in Trypanosoma brucei subspecies
Authors: Almeida Laila Viana , Coqueiro-dos-Santos Anderson , Rodriguez-Luiz Gabriela F. , McCulloch Richard , Bartholomeu Daniella Castanheira , Reis-Cunha João Luís
Published: September 2018

Although aneuploidy usually results in severe abnormalities in multicellular eukaryotes, recent data suggest that it could be beneficial for unicellular eukaryotes, such as yeast and trypanosomatid parasites, providing increased survival under stressful conditions. Among characterized trypanosomatids, Trypanosoma cruzi, Trypanosoma brucei and species from the genus Leishmania stand out due to their importance in public health, infecting around 20 million people worldwide. The presence of aneuploidies in T. cruzi and Leishmania was recently confirmed by analysis based on next generation sequencing (NGS) and fluorescence in situ hybridization, where they have been associated with adaptation during transmission between their insect vectors and mammalian hosts and in promoting drug resistance. Although chromosomal copy number variations (CCNVs) are present in the aforementioned species, PFGE and fluorescence cytophotometry analyses suggest that aneuploidies are absent from T. brucei. A re-evaluation of CCNV in T. b gambiense based on NGS reads confirmed the absence of aneuploidies in this subspecies. However, the presence of aneuploidies in the other two T. brucei subspecies, T. b. brucei and T. b. rhodesiense, has not been evaluated using NGS approaches. In the present work, we tested for aneuploidies in 26 T. brucei isolates, including samples from the three T. brucei subspecies, by both allele frequency and read depth coverage analyses. These analyses showed that none of the T. brucei subspecies presents aneuploidies, which could be related to differences in the mechanisms of DNA replication and recombination in these parasites when compared with Leishmania.
First Whole-Body Three-Dimensional Tomographic Imaging of Alpha Particle Emitting Radium-223
Authors: Abou Diane S. , Rittenbach Andrew , Tomlinson Ryan E. , Finley Paige A. , Tsui Benjamin , Simons Brian W. , Ulmert David , Riddle Ryan C. , Thorek Daniel LJ
Published: September 2018

Objective: Dose optimization and pharmacokinetic evaluation of alpha emitting Radium-223 dichloride (223RaCl2) by planar gamma camera or single photon emission computed tomographic (SPECT) imaging are hampered by the low photon abundance and injection activities. Here, we demonstrate SPECT of 223Ra using phantoms and small animal in vivo models. Methods: Line phantoms and mice bearing 223Ra were imaged using a next generation dedicated small animal SPECT by detecting the low energy photon emissions from 223Ra. Localization of the therapeutic agent was verified by whole body and whole limb autoradiography and its effect determined by immunofluorescence. Results: A state-of-the-art commercial small animal SPECT system equipped with a highly sensitive collimator enables collection of sufficient counts for three-dimensional reconstruction. Line sources of 223Ra in both air and in a water scattering phantom gave linear response functions with provide full-width-at-half-maximum of 1.45 mm. Early and late phase imaging of the pharmacokinetics of the radiopharmaceutical were captured. Uptake at sites of active bone remodeling were correlated with DNA damage from the alpha particle emissions. Conclusions: This work demonstrates the capability to noninvasively define the distribution of 223Ra, a recently approved alpha emitting radionuclide. This approach allows quantitative assessment of 223Ra distribution and may provide radiation dose optimization strategies to improve therapeutic response and ultimately to enable personalized treatment planning.
Efficient generation of endogenous fluorescent reporters by Nested CRISPR in Caenorhabditis elegans
Authors: Vicencio Jeremy , Martínez-Fernández Adrian , Serrat Xènia , Cerón Julián
Published: September 2018

CRISPR-based genome editing methods in model organisms are evolving at an extraordinary speed. Whereas the generation of deletion or missense mutants is quite straightforward, the production of endogenous fluorescent reporters is still inefficient. The use of plasmids with selection markers is an effective methodology, but often requires laborious and complicated cloning steps. We have established a cloning-free ribonucleoprotein-driven Nested CRISPR method that robustly produces endogenous fluorescent reporters. This methodology is based on the division of the GFP and mCherry sequences in three fragments. In the first step we use ssDNA donors (≤200 bp) to insert 5’ and 3’ fragments in the place of interest. In the second step, we use these sequences as homology regions for Homology Directed Repair (HDR) with a dsDNA donor (PCR product, ≈700 bp) including the middle fragment, thus completing the fluorescent protein sequence. This method is advantageous because the first step with ssDNA donors is known to be very efficient, and the second step, uses universal reagents, including validated PCR products and crRNAs, to create fluorescent reporters reaching reliable editing efficiencies as high as 40%. We have also used Nested CRISPR in a non-essential gene to produce a deletion mutant in the first step and a transcriptional reporter in the second step.

In the search of modifications to optimize the method, we tested synthetic sgRNAs, but we did not observe a significant increase in the efficacy compared to independently adding tracrRNA and crRNA to the injection mix. Conveniently, we also found that both steps of Nested CRISPR could be performed in a single injection. Finally, we discuss the utility of Nested CRISPR for targeted insertion of long DNA fragments in other systems and prospects of this method in the future.
Using Google Trends to Examine the Spatio-Temporal Incidence and Behavioral Patterns of Dengue Disease: A Case Study in Metropolitan Manila, Philippines
Authors: Ho Howell T. , Carvajal Thaddeus M. , Bautista John Robert , Capistrano Jayson Dale R. , Viacrusis Katherine M. , Hernandez Lara Fides T. , Watanabe Kozo
Published: September 2018

Dengue is a major public health concern and an economic burden in the Philippines. Despite the country’s improved dengue surveillance, it still suffers from various setbacks and therefore needs to be complemented with alternative approaches. Previous studies have demonstrated the potential of internet-based surveillance such as Google Dengue Trends (GDT) in supplementing current epidemiological methods for predicting future dengue outbreaks and patterns. With this, our study aims to assess the temporal relationship of GDT and dengue incidence in Metropolitan Manila from previous years and examine web search behavior of the population towards the disease. The study collated and organized the population statistics and reported dengue cases in Metropolitan Manila from respective government agencies to calculate the spatial and temporal dengue incidence. The relative search volume of the term ‘dengue’ and top dengue-related search queries in Metropolitan Manila were obtained and organized from the Google trends platform. Data processing of GDT and dengue incidence was performed by conducting an ‘adjustment’ procedure and subsequently used for correlation and cross-correlation analyses. Moreover, a thematic analysis was employed on the top dengue-related search queries. Results revealed a high temporal relationship between GDT and dengue incidence when either one of the variables is adjusted. Cross-correlation showed that there is delayed effect (1-2 weeks) of GDT to dengue incidence, demonstrating its potential in predicting future dengue outbreaks and patterns in Metropolitan Manila. Thematic analysis of dengue-related search queries indicated 5 categories namely; (a) dengue, (b) sign and symptoms of dengue, (c) treatment and prevention, (d) mosquito and (e) other diseases where the majority of the search queries was ‘signs and symptoms’ which indicate the health-seeking behavior of the population towards the disease.
Cross-linking/Mass Spectrometry: A Community-Wide, Comparative Study Towards Establishing Best Practice Guidelines
Authors: Iacobucci Claudio , Piotrowski Christine , Aebersold Ruedi , Amaral Bruno C. , Andrews Philip , Borchers Christoph , Brodie Nicolas I. , Bruce James E. , Chaignepain Stéphane , Chavez Juan D. , Claverol Stéphane , Cox Jürgen , Degliesposti Gianluca , Dong Meng-Qiu , Edinger Nufar , Emanuelsson Cecilia , Gay Marina , Götze Michael , Gozzo Fabio C. , Gutierrez Craig , Haupt Caroline , Heck Albert J. R. , Herzog Franz , Huang Lan , Hoopmann Michael R. , Kalisman Nir , Klykov Oleg , Kukačka Zdeněk , Liu Fan , MacCoss Michael J. , Mechtler Karl , Mesika Ravit , Moritz Robert L. , Nagaraj Nagarjuna , Nesati Victor , Ninnis Robert , Novák Petr , O’Reilly Francis J , Pelzing Matthias , Petrotchenko Evgeniy , Piersimoni Lolita , Plasencia Manolo , Pukala Tara , Rand Kasper D. , Rappsilber Juri , Reichmann Dana , Sailer Caroline , Sarnowski Chris P. , Scheltema Richard A. , Schmidt Carla , Schriemer David C. , Shi Yi , Skehel J. Mark , Slavin Moriya , Sobott Frank , Solis-Mezarino Victor , Stephanowitz Heike , Stengel Florian , Stieger Christian E. , Trnka Michael , Vilaseca Marta , Viner Rosa , Xiang Yufei , Yilmaz Sule , Zelter Alex , Ziemianowicz Daniel , Leitner Alexander , Sinz Andrea
Published: September 2018

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has largely increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats that are generally accepted in the field and that have shown to lead to high-quality results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. From the results obtained, common protocols will be established. Our study serves as basis for establishing best practice guidelines in the field for conducting cross-linking experiments, performing data analysis, and reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results.