bluuebunny/crossref_metadata_2025 huggingface dataset:
Just-in-Time Video Laryngoscopy Versus Direct Laryngoscopy for Neonatal Intubation
Authors: Grgurich Erin , Arnemann Cynthia , Amon Kim , Horton Rose , Carlson Jestin N.
Published: October 2016

As neonatal endotracheal intubation (ETI) is a low-frequency, high-consequence event, it is essential that providers have access to resources to aid in ETI. We sought to determine the impact of video laryngoscopy (VL) with just-in-time training on intubation outcomes over direct laryngoscopy (DL) when performed by neonatal nurses. We conducted a prospective, randomized, crossover study with neonatal nurses employed at a level 2 neonatal intensive care unit (NICU). Nurses performed both DL and VL on a neonatal mannequin using a CMAC (Karl Storz Corp, Tuttlingen, Germany) either with the assistance of the screen (VL) or without (DL). Before performing the intubation, providers were given a just-in-time, brief education presentation and allowed to practice with the device. Each ETI attempt was reviewed to obtain the percentage of glottic opening (POGO) score, time to intubation (TTI, time from insertion of the blade into the mouth until the first breath was delivered), and time from blade insertion until the best POGO score. We enrolled 19 participants, with a median (interquartile range) of 20 (9-26) years of experience and having a median of 2 (1-3) intubations within the past year. None had used VL in the NICU previously. Median TTI did not differ between DL and VL: 19.9 (15.3-41.5) vs 20.3 (17.9-24.4) (P = 1). POGO scores and the number of attempts also did not differ between DL and VL. In our simulated setting, just-in-time VL training provided similar intubation outcomes compared with DL in ETI performed by neonatal nurses. Just-in-time VL education may be an alternative to traditional DL for neonatal intubations.
X-linked Malformation and Cochlear Implantation
Authors: Smeds Henrik , Wales Jeremy , Asp Filip , Löfkvist Ulrika , Falahat Babak , Anderlid Britt-Marie , Anmyr Lena , Karltorp Eva
Published: October 2016

Objective:

To evaluate if cochlear implantation is safe and constitutes an option for hearing rehabilitation of children with x-linked inner ear malformation.

Study Design:

Retrospective patient review in combination with a multidisciplinary follow-up.

Setting:

Tertiary referral hospital and cochlear implant program.

Patients:

Ten children with severe-profound mixed hearing loss and radiological findings consistent with Incomplete Partition type 3 cochlear malformation received cochlear implants during the years 2007 to 2015. Nine of the children had a mutation affecting the gene POU3F4 on Xq21.

Intervention:

Cochlear implantation.

Main Outcome Measures:

Surgical events, intraoperative measures and electrical stimulation levels, hearing and spoken language abilities.

Results:

In all, 15 cochlear implantations were performed. In three cases the electrode was found to be in the internal auditory canal on intraoperative x-ray and repositioned successfully. One child had a postoperative rhinorrhea confirmed to be cerebrospinal fluid but this resolved on conservative treatment. No severe complications occurred. Postoperative electrical stimulation levels were higher in 9 of 10 children, as compared with typically reported average levels in patients with a normal cochlea. Eight patients developed spoken language to various degrees while two were still at precommunication level. However, speech recognition scores were lower than average pediatric cases.

Conclusion:

Cochlear implantation is a safe procedure for children with severe-profound mixed hearing loss related to POU3F4 mutation inner ear malformation. The children develop hearing and spoken language but outcome is below average for pediatric CI recipients.
Hearing Changes After Intratympanically Applied Steroids for Primary Therapy of Sudden Hearing Loss: A Meta-analysis Using Mathematical Simulations of Drug Delivery Protocols
Authors: Liebau Arne , Pogorzelski Olivia , Salt Alec N. , Plontke Stefan K.
Published: October 2016

Objective:

Controlled and uncontrolled studies with primary intratympanic or combined intratympanic and systemic application of glucocorticosteroids for idiopathic sudden hearing loss were analyzed by means of a meta-analysis in an attempt to establish optimal local drug delivery protocols.

Study Design:

A total of 25 studies with 28 treatment groups between January 2000 and June 2014 were selected that adequately described drug delivery protocols. Cochlear drug levels were calculated by a validated computer model of drug dispersion in the inner ear fluids based on the concentration and volume of glucocorticoids applied, the time the drug remained in the middle ear, and the specific timing of injections. Various factors were compared with hearing outcome, including baseline data, individual parameters of the application protocols, calculated peak concentration (C
max), and total dose (area under the curve).

Results:

There was no dependence of hearing outcome on individual parameters of the application protocol, C
max, or area under the curve. Final hearing threshold was notably independent of delay of treatment.

Conclusion:

During primary intratympanic or combined steroid therapy of idiopathic sudden hearing loss, the tendency toward early treatment having a positive effect on hearing improvement is thought to be a “sham effect,” likely related to spontaneous recovery. Change in pure-tone average may not be an adequate outcome parameter to assess effectiveness of the intervention, as it depends on the degree of initial hearing loss. Final pure-tone average provides a better alternative.
Nystagmus at the Onset of Vertiginous Attack in Ménière's Disease
Authors: Hirai Chiaki , Yamamoto Yukiko , Takeda Takamori , Tasaki Akihisa , Inaba Yuichiro , Kiyokawa Yusuke , Suzuki Yasuhiro , Tsutsumi Takeshi
Published: October 2016

Objective:

To clarify the direction and characteristics of nystagmus at the onset of a vertiginous attack in Ménière's disease.

Patients:

Two patients with Ménière's disease, whose nystagmus at the onset of a vertiginous attack was recorded using electronystagmography.

Interventions:

Diagnostic.

Main Outcome Measures:

Electronystagmographic recordings of nystagmus.

Results:

In both patients, nystagmus was directed toward the affected side over the entire course of the vertiginous attack. One patient experienced a severe sensation of vertigo and exhibited strong nystagmus from the onset of the attack. The other patient reported a mild sensation of vertigo, which was accompanied by intermittent nystagmus.

Conclusions:

Vertiginous attacks in Ménière's disease are accompanied by irritative nystagmus. The intensity and characteristics (e.g., continuous or intermittent expression) of the nystagmus may be associated with pathophysiological severity.
Implantation of Bone-Anchored Hearing Devices Through a Minimal Skin Punch Incision Versus the Epidermal Flap Technique
Authors: Dumon Thibaud , Wegner Inge , Sperling Neil , Grolman Wilko
Published: October 2016

Objective:

To compare the minimal skin punch incision without additional skin incision or soft tissue reduction with the epidermal flap technique and soft tissue reduction, for the implantation of percutaneous bone-anchored hearing devices.

Study Design:

Prospective cohort study.

Setting:

Tertiary care referral center.

Subjects and Methods:

Two hundred seventeen patients underwent 220 implantations. Sixty five cases underwent implantation by means of a skin punch resection without soft tissue reduction (punch group) and 155 cases underwent epidermal flap and soft tissue reduction (dermatome group). Main outcome measures were duration of surgery, perioperative adverse events, skin tolerance, and revision surgery.

Results:

The duration of surgery was shorter in the punch group (p < 0.001). The percentage of normal to moderate skin reactions, by Holgers classification, was higher in the punch group (90%) than in the dermatome group (84%). No severe reactions occurred in the punch group, but did occur in 7% in the dermatome group. These differences, although clinically important, did not reach statistical significance (p = 0.071). The rate of revision surgeries was not significantly different between the two groups. The indication for revision was different: mainly for skin issues in the dermatome group, against implant dislocation in the punch group.

Conclusion:

The implantation of the currently available percutaneous bone-anchored hearing implants with a minimal skin punch resection shortened duration of surgery and improved postoperative appearance, while preserving a good skin tolerance. In the punch group, there were less skin issues leading to revision surgery, however we did observe more implant dislocations needing revision surgery.
Can Endoscopic Bleeding Control Improve the Prognosis of Advanced Gastric Cancer Patients?
Authors: Park Hyungchul , Ahn Ji Yong , Jung Hwoon-Yong , Chun Joo Hyun , Nam Kwangwoo , Lee Jeong Hoon , Jung Kee Wook , Kim Do Hoon , Choi Kee Don , Song Ho June , Lee Gin Hyug , Kim Jin-Ho
Published: October 2016

Background:

Gastric bleeding is not rare and difficult to treat in gastric cancer patients. We investigated whether this affects survival and if successful bleeding control improves the prognosis.

Patients/Material and Methods:

We retrospectively reviewed medical records for 64 subjects who underwent endoscopic therapy for gastric cancer bleeding at Asan Medical Center from January 2012 to December 2014 (bleeding group). Each subject was matched 1:2 by age, sex, and American Joint Committee on Cancer staging with 128 randomly selected patients treated for stomach cancer during the same period (control group). Median survival, bleeding treatment methods, successful bleeding control, and rebleeding rate were investigated.

Results:

The median age was 58.5 years, the male to female ratio 4.3:1. The initial hemostasis rate was 73.4%. Most patients were treated with a single method (37 patients, 57.8%); the coagrasper (32/95 cases, 33.7%) was the most frequently used treatment. Among the 47 patients in which successful bleeding control was achieved, 17 (36.2%) experienced rebleeding after 3 days. The median survival was longer in the control than in the bleeding group (18.5 vs. 6.5 mo), and in the successful bleeding control than in the failed bleeding control group (8.5 vs. 1.8 mo). However, the successful bleeding control group had lower survival than the control group (18.5 vs. 8.5 mo). Multivariate analysis showed that the risk of bleeding was lower in Borrmann type II, IV cancer, but was higher in the patients using antiplatelet or anticoagulant.

Conclusions:

Successful bleeding control is essential for improving survival in bleeding gastric cancer patients.
Optical Diagnosis of Sessile Serrated Polyps
Authors: Vleugels Jasper L.A. , IJspeert Joep E.G. , Hazewinkel Yark , van der Vlugt Manon , Fockens Paul , Koens Lianne , Dekker Evelien
Published: October 2016

Background:

Optical diagnosis of diminutive (1 to 5 mm) polyps could result in a more cost-effective colonoscopy practice. Previous optical diagnosis studies did not incorporate the differentiation of sessile serrated polyps (SSPs). This study aimed to evaluate the impact of optical diagnosis of diminutive SSPs on the overall performance of endoscopic polyp differentiation in daily colonoscopy practice.

Methods:

Endoscopy data were prospectively collected between 2011 and 2014 in a colonoscopy center. Each endoscopist reported a real-time optical diagnosis (SSP, adenoma or hyperplastic polyp) for all lesions in a structured colonoscopy reporting system, using narrow band imaging at their discretion. Study outcomes were accuracy of optical diagnosis, surveillance interval agreement and negative predictive value for diminutive rectosigmoid neoplastic histology based on the optical diagnosis of diminutive polyps compared to histopathology.

Results:

Of 2853 removed diminutive polyps, 202 (7.1%) were histologically proven SSPs. Optical diagnosis of diminutive SSPs was accurate in 24.4%. Diminutive SSPs determined 6.9% of postpolypectomy surveillance assignments. Inaccurate optical diagnosis of diminutive SSPs led to lower surveillance interval agreement (78.1% vs. 53.3%,P<0.01) and pooled negative predictive value per polyp (84.3% vs. 50.0%;P<0.01) in patients with diminutive SSPs when compared to patients without diminutive SSPs. Accurate endoscopic identification of diminutive SSPs improved from 0% in 2011 to 47% in 2014 (P=0.02).

Conclusions:

Endoscopic characterization of diminutive SSPs is difficult, impairing overall performance of optical diagnosis in patients with diminutive SSPs. Future optical diagnosis studies should use validated trainings and classification algorithms that include differentiation of SSPs.
Quality of Sleep and Coexistent Psychopathology Have Significant Impact on Fatigue Burden in Patients With Inflammatory Bowel Disease
Authors: Hashash Jana G. , Ramos-Rivers Claudia , Youk Ada , Chiu Wai Kan , Duff Kyle , Regueiro Miguel , Binion David G. , Koutroubakis Ioannis , Vachon Ashley , Benhayon David , Dunn Michael A. , Szigethy Eva M.
Published: October 2016

Background:

Fatigue is common in inflammatory bowel disease (IBD) patients and is associated with factors such as psychopathology, sleep quality, and disease activity.

Goal:

To investigate the combined role of all the above factors in the burden of fatigue among IBD patients.

Study:

We conducted an observational study of adult patients enrolled in an IBD clinical research registry at a tertiary care clinic. Fatigue burden was defined by Item 1 of the Short-form IBD Questionnaire (SIBDQ), which is scored on a 7-point Likert scale. Crohn’s disease (CD) and ulcerative colitis (UC) disease activity were measured with the Harvey-Bradshaw Index or the UC Activity Index, respectively. Labs were obtained to assess anemia, vitamin deficiencies, and inflammatory markers. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Use of psychotropic medications and narcotics was used as proxy measure of psychopathology and pain.

Results:

Among 685 IBD patients enrolled in the registry, 631 (238 UC, 393 CD) had a complete SIBDQ. High fatigue burden was found in 57.5% of patients (64.4% CD, 46.2% UC). Fatigue burden was significantly associated with sleep disturbance (PSQI), SIBDQ, and disease activity. CD patients had more fatigue burden than UC patients. Multivariate regression showed that poor quality of life, sleep disturbance, and being on a psychotropic medication are significantly associated with fatigue burden for both UC and CD.

Conclusion:

Because fatigue is common in IBD patients, these findings suggest that attention to quality of sleep and psychopathology is as important as medical disease management.
Adherence to a Semiannual Surveillance Program for Hepatocellular Carcinoma in Patients With Liver Cirrhosis
Authors: Mancebo Alejo , González-Diéguez María Luisa , Navascués Carmen A. , Cadahía Valle , Varela María , Pérez Ramón , Rodrigo Luis , Rodríguez Manuel
Published: October 2016

Background:

Patient adherence to screening for hepatocellular carcinoma (HCC) is not well known. Our aims were to analyze the adherence to a surveillance program in a prospective cohort of cirrhotic patients and to examine its association with HCC stage at diagnosis.

Materials and Methods:

A total of 770 patients with cirrhosis were examined semiannually by ultrasound and alpha-fetoprotein at a tertiary center. We collected data on 17 variables at baseline. Suboptimal adherence was defined as failure to complete 2 consecutive screening rounds.

Results:

Over a median follow-up period of 42.0 months (interquartile range: 60.0), 125 patients (16.2%) had suboptimal adherence. Active or previous intravenous drug use [hazard ratio (HR), 5.33; 95% confidence interval (CI), 3.07-9.23], active alcohol consumption (HR, 3.03; 95% CI, 2.03-4.51), absence of liver decompensation before the inclusion in the program (HR, 1.65; 95% CI, 1.07-2.55) and aspartate transaminase/alanine transaminase ratio ≥1.6 (HR, 1.82; 95% CI, 1.23-2.70) were independent predictors of suboptimal adherence. Compared with those with optimal adherence, patients with suboptimal adherence had a more advanced HCC stage at diagnosis (P=0.015), they were less frequently treated with curative intention (P=0.078) and survived less (median: 14.2 mo; IQR: 36.0 vs. 22.7 mo; IQR: 47.4; P=0.160), although these differences were not significant.

Conclusions:

The adherence to the process of HCC surveillance can be considered as adequate among cirrhotic patients. Active alcohol consumption and a history of intravenous drug use are the strongest predictors of suboptimal adherence. These patients have a more advanced HCC stage at diagnosis and tend to be less frequently treated with curative intention.
Real-Time Non-Intrusive Assessment of Viewing Distance during Computer Use
Authors: Argilés Marc , Cardona Genís , Pérez-Cabré Elisabet , Pérez-Magrané Ramon , Morcego Bernardo , Gispets Joan
Published: October 2016

Purpose

To develop and test the sensitivity of an ultrasound-based sensor to assess the viewing distance of visual display terminals operators in real-time conditions.

Methods

A modified ultrasound sensor was attached to a computer display to assess viewing distance in real time. Sensor functionality was tested on a sample of 20 healthy participants while they conducted four 10-minute randomly presented typical computer tasks (a match-three puzzle game, a video documentary, a task requiring participants to complete a series of sentences, and a predefined internet search).

Results

The ultrasound sensor offered good measurement repeatability. Game, text completion, and web search tasks were conducted at shorter viewing distances (54.4 cm [95% CI 51.3–57.5 cm], 54.5 cm [95% CI 51.1–58.0 cm], and 54.5 cm [95% CI 51.4–57.7 cm], respectively) than the video task (62.3 cm [95% CI 58.9–65.7 cm]). Statistically significant differences were found between the video task and the other three tasks (all p < 0.05). Range of viewing distances (from 22 to 27 cm) was similar for all tasks (F = 0.996; p = 0.413).

Conclusions

Real-time assessment of the viewing distance of computer users with a non-intrusive ultrasonic device disclosed a task-dependent pattern.
The Visual Impact of Lens-Induced Astigmatism is Linked to Habitual Axis
Authors: Hughes Amy R. , Mallen Edward A. H. , Elliott David B.
Published: October 2016

Purpose

Many studies have assessed the visual impact of astigmatism by inducing it using loose trial lenses at set axes. There are conflicting opinions and some confusion about the results, but the reduction in vision is typically least with lens-induced with-the-rule astigmatism. In this study, we determined whether a participant’s habitual astigmatism influences the impact of lens-induced astigmatism on distance visual acuity (VA).

Methods

Participants included 35 adults (age range 19–79, average 41.3 ± 15.4 years), who were either astigmats (≥0.75DC; N = 21) or non-astigmatic controls (N = 14). Distance VA was measured using an automated FrACT (Freiburg VA) system with the participant’s habitual correction, and then with the addition of a +1.00DC lens at either 90 or 180 degrees (control) or at and perpendicular to the axis of habitual astigmatism (astigmats).

Results

The reduction in VA with induced astigmatism was significantly affected by whether the participant was a with-the-rule astigmat, against-the-rule astigmat, or non-astigmat (p = 0.006). Lens-induced astigmatism axis ≈ 180 (160–20°) reduced the VA less than axis ≈ 90 (70–120°) in the control group (reduction in mean VA of 0.32 SD ± 0.10 with 95% confidence intervals of [0.27,0.37] compared to 0.42 ± 0.09 [0.37,0.47] logMAR) and with-the-rule astigmats (reduction in VA of 0.31 SD ± 0.06 [0.27,0.35] compared to 0.45 SD ± 0.12 [0.38,0.52] logMAR). The against-the-rule astigmats had a very similar reduction in VA with the ≈+1.00DC axis 180 condition compared to the ≈+1.00DC axis 90 condition (reduction in VA of 0.26 SD ± 0.09 [0.21,0.31] compared to 0.25 SD ± 0.14 [0.17,0.33] logMAR).

Conclusions

The impact of lens-induced astigmatism was dependent on the refractive status of the participants. When investigating the impact of lens-induced astigmatism, it is important to consider the participants’ habitual axis of astigmatism.
Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas
Authors: Agaimy Abbas , Bieg Matthias , Michal Michael , Geddert Helene , Märkl Bruno , Seitz Jan , Moskalev Evgeny A. , Schlesner Matthias , Metzler Markus , Hartmann Arndt , Wiemann Stefan , Michal Michal , Mentzel Thomas , Haller Florian
Published: October 2016

Infantile myofibroma (MF) is an uncommon benign myofibroblastic tumor of infancy and childhood. Solitary adult MF shares similar features with infantile MF. The lesions occur in 3 clinicopathologic settings: solitary, multicentric, and generalized and can be either sporadic or familial. Traditionally, infantile MF has been included in the spectrum of infantile hemangiopericytoma. The recent World Health Organization classification listed MF, angioleiomyoma, and myopericytoma under the general heading of perivascular tumors in the sense of a morphologic spectrum of perivascular myoid cell neoplasms. Although activating germline PDGFRB mutations have recently been linked to familial infantile MF, the molecular pathogenesis of sporadic infantile and adult solitary MF remained unclear. In this study, we analyzed 25 solitary MFs without evidence of familial disease (9 infantile and 16 adult MFs) to address the question whether somatic PDGFRB mutations might be responsible for the sporadic form of the disease. Given the presumed histogenetic link of MF to myopericytoma and angioleiomyoma, we additionally analyzed a control group of 6 myopericytomas and 9 angioleiomyomas for PDGFRB mutations. We detected PDGFRB mutations in 6/8 (75%) analyzable infantile and in 11/16 (69%) adult MFs but in none of the angioleiomyomas or myopericytomas. In 2 infantile MFs, additional sequencing of the germline confirmed the somatic nature of PDGFRB mutations. To our knowledge, this is the first study reporting apparently somatic recurrent PDGFRB mutations as molecular driver events in the majority of sporadic infantile and adult solitary MFs. Our results suggest molecular distinctness of MF as compared with angioleiomyoma/myopericytoma. Investigation of more cases including those with atypical and worrisome features, as well as other mimickers in the heterogenous morphologic spectrum of MF, is mandatory for validating the potential diagnostic value of PDGFRB mutation testing as a possible surrogate in difficult-to-classify lesions.
Key Histopathologic Features of Liver Biopsies That Distinguish Biliary Atresia From Other Causes of Infantile Cholestasis and Their Correlation With Outcome
Authors: Russo Pierre , Magee John C. , Anders Robert A. , Bove Kevin E. , Chung Catherine , Cummings Oscar W. , Finegold Milton J. , Finn Laura S. , Kim Grace E. , Lovell Mark A. , Magid Margret S. , Melin-Aldana Hector , Ranganathan Sarangarajan , Shehata Bahig M. , Wang Larry L. , White Frances V. , Chen Zhen , Spino Catherine
Published: October 2016

The liver biopsy guides diagnostic investigation and therapy in infants with undiagnosed cholestasis. Histologic features in the liver may also have prognostic value in the patient with biliary atresia (BA). We assessed the relative value of histologic features in 227 liver needle biopsies in discriminating between BA and other cholestatic disorders in infants enrolled in a prospective Childhood Liver Disease Research Network (ChiLDReN) cohort study by correlating histology with clinical findings in infants with and without BA. In addition, we reviewed 316 liver biopsies from clinically proven BA cases and correlated histologic features with total serum bilirubin 6 months after hepatoportoenterostomy (the Kasai procedure, HPE) and transplant-free survival up to 6 years. Review pathologists were blinded to clinical information except age. Semiquantitative scoring of 26 discrete histologic features was based on consensus. Bile plugs in portal bile ducts/ductules, moderate to marked ductular reaction, and portal stromal edema had the largest odds ratio for predicting BA versus non-BA by logistic regression analysis. The diagnostic accuracy of the needle biopsy was estimated to be 90.1% (95% confidence interval [CI]: 85.2%, 94.9%), whereas sensitivity and specificity for a diagnosis of BA are 88.4% (95% CI: 81.4, 93.5) and 92.7% (95% CI: 84.8, 97.3), respectively. No histologic features were associated with an elevated serum bilirubin 6 months after HPE, although it (an elevated serum bilirubin) was associated with an older age at HPE. Higher stages of fibrosis, a ductal plate configuration, moderate to marked bile duct injury, an older age at HPE, and an elevated international normalized ratio were independently associated with a higher risk of transplantation.
Mantle Cell Lymphoma With MYC Rearrangement
Authors: Hu Zhihong , Medeiros L. Jeffrey , Chen Zi , Chen Weina , Li Shaoying , Konoplev Sergej N. , Lu Xinyan , Pham Lan V. , Young Ken H. , Wang Wei , Hu Shimin
Published: October 2016

MYC rearrangement in mantle cell lymphoma (MCL) is rare, and its clinicopathologic significance is not well defined. We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients. There were 12 men and 5 women with a median age of 61 years (range, 49 to 81 y). Fourteen patients had lymphadenopathy (Ann Arbor stage III/IV), and 3 patients presented with a leukemic pattern without lymphadenopathy. Thirteen of 14 patients with available karyotyping data had a complex karyotype. In 8 cases the partner chromosome locus was an IG locus: t(8;14) (n=7) and t(8;22) (n=1). When MYC rearrangement was detected, most patients had a high-risk MCL international prognostic index, and the lymphoma cells had histologically aggressive features. Immunophenotypic analysis showed that the lymphoma cells were positive for cyclin D1 (n=16/16), Myc (9/11), and P53 (n=9/9). The Ki-67 proliferation rate was high (≥60%) in 10/11 cases. All patients received chemotherapy. The median follow-up time was 23 months. Clinical follow-up was available for 14 patients and treatment response in 13 patients. Eleven of 13 patients had refractory or relapsed disease, and 11 patients died. In conclusion, MCL with MYC rearrangement is characterized by advanced-stage disease, aggressive morphologic features, a high proliferation rate, p53 expression, a complex karyotype, and a poor prognosis. We believe these neoplasms fit within the overall concept of double-hit lymphoma, and the designation double-hit MCL may be helpful. We also believe that MYC rearrangement in MCL conveys important prognostic information that should be incorporated into the pathology report.
Studying vertical microbiome transmission from mothers to infants by strain-level metagenomic profiling
Authors: Asnicar Francesco , Manara Serena , Zolfo Moreno , Truong Duy Tin , Scholz Matthias , Armanini Federica , Ferretti Pamela , Gorfer Valentina , Pedrotti Anna , Tett Adrian , Segata Nicola
Published: October 2016

The gut microbiome starts to be shaped in the first days of life and continues to increase its diversity during the first months. Several investigations are assessing the link between the configuration of the infant gut microbiome and infant health, but a comprehensive strain-level assessment of vertically transmitted microbes from mother to infant is still missing. We longitudinally collected fecal and breast milk samples from multiple mother-infant pairs during the first year of life, and applied shotgun metagenomic sequencing followed by strain-level profiling. We observed several specific strains including those fromBifidobacterium bifidum,Coprococcus comes, andRuminococcus bromii, that were present in samples from the same mother-infant pair, while being clearly distinct from those carried by other pairs, which is indicative of vertical transmission. We further applied metatranscriptomics to study thein vivoexpression of vertically transmitted microbes, for exampleBacteroides vulgatusandBifidobacteriumspp., thus suggesting that transmitted strains are functionally active in the two rather different environments of the adult and infant guts. By combining longitudinal microbiome sampling and newly developed computational tools for strain-level microbiome analysis, we showed that it is possible to track vertical transmission of members of the microbiome from mother to infants and characterize their transcriptional activity. Our work poses the basis for surveying at larger scale the sources of microbial diversity in the infants and starts associating these transmissions with the subsequent longer-term development of a healthy or dysbiotic microbiome.

Importance

Early infant exposure is important in the acquisition and ultimate development of a healthy infant microbiome. There is increasing support that the maternal microbial reservoir is a key route of microbial transmission, yet much is inferred from the observation of shared species in mother and infant. Common species,per se, does not necessarily equate vertical transmission as species exhibit considerable strain heterogeneity and it is therefore imperative to identify shared strains. We demonstrate here the potential of shotgun metagenomics and strain-level resolution to identify vertical transmission events via the maternal source. Combined with a metatranscriptomic approach, we show the potential not only to identify and track the fate of microbes in the early infant microbiome but also identify the metabolically active members. These approaches will ultimately provide important insights into the acquisition, development and community dynamics of the infant microbiome.
Transposable elements activity reveals punctuated patterns of speciation in mammals
Authors: Ricci Marco , Peona Valentina , Guichard Etienne , Taccioli Cristian , Boattini Alessio
Published: October 2016

Transposable elements (TEs) play an essential role in shaping eukaryotic genomes and generating variability. Our “Cold Genome” hypothesis postulates that speciation and TEs activity are strongly related in mammals. In order to test this hypothesis, we created two new parameters: the Density of Insertion (DI) and the Relative Rate of Speciation (RRS). The DI is the ratio between the number of TE insertions in a genome and its size, whereas the RRS is a conditional parameter designed to identify potential speciation bursts. Thus, by analyzing TEs insertions in mammals, we defined the genomes as “hot” (low DI) and “cold” (high DI). Then, comparing TEs activity among 16 intra-order pairs of mammalian species, 4 superorders of Eutheria and 29 taxonomical families of the whole Mammalia class, we showed that taxa with positive RRS correlate with “hot” genomes, whereas taxa with negative RRS correlate with “cold” genomes. In addition, our study supports the “Punctuated Equilibria” theory in mammals for both adaptive radiation and stasis.
The p150N domain of Chromatin Assembly Factor-1 regulates Ki-67 accumulation on the mitotic perichromosomal layer
Authors: Matheson Timothy D. , Kaufman Paul D.
Published: October 2016

Chromatin Assembly Factor 1 (CAF-1) deposits histones during DNA synthesis. The p150 subunit of human CAF-1 contains an N-terminal domain (p150N) that is dispensable for histone deposition but which promotes the localization of specific loci (Nucleolar-Associated Domains, or “NADs”) and proteins to the nucleolus during interphase. One of the p150N-regulated proteins is proliferation antigen Ki-67, whose depletion also decreases the nucleolar association of NADs. Ki-67 is also a fundamental component of the perichromosomal layer (PCL), a sheath of proteins surrounding condensed chromosomes during mitosis. We show here that a subset of p150 localizes to the PCL during mitosis, and that p150N is required for normal levels of Ki-67 accumulation on the PCL. This activity requires the Sumoylation Interacting Motif (SIM) within p150N, which is also required for the nucleolar localization of NADs and Ki-67 during interphase. In this manner, p150N coordinates both interphase and mitotic nuclear structures via Ki67.
Optimized functional annotation of ChIP-seq data
Authors: Khomtchouk Bohdan B. , Koehler William C. , Booven Derek J. Van , Wahlestedt Claes
Published: October 2016

Motivation

Different ChIP-seq peak callers often produce different output results from the same input. Since different peak callers are known to produce differentially enriched peaks with a large variance in peak length distribution and total peak count, accurately annotating peak lists with their nearest genes can be an arduous process. Functional genomic annotation of histone modification ChIP-seq data can be a particularly challenging task, as chromatin marks that have inherently broad peaks with a diffuse range of signal enrichment (e.g., H3K9me1, H3K27me3) differ significantly from narrow peaks that exhibit a compact and localized enrichment pattern (e.g., H3K4me3, H3K9ac). In addition, varying degrees of tissue-dependent broadness of an epigenetic mark can make it difficult to accurately and reliably link sequencing data to biological function. Thus, there exists an unmet need to develop a software program that can precisely tailor the computational analysis of a ChIP-seq dataset to the specific peak coordinates of the data and its surrounding genomic features.

Results

geneXtendeRoptimizes the functional annotation of ChIP-seq peaks by exploring relative differences in annotating ChIP-seq peak sets to variable-length gene bodies. In contrast to prior techniques,geneXtendeRconsiders peak annotations beyond just the closest gene, allowing users to investigate peak summary statistics for the first-closest gene, second-closest gene, …,nth-closest gene whilst ranking the output according to biologically relevant events and iteratively comparing the fidelity of peak-to-gene overlap across a user-defined range of upstream and downstream extensions on the original boundaries of each gene’s coordinates. We testedgeneXtendeRon 547 human transcription factor ChIP-seq ENCODE datasets and 198 human histone modification ChIP-seq ENCODE datasets, providing the analysis results as case studies.

Availability

ThegeneXtendeRR/Bioconductor package (including detailed introductory vignettes) is available under the GPL-3 Open Source license and is freely available to download from Bioconductor at:https://bioconductor.org/packages/geneXtendeR/

Author summary

geneXtendeRmakes functional annotation of ChIP-seq data more robust and precise, regardless of peak variability attributable to parameter tuning or peak caller algorithmic differences. Since different ChIP-seq peak callers produce differentially enriched peaks with large variance in peak length distribution and total peak count, annotating peak lists with their nearest genes can often be a noisy process where an adjacent second or third-closest gene may constitute a more viable biological candidate, e.g., during cases of linked genes that are located close to each other. As such, the goal ofgeneXtendeRis to robustly link differentially enriched peaks with their respective genes, thereby aiding experimental follow-up and validation in designing primers for a set of prospective gene candidates during qPCR.
The human functional genome defined by genetic diversity
Authors: Iulio Julia di , Bartha Istvan , Wong Emily H.M. , Yu Hung-Chun , Hicks Michael , Shah Naisha , Lavrenko Victor , Kirkness Ewen F. , Fabani Martin M. , Yang Dongchan , Jung Inkyung , Biggs William H. , Ren Bing , Venter J. Craig , Telenti Amalio
Published: October 2016

Large scale efforts to sequence whole human genomes provide extensive data on the non-coding portion of the genome. We used variation information from 11,257 human genomes to describe the spectrum of sequence conservation in the population. We established the genome-wide variability for each nucleotide in the context of the surrounding sequence in order to identify departure from expectation at the population level (context-dependent conservation). We characterized the population diversity for functional elements in the genome and identified the coordination of conserved sequences of distal andcisenhancers, chromatin marks, promoters, coding and intronic regions. The most context-dependent conserved regions of the genome are associated with unique functional annotations and a genomic organization that spreads up to one megabase. Importantly, these regions are enriched by over 100-fold of non-coding pathogenic variants. This analysis of human genetic diversity thus provides a detailed view of sequence conservation, functional constraint and genomic organization of the human genome. Specifically, it identifies highly conserved non-coding sequences that are not captured by analysis of interspecies conservation and are greatly enriched in disease variants.
How to fold intricately: using theory and experiments to unravel the properties of knotted proteins
Authors: Jackson Sophie E. , Suma Antonio , Micheletti Cristian
Published: October 2016

Over the years, advances in experimental and computational methods have helped us to understand the role of thermodynamic, kinetic and active (chaperone-aided) effects in coordinating the folding steps required to achieving a knotted native state. Here, we review such developments by paying particular attention to the complementarity of experimental and computational studies. Key open issues that could be tackled with either or both approaches are finally pointed out.
Probing the effect of uniaxial compression on cell migration
Authors: Srivastava Nishit , Kay Robert R , Kabla Alexandre J
Published: October 2016

The chemical, physical and mechanical properties of the extra-cellular environment have a strong effect on cell migration. Aspects such as pore-size or stiffness of the matrix influence the selection of the mechanism used by cells to propel themselves, including pseudopod or blebbing. How a cell perceives its environment, and how such a cue triggers a change in behaviour are largely unknown, but mechanics is likely to be involved. Because mechanical conditions are often controlled by modifying the composition of the environment, separating chemical and physical contributions is difficult and requires multiple controls. Here we propose a simple method to impose a mechanical compression on individual cells without altering the composition of the gel. Live imaging during compression provides accurate information about the cell’s morphology and migratory phenotype. UsingDictyosteliumas a model, we observe that a compression of the order of 500 Pa flattens the cells under gel by up to 50%. This uniaxial compression directly triggers a transition in the mode of migration, from primarily pseudopodial to bleb driven, in less than 30 sec. This novel device is therefore capable of influencing cell migration in real time and offers a convenient approach to systematically study mechanotransduction in confined environments.
Binary Relation Extraction from Biomedical Literature using Dependency Trees and SVMs
Authors: Sharma Anuj , Virvilis Vassilis , Lekka Tina , Andronis Christos
Published: October 2016

The goal of Biomedical relation extraction is to uncover high-quality relations from life science literature with diverse applications in the ﬁelds of Biology and Medicine. In the last decade, several methods can be found in published literature ranging from binary to complex relation extraction. In this work, we present a binary relation extraction system that relies on sentence level dependency features. We use a novel approach to map dependency tree based rules to feature vectors that can be used to train a classiﬁer. We build a SVM classiﬁer using these feature vectors and our experimental results show that it outperforms simple co-occurrence and rule-based systems. Through our experiments, using two ‘real-world’ examples, we quantify the positive impact of improved relation extraction on Literature Based Discovery.
Regulation of sleep plasticity by a thermo-sensitive circuit inDrosophila
Authors: Lamaze Angelique , Öztürk-Çolak Arzu , Fischer Robin , Peschel Nicolai , Koh Kyunghee , Jepson James E.C.
Published: October 2016

Sleep is a highly conserved and essential behaviour in many species, including the fruit fly Drosophila melanogaster. In the wild, sensory signalling encoding environmental information must be integrated with sleep drive to ensure that sleep is not initiated during detrimental conditions. However, the molecular and circuit mechanisms by which sleep timing is modulated by the environment are unclear. Here we introduce a novel behavioural paradigm to study this issue. We show that in male fruit flies, onset of the daytime siesta is delayed by ambient temperatures above 29°C. We term this effect Prolonged Morning Wakefulness (PMW). We show that signalling through the TrpA1 thermo-sensor is required for PMW, and that TrpA1 specifically impacts siesta onset, but not night sleep onset, in response to elevated temperatures. We identify two critical TrpA1-expressing circuits and show that both contact DN1p clock neurons, the output of which is also required for PMW. Finally, we identify the circadian blue-light photoreceptor CRYPTOCHROME as a molecular regulator of PMW. We propose a model in which the Drosophila nervous system integrates information encoding temperature, light, and time to dynamically control when sleep is initiated. Our results provide a platform to investigate how environmental inputs co-ordinately regulate sleep plasticity.
Reverse-engineering human olfactory perception from chemical features of odor molecules
Authors: Keller Andreas , Gerkin Richard C. , Guan Yuanfang , Dhurandhar Amit , Turu Gabor , Szalai Bence , Mainland Joel D. , Ihara Yusuke , Yu Chung Wen , Wolfinger Russ , Vens Celine , Schietgat Leander , De Grave Kurt , Norel Raquel ,   DREAM Olfaction Prediction Challenge Consortium, Stolovitzky Gustavo , Cecchi Guillermo , Vosshall Leslie B. , Meyer Pablo
Published: October 2016

Despite 25 years of progress in understanding the molecular mechanisms of olfaction, it is still not possible to predict whether a given molecule will have a perceived odor, or what olfactory percept it will produce. To address this stimulus-percept problem for olfaction, we organized the crowd-sourced DREAM Olfaction Prediction Challenge. Working from a large olfactory psychophysical dataset, teams developed machine learning algorithms to predict sensory attributes of molecules based on their chemoinformatic features. The resulting models predicted odor intensity and pleasantness with high accuracy, and also successfully predicted eight semantic descriptors (“garlic”, “fish”, “sweet”, “fruit”, “burnt”, “spices”, “flower”, “sour”). Regularized linear models performed nearly as well as random-forest-based approaches, with a predictive accuracy that closely approaches a key theoretical limit. The models presented here make it possible to predict the perceptual qualities of virtually any molecule with an impressive degree of accuracy to reverse-engineer the smell of a molecule.

One Sentence Summary

Results of a crowdsourcing competition show that it is possible to accurately predict and reverse-engineer the smell of a molecule.
CELL-TO-CELL MODELING OF THE INTERFACE BETWEEN ATRIAL AND SINOATRIAL ANISOTROPIC HETEROGENEOUS NETS
Authors: López Gabriel , Castellanos Norma P. , Godínez Rafael
Published: October 2016

ABSTRACT

The transition between Sinoatrial cells and Atrial cells in the Heart is not fully undefirst ood. Here we focus in cell-to-cell mathematical models involving typical Sinoatrial cells and Atrial cells connected with experimentally observed conductance values exclusively. We are interested mainly in the geometry of the microstructure of the conduction paths in the Sinoatrial Node. We show with some models that appropriate source-sink relationships between Atrial and Sinoatrial cells may occur according to certain geometric arrangements.
The genome-wide transcriptional response to varying RpoS levels inEscherichia coliK-12
Authors: Wong Garrett T. , Bonocora Richard P. , Schep Alicia N. , Beeler Suzannah M. , Lee Fong Anna J. , Shull Lauren M. , Batachari Lakshmi E. , Dillon Moira , Evans Ciaran , Becker Carla J. , Bush Eliot C. , Hardin Johanna , Wade Joseph T. , Stoebel Daniel M.
Published: October 2016

The alternative sigma factor RpoS is a central regulator of a many stress responses inEscherichia coli.The level of functional RpoS differs depending on the stress. The effect of these differing concentrations of RpoS on global transcriptional responses remains unclear. We investigated the effect of RpoS concentration on the transcriptome during stationary phase in rich media. We show that 23% of genes in theE. coligenome are regulated by RpoS level, and we identify many RpoS-transcribed genes and promoters. We observe three distinct classes of response to RpoS by genes in the regulon: genes whose expression changes linearly with increasing RpoS level, genes whose expression changes dramatically with the production of only a little RpoS (“sensitive” genes), and genes whose expression changes very little with the production of a little RpoS (“insensitive”). We show that sequences outside the core promoter region determine whether a RpoS-regulated gene in sensitive or insensitive. Moreover, we show that sensitive and insensitive genes are enriched for specific functional classes, and that the sensitivity of a gene to RpoS corresponds to the timing of induction as cells enter stationary phase. Thus, promoter sensitivity to RpoS is a mechanism to coordinate specific cellular processes with growth phase, and may also contribute to the diversity of stress responses directed by RpoS.

Importance

The sigma factor RpoS is a global regulator that controls the response to many stresses inEscherichia coli.Different stresses result in different levels of RpoS production, but the consequences of this variation are unknown. We describe how changing the level of RpoS does not influence all RpoS-regulated genes equally. The cause of this variation is likely the action of transcription factors that bind the promoters of the genes. We show that the sensitivity of a gene to RpoS levels explains the timing of expression as cells enter stationary phase, and that genes with different RpoS sensitivities are enriched for specific functional groups. Thus, promoter sensitivity to RpoS is a mechanism to coordinate specific cellular processes in response to stresses.
Enabling and controlling parenthood in publicly provided maternity healthcare: becoming a parent in Finland
Authors: Homanen Riikka
Published: October 2016

This article discusses practices of parental support in the maternity healthcare provided by the welfare state. Drawing on ethnographic material from clinics in Finland, I discuss maternity healthcare practices and processes as the specific contexts of subjectification to parenthood in the Nordic welfare state. The analysis shows that in both nurses’ (work) experience‐based knowledge and population‐statistical knowledge, parental competence is achieved largely through the ‘natural’ process of experiencing pregnant life. Care practices can be seen as enabling parenthood through respect for this process. Clinics encourage parents‐to‐be to self‐reflect and be self‐reliant. Emphasis on self‐reflection and self‐reliance has previously been interpreted as the state adoption of therapy culture, and as a response to market demands for the welfare state to offer to and require of its citizens more autonomy and choice. I argue, however, that the parental subject emerging from the practices of this welfare service cannot be reduced to a neoliberal reflexive individual for whom parenthood is an individual project and who is to blame for individual shortcomings. Equally, they are no mere disciplined product of governmentality being pushed to conform to an idealised parent figure derived from collective ideas of good parenthood.