bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anthropometric Analysis of the Dental Arches of Five-Year-Old Children With Cleft Lip and Palate
Authors: Rando Gabriela Mendonça , Ambrosio Eloá Cristina Passucci , Jorge Paula Karine , Prado Danielle Zola Almeida , Falzoni Maiara Miyuki Matsui , Carrara Cleide Felício Carvalho , Soares Simone , Machado Maria Aparecida Andrade Moreira , Oliveira Thais Marchini 
Published: July 2018

Abstract
This study aimed to analyze the dimensional alterations of the dental arches of 5-year-old children with cleft lip and palate and to compare these dimensions with children without oral clefts. One hundred twenty children were divided into the following groups: unilateral cleft lip (UCL), unilateral cleft lip and palate (UCLP), cleft palate (CP), and control (C). A specific software was used to digitize the dental casts and perform the anthropometric analyses through the measurement of transversal linear intercanine and intermolar distances on the maxilla and mandible. The intergroup comparisons of the maxillary dimensions exhibited that the intercanine distances of groups C and UCL were statistically greater than that of groups UCLP and CP. The intermolar distance was significantly smaller in group UCLP than in the other groups. No statistically significant difference occurred in the mandibular intercanine and intermolar distance among groups. The analysis of the superposition of the maxillary over the mandibular transversal distances showed statistically significant differences among groups. This study showed that at 5-year old, the children with cleft involving the palate had more maxillary dimensional alterations than those without cleft palate.
Design and implementation of the Western Pennsylvania regional Stop the Bleed initiative
Authors: Neal Matthew D. , Reynolds Benjamin R. , Bertoty David , Murray Keith J. , Peitzman Andrew B. , Forsythe Raquel M. 
Published: July 2018

BACKGROUND
Hemorrhage is the leading cause of preventable death in trauma, and nearly 40% of prehospital deaths can be attributed to blood loss. The Stop the Bleed program provides a structured curriculum for teaching hemorrhage control and the use of bleeding control kits. To overcome implementation barriers and to achieve the goal of making education on bleeding control as common as cardiopulmonary resuscitation, widespread implementation with outreach to the public and law enforcement is necessary.

METHODS
We provide a description and analysis of the implementation of a regional Stop the Bleed program, which includes a step-by-step guide to the design of this program provided as a template to guide attempts at large-scale Stop the Bleed program development.

RESULTS
Combining the efforts of regional trauma and nontrauma centers as a hub-and-spoke design, a region covering four states, 72 counties, and 30,000 square miles was targeted. A total of 27,291 individuals were trained in a 21-month period including 3,172 trainers, 19,310 lay public, and 4,809 law enforcement officers. A total of 436 bleeding control kits were distributed to 102 public schools, and tourniquets were provided to 4,809 law enforcement officers. Program development and community outreach resulted in official recognition of the program by the Pennsylvania State Senate.

CONCLUSIONS
With the use of a multicenter outreach program design with emphasis on law enforcement and public education while developing a train-the-trainer program, widespread and rapid dissemination of Stop the Bleed teaching is feasible. The general steps described in this manuscript may serve as a template for new or developing programs in other areas to increase the national exposure to Stop the Bleed.

LEVEL OF EVIDENCE
Economic/Decision study, level IV.
Fluoxetine-Induced Skin Picking and Compulsive Behaviors in a Preschool Girl
Authors: Çoşkun Fatma , Bilgiç Ayhan 
Published: July 2018

Abstract
Skin-picking disorder is regarded as a type of obsessive-compulsive and related disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in the treatment of skin-picking disorder. However, these agents can cause opposite effects in some cases. There is a report on SSRI-induced skin-picking disorder in adults. However, to our knowledge, there are no data regarding SSRI-induced skin picking in children. We present the case of a preschool girl with separation anxiety disorder who displayed skin-picking and compulsive-asking behaviors after fluoxetine therapy.
Searching for sympatric speciation in the genomic era
Authors: Richards Emilie J , Servedio Maria R. , Martin Christopher H 
Published: July 2018

AbstractSympatric speciation illustrates how natural and sexual selection may create new species in isolation without geographic barriers. However, recent genomic reanalyses of classic examples of sympatric speciation have revealed complex histories of secondary gene flow. Thus, there is a need to revisit how to connect the diverse theoretical models of sympatric speciation and their predictions to empirical case studies in the face of widespread gene flow. We summarize theoretical differences between sympatric speciation and speciation-with-gene-flow models and propose genomic analyses for distinguishing which models apply to case studies based on the timing and function of adaptive introgression. Investigating whether secondary gene flow contributed to reproductive isolation is necessary to test whether predictions of theory are ultimately borne out in nature.
Identification of novel mutational signatures in Asian oral squamous cell carcinomas associated with bacterial infections
Authors: Boot Arnoud , Ng Alvin W.T. , Chong Fui Teen , Ho Szu-Chi , Yu Willie , Tan Daniel S.W. , Iyer N. Gopalakrishna , Rozen Steven G. 
Published: July 2018

AbstractMutational signatures can reveal the history of mutagenic processes that cells were exposed to prior to and during tumourigenesis. We expect that as-yet-undiscovered mutational processes will shed further light on mutagenesis leading to carcinogenesis. With this in mind, we analyzed the mutational spectra of 36 Asian oral squamous cell carcinomas. The mutational spectra of two samples from patients who presented with oral bacterial infections, showed novel mutational signatures. One of these novel signatures, SBS_AnT, is characterized by a preponderance of thymine mutations, strong transcriptional strand bias, and striking enrichment for adenines in the 4 base pairs 5’ of mutation sites. Examination of publicly available sequencing data revealed SBS_AnT in 25 tumours from several mucosal tissue types, all of which harbour human symbionts or are adjacent to tissues that harbour symbionts. Data in a preprint released while this manuscript was in revision strongly suggest that the bacterial compound colibactin causes SBS_AnT.
The impact of 10-valent Pneumococcal Conjugate Vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children
Authors: Silaba Micah , Ooko Michael , Bottomley Christian , Sande Joyce , Benamore Rachel , Park Kate , Ignas James , Maitland Kathryn , Mturi Neema , Makumi Anne , Otiende Mark , Kagwanja Stanley , Safari Sylvester , Ochola Victor , Bwanaali Tahreni , Bauni Evasius , Gleeson Fergus , Knoll Maria Deloria , Adetifa Ifedayo , Marsh Kevin , Williams Thomas N , Kamau Tatu , Sharif Shahnaaz , Levine Orin S , Hammitt Laura L , Scott J Anthony G 
Published: July 2018

AbstractBackgroundPneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes but the burden of pneumococcal disease in developing countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the impact of PCV on pneumonia incidence.MethodsWe linked prospective hospital surveillance for clinically-defined WHO severe or very-severe pneumonia at Kilifi County Hospital from 2002-2015 to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45,000 children aged <5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January 2011. In Kilifi, there was a catch-up campaign for children aged <5 years. We estimated the impact of PCV10 on pneumonia incidence through interrupted time series analysis accounting for seasonal and temporal trends.FindingsThe incidence of admission with clinically-defined pneumonia in 2002/3 was 21·7/1000/year in children aged 2-59 months. This declined progressively over 13 years. By the end of March 2011, 61·1% of children aged 2-11 months received ≥2 doses and 62·3% of children aged 12-59 months received ≥1 dose of PCV10. Adjusted incidence rate ratios for admissions with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated with PCV10 introduction, were 0·52 (95% CI 0·32-0·86), 0·73 (95% CI 0·54-0·97) and 0·63, (95% CI 0·31-1·26), respectively. The annual incidence of clinically-defined pneumonia in December 2010 was 12·2/1000; this was reduced by 3·3/1000 with PCV10 introduction.InterpretationOver 13 years, hospitalisations for clinically-defined pneumonia declined progressively at Kilifi County Hospital but fell abruptly by 27% in association with PCV10 introduction. The incidence of radiologically-confirmed pneumonia fell by 48%. The burden of childhood pneumonia in Kilifi, Kenya, has been reduced substantially by PCV10.FundingGavi, Wellcome Trust
A randomised controlled trial of an Intervention to Improve Compliance with the ARRIVE guidelines (IICARus)
Authors: Hair Kaitlyn , Macleod Malcolm , Sena Emily ,   Study steering committee, Howells David , Bath Philip ,   Study management committee, Irvine Cadi , MacCallum Catriona , Morrison Gavin , Clark Alejandra , Alvino Gina , Dohm Michelle ,   Programming and data management, Liao Jing , Sena Chris ,   Redactions, Moreland Rosie ,   Design of outcome assessment platform, Cramond Fala , Irvine Cadi , Liao Jing , Currie Gillian L. , Bahor Zsanett , Grill Paula , Bannach-Brown Alexandra ,   Outcome assessment, Hair Kaitlyn , Marcu Daniel-Cosmin , Antar Sarah , Irvine Cadi , Blazek Katrina , Konold Timm , Dingwall Monica , Hohendorf Victoria , Hosh Mona , Grill Paula , Gerlei Klara Zsofia , Wever Kimberley Elaine , Sena Emily , Jones Victor , Quinn Terence J , Karp Natasha A , Freymann Jennifer , Shek Anthony , Gregorc Teja , Rinaldi Arianna , Jheeta Privjyot , Nazzal Ahmed , Henshall David Ewart , Storey Joanne , Baginskaite Julija , de Oliveira Cilene Lino , Laban Kamil , Charbonney Emmanuel , Lynn Savannah A. , Cascella Marco , Wheater Emily , Baker Daniel , Currie Gillian L. , Cheyne Ryan , Christopher Edward , Roncon Paolo , De-Souza Evandro Araújo , Warda Mahmoud , Corke Sarah , Ammar Zeinab , O’Connor Leigh , Devonshire Ian M. ,   Reconciliation, Hair Kaitlyn , Marcu Daniel-Cosmin , Antar Sarah , Konold Timm , Dingwall Monica , Sena Emily , Grill Paula , McCann Sarah K. ,   Data analysis, Liao Jing , Gray Laura J , Ayder Ezgi Tanriver ,   Writing committee
Published: July 2018

AbstractThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines. In a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March-June 2015) were allocated to either requested completion of an ARRIVE checklist or current standard practice. We measured the change in proportion of manuscripts meeting all ARRIVE guideline checklist items between groups. We randomised 1,689 manuscripts, 1,269 were sent for peer review and 762 accepted for publication. The request to complete an ARRIVE checklist had no effect on full compliance with the ARRIVE guidelines. Details of animal husbandry (ARRIVE sub-item 9a) was the only item to show improved reporting, from 52.1% to 74.1% (X2=34.0, df=1, p=2.1×10−7). These results suggest that other approaches are required to secure greater implementation of the ARRIVE guidelines.
Multi-omic and multi-view clustering algorithms: review and cancer benchmark
Authors: Rappoport Nimrod , Shamir Ron 
Published: July 2018

AbstractHigh throughput experimental methods developed in recent years have been used to collect large biomedical omics datasets. Clustering of such datasets has proven invaluable for biological and medical research, and helped reveal structure in data from several domains. Such analysis is often based on investigation of a single omic. The decreasing cost and development of additional high throughput methods now enable measurement of multi-omic data. Clustering multi-omic data has the potential to reveal further systems-level insights, but raises computational and biological challenges. Here we review algorithms for multi-omics clustering, and discuss key issues in applying these algorithms. Our review covers methods developed specifically for multi-omic data as well as generic multi-view methods developed in the machine learning community for joint clustering of multiple data types.In addition, using cancer data from TCGA, we perform an extensive benchmark spanning ten different cancer types, providing the first systematic benchmark comparison of leading multi-omics and multiview clustering algorithms. The results highlight several key questions regarding the use of single-vs. multi-omics, the choice of clustering strategy, the power of generic multi-view methods and the use of approximated p-values for gauging solution quality. Due to the rapidly increasing use of multi-omics data, these issues may be important for future progress in the field.
The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations
Authors: Kariev Alisher M , Green Michael E 
Published: July 2018

ABSTRACTOver two-thirds of a century ago, Hodgkin and Huxley proposed the existence of voltage gated ion channels (VGIC) to carry Na+and K+ions across the cell membrane to create the nerve impulse, in response to depolarization of the membrane. The channels have multiple physiological roles, and play a central role in a wide variety of diseases when they malfunction. The first channel structure was found by MacKinnon and coworkers in 1998. Subsequently the structure of a number of VGIC was determined in the open (ion conducting) state. This type of channel consists of four voltage sensing domains (VSD), each formed from four transmembrane (TM) segments, plus a pore domain through which ions move. Understanding the gating mechanism (how the channel opens and closes) requires structures. One TM segment (S4) has an arginine in every third position, with one such segment per domain. It is usually assumed that these arginines are all ionized, and in the resting state are held toward the intracellular side of the membrane by voltage across the membrane. They are assumed to move outward (extracellular direction) when released by depolarization of this voltage, producing a capacitive gating current and opening the channel. We suggest alternate interpretations of the evidence that led to these models. Measured gating current is the total charge displacement of all atoms in the VSD; we propose that the prime, but not sole, contributor is proton motion, not displacement of the charges on the arginines of S4. It is known that the VSD can conduct protons. Quantum calculations on the Kv1.2 potassium channel VSD show how; the key is the amphoteric nature of the arginine side chain, which allows it to transfer a proton; this appears to be the first time the arginine side chain has had its amphoteric character considered. We have calculated one such proton transfer in detail: this proton starts from a tyrosine that can ionize, transferring to the NE of the third arginine on S4; that arginine’s NH then transfers a proton to a glutamate. The backbone remains static. A mutation predicted to affect the proton transfer has been qualitatively confirmed experimentally, from the change in the gating current-voltage curve. The total charge displacement in going from a normal closed potential of −70 mV across the membrane to 0 mV (open), is calculated to be approximately consistent with measured values, although the error limits on the calculation require caution in interpretation.
Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature
Authors: O’Sullivan Mary E. , Poitevin Frédéric , Sierra Raymond G. , Gati Cornelius , Han Dao E. , Rao Yashas , Aksit Fulya , Ciftci Halilibrahim , Corsepius Nicholas , Greenhouse Robert , Hayes Brandon , Hunter Mark S. , Liang Mengling , McGurk Alex , Mbgam Paul , Obrinsky Trevor , Pardo-Avila Fátima , Seaberg Matt , Cheng Alan G. , Ricci Anthony J. , DeMirci Hasan 
Published: July 2018

ABSTRACTThe bacterial 30S ribosomal subunit is a primary antibiotic target. Despite decades of discovery, the mechanisms by which antibiotic binding induces ribosomal dysfunction are not fully understood. Ambient temperature crystallographic techniques allow more biologically relevant investigation of how local antibiotic binding site interactions trigger global subunit rearrangements that perturb protein synthesis. Here, the structural effects of 2-deoxystreptamine (paromomycin and sisomicin), a novel sisomicin derivative, N1-methyl sulfonyl sisomicin (N1MS) and the non-deoxystreptamine (streptomycin) aminoglycosides on the ribosome at ambient and cryogenic temperatures were examined. Comparative studies led to three main observations. First, individual aminoglycoside-ribosome interactions in the decoding center were similar for cryogenic vs ambient temperature structures. Second, analysis of a highly conserved GGAA tetraloop of h45 revealed aminoglycoside-specific conformational changes, which are affected by temperature only for N1MS. We report the h44/h45 interface in varying states, that is, engaged, disengaged and in equilibrium. Thirdly, we observe aminoglycoside-induced effects on 30S domain closure, including a novel intermediary closure state, which is also sensitive to temperature. Analysis of three ambient and five cryogenic crystallography datasets reveal a correlation between h44/h45 engagement and domain closure. These observations illustrate the role of ambient temperature crystallography in identifying dynamic mechanisms of ribosomal dysfunction induced by local drug-binding site interactions. Together these data identify tertiary ribosomal structural changes induced by aminoglycoside binding that provides functional insight and targets for drug design.
First- and second-order contributions to depth perception in anti-correlated random dot stereograms
Authors: Asher Jordi M. , Hibbard Paul B. 
Published: July 2018

ABSTRACTThe binocular energy model of neural responses predicts that depth from binocular disparity might be perceived in the reversed direction when the contrast of dots presented to one eye is reversed. While reversed depth has been found using anti-correlated random-dot stereogram (ACRDS) the findings are inconsistent across studies. The mixed findings may be accounted for by the presence of a gap between the target and surround, or as a result of overlap of dots around the vertical edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2 or 38.4 arc min) (2) the correlation of dots or (3) the border orientation (circular target, or horizontal or vertical edge) affected the perception of depth. Reversed depth from ACRDS (circular no-gap condition) was seen by a minority of participants, but this effect reduced as the gap size increased. Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with the effect increasing with the gap size. The inconsistency across conditions can be accounted for by the relative reliability of first- and second-order depth detection mechanisms, and the coarse spatial resolution of the latter.
Recurrent PD-L1 Structural Rearrangements in Natural Killer/T Cell Lymphoma Patients with Complete Response to PD-1 Blockade Therapy
Authors: Lim Jing-Quan , Tang Tiffany , Cai Qing-qing , Tan Daryl , Nairismägi Maarja-Liisa , Laurensia Yurike , Chia Burton Kuan Hui , Peng Rou-Jun , Iqbal Jabed , Huang Da Chuan , Song Tammy , Pang Wan Lu , Cheah Daryl Ming Zhe , Young Ng Cedric Chuan , Rajasegaran Vikneswari , Hong Huangming , Tse Eric , Mow Benjamin , Cai Qi Chun , Poon Li-Mei , Tan Jing , Grigoropoulos Nicholas Francis , Goh Yeow Tee , Phipps Colin , Rötzschke Olaf , Cheng Chee Leong , Lee Yuh Shan , Loh Yvonne , Tao Miriam , Farid Mohamad , Au-Yeung Rex , Chan Thomas Sau-Yan , Ng Siok-Bian , Kwong Yok-Lam , Hwang William , Chng Wee-Joo , Tousseyn Thomas , Tan Patrick , Teh Bin Tean , Khor Chiea Chuen , Rozen Steve ,   ICGC Blood Cancer T-cell and NK-cell lymphoma group, Bei Jin-Xin , Lin Tongyu , Lim Soon Thye , Ong Choon Kiat 
Published: July 2018

Abstract:This study aims to identify recurrent genetic alterations in relapsed or refractory (RR) natural-killer/T-cell lymphoma (NKTL) patients who have achieved complete response (CR) with programmed cell death 1 (PD-1) blockade therapy. Seven of the eleven patients treated with pembrolizumab achieved CR while the remaining four had progressive disease (PD). Using whole genome sequencing (WGS), we found recurrent clonal structural rearrangements (SR) of the PD-L1 gene in four of the seven (57%) CR patients’ pretreated tumors. These PD-L1 SRs consist of inter-chromosomal translocations, tandem duplication and micro-inversion that disrupted the suppressive function of PD-L1 3’UTR. Interestingly, recurrent JAK3-activating (p.A573V) mutations were also validated in two CR patients’ tumors that did not harbor the PD-L1 SR. Importantly, these mutations were absent in the four PD cases. With immunohistochemistry (IHC), PD-L1 positivity could not discriminate patients who archived CR (range: 6%-100%) from patients who had PD (range: 35%-90%). PD-1 blockade with pembrolizumab is a potent strategy for RR NKTL patients and genomic screening could potentially accompany PD-L1 IHC positivity to better select patients for anti-PD-1 therapy.
Development of an imaging toolbox to assess the therapeutic potential and biodistribution of macrophages in a mouse model of multiple organ dysfunction
Authors: Sharkey Jack , Ressel Lorenzo , Brillant Nathalie , Wilm Bettina , Park B. Kevin , Murray Patricia 
Published: July 2018

AbstractCell-based regenerative medicine therapies require robust preclinical safety, efficacy, biodistribution and engraftment data prior to clinical testing. To address these challenges, we have developed an imaging toolbox comprising multi-spectral optoacoustic tomography and ultrasonography, which allows the degree of kidney, liver and cardiac injury and the extent of functional recovery to be assessed non-invasively in a mouse model of multi-organ dysfunction. This toolbox allowed us to determine the therapeutic effects of adoptively transferred M2 macrophages. Using bioluminescence imaging, we could then investigate the association between amelioration and biodistribution. Macrophage therapy improved kidney and liver function to a limited extent, but did not ameliorate histological damage. No improvement in cardiac function was observed. Biodistribution analysis showed that macrophages homed and persisted in the injured kidneys and liver, but did not populate the heart. Our data suggest that the limited improvement observed in kidney and liver function could be mediated by M2 macrophages.