bluuebunny/crossref_metadata_2025 huggingface dataset:
Dichotic integration of acoustic-phonetic information: Competition from extraneous formants increases the effect of second-formant attenuation on intelligibility
Authors: Roberts Brian , Summers Robert J.
Published: March 2019

Differences in ear of presentation and level do not prevent effective integration of concurrent speech cues such as formant frequencies. For example, presenting the higher formants of a consonant-vowel syllable in the opposite ear to the first formant protects them from upward spread of masking, allowing them to remain effective speech cues even after substantial attenuation. This study used three-formant (F1+F2+F3) analogues of natural sentences and extended the approach to include competitive conditions. Target formants were presented dichotically (F1+F3; F2), either alone or accompanied by an extraneous competitor for F2 (i.e., F1±F2C+F3; F2) that listeners must reject to optimize recognition. F2C was created by inverting the F2 frequency contour and using the F2 amplitude contour without attenuation. In experiment 1, F2C was always absent and intelligibility was unaffected until F2 attenuation exceeded 30 dB; F2 still provided useful information at 48-dB attenuation. In experiment 2, attenuating F2 by 24 dB caused considerable loss of intelligibility when F2C was present, but had no effect in its absence. Factors likely to contribute to this interaction include informational masking from F2C acting to swamp the acoustic-phonetic information carried by F2, and interaural inhibition from F2C acting to reduce the effective level of F2.
The Effects of Augmented Feedback on Sprint, Jump, and Strength Adaptations in Rugby Union Players After a 4-Week Training Program
Authors: Weakley Jonathon , Till Kevin , Sampson John , Banyard Harry , Leduc Cedric , Wilson Kyle , Roe Greg , Jones Ben
Published: March 2019

Purpose: Feedback can enhance acute physical performance. However, its effects on physical adaptation have received little attention. Therefore, the purpose of this study was to determine the effect of feedback during a 4-wk training program on jump, sprint, and strength adaptations. Methods: A total of 28 semiprofessional male rugby union players were strength-matched into 2 groups (feedback and nonfeedback). During the 4-wk training program, the Feedback group received immediate, objective feedback on (1) mean concentric velocity during resistance training repetitions, (2) distance feedback for standing broad jumps, and (3) time for sprints. The Nonfeedback group was not provided additional information. Across the 4-wk mesocycle, subjects completed 3 strength and conditioning sessions per week. Countermovement jump, standing long jump, 10- and 20-m sprint, and 3-repetition-maximum barbell back squat and bench press were measured before and after the training intervention. Magnitude-based inferences assessed meaningful changes within and between groups. Results: The Feedback group showed small to moderate improvements in outcome measures, whereas the Nonfeedback group demonstrated trivial to small improvements. Improvements in countermovement-jump relative peak power (effect size ± 90% confidence limits: 0.34 ± 0.42), 10-m (0.20 ± 0.35) and 20-m sprints (0.40 ± 0.21), and 3-repetition-maximum back squats (0.23 ± 0.17) were possibly to likely greater for the Feedback condition than for Nonfeedback. Conclusions: Providing augmented feedback during strength and conditioning routines can enhance training adaptations compared with athletes who do not receive feedback. Consequently, practitioners should consider providing kinematic outputs, displacement, or sprint time at the completion of each repetition as athletes train.
Evaluation of
Aspergillus
-Specific Lateral-Flow Device Test Using Serum and Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis
Authors: Takazono Takahiro , Ito Yuya , Tashiro Masato , Nishimura Keitaro , Saijo Tomomi , Yamamoto Kazuko , Imamura Yoshifumi , Miyazaki Taiga , Yanagihara Katsunori , Mukae Hiroshi , Izumikawa Koichi
Published: March 2019

The
Aspergillus
-specific lateral-flow device (AspLFD) test is a newly developed point-of-care diagnostic method for invasive pulmonary aspergillosis. However, evidence of the diagnostic performance of the AspLFD for chronic pulmonary aspergillosis (CPA) is limited.
SUMO1 Modification Facilitates Avibirnavirus Replication by Stabilizing Polymerase VP1
Authors: Wu Huansheng , Yang Hui , Ji Gang , Zheng Tuyuan , Zhang Yina , Deng Tingjuan , Zheng Xiaojuan , Zhou Jiyong , Hu Boli
Published: March 2019

SUMOylation is an extensively discussed posttranslational modification in diverse cellular biological pathways. However, there is limited understanding about SUMOylation of viral proteins of IBDV during infection. In the present study, we revealed a SUMO1 modification of VP1 protein, the RNA-dependent RNA polymerase of avibirnavirus infectious bursal disease virus (IBDV). The required site of VP1 SUMOylation comprised residues
404
I and
406
I of SUMO interaction motif 3, which was essential for maintaining its stability by inhibiting K48-linked ubiquitination. We also showed that IBDV with SUMOylation-deficient VP1 had decreased replication ability. These data demonstrated that the SUMOylation of IBDV VP1 played an important role in maintaining IBDV replication.
Draft Genome Sequence and Annotation of Acinetobacter junii MHI21018, Isolated from Bovine Colostrum
Authors: Kröger Carsten , Schauer Kristina , Clerkin Seán R. , Märtlbauer Erwin , Fleming Alastair B.
Published: March 2019

We report here the draft genome sequence of
Acinetobacter junii
MHI21018, isolated in 2009 from bovine colostrum. The draft genome sequence is composed of 3,267,995 bp, has a GC content of 38.54%, and was assembled into 114 contigs (contig size, >500 bp) with an
N
50
value of 72,566 bp.
Genome Sequence of the Black Yeast Exophiala lecanii-corni
Authors: Schultzhaus Zachary , Cuomo Christina A. , Wang Zheng
Published: March 2019

The genome sequence of
Exophiala lecanii-corni
, a melanized dimorphic fungus with the capability of degrading several volatile organic compounds, was sequenced using PacBio single-molecule real-time (SMRT) sequencing to assist with understanding the molecular basis of its uncommon morphological and metabolic characteristics. The assembled draft genome is presented here.
Apneic oxygenation via nasal cannula for intubation of a premature neonate with multiple airway anomalies
Authors: Staudt Genevieve E , Reddy Srijaya K , Moore Alexander D
Published: March 2019

Intubating a neonate under non-emergent conditions may be quite stressful, even for experienced providers, due to the potential for rapid oxygen desaturation. Pulmonary physiology and increased metabolic oxygen demand in this patient population contribute to accelerated oxygen desaturation during induction of anaesthesia and intubation. Using a nasal cannula, placed prior to induction of anaesthesia and left in place until the airway is secured, is a simple and effective way to provide apneic oxygenation and may help maintain adequate oxygen saturation. This technique may be particularly useful for patients who require additional time for intubation, including those with suspected difficult airways.
Sex differences and correlates of poor glycaemic control in type 2 diabetes: a cross-sectional study in Brazil and Venezuela
Authors: G Duarte Fernanda , da Silva Moreira Sandra , Almeida Maria da Conceição C , de Souza Teles Carlos A , Andrade Carine S , Reingold Art L , Moreira Jr Edson D
Published: March 2019

Objective

Examine whether glycaemic control varies according to sex and whether the latter plays a role in modifying factors associated with inadequate glycaemic control in patients with type 2 diabetes (T2D) in Brazil and Venezuela.

Design, setting and participants

This was a cross-sectional, nationwide survey conducted in Brazil and Venezuela from February 2006 to June 2007 to obtain information about glycaemic control and its determinants in patients with diabetes mellitus attending outpatient clinics.

Main outcome measures

Haemoglobin A1c (HbA1c) level was measured by liquid chromatography, and patients with HbA1c ≥7.0% (53 mmol/mol) were considered to have inadequate glycaemic control. The association of selected variables with glycaemic control was analysed by multivariate linear regression, using HbA1c as the dependent variable.

Results

A total of 9418 patients with T2D were enrolled in Brazil (n=5692) and in Venezuela (n=3726). They included 6214 (66%) women and 3204 (34%) men. On average, HbA1c levels in women were 0.13 (95% CI 0.03 to 0.24; p=0.015) higher than in men, after adjusting for age, marital status, education, race, country, body mass index, duration of disease, complications, type of healthcare, adherence to diet, adherence to treatment and previous measurement of HbA1c. Sex modified the effect of some factors associated with glycaemic control in patients with T2D in our study, but had no noteworthy effect in others.

Conclusions

Women with T2D had worse glycaemic control than men. Possible causes for poorer glycaemic control in women compared with men include differences in glucose homeostasis, treatment response and psychological factors. In addition, sex modified factors associated with glycaemic control, suggesting the need to develop specific treatment guidelines for men and women.
Study protocol for a randomised, double-blind, placebo-controlled clinical trial of duloxetine for the treatment and prevention of musculoskeletal pain: altering the transition from acute to chronic pain (ATTAC pain)
Authors: Strauss Daniel H , Santhanam Divya R , McLean Samuel A , Beaudoin Francesca L
Published: March 2019

Introduction

Chronic musculoskeletal pain affects a substantial portion of adults visiting the emergency department (ED). Current treatment is limited in scope and does not effectively reduce musculoskeletal pain in patients. The study will evaluate the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor Food and Drug Administration approved for the treatment of chronic pain, as a promising option in its prevention. The proposed study may present a well-tolerated and effective non-opioid treatment for patients with acute musculoskeletal pain that may also be effective in preventing the transition to persistent or chronic musculoskeletal pain.

Methods and analysis

The primary outcome of this study will be to assess the tolerability and preliminary effectiveness of duloxetine in patients with acute musculoskeletal pain. The study will take place at two EDs in Rhode Island, USA. The study will involve randomisation to one of three arms: duloxetine 30 mg, duloxetine 60 mg or placebo. Tolerability will be assessed by comparing the proportion of participants that report an adverse event and that drop-out across the three study arms. Effectiveness will be determined by self-reported pain over 6 weeks of follow-up. Specifically, we will compare the proportion of participants with persistent pain (ongoing pain at 6-week follow-up), across the three study arms. 60 adults (aged 18–59) presenting to the ED with acute axial musculoskeletal pain within 7 days of onset are expected to be enrolled in the proposed study.

Ethics and dissemination

Ethics approval was obtained by the Institutional Review Board (IRB). These results will be published in a peer reviewed scientific journal and presented at one or more scientific conferences.

Trial registration number

NCT03315533.
Effect of sex on specialty training application outcomes: a longitudinal administrative data study of UK medical graduates
Authors: Woolf Katherine , Jayaweera Hirosha , Unwin Emily , Keshwani Karim , Valerio Christopher , Potts Henry
Published: March 2019

Objectives

To examine sex differences in the specialty training recruitment outcomes of UK medical graduates; and whether sex differences were explained by prior academic attainment and previous fitness to practise (FtP) declarations.

Design

Retrospective longitudinal cohort study.

Setting

Administrative data on entrants to all UK medical schools from the UK Medical Education Database.

Participants

10 559 doctors (6 155; 58% female) who entered a UK medical school in 2007 or 2008 and were eligible to apply for specialty training by 2015.

Primary outcome measure

Odds of application, offer and acceptance to any specialty training programme, and on to each of the nine largest training programmes, adjusting for sex, other demographics, prior academic attainment, FtP declaration and medical school.

Results

Across all specialties, there were no sex differences in applications for specialty training, but women had increased odds of getting an offer (OR=1.40; 95% CI=1.25 to 1.57; p<0.001) and accepting one (OR=1.43; 95% CI=1.19 to 1.71; p<0.001). Seven of the nine largest specialties showed significant sex differences in applications, which remained after adjusting for other factors. In the adjusted models, Paediatrics (OR=1.57; 95% CI=1.01 to 2.46; p=0.046) and general practice (GP) (OR=1.23; 95% CI=1.03 to 1.46; p=0.017) were the only specialties to show sex differences in offers, both favouring women. GP alone showed sex differences in acceptances, with women being more likely to accept (OR=1.34; 95% CI=1.03 to 1.76; p=0.03). Doctors with an FtP declaration were slightly less likely to apply to specialty training overall (OR=0.84; 95% CI=0.71 to 1.00; p=0.048) and less likely to accept an offer to any programme (OR=0.71; 95% CI=0.52 to 0.98; p=0.036), after adjusting for confounders.

Conclusions

Sex segregation between medical specialties is due to differential application, although research is needed to understand why men are less likely to be offered a place on to GP and Paediatrics training, and if offered GP are less likely to accept.
Prematurity detection evaluating interaction between the skin of the newborn and light: protocol for the preemie-test multicentre clinical trial in Brazilian hospitals to validate a new medical device
Authors: Reis Zilma Silveira Nogueira , Guimarães Rodney Nascimento , Rego Maria Albertina Santiago , Maia de Castro Romanelli Roberta , Gaspar Juliano de Souza , Vitral Gabriela Luiza Nogueira , dos Reis Marconi Augusto Aguiar , Colósimo Enrico Antônio , Neves Gabriela Silveira , Vale Marynea Silva , Nader Paulo de Jesus Hartamann , de Moura Marta David Rocha , de Aguiar Regina Amélia Pessoa Lopes
Published: March 2019

Introduction

Recognising prematurity is critical in order to attend to immediate needs in childbirth settings, guiding the extent of medical care provided for newborns. A new medical device has been developed to carry out the preemie-test, an innovative approach to estimate gestational age (GA), based on the photobiological properties of the newborn’s skin. First, this study will validate the preemie-test for GA estimation at birth and its accuracy to detect prematurity. Second, the study intends to associate the infant’s skin reflectance with lung maturity, as well as evaluate safety, precision and usability of a new medical device to offer a suitable product for health professionals during childbirth and in neonatal care settings.

Methods and analysis

Research protocol for diagnosis, single­group, single­blinding and single­arm multicenter clinical trial with a reference standard. Alive newborns, with 24 weeks or more of pregnancy age, will be enrolled during the first 24 hours of life. Sample size is 787 subjects. The primary outcome is the difference between the GA calculated by the photobiological neonatal skin assessment methodology and the GA calculated by the comparator antenatal ultrasound or reliable last menstrual period (LMP). Immediate complications caused by pulmonary immaturity during the first 72 hours of life will be associated with skin reflectance in a nested case–control study.

Ethics and dissemination

Each local independent ethics review board approved the trial protocol. The authors intend to share the minimal anonymised dataset necessary to replicate study findings.

Trial registration number

RBR-3f5bm5.
Distributions of the National Early Warning Score (NEWS) across a healthcare system following a large-scale roll-out
Authors: Scott Lauren J , Redmond Niamh M , Garrett Joanna , Whiting Penny , Northstone Kate , Pullyblank Anne
Published: March 2019

Background

Early warning scores (EWS) were developed in acute hospital settings to improve recognition and response to patient deterioration. In 2012, the UK Royal College of Physicians developed the National Early Warning Score (NEWS) to standardise EWS across the NHS. Its use was also recommended outside acute hospital settings; however, there is limited information about NEWS in these settings. From March 2015, NEWS was implemented across the healthcare system in the West of England, with the aim that NEWS would be calculated for all patients prior to referral into acute care.

Aim

To describe the distribution and use of NEWS in out-of-hospital settings for patients with acute illness or long-term conditions, following system wide implementation.

Method

Anonymised data were obtained from 115 030 emergency department (ED) attendances, 1 137 734 ambulance electronic records, 31 063 community attendances and 15 160 general practitioner (GP) referrals into secondary care, in the West of England. Descriptive statistics are presented.

Results

Most attendance records had NEWS=0–2: 80% in ED, 67% of ambulance attendances and 72% in the community. In contrast, only 8%, 18% and 11% of attendances had NEWS ≥5 (the trigger for escalation of care in-hospital), respectively. Referrals by a GP had higher NEWS on average (46% NEWS=0–2 and 30% NEWS ≥5). By April 2016, the use of NEWS was reasonably stable in ED, ambulance and community populations, and still increasing for GP referrals.

Conclusions

NEWS ≥5 occurred in less than 20% of ED, ambulance and community populations studied and 30% of GP referrals. This suggests that in most out-of-hospital settings studied, high scores are reasonably uncommon.
Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis
Authors: Wang Pin , Wang Yunshan , Langley Sasha A , Zhou Yan-Xia , Jen Kuang-Yu , Sun Qi , Brislawn Colin , Rojas Carolina M , Wahl Kimberly L , Wang Ting , Fan Xiangshan , Jansson Janet K , Celniker Susan E , Zou Xiaoping , Threadgill David W , Snijders Antoine M , Mao Jian-Hua
Published: March 2019

Objective

The Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum.

Design

We monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels ofISG15by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis.

Results

CC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identifiedNfκb1as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS.

Conclusions

CC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.
Comparison of hydrosonography and transvaginal ultrasonography in the detection of intracavitary pathologies in women with abnormal uterine bleeding
Authors: Guven M. A. , Bese T. , Demirkiran F.
Published: March 2019

Background

The aim of the study was to compare the accuracy of hydrosonography with that of transvaginal ultrasonography in detection of intracavitary pathologies in patients with history of abnormal uterine bleeding.

Study design

Prospective, randomized, and unblinded study.

Material and methods

A total of 197 women (n= 130 premenopausal andn= 67 postmenopausal) aged between 23 and 71 years (mean age 45.7 ± 8.9) presenting with a history of abnormal uterine bleeding were included into the study. Hydrosonography was carried out by experienced gynecologists, on the same setting in an outpatient clinic immediately after the performance of transvaginal sonography. The finally obtained surgical-pathologic findings were compared with the results obtained from transvaginal sonography and hydrosonography. Sensitivity, specificity, positive, and negative predictive values were calculated for each procedure.

Results

The surgical-pathologic examination confirmed normal physiologic endometrium in 50 (48%) of 104 women who were said to have normal endometrium on transvaginal sonography. Seventy (75%) of 93 women diagnosed of intracavitary pathologies on transvaginal sonography were confirmed by surgical-pathologic findings. The sensitivity, specificity, positive predictive value, and negative predictive value of transvaginal sonography in the detection of intracavitary pathology were 56, 68, 75, and 48%, respectively. Surgical-pathologic results revealed intracavitary pathologies in 23 (30%) of 76 women who were said to have normal endometrium on hydrosonography. Among 121 women diagnosed of intracavitary pathologies on hydrosonography, 101 (81%) women were confirmed after histological evaluation of the surgical specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of hydrosonography in the detection of intracavitary pathology were 81, 73, 83, and 70%, respectively. Sensitivity and negative predictive value were significantly higher with hydrosonography. There were five cases of endometrial malignancy in which one of the case of malignancy was on polyp and two cases of endometrial hyperplasia with atypia which were not stated on sonographic results.

Conclusion

Hydrosonography is more accurate than transvaginal ultrasography in the detection of intracavitary pathologies in women with abnormal uterine bleeding.
Chemoradiation for primary invasive squamous carcinoma of the vagina
Authors: Dalrymple J. L. , Russell A. H. , Lee S. W. , Scudder S. A. , Leiserowitz G. S. , Kinney W. K. , Smith L. H.
Published: March 2019

Objective

To report outcomes for patients with primary, invasive, squamous carcinoma of the vagina treated with chemoradiation.

Methods

Between 1986 and 1996, 14 patients were treated with primary therapy consisting of synchronous radiation and chemotherapy. Patients were judged not to be surgical candidates based on tumor size, location, and concerns related to urinary, bowel, or sexual function. Three patients were FIGO stage I, ten patients stage II, and one patient stage III. Radiation consisted of teletherapy alone (six patients) or in combination with intravaginal brachytherapy (eight patients). Total radiation dose ranged from 5700 to 7080 cGy (median 6300 cGy). Chemotherapy consisted of 5-fluorouracil alone (seven patients), or with cisplatin (six patients) or mitomycin-C (one patient).

Results

One patient failed locally at 7 months and died of disease at 11 months. Four patients died of intercurrent illness (46, 92, 104, 109 months) and nine are alive and cancer-free 74–168 months after treatment (median 100 months). There were no vesicovaginal or enterovaginal fistulae.

Conclusions

Radiation with synchronous chemotherapy is an effective treatment for squamous carcinoma of the vagina. Cancer control outcomes compare favorably with previously published results employing higher dose radiation as monotherapy.
Correlation between histological criteria and human papillomavirus presence based on PCR assay in cervical biopsies
Authors: Salvia P. N. D. , Bergo S. M. , Bonesso-Sabadini P. I. P. , Tagliarini E. B. , Hackel C. , De Angelo Andrade L. A. L.
Published: March 2019

The aim was to correlate histological findings in cervix lesions to human papillomavirus (HPV), as detected by polymerase chain reaction (PCR). One hundred and seven women with atypical Pap smear were submitted to colposcopic examination, and suspicious images were biopsied. The PCR assay was performed with the primers MY09/11 and GP05/06+ and, as control, the beta-globin gene was amplified. The morphological findings were correlated to HPV positivity: parakeratosis, acanthosis, koilocytotic atypia (KA), binucleation, dyskeratosis, and number of mitoses. From 107 patients, 61 biopsies were taken: 11 chronic cervicitis (CC), 36 cervical intraepithelial neoplasia (CIN) (13 CIN I; 10 CIN II; 13 CIN III), and 14 suggestive for HPV (SHPV). DNA extraction was not possible in eight cases. HPV was found in 35% CC, 77% CIN, and 64% SHPV. The analysis did not indicate any morphological criteria strongly related to HPV. The findings with highest sensitivity for HPV were KA (88.89%) and binucleation (75%), but with low specificity of 29.41 and 52.94%, respectively. The higher predictive positive values (PV+) for HPV were also KA (72.73%) and binucleation (77.14%). Considering KA, dyskeratosis and binucleation together, PV+was 72.41%. Conclusion: Although indicative, none of the studied morphological criteria was always related to PCR virus detection, denoting some limitations for histological diagnosis.
Comparison of hepatocyte growth factor levels of epithelial ovarian cancer cyst fluids with benign ovarian cysts
Authors: Baykal C. , Demirtaş E. , Al A. , Ayhan A. , YÜCE K. , Tulunay G. , KÖSE M. F. , Ayhan A.
Published: March 2019

Hepatocyte growth factor (HGF) is known to take role in oncogenesis and tumoral behavior of the tumors of the organs that contain mesenchymal and epithelial cells together. This study aims to compare HGF levels in cyst fluids of epithelial ovarian cancer and benign ovarian cysts and look for the role of HGF in ovarian carcinogenesis. Twenty-four consecutive patients with ovarian cancer and 34 with benign cysts of ovary were recruited prospectively at Gynecologic Oncology Departments of SSK Ankara Maternity Hospital and Hacettepe University School of Medicine between 2001 and 2002. Cyst fluids were collected during primary staging in cancer patients and during laparatomy for benign patients. HGF levels were measured by enzyme-linked immunosorbent assay method. Median HGF levels of the benign ovarian cysts and epithelial ovarian tumoral fluids were found as 3822 pg/ml (85–15,253 pgr/ml) and 12,962 pgr/ml (4136–16,025 pgr/ml), respectively. Malign cyst fluids have higher HGF levels when compared with benign ovarian cysts (P< 0.01). This finding suggests that HGF may take a paracrine role in oncogenic differentiation and tumoral development of epithelial ovarian cancers. Mechanisms that take role in HGF secretion and the answers of the neighboring epithelial cells to HGF during tumoral development need to be investigated.
Synchronous mucinous adenocarcinoma of the endometrium and mucinous cystadenoma of bilateral ovaries presenting during fertility therapy
Authors: Gotoh T. , Hayashi N. , Takeda S. , Itoyama S. , Takano M. , Kikuchi Y.
Published: March 2019

We describe a very rare case of synchronous mucinous tumor of the endometrium and ovaries presenting during ovulation induction. A 31-year-old woman received ovulation induction for 5-year primary infertility. Ultrasonography revealed mucus retention in the uterine cavity and bilateral multicystic ovaries during ovulation induction. Atypical hyperplasia was diagnosed by endometrial curettage. Repeated procedures including ovarian cystectomy, endometrial curettage andin vitrofertilization combined with progestine therapy resulted in no pregnancy but rapid recurrences. She finally underwent simple hysterectomy and bilateral salpingo-oophorectomy. Microscopic examination revealed mucinous cystadenoma in the both ovaries and well differentiated mucinous adenocarcinoma of the endometrium.
Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing
Authors: Iwama Kazuhiro , Mizuguchi Takeshi , Takeshita Eri , Nakagawa Eiji , Okazaki Tetsuya , Nomura Yoshiko , Iijima Yoshitaka , Kajiura Ichiro , Sugai Kenji , Saito Takashi , Sasaki Masayuki , Yuge Kotaro , Saikusa Tomoko , Okamoto Nobuhiko , Takahashi Satoru , Amamoto Masano , Tomita Ichiro , Kumada Satoko , Anzai Yuki , Hoshino Kyoko , Fattal-Valevski Aviva , Shiroma Naohide , Ohfu Masaharu , Moroto Masaharu , Tanda Koichi , Nakagawa Tomoko , Sakakibara Takafumi , Nabatame Shin , Matsuo Muneaki , Yamamoto Akiko , Yukishita Shoko , Inoue Ken , Waga Chikako , Nakamura Yoko , Watanabe Shoko , Ohba Chihiro , Sengoku Toru , Fujita Atsushi , Mitsuhashi Satomi , Miyatake Satoko , Takata Atsushi , Miyake Noriko , Ogata Kazuhiro , Ito Shuichi , Saitsu Hirotomo , Matsuishi Toyojiro , Goto Yu-ichi , Matsumoto Naomichi
Published: March 2019

Background

Rett syndrome (RTT) is a characteristic neurological disease presenting with regressive loss of neurodevelopmental milestones. Typical RTT is generally caused by abnormality of methyl-CpG binding protein 2 (MECP2). Our objective to investigate the genetic landscape ofMECP2-negative typical/atypical RTT and RTT-like phenotypes using whole exome sequencing (WES).

Methods

We performed WES on 77MECP2-negative patients either with typical RTT (n=11), atypical RTT (n=22) or RTT-like phenotypes (n=44) incompatible with the RTT criteria.

Results

Pathogenic or likely pathogenic single-nucleotide variants in 28 known genes were found in 39 of 77 (50.6%) patients. WES-based CNV analysis revealed pathogenic deletions involving six known genes (includingMECP2) in 8 of 77 (10.4%) patients. Overall, diagnostic yield was 47 of 77 (61.0 %). Furthermore, strong candidate variants were found in four novel genes: a de novo variant in each of ATPase H+transporting V0 subunit A1 (ATP6V0A1), ubiquitin-specific peptidase 8 (USP8) and microtubule-associated serine/threonine kinase 3 (MAST3), as well as biallelic variants in nuclear receptor corepressor 2 (NCOR2).

Conclusions

Our study provides a new landscape including additional genetic variants contributing to RTT-like phenotypes, highlighting the importance of comprehensive genetic analysis.
NAA10 polyadenylation signal variants cause syndromic microphthalmia
Authors: Johnston Jennifer J , Williamson Kathleen A , Chou Christopher M , Sapp Julie C , Ansari Morad , Chapman Heather M , Cooper David N , Dabir Tabib , Dudley Jeffrey N , Holt Richard J , Ragge Nicola K , Schäffer Alejandro A , Sen Shurjo K , Slavotinek Anne M , FitzPatrick David R , Glaser Thomas M , Stewart Fiona , Black Graeme CM , Biesecker Leslie G
Published: March 2019

Background

A single variant in NAA10 (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify causative variants in families with syndromic X-linked microphthalmia.

Methods

Three families, including 15 affected individuals with syndromic X-linked microphthalmia, underwent analyses including linkage analysis, exome sequencing and targeted gene sequencing. The consequences of two identified variants in NAA10 were evaluated using quantitative PCR and RNAseq.

Results

Genetic linkage analysis in family 1 supported a candidate region on Xq27-q28, which included NAA10. Exome sequencing identified a hemizygous NAA10 polyadenylation signal (PAS) variant, chrX:153,195,397T>C, c.*43A>G, which segregated with the disease. Targeted sequencing of affected males from families 2 and 3 identified distinct NAA10 PAS variants, chrX:g.153,195,401T>C, c.*39A>G and chrX:g.153,195,400T>C, c.*40A>G. All three variants were absent from gnomAD. Quantitative PCR and RNAseq showed reduced NAA10 mRNA levels and abnormal 3′ UTRs in affected individuals. Targeted sequencing of NAA10 in 376 additional affected individuals failed to identify variants in the PAS.

Conclusion

These data show that PAS variants are the most common variant type in NAA10-associated syndromic microphthalmia, suggesting reduced RNA is the molecular mechanism by which these alterations cause microphthalmia/anophthalmia. We reviewed recognised variants in PAS associated with Mendelian disorders and identified only 23 others, indicating that NAA10 harbours more than 10% of all known PAS variants. We hypothesise that PAS in other genes harbour unrecognised pathogenic variants associated with Mendelian disorders. The systematic interrogation of PAS could improve genetic testing yields.
Endovascular thrombectomy in pediatric patients with large vessel occlusion
Authors: Shoirah Hazem , Shallwani Hussain , Siddiqui Adnan H , Levy Elad I , Kenmuir Cynthia L , Jovin Tudor G , Levitt Michael R , Kim Louis J , Griauzde Julius , Pandey Aditya S , Gemmete Joseph J , Abruzzo Todd , Arthur Adam S , Elijovich Lucas , Hoit Daniel , Cheema Ahmed , Aghaebrahim Amin , Sauvageau Eric , Hanel Ricardo , Ringer Andrew J , Nascimento Fábio A , Kan Peter , Mocco J
Published: March 2019

Background

Pediatric acute ischemic stroke with underlying large vessel occlusion is a rare disease with significant morbidity and mortality. There is a paucity of data about the safety and outcomes of endovascular thrombectomy in these cases, especially with modern devices.

Methods

We conducted a retrospective review of all pediatric stroke patients who underwent endovascular thrombectomy in nine US tertiary centers between 2008 and 2017.

Results

Nineteen patients (63.2% male) with a mean (SD) age of 10.9(6) years and weight 44.6 (30.8) kg were included. Mean (SD) NIH Stroke Scale (NIHSS) score at presentation was 13.9 (5.7). CT-based assessment was obtained in 88.2% of the patients and 58.8% of the patients had perfusion-based assessment. All procedures were performed via the transfemoral approach. The first-pass device was stentriever in 52.6% of cases and aspiration in 36.8%. Successful revascularization was achieved in 89.5% of the patients after a mean (SD) of 2.2 (1.5) passes, with a mean (SD) groin puncture to recanalization time of 48.7 (37.3) min (median 41.5). The mean (SD) reduction in NIHSS from admission to discharge was 10.2 (6.2). A good neurological outcome was achieved in 89.5% of the patients. One patient had post-revascularization seizure, but no other procedural complications or mortality occurred.

Conclusions

Endovascular thrombectomy is safe and feasible in selected pediatric patients. Technical and neurological outcomes were comparable to adult literature with no safety concerns with the use of standard adult devices in patients as young as 18 months. This large series adds to the growing literature but further studies are warranted.
Endovascular mechanical thrombectomy for acute stroke in young children
Authors: Sun Lisa R , Felling Ryan J , Pearl Monica Smith
Published: March 2019

Background

Mechanical thrombectomy has emerged as a standard of care for acute stroke from large vessel occlusion in adults but remains controversial in children. Cerebral vessels are nearly adult size by 5 years of age but the technical feasibility of achieving recanalization in younger and smaller children with current endovascular tools remains unclear.

Objective

To systematically review the literature on mechanical thrombectomy for stroke in children less than 5 years of age.

Results

Mechanical thrombectomy for acute stroke has been reported in 11 children under the age of 5 years (range 9 months to 4 years). The mean time from symptom onset to groin puncture was 12 hours (range 4–50 hours). Complete recanalization was achieved in 7/12 (58%) vessels attempted, and partial recanalization in 4/12 (33%). Two procedure related complications were reported, with small vessel size felt to be contributory to basilar vasospasm in one case. Favorable neurological outcomes were reported in 7 cases (64%).

Conclusions

Our review of the literature demonstrates that mechanical thrombectomy for acute ischemic stroke may be feasible in carefully selected infants and young children less than 5 years of age using currently available devices. Efficacy in promoting better neurologic outcomes remains unproven, and other questions persist, including whether complications such as vasospasm occur more frequently in young children compared with adults. Further study is needed to determine the safety and efficacy of pediatric mechanical thrombectomy. These data suggest that young children should not be excluded from future studies or clinical treatment on the basis of age alone.
Impact of procedural time on clinical and angiographic outcomes in patients with acute ischemic stroke receiving endovascular treatment
Authors: Hassan Ameer E , Shariff Umar , Saver Jeffrey L , Goyal Mayank , Liebeskind David , Jahan Reza , Qureshi Adnan I
Published: March 2019

Background

Procedural time in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy may affect clinical outcomes. We performed a pooled analysis of the effect of procedural time on clinical outcomes using data from three prospective endovascular treatment trials.

Objective

To examine the relationship between endovascular procedural time and clinical outcomes of patients with AIS following endovascular treatment.

Methods

We analyzed data from SWIFT, STAR, and SWIFT PRIME studies, including baseline characteristics: National Institutes of Health Stroke Scale (NIHSS) score on admission, intracranial hemorrhage rates, and modified Rankin Scale score at 3 months. The Thrombolysis in Cerebral Infarction (TICI) scale was used to grade postprocedure recanalization. We recorded two procedural time intervals: (1) symptom onset to groin puncture and (2) groin puncture to angiographic recanalization. A multivariate analysis was performed using a logistic regression model to analyze predictors of unfavorable outcome.

Results

We analyzed 301 patients who had undergone endovascular treatment and had near-complete or complete recanalization (TICI 2b or 3). At 3 months, 122 patients (40.5%) had unfavorable outcomes. The rate of favorable outcomes was significantly higher when the procedural time was <60 min compared with ≥60 min (62% vs 45%, p=0.020). Predictors of unfavorable outcome at 3 months were age (unit 10 years, OR=0.62, 95% CI 0.46 to 0.82, p<0.001), onset to groin puncture time (unit hour, OR=0.61, 95% CI 0.48 to 0.77, p<0.001), groin puncture to recanalization (unit 10 min, OR=0.89, 95% CI 0.80 to 0.99, p=0.032), baseline NIHSS score (20–28 vs 8–10, OR=0.17, 95% CI 0.05 to 0.62, p=0.018), and collaterals (OR=1.48, 95% CI 1.04 to 2.10, p=0.029).

Conclusion

Procedural time in patients with stroke undergoing mechanical thrombectomy may be an important determinant of favorable outcomes in those with recanalization.
Choose to test: self-selected testing for sexually transmitted infections within an online service
Authors: Syred Jonathan , Holdsworth Gillian , Howroyd Chris , Spelman Kez , Baraitser Paula
Published: March 2019

Objective

To describe the outcomes of user-led, choice of test within an online sexual health service.

Methods

We analysed routinely collected data from a free, online sexual health service in Essex, UK that enabled users to select their tests. The service website provided information on all sexually transmitted infections, recommended a testing package based on sexuality and ethnicity, and invited users to modify this if they chose. Data on orders were analysed for the 6 months before (May–October 2016) and after (October–April 2017) implementation.

Results

We compared 7550 orders from 6253 users before and 9785 orders from 7772 users after implementation. There was no difference in the proportion of chlamydia (p=0.57) or gonorrhoea (p=0.79) tests that were positive between the two periods. HIV and syphilis positives were too few in our sample during both periods for analysis. During implementation, men who have sex with men (530 users) were offered genital, rectal and oral chlamydia and gonorrhoea testing plus HIV and syphilis testing. In 17.2% of orders, users removed tests. Black or ethnic minority users excluding those who reported as men who have sex with men (805 users) were offered chlamydia, gonorrhoea and HIV testing. In 77.9% of orders, users added a test. All other users were offered chlamydia and gonorrhoea tests only. In 65.2% of orders, users added tests. We observed a reduction in orders of 3083 blood tests (31%).

Conclusion

Users engaged with the ‘choose to test’ intervention. Although a majority added tests, the intervention was cost saving by reducing the HIV and syphilis tests ordered.
Mapping black ash dominated stands using geospatial and forest inventory data in northern Minnesota, USA
Authors: Engelstad Peder S. , Falkowski Michael J. , D’Amato Anthony W. , Slesak Robert A. , Palik Brian J. , Domke Grant M. , Russell Matthew B.
Published: March 2019

Emerald ash borer (EAB; Agrilus planipennis Fairmaire, 1888) has been a persistent disturbance for ash forests in the United States since 2002. Of particular concern is the impact that EAB will have on the ecosystem functioning of wetlands dominated by black ash (Fraxinus nigra Marsh.). In preparation, forest managers need reliable and complete maps of black ash dominated stands. Traditionally, forest survey data from the United States Forest Inventory and Analysis (FIA) Program have provided rigorous measures of tree species at large spatial extents but are limited when providing estimates for smaller management units (e.g., stands). Fortunately, geospatial data can extend forest survey information by generating predictions of forest attributes at scales finer than those of the FIA sampling grid. In this study, geospatial data were integrated with FIA data in a randomForest model to estimate and map black ash dominated stands in northern Minnesota in the United States. The model produced low error rates (overall error = 14.5%; area under the curve (AUC) = 0.92) and was strongly informed by predictors from soil saturation and phenology. These results improve upon FIA-based spatial estimates at national extents by providing forest managers with accurate, fine-scale maps (30 m spatial resolution) of black ash stand dominance that could ultimately support landscape-level EAB risk and vulnerability assessments.
Multiscale Multifractal Detrended Cross-Correlation Analysis of High-Frequency Financial Time Series
Authors: Huang Jingjing , Gu Danlei
Published: March 2019

In order to obtain richer information on the cross-correlation properties between two time series, we introduce a method called multiscale multifractal detrended cross-correlation analysis (MM-DCCA). This method is based on the Hurst surface and can be used to study the non-linear relationship between two time series. By sweeping through all the scale ranges of the multifractal structure of the complex system, it can present more information than the multifractal detrended cross-correlation analysis (MF-DCCA). In this paper, we use the MM-DCCA method to study the cross-correlations between two sets of artificial data and two sets of 5[Formula: see text]min high-frequency stock data from home and abroad. They are SZSE and SSEC in the Chinese market, and DJI and NASDAQ in the US market. We use Hurst surface and Hurst exponential distribution histogram to analyze the research objects and find that SSEC, SZSE and DJI, NASDAQ all show multifractal properties and long-range cross-correlations. We find that the fluctuation of the Hurst surface is related to the positive and negative of [Formula: see text], the change of scale range, the difference of national system, and the length of time series. The results show that the MM-DCCA method can give more abundant information and more detailed dynamic processes.
New meso-tetrafluorenylethynyl porphyrin platform
Authors: Zhang Xu , Paul-Roth Christine O.
Published: March 2019

To improve conjugation between a central porphyrin core and its peripheral fluorenyl antennae, we have introduced in the meso-tetrafluorenyl porphyrin (TFP-Bu) unit an ethynyl spacer at the meso positions. By this means, we have synthesized and characterized a new meso-alkynyl fluorenyl porphyrin (TAFlP). We discuss the effect of this extra extension of the [Formula: see text] manifold on the optical properties. This enlarged porphyrin core, TAFlP, is foreseen as a key building block for the design of new dendrimers for theranostic applications. The constant improvement of porphyrin-based dendrimers featuring conjugated fluorenyl dendrons is recalled herein and demonstrates the important role of the central core structure in determining linear and nonlinear optical properties. Further improvement of these properties seems possible with TAFlP-like structures based on observations made for dendrimers recently obtained. This makes the exploration of such new molecular architectures appealing for photodynamic therapy (PDT) and related applications.
Consumptive coagulopathy is associated with organ dysfunction during PICS
Authors: Winer Leah K. , Beckmann Nadine , Veile Rosalie A. , Goodman Michael D. , Caldwell Charles C. , Nomellini Vanessa
Published: March 2019

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Although sepsis is characterized by early hypercoagulability and delayed hypocoagulability, coagulopathy during chronic critical illness is not fully understood. The objective of this study was to determine whether sepsis-induced PICS is associated with coagulation abnormalities. Using our previously described murine PICS model, outbred mice underwent cecal ligation and puncture, and coagulability was characterized after 8 days. We found that during PICS the spleen became markedly enlarged with increased splenocytes and splenic megakaryocytes without a concomitant increase in circulating platelets. Microscopy revealed a nearly sevenfold increase in pulmonary microvascular thrombi in PICS mice, along with significantly decreased pulmonary tidal volumes and inspiratory times and with significantly increased respiratory rates. Thromboelastometry showed that PICS mice had significantly delayed clot initiation time but increased clot firmness. Finally, PICS mice displayed delayed thrombin production and decreased overall thrombin concentrations. All together, these data demonstrate a general dysregulation of coagulation resulting in microthrombus formation and compromised lung function. On the basis of these findings, we propose that consumptive coagulopathy constitutes another cardinal feature of PICS and may contribute to the ongoing tissue damage and multiple organ failure that can occur in chronic critical illness.