bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a New Patient-reported Outcome Measure for Ear Conditions: The EAR-Q
Authors: Klassen Anne F. , Longmire Natasha M. , Bulstrode Neil W. , Fisher David M. , Kasrai Leila , O’Hara Justine , Panchapakesan Vivek , Pusic Andrea L. , Stewart Ken , Tsangaris Elena , Ziolkowski Natalia , Wong Riff Karen W. Y.
Published: August 2018

Background:

Patient-reported outcome measures are widely used to improve health services and patient outcomes. The aim of our study was to describe the development of 2 ear-specific scales designed to measure outcomes important to children and young adults with ear conditions, such as microtia and prominent ears.

Methods:

We used an interpretive description qualitative approach. Semi-structured qualitative and cognitive interviews were performed with participants with any type of ear condition recruited from plastic surgery clinics in Canada, Australia, United States, and United Kingdom. Participants were interviewed to elicit new concepts. Interviews were audio-recorded, transcribed, and coded using the constant comparison approach. Experts in ear reconstruction were invited to provide input via an online Research Electronic Data Capture survey.

Results:

Participants included 25 patients aged 8–21 years with prominent ears (n = 9), microtia (n = 14), or another condition that affected ear appearance (n = 2). Analysis of participant qualitative data, followed by cognitive interviews and expert input, led to the development and refinement of an 18-item ear appearance scale (eg, size, shape, look up close, look in photographs) and a 12-item adverse effects scale (eg, itchy, painful, numb).

Conclusions:

The EAR-Q in currently being field-tested internationally. Once finalized, we anticipate the EAR-Q will be used in clinical practice and research to understand the patient’s perspective of outcomes following ear surgery.
Current Challenges of Plastic Surgical Care in Sub-Saharan Africa (Maputo, Mozambique)
Authors: Guzman Kevin J. , Gemo Natacha , Martins Deborah B. , Santos Pedro , DeUgarte Daniel A. , Ademo Fatima , Kulber David , Issufo Celma
Published: August 2018

Background:

Limited data exist on plastic surgery practices in Sub-Saharan Africa. The aim of this study was to characterize the spectrum of disease and operative procedures at a teaching hospital in Maputo, Mozambique to help understand the challenges of providing care for the local providers and to provide contextual relevance for training through partnerships.

Methods:

A mixed-methods approach was utilized to perform an ongoing needs assessment. A retrospective review was performed of plastic surgery operative records, ward admissions records, and death records in a tertiary-care hospital in Maputo, Mozambique for the period January 2015 to December 2015.

Results:

Limited resources (equipment, block-time, personnel, and perioperative services) were observed. The most common diagnoses for the 455 patients evaluated were burns (44%) and neoplasms (17%). Congenital abnormalities accounted for only 1% of the patient diagnoses. Of the 408 procedures performed, the majority were skin grafts (43%) and skin excisions (31%). Sepsis from burns accounted for 70% of documented deaths (14/20). The mean number of days to skin grafting for inpatients was 53 days.

Conclusion:

We observed a large burden of burns and skin graft procedures at a public referral teaching hospital in Mozambique. Our findings provide contextual relevance to help focus public health efforts and improve plastic surgery training and practices.
INTRAOCULAR JARISCH–HERXHEIMER REACTION IN LEMIERRE SYNDROME
Authors: Ramtohul Prithvi , Boulicot-Seguin Céline , Marc Caroline
Published: August 2018

Purpose:

To report an intraocular Jarisch–Herxheimer reaction induced by Lemierre syndrome antibiotherapy.

Methods:

Case report.

Results:

A 43-year-old-man presented with an acute onset of bilateral blurred vision few days after intravenous antibiotic administration for Lemierre syndrome. Best-corrected visual acuity was 20/32 in both eyes. Examination revealed bilateral cystoid macular edema and peripheral retinal vasculitis, persisting despite Lemierre syndrome recovery with antibiotics. Intravitreal injection of ranibizumab 0.5 mg (0.05 mL) was performed in both eyes. After 1 month, cystoid macular edema and retinal vasculitis were totally resolved, and best-corrected visual acuity increased to 20/20 in both eyes. The paradoxical worsening of the patient's best-corrected visual acuity after initiating antibiotherapy evokes a Jarisch–Herxheimer reaction. The result of this single intravitreal injection of ranibizumab was sustained; best-corrected visual acuity remained unchanged (20/20 in both eyes), and no recurrence of cystoid macular edema or retinal vasculitis was found after 4-year follow-up.

Conclusion:

To the best of our knowledge, this is the first reported case of an isolated intraocular Jarisch–Herxheimer reaction induced by Lemierre syndrome antibiotherapy and successfully treated with a single intravitreal injection of ranibizumab.
LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA
Authors: Wetzel Barbara , Mylonas Georgios , Puntus Thomas , Prager Franz , Bernhart Clemens , Amon Michael
Published: August 2018

Purpose:

The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.

Methods:

Retrospective case report.

Results:

A 55-year-old non–insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.

Conclusion:

Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Successfully Improving Visual Acuity in Keratitis–Ichthyosis–Deafness Syndrome Utilizing Gas-Permeable Lenses: A Case Report
Authors: Strul Sasha , Straughn Penny
Published: August 2018

There is currently no well-defined guideline for treatment and management of patients with keratitis–ichthyosis–deafness (KID) syndrome, and most patients will face disabling vision loss due to corneal neovascularization and cicatrization. We offer this case as an example of how we can improve visual acuity (VA) and quality of life even in advanced cases of corneal neovascularization. We showcase the use of gas-permeable (GP) contact lenses to provide useful, functional VA in a patient with long-standing visual impairment secondary to corneal neovascularization and irregularity due to KID syndrome. The patient's VA improved from 20/200 both eyes (OU) to 20/40 OU with successful fitting of GP lenses, which additionally relieved the patient's otherwise intractable monocular diplopia.
Prognosis of Biliary Atresia After 2‐year Survival With Native Liver
Authors: Witt Mauri , van Wessel Daan B.E. , de Kleine Ruben H.J. , Bruggink Janneke L.M. , Hulscher Jan B.F. , Verkade Henkjan J. ,   NeSBAR (Netherlands Study group on Biliary Atresia Registry)
Published: August 2018

Objectives:

The aim of the study is to determine the prognosis of patients with biliary atresia after 2 years of native liver survival (NLS) and to identify prognostic factors for continued NLS after 2 years of age.

Methods:

We retrospectively analyzed perioperative, laboratory, and outcome parameters of all biliary atresia patients in The Netherlands between January 1987 and June 2015 with NLS of at least 2 years. We compared parameters between patients who continued to have their native liver (NLS+) to those who did not, either by transplant or death (NLS−).

Results:

We included 100 patients. Upon a median follow‐up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre‐transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were 89%, 72%, 60%, 54%, respectively. Corresponding overall survival rates were 98%, 90%, 87%, 87%, respectively. Six months post‐Kasai, NLS+ patients had higher clearance of jaundice (COJ) rate, significantly lower total and direct serum bilirubin, aspartate‐aminotransferase and alkaline phosphatase levels, compared with NLS− patients (each P < 0.05). Cox regression could only assess a significant effect of COJ on continued NLS. Main indications for LTx after the age of 2 were irreversible jaundice and portal hypertension.

Conclusions:

Eighty‐seven percent of patients with 2‐year NLS reach adult age and more than 50% with their native liver. A pre‐transplant mortality of 6%, however, exists among patients who reach the age of 2 years with their native livers. Early life parameters, other than COJ, did not have a significant effect on continued NLS after 2 years of age.
Risk Markers for Significant Bleeding and Thrombosis in Pediatric Acute Promyelocytic Leukemia; Report From the Children’s Oncology Group Study AAML0631
Authors: Rajpurkar Madhvi , Alonzo Todd A. , Wang Yi-Cheng , Gerbing Robert B. , Gamis Alan S. , Feusner James H. , Gregory John , Kutny Matthew A.
Published: August 2018

Acute promyelocytic leukemia (APL) is characterized by a heightened risk of coagulopathy with significant morbidity and mortality. Here we report our evaluation of presenting white blood cell (WBC) and the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scoring system as markers for early death and nonlethal coagulopathy in pediatric APL. We evaluated 79 pediatric patients treated on a Children’s Oncology Group phase III clinical trial. There were 4 early deaths and 13 nonlethal, clinically significant (grade III to IV) coagulopathy events during induction. Elevated presenting WBC was significantly associated with early death but not with both lethal and nonlethal coagulopathy events. An ISTH DIC score of ≥5 (the original ISTH criteria for overt DIC) was not associated with either early deaths or coagulopathy events. An ISTH DIC score threshold of 6, however, was significantly associated with early death (12% score ≥6 vs. 0% score <6) and with both lethal and nonlethal coagulopathy events (35% score ≥6 vs. 11% score <6). In pediatric APL patients, the presenting WBC is a marker for risk of early death. Although the ISTH score using a cutoff of ≥6 showed improved correlation with adverse coagulation events during induction, the sensitivity was only 70.6% (95% confidence interval, 44.0%-89.7%) and the specificity was 64.5% (95% confidence interval, 51.3%-76.3%). Thus, there is a strong need to identify other biomarkers that can predict APL-associated coagulopathy.
Randomized Study of Early Continuous Positive Airways Pressure in Acute Respiratory Failure in Children With Impaired Immunity (SCARF) ISRCTN82853500*
Authors: Peters Mark J. , Agbeko Rachel , Davis Peter , Klein Nigel , Zenasni Zohra , Jones Amy , Mackerness Christine , George Susan , Veys Paul , Ray Samiran , Mouncey Paul R. , Harrison David A. , Rowan Kathy
Published: August 2018

Objectives:

Previous trials in adults with impaired immunity and respiratory failure suggest that early noninvasive ventilation avoids endotracheal intubation and improves survival. No randomized clinical trials have addressed this question in children.

Design:

We undertook an open, parallel-group randomized trial in three pediatric hospitals.

Subjects:

Children with impaired immunity and acute respiratory failure defined as tachypnoea (> 90th centile); a new requirement for supplemental oxygen; and new chest radiograph infiltrates.

Interventions:

Children were randomly assigned to early PICU admission for continuous positive airways pressure (early continuous positive airways pressure) or to standard care. The primary outcome was endotracheal intubation by 30 days.

Measurements and Main Results:

One-hundred fourteen children met inclusion criteria of whom 42 were randomized between January 2013 and January 2016. There was no significant difference in endotracheal intubation by 30 days with early continuous positive airways pressure (10/21; 48%) compared with standard care (5/21; 24%), odds ratio 2.9 (0.8–10.9), p value equals to 0.11. However, 30-day mortality was significantly higher with early continuous positive airways pressure (7/21; 33%) compared with standard care (1/21; 5%), odds ratio 10.0 (1.1–90.6), p value equals to 0.041. Mortality at 90 days was early continuous positive airways pressure (11/21; 52%) versus standard care (4/21; 19%), odds ratio 4.7 (1.2–18.6), p value equals to 0.029, whereas mortality at 1 year was similar early continuous positive airways pressure (13/21; 61.9%) versus standard care (9/21; 42.7%), odds ratio 2.2 (0.6–7.4), p value equals to 0.22. There were two serious adverse events: early continuous positive airways pressure (pneumothorax) and standard care (hemothorax).

Conclusions:

This study provided no evidence to support early PICU admission for continuous positive airways pressure in children with acute respiratory failure and impaired immunity. There was a trend toward increased endotracheal intubation and a higher early mortality in the early continuous positive airways pressure group.
Congenital Chagas disease: current diagnostics, limitations and future perspectives
Authors: Messenger Louisa A. , Bern Caryn
Published: August 2018

Purpose of review

Congenital transmission is an important route of Trypanosoma cruzi infection, both in Latin America and internationally, with considerable populations of infected women of child-bearing age residing in the United States and Europe. This review examines recent literature on congenital Chagas disease, with a focus on the changing clinical spectrum and potential new diagnostic tools.

Recent findings

Vertical transmission occurs in approximately 5–10% of births from T. cruzi-infected mothers. Historically, congenital Chagas disease was associated with high levels of neonatal morbidity and mortality. Bolivian birth cohort data from the early 1990s to the present indicate that the incidence of symptomatic neonatal disease has declined. Treatment with trypanocides is greater than 90% effective and well tolerated in infants. Current programs face challenges from the multistep screening algorithm, low sensitivity of microscopy and high loss to follow-up.

Congenital Chagas disease remains an important contributor to the global disease burden because of T. cruzi. PCR and related molecular techniques represent the most sensitive diagnostic modalities for early detection but require further optimization for resource-limited settings. Several novel diagnostic tests show promise for the future but further validation and adaptation to field settings are needed.
Updates on the management of neurocysticercosis
Authors: White A. Clinton , Garcia Hector H.
Published: August 2018

Purpose of review

The goal of this review is highlight recent developments regarding neurocysticercosis, including recently developed guidelines.

Recent findings

Recent diagnostic criteria highlight the importance of neuroimaging in establishing a diagnosis. Monoclonal antibody-based antigen detection and the enzyme-linked immunotransfer blot can be confirmatory. Management should be guided by the form of disease. Single enhancing lesions and one to two viable parenchymal cysticerci can be treated with short courses of albendazole and corticosteroid. Multiple parenchymal lesions should be treated with the combination of corticosteroids, albendazole, and praziquantel. Ventricular cysticerci should be removed when possible, often by minimally invasive surgery. Subarachnoid cysticercosis often requires prolonged courses of antiparasitic and anti-inflammatory treatment.

Neurocysticerocis represents a spectrum of disease that is a common cause of neurologic disease worldwide. Management needs to be guided by the number and location of the parasites and the host response.
A Nurse’s Perspective on Visual Rehabilitation of Outpatients With Low Vision in China
Authors: Ni Lingzhi , Li Keke , Jiang Longfei , Chen Jie , Chen Yanyan , Li Xiaoman , Lin Na , Thorn Frank , Deng Ruzhi
Published: August 2018

Purpose

The purposes of the study were to analyze patient use and satisfaction with low vision aids (LVAs) at the Wenzhou Medical University Low Vision and Rehabilitation Center and to assess the promotion of visual rehabilitation services as a new responsibility for nurses in China.

Methods

Records of 178 patients with low vision (LV) from the Low Vision and Rehabilitation Center examined between October 2015 and October 2016 included basic patient information (e.g., age, diagnosis, visual acuity, educational level) and use of LVAs (patients’ own aids, daily duration of LVA use, or refusal to use aids).

Results

Sixty percent owned LVAs. Of these, 66% were obtained from a hospital, 26% were obtained from commercial stores, and others were obtained from government or gifts. Patients reported that use of LVAs was reduced because of visual fatigue (39%), inconvenience (22%), and lack of benefit (12%). Reasons for the 40% who had never used visual rehabilitation were nonreferral by doctors (76%), refusal because of inconvenience, discomfort and cosmetics (20%), or a preference for other treatments (4%).

Conclusions

Greater awareness of LV rehabilitation by nurses, ophthalmologists, patients, and the public is necessary. Additional government support for LV rehabilitation is also required.
National Longitudinal Comparison of Patients Undergoing Surgical Management of Craniosynostosis
Authors: Wu Robin T. , Shultz Blake N. , Gabrick Kyle S. , Abraham Paul F. , Cabrejo Raysa , Persing John A. , Alperovich Michael
Published: August 2018

Purpose:

Limited cross-institutional studies compare strip craniectomy versus cranial vault remodeling (CVR) for craniosynostosis management. Given competing surgical preferences, the authors conducted a large-scale analysis of socioeconomic differences, costs, and complications between treatment options.

Methods:

Nonsyndromic craniosynostosis patients receiving strip craniectomies or CVR were identified in the Kids’ Inpatient Database for years 2000 to 2009. Demographics, socioeconomic background, hospital characteristics, charge, and outcomes were tabulated. Univariate and multivariate analyses were performed for comparison.

Results:

Two hundred fifty-one strip craniectomies and 1811 CVR patients were captured. Significantly more strip craniectomy patients were White while more CVR patients were Hispanic or Black (P < 0.0001). Strip craniectomy patients more often had private insurance and CVR patients had Medicaid (P < 0.0001). Over time, CVR trended toward treating a higher proportion of Hispanic and Medicaid patients (P = 0.036). Peri-operative charges associated with CVR were $27,962 more than strip craniectomies, and $11,001 after controlling for patient payer, income, bedsize, and length of stay (P < 0.0001). Strip craniectomies were performed more frequently in the West and Midwest, while CVR were more common in the South (P = 0.001). Length of stay was not significant. Postsurgical complications were largely equivocal; CVR was associated with increased accidental puncture (P = 0.025) and serum transfusion (P = 0.002).

Conclusion:

Our national longitudinal comparison demonstrates widening socioeconomic disparities between strip craniectomy and CVR patients. Cranial vault remodeling is more commonly performed in underrepresented minorities and patients with Medicaid, while strip craniectomy is common in the White population and patients with private insurance. While hospital charges and complications were higher among CVR, differences were smaller than expected.
Cost-effectiveness of Randomized Study of Laparoscopic Versus Open Bilateral Inguinal Hernia Repair
Authors: Ielpo Benedetto , Nuñez-Alfonsel Javier , Duran Hipolito , Diaz Eduardo , Fabra Isabel , Caruso Riccardo , Malavé Luis , Ferri Valentina , Barzola Ernesto , Quijano Yolanda , Vicente Emilio
Published: August 2018

Objective:

The aim of this study is to compare the clinical and cost-effective outcomes of the open Lichtenstein repair (OL) and laparoscopic trans-abdominal preperitoneal (TAPP) repair for bilateral inguinal hernias.

Summary Background Data:

A cost-effective analysis of laparoscopic versus open inguinal hernia repair is still not well addressed, especially regarding bilateral hernia.

Methods:

This is a clinical and cost-effectiveness analysis within a randomized prospective study conducted at Sanchinarro University Hospital.

Cases of primary, reducible bilateral inguinal hernia were included and randomized using a simple randomization program.

The outcome parameters included surgical and postoperative costs, quality adjusted life years (QALY), and incremental cost per QALY gained or the incremental cost effectiveness ratio.

Results:

Between March 2013 and January 2017, 165 patients were enrolled in this study (81 of them underwent TAPP and 84 OL).

The TAPP procedure had less early postoperative pain (P = 0.037), a shorter length of stay (P = 0.001), and fewer postoperative complications (P = 0.002) when compared with the OL approach. The overall cost of TAPP procedure was higher compared with the OL cost (1,683.93€ vs 1192.83€, P = 0.027). The mean QALYs at 1 year for TAPP (0.8094) was higher than that associated with OL (0.6765) (P = 0.018). At a willingness-to-pay threshold of 20,000 € and 30,000 €, there was a 95.38% and 97.96% probability that TAPP was more cost-effective relative to OL.

Conclusions:

The TAPP procedure for bilateral inguinal hernia appears to be more cost-effective compared with OL.
Norman Sheppard. 16 May 1921—10 April 2015
Authors: Turner James J. , Chesters Michael A.
Published: August 2018

Norman Sheppard was an exceptional man as scientist, teacher and administrator, but he was also kind, generous, honourable and extremely modest. He was the international expert on the application of vibrational spectroscopy to molecular structure, in solids, on surfaces, in solution and in the gas phase. One significant feature of his science was that he was always on the lookout for new developments in spectroscopy to apply to chemical structure (e.g. NMR, RAIRS, EELS). Always passionate about expanding higher education opportunities, he moved from Cambridge in 1964—as Professor of Chemical Physics—to help Professor Alan Katritzky (FRS) found the chemistry department at the new University of East Anglia. He was heavily involved in national and international matters: council member of the Royal Society; president of the Faraday Division of the Royal Society of Chemistry; member of the Infrared and Raman Discussion Group and first chairman of the NMR Discussion Group; member of the International Union of Pure and Applied Chemistry and several of its committees. His early work in two major areas of spectroscopy was very important in underpinning their use in chemical analysis, central to industry and forensic science. He was a devoted family man. In his spare time he was fascinated by architecture, nature and photography. Latterly he became interested in the science–religion debate and the philosophy of science.
Lidocaine is a nocebo treatment for trigeminally mediated magnetic orientation in birds
Authors: Engels Svenja , Treiber Christoph Daniel , Salzer Marion Claudia , Michalik Andreas , Ushakova Lyubov , Keays David Anthony , Mouritsen Henrik , Heyers Dominik
Published: August 2018

Even though previously described iron-containing structures in the upper beak of pigeons were almost certainly macrophages, not magnetosensitive neurons, behavioural and neurobiological evidence still supports the involvement of the ophthalmic branch of the trigeminal nerve (V1) in magnetoreception. In previous behavioural studies, inactivation of putative V1-associated magnetoreceptors involved either application of the surface anaesthetic lidocaine to the upper beak or sectioning of V1. Here, we compared the effects of lidocaine treatment, V1 ablations and sham ablations on magnetic field-driven neuronal activation in V1-recipient brain regions in European robins. V1 sectioning led to significantly fewer Egr-1-expressing neurons in the trigeminal brainstem than in the sham-ablated birds, whereas lidocaine treatment had no effect on neuronal activation. Furthermore, Prussian blue staining showed that nearly all iron-containing cells in the subepidermal layer of the upper beak are nucleated and are thus not part of the trigeminal nerve, and iron-containing cells appeared in highly variable numbers at inconsistent locations between individual robins and showed no systematic colocalization with a neuronal marker. Our data suggest that lidocaine treatment has been a nocebo to the birds and a placebo for the experimenters. Currently, the nature and location of any V1-associated magnetosensor remains elusive.
Mesoscale substrate curvature overrules nanoscale contact guidance to direct bone marrow stromal cell migration
Authors: Werner Maike , Kurniawan Nicholas A. , Korus Gabriela , Bouten Carlijn V. C. , Petersen Ansgar
Published: August 2018

The intrinsic architecture of biological tissues and of implanted biomaterials provides cells with large-scale geometrical cues. To understand how cells are able to sense and respond to complex structural environments, a deeper insight into the cellular response to multi-scale and conflicting geometrical cues is needed. In this study, we subjected human bone marrow stromal cells (hBMSCs) to mesoscale cylindrical surfaces (diameter 250–5000 µm) and nanoscale collagen fibrils (diameter 100–200 nm) that were aligned perpendicular to the cylinder axis. On flat surfaces and at low substrate curvatures (cylinder diameter
d
> 1000 µm), cell alignment and migration were governed by the nanoscale collagen fibrils, consistent with the contact guidance effect. With increasing surface curvature (decreasing cylinder diameter,
d
< 1000 µm), cells increasingly aligned and migrated along the cylinder axis, i.e. the direction of zero curvature. An increase in phosphorylated myosin light chain levels was observed with increasing substrate curvature, suggesting a link between substrate-induced cell bending and the F-actin–myosin machinery. Taken together, this work demonstrates that geometrical cues of up to 10× cell size can play a dominant role in directing hBMSC alignment and migration and that the effect of nanoscale contact guidance can even be overruled by mesoscale curvature guidance.
The SNARC effect is associated with worse mathematical intelligence and poorer time estimation
Authors: Kramer Peter , Bressan Paola , Grassi Massimo
Published: August 2018

Interactions between the ways we process space, numbers and time may arise from shared and innate generic magnitude representations. Alternatively or concurrently, such interactions could be due to the use of physical magnitudes, like spatial extent, as metaphors for more abstract ones, like number and duration. That numbers might be spatially represented along a mental number line is suggested by the SNARC effect: faster left-side responses to small single digits, like 1 or 2, and faster right-side responses to large ones, like 8 or 9. Previously, we found that time estimation predicts mathematical intelligence and speculated that it may predict spatial ability too. Here, addressing this issue, we test—on a relatively large sample of adults and entirely within subjects—the relationships between (a) time: proficiency at producing and evaluating durations shorter than one second, (b) space: the ability to mentally rotate objects, (c) numbers: mathematical reasoning skills, and (d) space–number associations: the SNARC effect. Better time estimation was linked to greater mathematical intelligence and better spatial skills. Strikingly, however, stronger associations between space and numbers predicted worse mathematical intelligence and poorer time estimation.
Factors affecting
N
-nitrosodimethylamine formation from poly(diallyldimethyl-ammonium chloride) degradation during chloramination
Authors: Tan Siying , Jiang Shaojie , Li Xiaoyu , Yuan Qiuhong
Published: August 2018

Poly(diallyldimethylammonium chloride) (polyDADMAC) has been shown to be an important precursor of the probable human carcinogen
N
-nitrosodimethylamine (NDMA) when in contact with chloramine. In this study, we conducted an orthogonal experiment design to evaluate the effects of pH values, ammonia, bromide, natural organic matter (NOM) and monochloramine dosages on the formation of NDMA from polyDADMAC during chloramination. Meanwhile, single-factor experiments of pH, bromide and NOM prove the results of orthogonal experiment. The results supported that pH was the most critical factor affecting NDMA formation from polyDADMAC during chloramination, and the highest NDMA formation from polyDADMAC occurred at pH near 7 due to released DMA from polyDADMAC degradation and the critical importance of low concentrations of dichloramine in water. In the presence of excess bromide, the NDMA formation was enhanced significantly at all different pH values owing to bromochloramine, which has higher electronegativity of the brominated nitrogen atom than monochloramine or dichloramine. The NDMA formation from polyDADMAC in the presence of NOM was 41.7% lower than NDMA formation in the absence of NOM. The overwhelming majority of NDMA formation from polyDADMAC under simulated conditions was lower than the current advisory levels (i.e. 9 ng l
−1
in Ontario, 10 ng l
−1
in California).
Gene Content Evolution in the Arthropods
Authors: Thomas Gregg W.C. , Dohmen Elias , Hughes Daniel S.T. , Murali Shwetha C. , Poelchau Monica , Glastad Karl , Anstead Clare A. , Ayoub Nadia A. , Batterham Phillip , Bellair Michelle , Binford Gretta J. , Chao Hsu , Chen Yolanda H. , Childers Christopher , Dinh Huyen , Doddapaneni HarshaVardhan , Duan Jian J. , Dugan Shannon , Esposito Lauren A. , Friedrich Markus , Garb Jessica , Gasser Robin B. , Goodisman Michael A.D. , Gundersen-Rindal Dawn E. , Han Yi , Handler Alfred M. , Hatakeyama Masatsugu , Hering Lars , Hunter Wayne B. , Ioannidis Panagiotis , Jayaseelan Joy C. , Kalra Divya , Khila Abderrahman , Korhonen Pasi K. , Lee Carol Eunmi , Lee Sandra L. , Li Yiyuan , Lindsey Amelia R.I. , Mayer Georg , McGregor Alistair P. , McKenna Duane D. , Misof Bernhard , Munidasa Mala , Munoz-Torres Monica , Muzny Donna M. , Niehuis Oliver , Osuji-Lacy Nkechinyere , Palli Subba R. , Panfilio Kristen A. , Pechmann Matthias , Perry Trent , Peters Ralph S. , Poynton Helen C. , Prpic Nikola-Michael , Qu Jiaxin , Rotenberg Dorith , Schal Coby , Schoville Sean D. , Scully Erin D. , Skinner Evette , Sloan Daniel B. , Stouthamer Richard , Strand Michael R. , Szucsich Nikolaus U. , Wijeratne Asela , Young Neil D. , Zattara Eduardo E. , Benoit Joshua B. , Zdobnov Evgeny M. , Pfrender Michael E. , Hackett Kevin J. , Werren John H. , Worley Kim C. , Gibbs Richard A. , Chipman Ariel D. , Waterhouse Robert M. , Bornberg-Bauer Erich , Hahn Matthew W. , Richards Stephen
Published: August 2018

Background

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.

Results

Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality and chemoperception.

Conclusions

These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.
Inference of genomic spatial organization from a whole genome bisulfite sequencing sample
Authors: Raineri Emanuele , Serra François , Beekman Renée , García Torre Beatriz , Vilarrasa-Blasi Roser , Martin-Subero Iñaki , Martí-Renom Marc A. , Gut Ivo , Heath Simon
Published: August 2018

Common approaches to characterize the structure of the DNA in the nucleus, such as the different Chromosome Conformation Capture methods, have not currently been widely applied to different tissue types due to several practical difficulties including the requirement for intact cells to start the sample preparation. In contrast, techniques based on sodium bisulfite conversion of DNA to assay DNA methylation, have been widely applied to many different tissue types in a variety of organisms. Recent work has shown the possibility of inferring some aspects of the three dimensional DNA structure from DNA methylation data, raising the possibility of three dimensional DNA structure prediction using the large collection of already generated DNA methylation datasets. We propose a simple method to predict the values of the first eigenvector of the Hi-C matrix of a sample (and hence the positions of the A and B compartments) using only the GC content of the sequence and a single whole genome bisulfite sequencing (WGBS) experiment which yields information on the methylation levels and their variability along the genome. We train and test our model on 10 samples for which we have data from both bisulfite sequencing and chromosome conformation experiments and our most relevant finding is that the variability of DNA methylation along the sequence is often a better predictor than methylation itself. We then run a prediction on 206 DNA methylation profiles produced by the Blueprint project and use ChIP-Seq and RNA-Seq data to confirm that the forecasted eigenvector delineates correctly the physical chromatin compartments observed with the Hi-C experiment.
Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis
Authors: Ramesh Akshaya , Nakielny Sara , Hsu Jennifer , Kyohere Mary , Byaruhanga Oswald , Bourcy Charles de , Egger Rebecca , Dimitrov Boris , Juan Yun-Fang , Sheu Jonathan , Wang James , Kalantar Katrina , Langelier Charles , Ruel Theodore , Mpimbaza Arthur , Wilson Michael R. , Rosenthal Philip J. , DeRisi Joseph L.
Published: August 2018

Background

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. We built and employed IDseq, a cloud-based, open access, bioinformatics platform and service to identify microbes from metagenomic next-generation sequencing of tissue samples. In this pilot study, we evaluated blood, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda.

Results

The most common pathogens identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from blood; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. Among other potential pathogens, we identified one novel orthobunyavirus, tentatively named Nyangole virus, from the blood of a child diagnosed with malaria and pneumonia, and Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis. We also identified two novel human rhinovirus C species.

Conclusions

This exploratory pilot study demonstrates the utility of mNGS and the IDseq platform for defining the molecular landscape of febrile infectious diseases in resource limited areas. These methods, supported by a robust data analysis and sharing platform, offer a new tool for the surveillance, diagnosis, and ultimately treatment and prevention of infectious diseases.
Transcriptome analyses of tumor-adjacent somatic tissues reveal genes co-expressed with transposable elements
Authors: Chung Nicky , Jonaid G.M. , Quinton Sophia , Ross Austin , Sexton Corinne E. , Alberto Adrian , Clymer Cody , Churchill Daphnie , Leija Omar Navarro , Han Mira V.
Published: August 2018

Background

Despite the long-held assumption that transposons are normally only expressed in the germ-line, recent evidence shows that transcripts of transposable element (TE) sequences are frequently found in the somatic cells. However, the extent of variation in TE transcript levels across different tissues and different individuals are unknown, and the co-expression between TEs and host gene mRNAs have not been examined.

Results

Here we report the variation in TE derived transcript levels across tissues and between individuals observed in the non-tumorous tissues collected for The Cancer Genome Atlas. We found core TE co-expression modules consisting mainly of transposons, showing correlated expression across broad classes of TEs. Despite this co-expression within tissues, there are individual TE loci that exhibit tissue-specific expression patterns, when compared across tissues. The core TE modules were negatively correlated with other gene modules that consisted of immune response genes in interferon signaling. KRAB Zinc Finger Proteins (KZFPs) were over-represented gene members of the TE modules, showing positive correlation across multiple tissues. But we did not find overlap between TE-KZFP pairs that are co-expressed and TE-KZFP pairs that are bound in published ChIP-seq studies.

Conclusions

We find unexpected variation in TE derived transcripts, within and across non-tumorous tissues. We describe a broad view of the RNA state for non-tumorous tissues exhibiting higher level of TE transcripts. Tissues with higher level of TE transcripts have a broad range of TEs co-expressed, with high expression of a large number of KZFPs, and lower RNA levels of immune genes.
Signals of variation in human mutation rate at multiple levels of sequence context
Authors: Aikens Rachael C. , Johnson Kelsey E. , Voight Benjamin F.
Published: August 2018

Our understanding of mutation rate helps us build evolutionary models and make sense of genetic variation. Recent work indicates that the frequencies of specific mutation types have been elevated in Europe, and that many more, subtler signatures of global polymorphism variation may yet remain unidentified. Here, we present an analysis of the 1,000 Genomes Project (phase 3), suggesting additional putative signatures of mutation rate variation across populations and the extent to which they are shaped by local sequence context. First, we compiled a list of the most significantly variable polymorphism types in a cross-continental statistical test. Clustering polymorphisms together, we observed four sets of substitution types that showed similar trends of relative mutation rate across populations, and describe the patterns of these mutational clusters among continental groups. For the majority of these signatures, we found that a single flanking base pair of sequence context was sufficient to determine the majority of enrichment or depletion of a mutation type. However, local genetic context up to 2-3 base pairs away contributes additional variability, and helps to interpret a previously noted enrichment of certain polymorphism types in some East Asian groups. Building our understanding of mutation rate in this way can help us to construct more accurate evolutionary models and better understand the mechanisms that underlie genetic change.
Overlaps in Brain Dynamic Functional Connectivity between Schizophrenia and Autism Spectrum Disorder
Authors: Andriamananjara Andry , Muntari Rayan , Crimi Alessandro
Published: August 2018

Schizophrenia and autism share some genotipic and phenotypic aspects as connectome miswiring and common cognitive deficits. Currently, there are no medical tests available for either disorders, and diagnostics for both of them include direct reports of relatives and clinical evaluation by a psychiatrist. Despite several medical imaging biomarkers have been proposed in the past, novel effective biomarkers or improvements of the existing ones is still need. This work proposes a dynamic functional connectome analysis combined with machine learning techniques to complement the present diagnostic procedure. We used the moving window technique to locate a set of dynamic functional connectivity states, and then use them as features to classify subjects as autism/schizophrenia or control. Moreover, by using dynamic functional connectivity measures we investigate the question whether those two disorders overlap, namely whether schizophrenia is part of the autism spectrum and which brain region could be involved in both disorders. The results reveal that both static and dynamic functional connectivity can be used to classify subjects with schizophrenia or autism. Lastly, some brain regions show similar functional flexibility in both autism and schizophrenia cohorts giving further possible proofs of their overlaps.
Molecular Heterogeneity and Early Metastatic Clone Selection in Testicular Germ Cell Cancer Development
Authors: Dorssers Lambert C.J. , Gillis Ad J.M. , Stoop Hans , Marion Ronald van , Nieboer Marleen M. , Riet Job van , van de Werken Harmen J.G. , Oosterhuis J. Wolter , Ridder Jeroen de , Looijenga Leendert H.J.
Published: August 2018

Background

Testicular germ cell cancer (TGCC), being the most frequent malignancy in young Caucasian males, is initiated from an embryonic germ cell. This study determines intratumor heterogeneity to unravel tumor progression from initiation till metastasis.

Methods

In total 42 purified samples of four treatment-resistant nonseminomatous TGCC (NS) were investigated, including the precursor germ cell neoplasia in situ (GCNIS) and metastatic specimens, using whole genome- and targeted sequencing. Their evolution was reconstructed.

Results

Intratumor molecular heterogeneity did not correspond to the supposed primary tumor histological evolution. Metastases after systemic treatment could be derived from cancer stem cells not identified in the primary cancer. GCNIS mostly lacked the molecular marks of the primary NS and comprised dominant clones that failed to progress. A BRCA-like mutational signature was observed without evidence for direct involvement ofBRCA1andBRCA2genes.

Conclusions

Our data strongly support the hypothesis that NS is initiated by whole genome duplication, followed by chromosome copy number alterations in the cancer stem cell population, and accumulation of low numbers of somatic mutations. These observations of heterogeneity at all stages of tumorigenesis should be considered when treating patients with GCNIS-only disease, or with clinically overt NS.
Neural processing of communication signals: The extent of sender-receiver matching varies across species ofApteronotus
Authors: Allen K.M. , Marsat G.
Published: August 2018

As communication signal properties change, through genetic drift or selective pressure, the sensory systems that receive these signals must also adapt to maintain sensitivity and adaptability in an array of contexts. Shedding light on this process helps us understand how sensory codes are tailored to specific tasks. In a species of weakly electric fish,Apteronotus albifrons, we examined the unique neurophysiological properties that support the encoding of electrosensory communication signals that the animal encounters in social exchanges. We compare our findings to known coding properties of the closely related species,Apteronotus leptorhynchus, to establish how these animals differ in their ability to encode their distinctive communication signals. While there are many similarities between these two species, we found notable differences leading to relatively poor coding of the details of chirp structure occurring on high-frequency background beats. As a result, small differences in chirp properties are poorly resolved by the nervous system. We performed behavioral tests to relateA. albifronschirp coding strategies to its use of chirps during social encounters. Our results suggest thatA. albifronsdo not exchange frequent chirps in non-breeding condition, particularly when the beat frequency is high. These findings parallel the mediocre chirp coding accuracy in that they both point to a reduced reliance on frequent and rich exchange of information through chirps during these social interactions. Therefore, our study suggests that neural coding strategies in the central nervous system vary across species in a way that parallels the behavioral use of the sensory signals.

SIGNIFICANCE

Sender-receiver matching is a phenomenon commonly observed in the peripheral nervous system. It enables communication production and reception to evolve together so that conspecifics remain sensitive to important signals. In this manuscript we examine this phenomenon in the central nervous system of the weakly electric fishA. albifronsand compare its processing of communication signals to a closely related species (A. leptorhynchus).Although some differences across the two species can help tailor the system for processing species-specific signals, our data indicate that encoding of communication signals inA. albifronsis not as sensitive as inA. leptorhynchusfor certain categories of signals. Our data support the idea that the extent of sender-receiver matching can vary as a function of behavioral needs.