bluuebunny/crossref_metadata_2025 huggingface dataset:
0.5- to 1-Fold Intervertebral Distraction Is a Protective Factor for Adjacent Segment Degeneration in Single-level Anterior Cervical Discectomy and Fusion
Authors: Xiong Wuyi , Zhou Jiaming , Sun Chao , Chen Zhao , Guo Xing , Huo Xiaoyang , Liu Shiwei , Li Jingchao , Xue Yuan
Published: August 2019

Study Design.

Retrospective analysis.

Objective.

This study aimed to compare the clinical and radiological outcomes of different degrees of distraction in anterior cervical discectomy and fusion (ACDF) and evaluate the risk factors for adjacent segment degeneration (ASD).

Summary of Background Data.

ASD is a common complication following ACDF. Inadequate distraction of the intervertebral space during surgery is associated with ASD; however, there is still an ongoing debate regarding what degree of distraction is appropriate.

Methods.

This retrospective study enrolled 130 patients who underwent single-level ACDF for cervical degenerative disc disease and were followed up at least 2 years. The patients were divided into the following three groups according to the degree of distraction (≤0.5, 0.5–1, ≥1): insufficient distraction group (ID group), appropriate distraction group (AD group), and excessive distraction group (ED group). The clinical outcomes and radiological parameters were evaluated before and after operation and at the last follow-up. Risk factors for ASD were identified through logistic regression analysis.

Results.

A significant difference was found in the Visual Analog Scale values between the AD group and ED group at the final follow-up. Moreover, the highest upper segmental disc height (DH), highest lower segmental DH, and lowest incidence of ASD were found in the AD group among the three groups at last follow up. Logistic regression analysis revealed that segmental kyphosis (odds ratio = 2.821, P = 0.020) was a risk factor for the occurrence of ASD and 0.5- to 1-fold distraction (odds ratio = 0.350, P = 0.025) was a protective factor.

Conclusion.

Good clinical and radiological outcomes were achieved in ACDF with 0.5- to 1-fold distraction. Segmental kyphosis is a risk factor for ASD in ACDF, whereas 0.5- to 1-fold distraction is a protective factor of ASD.

Level of Evidence: 4
The Ob/Gyn and the transgender patient
Authors: Jarin Jason
Published: August 2019

Purpose of review

Over the last few years, awareness and visibility of transgender individuals have exponentially grown. With this growth comes the need for medical providers who understand the unique needs of this population. The present review serves to help obstetrician–gynecologists recognize their important role in the care of these patients.

Recent findings

Although long-term data are still lacking in the medical care of individuals with gender dysphoria, standards of care for the medical treatment of transgender patients and long-term screening recommendations in the primary care setting were discussed.

Given their surgical expertise and experience with hormone management, obstetrician–gynecologists are in a unique position to provide quality healthcare in this population.
Skin Protein Profile after Major Weight Loss and Its Role in Body Contouring Surgery
Authors: Gallo José Renato B. , Maschio-Signorini Larissa B. , Cabral Celso R. B. , de Campos Zuccari Debora A. P. , Nogueira Maurício L. , Bozola Antônio R. , Cury Patricia M. , Vidotto Alessandra
Published: August 2019

Background:

Chronic inflammation during morbid obesity significantly alters cutaneous tissue. Large weight loss achieved after bariatric surgery minimizes or halts damage caused by metabolic syndrome, but further deteriorates the clinical condition of skin. Postbariatric skin flaccidity produces major difficulties to plastic surgery. In this study, we analyzed differences in protein composition of the skin between patients with morbid obesity and those after large weight loss and established correlations between differentially expressed proteins and clinical characteristics of postbariatric skin tissue, to improve body contouring surgery techniques.

Methods:

Skin fragments were removed from the abdomen of 32 patients, who were allocated into 3 groups: morbidly obese, large weight loss without surgery, and postbariatric surgery. Samples were subjected to proteomic analysis, and the protein profiles of the groups were compared. Six differentially expressed proteins of clinical interest were validated by immunohistochemistry and statistical analysis.

Results:

Comparative analyses confirmed differences in protein profile of the skin between morbidly obese and large weight loss groups. A persistent increase in inflammatory markers such as haptoglobin was observed in all groups and decrease in the expression of collagen XIV, which regulates the physical properties of cutaneous tissue, was observed in the postbariatric group.

Conclusions:

High expression of haptoglobin associated with the decrease of Collagen XIV, vinculin, and periplakin in the groups after major weight losses, mainly postbariatric, confirm that the inflammatory lesion remains active in the skin and causes changes in its structural organization, with serious repercussions on its clinical characteristics and physical properties.
Postoperative Ketorolac Administration Is Not Associated with Hemorrhage in Cranial Vault Remodeling for Craniosynostosis
Authors: Tuncer Fatma , Knackstedt Rebecca , Murthy Ananth , Patel Niyant
Published: August 2019

Background:

Nonsteroidal anti-inflammatory drugs have been used as part of multimodal postoperative analgesic regimens to reduce the necessity of opioids. However, due to its effect on platelet function, there is a hesitation to utilize ketorolac postoperatively. The goal of this study is to analyze our experience utilizing ketorolac in patients who underwent major cranial vault remodeling (CVR) for craniosynostosis with an emphasis on postoperative hemorrhage and complications.

Methods:

A retrospective review was performed for all patients undergoing CVR for craniosynostosis from 2013 to 2017. Primary outcomes were hemorrhagic complications. Secondary outcomes included length of stay, emesis, and doses of pain medication.

Results:

Seventy-four consecutive patients met inclusion criteria. Forty-three (58.1%) received ketorolac. Seven in the ketorolac group (16%) and 9 in the control group (29%) received intraoperative blood transfusion (P = 0.25). One in the ketorolac group (2.3%) and 2 in the control group (3.1%) necessitated postoperative transfusion (P = 0.56). Patients who received ketorolac required less morphine doses (2.1 versus 3.3 doses; P = 0.02) and had a reduced length of stay (2.1 versus 2.6 nights; P = 0.04).

Conclusions:

This is the first study to demonstrate that postoperative ketorolac is not associated with an increase in hemorrhagic complications or transfusion risk in children who underwent CVR for craniosynostosis. Patients administered ketorolac required less morphine and had a hospital length of stay. We hope this study stimulates more well-done prospective trials analyzing the role that ketorolac can play in an effective and safe postoperative analgesia regimen.
A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society
Authors: Tsubota Kazuo , Yokoi Norihiko , Watanabe Hitoshi , Dogru Murat , Kojima Takashi , Yamada Masakazu , Kinoshita Shigeru , Kim Hyo-Myung , Tchah Hung-Won , Hyon Joon Young , Yoon Kyung Chul , Seo Kyoung Yul , Sun Xuguang , Chen Wei , Liang Lingyi , Li Mingwu , Tong Louis , Hu Fung-Rong , Puangsricharern Vilavun , Lim-Bon-Siong Ruben , Yong Then Kong , Liu Zuguo , Shimazaki Jun ,   Members of The Asia Dry Eye Society
Published: August 2019

The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as “Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage.” The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film–oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film–oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.
Tear Organic Acid Analysis After Corneal Collagen Crosslinking in Keratoconus
Authors: Sağlik Ayhan , Koyuncu İsmail , Soydan Adem , Sağlik Ferdağ , Gönel Ataman
Published: August 2019

Objectives:

This study examined changes in the levels of organic acids, which are important tear metabolites, after corneal collagen crosslinking (CXL) treatment for keratoconus.

Methods:

This prospective, nonrandomized, interventional case series included a single eye from 24 patients who were scheduled to receive CXL treatment (Dresden protocol) for progressive keratoconus. Before CXL treatment and at 6 months after treatment, tears were collected in capillary tubes. The patients were separated into four groups as males, females, and ages 18 years younger and >18 older. The organic acid profiles of the tear samples were analyzed using mass spectrometry.

Results:

An evaluation was made of 12 females and 12 males with a mean age of 19.20±4.06 years (range: 12‒27 years). The greatest percentage increase in organic acids after CXL treatment was observed for N-acetyl-L-aspartic acid (66% increase). The organic acid showing the greatest decrease was 3-OH butyric acid (61% decrease). A decrease of 46% was found (P=0.263) in the lactic acid/malic acid ratio.

Conclusion:

Metabolomic studies of tears could facilitate a new and objective process in the follow-up period or in the determination of prognosis after CXL treatment for diseases such as keratoconus, which has a multifactorial etiology.
Cigarette Smoking and Mortality in Patients With Pancreatic Cancer
Authors: Ben Qi-Wen , Liu Jun , Sun Yun-Wei , Wang Li-Fu , Zou Duo-Wu , Yuan Yao-Zong
Published: August 2019

Current evidence on cigarette smoking associated with pancreatic cancer mortality is limited. We searched MEDLINE, Web of Science, and Embase databases to identify relevant studies published through January 31, 2018. A random-effects model was used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 20 studies were retrieved, involving 2,517,623 participants. Of these, more than 15,341 patients with pancreatic cancer died. Compared with never smokers, current (summary HR, 1.56; 95% CI, 1.34–1.83) and former (summary HR, 1.15; 95% CI, 1.06–1.26) smokers had elevated risk of total mortality in patients diagnosed with pancreatic cancer. This effect of cigarette smoking is observed both in the Western regions and the Asia-Pacific regions. This effect of smoking is independent of alcohol use, body mass index, and history of diabetes but is modified by tumor stage and study settings. Dose-response associations between smoking and pancreatic cancer mortality were revealed for smoking intensity, cumulative amount of cigarettes smoked, and duration of smoking. Cigarette smoking was associated with an increase in total mortality for patients with pancreatic cancer. Future studies should further clarify the role of smoking as an effect modifier in treatment trials of pancreatic cancer.
Validation of a Korean Version of the Spiritual Care Competence Scale
Authors: Kang Kyung-Ah , Choi Youngsim , Kim Shin-Jeong
Published: August 2019

This study aimed to examine the reliability and validity of a scale to assess the competence of Korean nurses who provide spiritual care for patients with terminal illnesses. The reliability and validity were examined using Cronbach α, item analysis, and exploratory factor analysis. The participants were 248 hospice nurses working at 40 hospices and palliative hospitals in South Korea. The results showed that the reliability was high, as indicated by a Cronbach α of .942. The exploratory factor analysis revealed 6 dimensions (assessment and implementation of spiritual care, professionalization and improvement of the quality of spiritual care, personal support and patient counseling, referral to professionals, attitude toward the patient’s spirituality, and communication) with 27 items. The 6 factors explained 68.20% of the variance in the Korean version of the Spiritual Care Competence Scale. From the results, the Korean version of the Spiritual Care Competence Scale may serve as an appropriate measure for provision of spiritual care for patients with terminal illness. In addition, it may be useful in assessing hospice and palliative nurses’ ability for spiritual care.
Transcutaneous Pacing of a 4-Year-Old Child
Authors: Jones David , Ran Ran
Published: August 2019

Complete heart block is rare in children and is usually owing to congenital abnormalities. These children are often pacemaker dependent. However, pacemaker complications can require emergency interventions, including external pacing. This case presents a child in complete heart block requiring external pacing and then discusses some of the literature behind such interventions.
Pulmonary Vasodilation by Intravenous Infusion of Organic Mononitrites Of 1,2-Propanediol in Acute Pulmonary Hypertension Induced by Aortic Cross Clamping and Reperfusion: A Comparison With Nitroglycerin in Anesthetized Pigs
Authors: Nilsson Kristofer F. , Gozdzik Waldemar , Zielinski Stanislaw , Ratajczak Kornel , Göranson Sofie P. , Rodziewicz Sylwia , Harbut Piotr , Barteczko-Grajek Barbara , Albert Johanna , Frostell Claes
Published: August 2019

Introduction:

Suprarenal aortic cross clamping (SRACC) and reperfusion may cause acute pulmonary hypertension and multiple organ failure.

Hypothesis:

The organic mononitrites of 1,2-propanediol (PDNO), an nitric oxide donor with a very short half-life, are a more efficient pulmonary vasodilator and attenuator of end-organ damage and inflammation without significant side effects compared with nitroglycerin and inorganic nitrite in a porcine SRACC model.

Methods:

Anesthetized and instrumented domestic pigs were randomized to either of four IV infusions until the end of the experiment (n = 10 per group): saline (control), PDNO (45 nmol kg−1 min−1), nitroglycerin (44 nmol kg−1 min−1), or inorganic nitrite (a dose corresponding to PDNO). Thereafter, all animals were subjected to 90 min of SRACC and 10 h of reperfusion and protocolized resuscitation. Hemodynamic and respiratory variables as well as blood samples were collected and analysed.

Results:

During reperfusion, mean pulmonary arterial pressure and pulmonary vascular resistance were significantly lower, and stroke volume was significantly higher in the PDNO group compared with the control, nitroglycerin, and inorganic nitrite groups. In parallel, mean arterial pressure, arterial oxygenation, and fraction of methaemoglobin were similar in all groups. The serum concentration of creatinine and tumor necrosis factor alpha were lower in the PDNO group compared with the control group during reperfusion.

Conclusions:

PDNO was an effective pulmonary vasodilator and appeared superior to nitroglycerin and inorganic nitrite, without causing significant systemic hypotension, impaired arterial oxygenation, or methaemoglobin formation in an animal model of SRACC and reperfusion. Also, PDNO may have kidney-protective effects and anti-inflammatory properties.
Evaluating Disability-Related Quality of Life in Women With Chronic Pelvic Pain
Authors: Ye Alice L. , Adams William , Westbay Lauren C. , Fitzgerald Colleen M.
Published: August 2019

Objectives

The primary aim of this study was to describe quality of life (QOL) in women with chronic pelvic pain using the Pain Disability Index (PDI). A secondary goal was to assess the measurement properties and validity of the PDI for this population.

Methods

This study was a cross-sectional retrospective chart review. In the setting of an outpatient female pelvic pain clinic, we included data from an initial evaluation of patients 16 years and older with chronic pelvic pain (N = 317) from 2012 to 2017. Quality of life was measured using the PDI and previously validated measures for depression and anxiety.

Results

The mean PDI score across all patients was similar to previously reported means for similar chronic pain populations. Patients experienced the most disability in their sexual activities. The most common cause of chronic pelvic pain was pelvic floor myofascial pain. Common diagnostic categories covered gynecologic, urologic, gastrointestinal, musculoskeletal, and neurological causes. The PDI was unable to discriminate between diagnoses. On average, patients qualified for mild depression and anxiety diagnoses. Results from a confirmatory factor analysis revealed the original factor structure for the PDI fits this population.

Conclusions

The PDI shows promise as a questionnaire for QOL and could be a valuable clinician tool for tracking QOL in the chronic pelvic pain population. Additional research should be focused on assessing its ability to measure minimum clinically significant change over time.
Documentation, structural health monitoring and numerical modelling for damage assessment of the Morris Island Lighthouse
Authors: Blyth Anna , Napolitano Rebecca , Glisic Branko
Published: August 2019

Heritage structures serve as invaluable records of cultural achievement that should be preserved for future generations. To ensure the successful preservation of these structures, there must be an affordable and effective way to conduct conservation. The objective of this work is to outline an efficient workflow for the structural analysis of preservation projects through a case study on the Morris Island Lighthouse in Charleston, South Carolina. Thorough documentation of the cultural significance and structural condition of the lighthouse was completed through archival research, photogrammetry and crack mapping. Structural Health Monitoring and Distinct Element Modelling were used to analyse past structural damage and the present condition. The behaviour of masonry and crack propagation was evaluated under gravity, wind, wave and seismic loading. The results of these analyses were summarized in a virtual tour and informational modelling environment, which allows the results to be accessed and associated with their physical location on the structure. The benefits and limitations of this process are discussed, and a standardized workflow for efficient structural analysis of cultural heritage is proposed.

This article is part of the theme issue ‘Environmental loading of heritage structures’.
La Jument lighthouse: a real-scale laboratory for the study of giant waves and their loading on marine structures
Authors: Filipot J.-F. , Guimaraes P. , Leckler F. , Hortsmann J. , Carrasco R. , Leroy E. , Fady N. , Accensi M. , Prevosto M. , Duarte R. , Roeber V. , Benetazzo A. , Raoult C. , Franzetti M. , Varing A. , Le Dantec N.
Published: August 2019

This paper presents results from an experiment designed to improve the understanding of the relationship between extreme breaking waves and their mechanical loading on heritage offshore lighthouses. The experiment, conducted at La Jument, an iconic French offshore lighthouse, featured several records of wave, current and structure accelerations acquired during severe storm conditions, with individual waves as high as 24 m. Data analysis focuses on a storm event marked by a strong peak in the horizontal accelerations measured inside La Jument. Thanks to stereo-video wave measurements synchronized to the acceleration record we were able to identify and describe the breaking wave responsible for this intense loading. Our observations suggest that this giant wave (19 m high) had a crest elevation high enough to directly hit the lighthouse tower, above the substructure. This paper reveals the potential for conducting ambitious field experiments from offshore lighthouses in order to collect valuable storm waves and wave loading observations. This offers a possible second service life for these heritage structures as
in situ
laboratories dedicated to the study of the coastal hydrodynamics and its interaction with marine structures.

This article is part of the theme issue ‘Environmental loading of heritage structures’.
Structural response of French offshore heritage lighthouses
Authors: Denarié Emmanuel , Fady Nicolas
Published: August 2019

Offshore lighthouses are a remarkable historical heritage often over 100 years old. The management of their ageing is a challenge and requires a thorough understanding of their structural response under wave loading. With this aim in view, the dynamic response of the ‘La Jument’ lighthouse in the French Iroise Sea was characterizedin situ, with accelerometers, under the action of a breaking wave, during a winter storm in January 2018. Detailed exploitation of the measurement data complemented by photographic documentation of the same wave event helped determine eigenfrequencies and damping coefficients of the structure as well as the likely orientation of the wave and the position of its crest with respect to the lighthouse tower. The results of these analyses were put into perspective with those of literature and more specifically from three-dimensional finite element modelling of the structural response of the lighthouse under the action effects of breaking waves.

This article is part of the theme issue ‘Environmental loading of heritage structures’.
A Bayesian model updating framework for robust seismic fragility analysis of non-isolated historic masonry towers
Authors: Bartoli Gianni , Betti Michele , Marra Antonino Maria , Monchetti Silvia
Published: August 2019

Seismic assessment of existing masonry structures requires a numerical model able to both reproduce their nonlinear behaviour and account for the different sources of uncertainties; the latter have to be dealt with since the unavoidable lack of knowledge on the input parameters (material properties, geometry, boundary conditions, etc.) has a relevant effect on the reliability of the seismic response provided by the numerical approaches. The steadily increasing necessity of combining different sources of information/knowledge makes the Bayesian approach an appealing technique, not yet fully investigated for historic masonry constructions. In fact, while the Bayesian paradigm is currently employed to solve inverse problems in several sectors of the structural engineering domain, only a few studies pay attention to its effectiveness for parameter identification on historic masonry structures. This study combines a Bayesian framework with probabilistic structural analyses: starting from the Bayesian finite element model updating by using experimental data it provides the definition of robust seismic fragility curves for non-isolated masonry towers. A comparison between this method and the standard deterministic approach illustrates its benefits.

This article is part of the theme issue ‘Environmental loading of heritage structures’.
Stochastic subspace identification of modal parameters during ice–structure interaction
Authors: Nord Torodd S. , Petersen Øyvind W. , Hendrikse Hayo
Published: August 2019

Identifying the modal parameters of structures located in ice-infested waters may be challenging due to the interaction between the ice and structure. In this study, both simulated data from a state-of-the-art ice–structure interaction model and measured data of ice–structure interaction were both used in conjunction with a covariance-driven stochastic subspace identification method to identify the modal parameters and their corresponding variances. The variances can be used to assign confidence to the identified eigenfrequencies, and effectively eliminate the eigenfrequencies with large variances. This enables a comparison between the identified eigenfrequencies for different ice conditions. Simulated data were used to assess the accuracy of the identified modal parameters during ice–structure interactions, and they were further used to guide the choice of parameters for the subspace identification when applied to measured data. The measured data consisted of 150 recordings of ice actions against the Norströmsgrund lighthouse in the Northern Baltic Sea. The results were sorted into groups defined by the observed ice conditions and governing ice failure mechanisms during the ice–structure interaction. The identified eigenfrequencies varied within each individual group and between the groups. Based on identified modal parameters, we suggested which eigenmodes play an active role in the interaction processes at the ice–structure interface and discussed the possible sources of errors.

This article is part of the theme issue ‘Environmental loading of heritage structures’.
The needs for diagnostic imaging in cases of group A streptococcal meningitis in children: a case report and review of the literature
Authors: van Dijk Lise , Wolfs Tom F. W. , Debast Sylvia B. , Langenhorst Veerle V. J.
Published: August 2019

Group A streptococcus (GAS) is a rare cause of bacterial meningitis in children and is associated with a high cerebral complication rate. In this case report, we present a 9-year-old girl with GAS meningitis complicated with cerebritis. Clear guidelines about choice of treatment and indications of follow-up by imaging tests are lacking, making GAS meningitis unpredictable and difficult to treat. Eventually, we found 25 paediatric cases of GAS meningitis presented in the literature and reviewed their treatment choices, outcomes and follow-up by imaging tests. Penicillin and ceftriaxone are most preferred for the treatment of GAS meningitis and adding rifampicin to the antibiotic treatment could be of potential benefit. When considering the duration of antibiotic treatment and follow-up by imaging tests, no clear recommendations were found. We found that GAS meningitis is associated with higher mortality and cerebral complication rates compared to other, more common, bacterial causes of meningitis in children. This should alert the clinician to consider imaging tests routinely, even if the patient improves clinically. We advise clinicians to routinely evaluate for possible cerebral complications through magnetic resonance imaging (MRI) scans. When cerebral complications are found, antibiotic treatment should be prolonged and adding rifampicin to the antibiotic regime may be considered.
From cell culture to cynomolgus macaque: infection models show lineage-specific virulence potential of Coxiella burnetii
Authors: Metters Georgina , Norville Isobel H. , Titball Richard W. , Hemsley Claudia M.
Published: August 2019

Coxiella burnetii

is an obligate intracellular pathogen that causes the zoonotic disease Q fever in humans, which can occur in either an acute or a chronic form with serious complications. The bacterium has a wide host range, including unicellular organisms, invertebrates, birds and mammals, with livestock representing the most significant reservoir for human infections. Cell culture models have been used to decipher the intracellular lifestyle of

C. burnetii

, and several infection models, including invertebrates, rodents and non-human primates, are being used to investigate host–pathogen interactions and to identify bacterial virulence factors and vaccine candidates. However, none of the models replicate all aspects of human disease. Furthermore, it is becoming evident that

C. burnetii

isolates belonging to different lineages exhibit differences in their virulence in these models. Here, we compare the advantages and disadvantages of commonly used infection models and summarize currently available data for lineage-specific virulence.
A Single-Cell Transcriptome Atlas for Zebrafish Development
Authors: Farnsworth Dylan R. , Saunders Lauren , Miller Adam C.
Published: August 2019

The ability to define cell types and how they change during organogenesis is central to our understanding of animal development and human disease. Despite the crucial nature of this knowledge, we have yet to fully characterize all distinct cell types and the gene expression differences that generate cell types during development. To address this knowledge gap, we produced an Atlas using single-cell RNA-sequencing methods to investigate gene expression from the pharyngula to early larval stages in developing zebrafish. Our single-cell transcriptome Atlas encompasses transcriptional profiles from 44,102 cells across four days of development using duplicate experiments that confirmed high reproducibility. We annotated 220 identified clusters and highlighted several strategies for interrogating changes in gene expression associated with the development of zebrafish embryos at single-cell resolution. Furthermore, we highlight the power of this analysis to assign new cell-type or developmental stage-specific expression information to many genes, including those that are currently known only by sequence and/or that lack expression information altogether. The resulting Atlas is a resource of biologists to generate hypotheses for genetic (mutant) or functional analysis, to launch an effort to define the diversity of cell-types during zebrafish organogenesis, and to examine the transcriptional profiles that produce each cell type over developmental time.
Modulation of human intracranial theta oscillations during freely moving spatial navigation and memory
Authors: Aghajan Zahra M. , Villaroman Diane , Hiller Sonja , Wishard Tyler J. , Topalovic Uros , Christov-Moore Leonardo , Shaterian Nader , Hasulak Nicholas R. , Knowlton Barbara , Eliashiv Dawn , Rao Vikram , Fried Itzhak , Suthana Nanthia
Published: August 2019

How the human brain supports accurate navigation of a learned environment has been an active topic of research for nearly a century1–5. In rodents, the theta rhythm within the medial temporal lobe (MTL) has been proposed as a neural basis for fragmenting incoming information and temporally organizing experiences and is thus widely implicated in spatial and episodic memory6. In addition, high-frequency theta (~8Hz) is associated with navigation, and loss of theta results in spatial memory deficits in rats 7. Recently, high-frequency theta oscillations during ambulatory movement have been identified in humans8,9, though their relationship to spatial memory remains unexplored. Here, we were able to record MTL activity during spatial memory and navigation in freely moving humans immersed in a room-scale virtual reality (VR) environment. Naturalistic movements were captured using motion tracking combined with wireless VR in participants implanted with an intracranial electroencephalographic (iEEG) recording system for the treatment of epilepsy. We found that prevalence of theta oscillations across brain sites during both learning and recall of spatial locations during ambulatory navigation is critically linked to memory performance. This finding supports the reinstatement hypothesis of episodic memory—thought to underlie our ability to recreate a prior experience10–12—and suggests that theta prevalence within the MTL may act as a potential representational state for memory reinstatement during spatial navigation. Additionally, we found that theta power is hexadirectionally modulated13–15 as a function of the direction of physical movement, most prominently after learning has occurred. This effect bears a resemblance to the rodent grid cell system16 and suggests an analog in human navigation. Taken together, our results provide the first characterization of neural oscillations in the human MTL during ambulatory spatial memory tasks and provide a platform for future investigations of neural mechanisms underlying freely moving navigation in humans.
Interplay between metrical and semantic processing in French: an N400 study
Authors: Rietmolen Noémie te , Yagoubi Radouane El , Astésano Corine
Published: August 2019

French accentuation is held to belong to the level of the phrase. Consequently French is considered ‘a language without accent’ with speakers that are ‘deaf to stress’. Recent ERP-studies investigating the French initial accent (IA) however demonstrate listeners to not only discriminate between different stress patterns, but also expect words to be marked with IA early in the process of speech comprehension. Still, as words were presented in isolation, it remains unclear whether the preference applied to the lexical or to the phrasal level. In the current ERP-study, we address this ambiguity and manipulate IA on words embedded in a sentence. Furthermore, we orthogonally manipulate semantic congruity to investigate the interplay between accentuation and later speech processing stages. Results reveal an early fronto-centrally located negative deflection when words are presented without IA, indicating a general dispreference for words presented without IA. Additionally, we found an effect of semantic congruity in the centro-parietal region (the traditional region for N400), which was bigger for words without IA than for words with IA. Furthermore, we observed an interaction between metrical structure and semantic congruity such that ±IA continued to modulate N400 amplitude fronto-centrally, but only in the sentences that were semantically incongruent. The results indicate that presenting word without initial accent hinders semantic conflict resolution. This interpretation is supported by the behavioral data which show that participants were slower and made more errors words had been presented without IA. As participants attended to the semantic content of the sentences, the finding underlines the automaticity of stress processing and indicates that IA may be encoded at a lexical level where it facilitates semantic processing.
Detecting differential alternative splicing events in scRNA-seq with or without UMIs
Authors: Hu Yu , Wang Kai , Li Mingyao
Published: August 2019

Analysis of alternative splicing in single-cell RNA sequencing (scRNA-seq) is challenging due to its inherent technical noise and generally low sequencing depth. We present SCATS (Single-Cell Analysis of Transcript Splicing) for differential alternative splicing (DAS) analysis for scRNA-seq data with or without unique molecular identifiers (UMIs). By modeling technical noise and grouping exons that originate from the same isoform(s), SCATS achieves high sensitivity to detect DAS events compared to Census, DEXSeq and MISO, and these events were confirmed by qRT-PCR experiment.
Spherical deconvolution with tissue-specific response functions and multi-shell diffusion MRI to estimate multiple fiber orientation distributions (mFODs)
Authors: De Luca Alberto , Guo Fenghua , Froeling Martijn , Leemans Alexander
Published: August 2019

In diffusion MRI, spherical deconvolution approaches can estimate local white matter (WM) fiber orientation distributions (FOD) which can be used to produce fiber tractography reconstructions. The applicability of spherical deconvolution to grey matter (GM), however, is still limited, despite its critical role as start/endpoint of WM fiber pathways. The advent of multi-shell diffusion MRI data offers additional contrast to model the GM signal but, to date, only isotropic models have been applied to GM. Evidence from both histology and high-resolution diffusion MRI studies suggests a marked anisotropic character of the diffusion process in GM, which could be exploited to improve the description of the cortical organization. In this study, we investigated whether performing spherical deconvolution with tissue specific models of both WM and GM can improve the characterization of the latter while retaining state-of-the-art performances in WM. To this end, we developed a framework able to simultaneously accommodate multiple anisotropic response functions to estimate multiple, tissue-specific, fiber orientation distributions (mFODs). As proof of principle, we used the diffusion kurtosis imaging model to represent the WM signal, and the neurite orientation dispersion and density imaging (NODDI) model to represent the GM signal. The feasibility of the proposed approach is shown with numerical simulations and with data from the Human Connectome Project (HCP). The performance of our method is compared to the current state of the art, multi-shell constrained spherical deconvolution (MSCSD). The simulations show that with our new method we can accurately estimate a mixture of two FODs at SNR≥50. With HCP data, the proposed method was able to reconstruct both tangentially and radially oriented FODs in GM, and performed comparably well to MSCSD in computing FODs in WM. When performing fiber tractography, the trajectories reconstructed with mFODs reached the cortex with more spatial continuity and for a longer distance as compared to MSCSD and allowed to reconstruct short trajectories tangential to the cortical folding. In conclusion, we demonstrated that our proposed method allows to perform spherical deconvolution of multiple anisotropic response functions, specifically improving the performances of spherical deconvolution in GM tissue.

Highlights

We introduce a novel framework to perform spherical deconvolution with multiple anisotropic response functions (mFOD)

We show that the proposed framework can be used to improve the FOD estimation in the cortical grey matter

Fiber tractography performed with mFOD reaches the cortical GM with more coverage and contiguity than with previous methods

The proposed framework is a first step towards GM to GM fiber tractography
Antibody binding epitope Mapping (AbMap) of two hundred antibodies in a single run
Authors: Qi Huan , Ma Mingliang , Hu Chuansheng , Xu Zhao-wei , Wu Fan-lin , Wang Nan , Lai Dan-yun , Li Yang , Guo Shu-juan , Zhao Xiaodong , Li Hua , Tao Sheng-ce
Published: August 2019

Epitope mapping is essential for the understanding how an antibody works. Given millions of antibodies short of epitope information, there is an urgent need for high-throughput epitope mapping. Here we combined a commercial phage displayed random peptide library of 109diversity with next generation sequencing to developAntibodybinding epitopeMapping (AbMap) technology. Over two hundred antibodies were analyzed in a single test and epitopes were determined for >50% of them. Strikingly, the antibodies were able to recognize different proteins from multiple species with similar epitopes. We successfully identified the epitopes of 14 anti-PD-1 antibodies, including Sintilimab (i.e., L128, A129 and P130), and confirmed that the binding epitopes of Nivolumab and Sintilimab are very close to the binding interface of PD-1 and PD-L1. The predicted conformational epitopes of Pembrolizumab and Nivolumab are consistent with their antibody-antigen co-crystal structures. AbMap is the first technology enables high-throughput epitope mapping.

Highlights

The first technology enables epitope mapping of two hundred antibodies in a single run

Linear epitope was determined for >50% of the antibodies

Distinct epitopes of 14 anti-PD-1 antibodies, including Sintilimab, were determined

The predicted conformational epitopes of Pembrolizumab and Nivolumab are consistent with the known antibody-antigen co-crystal structures
PASER for automated analysis of neural signals recorded in pulsating magnetic fields
Authors: Brouns Terence , Celikel Tansu
Published: August 2019

Thanks to the advancements in multichannel intracranial neural recordings, magnetic neuroimaging and magnetic neurostimulation techniques (including magnetogenetics), it is now possible to perform large-scale high-throughput neural recordings while imaging or controlling neural activity in a magnetic field. Analysis of neural recordings performed in a switching magnetic field, however, is not a trivial task as gradient and pulse artefacts interfere with the unit isolation. Here we introduce a toolbox called PASER, Processing and Analysis Schemes for Extracellular Recordings, that performs automated denoising, artefact removal, quality control of electrical recordings, unit classification and visualization. PASER is written in MATLAB and modular by design. The current version integrates with third party applications to provide additional functionality, including data import, spike sorting and the analysis of local field potentials. After the description of the toolbox, we evaluate 9 different spike sorting algorithms based on computational cost, unit yield, unit quality and clustering reliability across varying conditions including self-blurring and noise-reversal. Implementation of the best performing spike sorting algorithm (KiloSort) in the default version of the PASER provides the end user with a fully automated pipeline for quantitative analysis of broadband extracellular signals. PASER can be integrated with any established pipeline that sample neural activity with intracranial electrodes. Unlike the existing algorithmic solutions, PASER provides an end-to-end solution for neural recordings made in switching magnetic fields independent from the number of electrodes and the duration of recordings, thus enables high-throughput analysis of neural activity in a wide range of electro-magnetic recording conditions.
SVFX: a machine-learning framework to quantify the pathogenicity of structural variants
Authors: Kumar Sushant , Harmanci Arif , Vytheeswaran Jagath , Gerstein Mark B.
Published: August 2019

A rapid decline in sequencing cost has made large-scale genome sequencing studies feasible. One of the fundamental goals of these studies is to catalog all pathogenic variants. Numerous methods and tools have been developed to interpret point mutations and small insertions and deletions. However, there is a lack of approaches for identifying pathogenic genomic structural variations (SVs). That said, SVs are known to play a crucial role in many diseases by altering the sequence and three-dimensional structure of the genome. Previous studies have suggested a complex interplay of genomic and epigenomic features in the emergence and distribution of SVs. However, the exact mechanism of pathogenesis for SVs in different diseases is not straightforward to decipher. Thus, we built an agnostic machine-learning-based workflow, called SVFX, to assign a “pathogenicity score” to somatic and germline SVs in various diseases. In particular, we generated somatic and germline training models, which included genomic, epigenomic, and conservation-based features for SV call sets in diseased and healthy individuals. We then applied SVFX to SVs in six different cancer cohorts and a cardiovascular disease (CVD) cohort. Overall, SVFX achieved high accuracy in identifying pathogenic SVs. Moreover, we found that predicted pathogenic SVs in cancer cohorts were enriched among known cancer genes and many cancer-related pathways (including Wnt signaling, Ras signaling, DNA repair, and ubiquitin-mediated proteolysis). Finally, we note that SVFX is flexible and can be easily extended to identify pathogenic SVs in additional disease cohorts.
Glycopeptide variable window SWATH for improved Data Independent Acquisition glycoprotein analysis
Authors: Zhou Chun , Schulz Benjamin L.
Published: August 2019

N-glycosylation plays an essential role in regulating protein folding and function in eukaryotic cells. Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH) has proven useful as a data independent acquisition (DIA) MS method for analysis of glycoproteins and their glycan modifications. By separating the entire m/z range into consecutive isolation windows, DIA-MS allows comprehensive MS data acquisition and high-sensitivity detection of molecules of interest. Variable width DIA windows allow optimal analyte measurement, as peptide ions are not evenly distributed across the full m/z range. However, the m/z distribution of glycopeptides is different to that of unmodified peptides because of their large glycan structures. Here, we improved the performance of DIA glycoproteomics by using variable width windows optimized for glycopeptides. This method allocates narrow windows at m/z ranges rich in glycopeptides, improving analytical specificity and performance. We show that related glycoforms must fall in separate windows to allow accurate glycopeptide measurement. We demonstrate the utility of the method by comparing the cell wall glycoproteomes of wild-type and N-glycan biosynthesis deficient yeast and showing improved measurement of glycopeptides with different glycan structures. Our results highlight the importance of appropriately optimized DIA methods for measurement of post-translationally modified peptides.
The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components
Authors: Teramoto Machiko , Sugawara Ryo , Minegishi Katsura , Uchikawa Masanori , Takemoto Tatsuya , Kuroiwa Atsushi , Ishii Yasuo , Kondoh Hisato
Published: August 2019

In the anterior foregut (AFG) of mouse embryos, the transcription factor SOX2 is expressed in the epithelia of the esophagus and proximal branches of respiratory organs comprising the trachea and bronchi, whereas NKX2.1 is expressed only in the epithelia of respiratory organs. Previous studies using hypomorphic Sox2 alleles have indicated that reduced SOX2 expression causes the esophageal epithelium to display some respiratory organ characteristics. In the present study, we produced mouse embryos with AFG-specific SOX2 deficiency. In the absence of SOX2 expression, a single NKX2.1-expressing epithelial tube connected the pharynx and the stomach, and a pair of bronchi developed in the middle of the tube. Expression patterns of NKX2.1 and SOX9 revealed that the anterior and posterior halves of SOX2-deficient AFG epithelial tubes assumed the characteristics of the trachea and bronchus, respectively. In addition, we found that mesenchymal tissues surrounding the SOX2-deficient NKX2.1-expressing epithelial tube changed to those surrounding the trachea and bronchi in the anterior and posterior halves, as indicated by the arrangement of smooth muscle cells and SOX9-expressing cells and by the expression of Wnt4 (esophagus specific), Tbx4 (respiratory organ specific), and Hoxb6 (distal bronchus specific). The impact of mesenchyme-derived signaling on the early stage of AFG epithelial specification has been indicated. Our study demonstrated an opposite trend where epithelial tissue specification causes concordant changes in mesenchymal tissues, indicating a reciprocity of epithelial-mesenchymal interactions.