bluuebunny/crossref_metadata_2025 huggingface dataset:
Sepsis-Associated 30-Day Risk-Standardized Readmissions: Analysis of a Nationwide Medicare Sample*
Authors: Norman Brett C. , Cooke Colin R. , Ely E. Wes , Graves John A.
Published: May 2017

Objectives:

To determine national readmission rates among sepsis survivors, variations in rates between hospitals, and determine whether measures of quality correlate with performance on sepsis readmissions.

Design:

Cross-sectional study of sepsis readmissions between 2008 and 2011 in the Medicare fee-for-service database.

Setting:

Acute care, Medicare participating hospitals from 2008 to 2011.

Patients:

Septic patients as identified by International Classification of Diseases, Ninth Revision codes using the Angus method.

Interventions:

None.

Measurements and Main Results:

We generated hospital-level, risk-standardized, 30-day readmission rates among survivors of sepsis and compared rates across region, ownership, teaching status, sepsis volume, hospital size, and proportion of underserved patients. We examined the relationship between risk-standardized readmission rates and hospital-level composite measures of quality and mortality. From 633,407 hospitalizations among 3,315 hospitals from 2008 to 2011, median risk-standardized readmission rates was 28.7% (interquartile range, 26.1–31.9). There were differences in risk-standardized readmission rates by region (Northeast, 30.4%; South, 29.6%; Midwest, 28.8%; and West, 27.7%; p < 0.001), teaching versus nonteaching status (31.1% vs 29.0%; p < 0.001), and hospitals serving the highest proportion of underserved patients (30.6% vs 28.7%; p < 0.001). The best performing hospitals on a composite quality measure had highest risk-standardized readmission rates compared with the lowest (32.0% vs 27.5%; p < 0.001). Risk-standardized readmission rates was lower in the highest mortality hospitals compared with those in the lowest (28.7% vs 30.7%; p < 0.001).

Conclusions:

One third of sepsis survivors were readmitted and wide variation exists between hospitals. Several demographic and structural factors are associated with this variation. Measures of higher quality in-hospital care were correlated with higher readmission rates. Several potential explanations are possible including poor risk standardization, more research is needed.
Nurses’ Perception of Challenges in the Use of an Electronic Nursing Documentation System
Authors: Heidarizadeh Khadijeh , Rassouli Maryam , Manoochehri Houman , Zagheri Tafreshi Mansoureh , Kashef Ghorbanpour Reza
Published: May 2017

This qualitative study was based on the Technology Acceptance Model and conducted through directed content analysis to explore perceptions of nurses in Iran of the challenges of using an electronic documentation system. Participants were selected through purposive sampling via interview from a teaching hospital in western Iran. Data were analyzed using MAXQDA 10. Data consistency was ensured through validation methods and by the researcher’s prolonged engagement in the subject. Twelve codes, four subcategories, and two main categories (“perceived usefulness” and “perceived difficulty”) emerged from the analysis of the data based on the Technology Acceptance Model. “Perceived usefulness” consisted of the subcategories “subjective norms” and “experienced benefits”; and “perceived difficulty” contained the subcategories “rationalization” as well as “challenges in accepting change.” According to the Technology Acceptance Model, to promote acceptance of this system, the benefits of usage should be highlighted. The biggest hurdle to acceptance is familiarity and comfort with previous methods.
A Literature Review of Psychosocial Comorbidities Related to Working Capacity After Aneurysmal Subarachnoid Hemorrhage
Authors: Turi Eleanor , Conley Yvette , Stanfill Ansley Grimes
Published: May 2017

Objective: The aim of this study was to describe literature regarding the impact of psychosocial comorbidities on working capacity after aneurysmal subarachnoid hemorrhage (aSAH). Design/Methods: This study is a review of the literature using PubMed, CINAHL, PyschINFO, and Google Scholar. Results: Patients with aSAH affected by depression, anxiety, cognitive impairment, or posttraumatic stress disorder are less likely to return to work, although there are mixed results. These may be due to inconsistent inclusion, adjustment of demographic and clinical variables shown to be associated with return to work, and differences in instrumentation and sample size. Conclusions: Working capacity after aSAH is likely affected by poor psychosocial outcomes, but future research should consider the standardization of demographic and clinical data, use standardized measurement tools, and consider the interrelatedness between psychosocial comorbidities.
Which Combination Treatment Is Better for Spinal Metastasis: Percutaneous Vertebroplasty With Radiofrequency Ablation, 125I Seed, Zoledronic Acid, or Radiotherapy?
Authors: Lu Chun-Wen , Shao Jie , Wu Yu-Gang , Wang Chao , Wu Jin-Hui , Lv Run-Xiao , Ding Mu-Chen , Shi Zhi-Cai , Mao Ning-Fang
Published: May 2017

Background:

Percutaneous vertebroplasty (PVP) can not only alleviate pain but also restore mechanical stability with injection of bone cement, whereas it exhibits a poor effect on antitumor activity. But through combinations with other therapies, it may be possible to achieve the maximum effect in clinical treatment. Thus, this study is designed to assess the clinical efficacy of PVP separately combined with 4 ways for spinal metastasis (SM) treatment.

Study Question:

Which combination treatment is better for spinal metastasis, percutaneous vertebroplasty with radiofrequency ablation, 125I seed, zoledronic acid or radiotherapy?

Study Design:

A total of 169 patients with SM were retrospectively recruited and randomly assigned to 4 groups to receive 4 different ways separately: 49 patients (group A) received PVP plus 125I seed, 51 (group B) received PVP plus radiofrequency ablation (RFA), 38 (group C) underwent PVP plus zoledronic acid (ZA), and 31 (group D) underwent PVP plus radiotherapy (RT).

Measures and Outcomes:

All of them underwent routine examinations before operation. Visual analog scale (VAS), World Health Organization (WHO) Pain Relief, and ODI were applied to evaluate pain relief and motor function.

Results:

PVP plus RT achieved the best efficacy in relieving pains, with the highest WHO Pain Relief (P < 0.05). The PVP plus RFA exhibited lowest ODI, suggesting the best outcome after treatment (P < 0.05). The PVP plus 125I showed the lowest VAS score, but it was the worst to improve the routine exercise ability and relieve pains from patients. The PVP plus ZA presented higher VAS and ODI (P < 0.05).

Conclusions:

PVP combined with 125I seed exhibited the best clinical efficacy in terms of VAS, PVP combined with RT was the best choice in terms of WHO Pain Relief, and PVP combined with RFA showed the best effect in terms of ODI for the treatment of SM.
Coley's toxin and BCG vaccine in prevention and treatment of malignant melanoma in humans
Authors: Kucerova Petra , Vlasakova Jitka , Cervinkova Monika
Published: May 2017

Malignant melanoma is the most severe form of skin cancers in humans. Incidence of this malignancy is still increasing worldwide. The highest incidence is mentioned in Australia (50–60/100,000 of cases). Success of malignant melanoma therapy depends on the stage of disease revelation. Localized cutaneous melanoma is generally well curable. The main problem is the treatment of advanced malignant melanoma with distant metastases. Therapy of this malignancy is based on surgical resection of lesion, chemotherapy, immunotherapy, biochemotherapy, and so on. The current results of malignant melanoma treatment are unfortunately often unsatisfactory. Improvement and enhancement of efficacy of contemporary immunotherapeutic methods should be in the forefront of interest. Renaissance of the old concepts of immunotherapy (Coley's toxin and Bacillus Calmette-Guérin vaccine administration) could be one way to reduce possible adverse effect of standard methods of malignant melanoma treatment.
Outcomes for End-of-Life Patients With Anticipatory Grieving
Authors: Johnson Julie , Lodhi Muhammad Kamran , Cheema Umer , Stifter Janet , Dunn-Lopez Karen , Yao Yingwei , Johnson Andrew , Keenan Gail M. , Ansari Rashid , Khokhar Ashfaq , Wilkie Diana J.
Published: May 2017

Anticipatory grieving, grief associated with an impending loss, is common for patients facing end of life or for their families. There is little research on the outcomes of interventions for anticipatory grieving among hospitalized patients. A descriptive, comparative analysis of an existing valid and reliable data set that was obtained through routine nursing clinical practice using standardized nursing terminologies was completed. We applied data mining techniques on a targeted data set consisting of hospital episodes for end-of-life patients who were given a diagnosis of anticipatory grieving. Less than 50% of the patients given a diagnosis of anticipatory grieving met the expected ratings of monitored nursing outcomes at the time of death or discharge. Specifically, for the spiritual health outcome, only more than 50% of the patients met the expected outcome rating. For the comfortable death outcome, only 45.9% of the patients met the outcome rating. For the comfortable death outcome, patients were significantly more likely not to meet the expected outcome rating if they were also given a diagnosis belonging to the physical comfort class (χ2(1) = 8.99, P < .003). These results demonstrate that expected outcomes are not being met and suggest the need of better education for the clinicians about the diagnosis and treatment of anticipatory grieving.
Describing Transitional Palliative Nursing Care Using a Standardized Terminology
Authors: Holland Diane E. , Vanderboom Catherine E. , Dose Ann Marie , Delgado Adriana M. , Austin Christine M. , Ingram Cory J. , Wild Ellen M. , Monsen Karen A.
Published: May 2017

We used a standardized terminology to describe patient problems and the nursing care provided in a pilot study of a transitional palliative care intervention with patients and caregivers. Narrative phrases of a nurse's documentation were mapped to the Omaha System (problem, intervention, and target). Over the course of the intervention, 109 notes (1473 phrases) were documented for 9 adults discharged home (mean age, 68 years; mean number of morbid conditions, 7.1; mean number of medications, 15.4). Thirty-one of the 42 Omaha System problems were identified; the average number of problems per patient was 13. Phrases were mapped to all 4 problem domains (environmental, 2.6%; health-related behaviors, 52.3%; physiological, 30.8%; and psychosocial, 14.3%). Surveillance phrases were the most frequent (72.4%); case management phrases were at 20.9%, and teaching, guidance, and counseling phrases were at 6.7%. The number of problems documented per patient correlated with the time between the first and last notes (ρ = 0.76; P = .02) but not with the number of notes per patient (ρ = 0.51; P = .16). These results are the first to describe nursing interventions in transitioning palliative care from hospital to home with a standardized terminology. Linking interventions to patient problems is critical for describing effective strategies in transitioning palliative care from hospital to home.
Enhancing Baccalaureate Nursing Students’ Perception of Competence and Confidence During an Alternative Dedicated Education Unit Experience
Authors: Schecter Rose , Gallagher Joan , Ryan Marybeth
Published: May 2017

This quasiexperimental pilot study explored the effect three consecutive adult health Dedicated Education Unit (DEU) clinical placements would have on baccalaureate nursing students' self-perception of growth in competence and confidence. A Likert-type Competence/Confidence Self-Assessment Scale was constructed as a pretest/posttest measure; competence and confidence posttest means increased in each course. The study provides nursing professional development practitioners with information about the alternative DEU concept, its effect on student outcomes, and benefits nursing staff can gain by participating in a DEU experience.
Systematic Review and Meta-Analysis of Perioperative Outcomes of Peroral Endoscopic Myotomy (POEM) and Laparoscopic Heller Myotomy (LHM) for Achalasia
Authors: Awaiz Aiman , Yunus Rossita M. , Khan Shahjahan , Memon Breda , Memon Muhammed A.
Published: May 2017

Aims and Objectives:

Laparoscopic Heller myotomy (LHM) is the preferred surgical method for treating achalasia. However, peroral endoscopic myotomy (POEM) is providing good short-term results. The objective of this systematic review and meta-analysis was to compare the safety and efficacy of LHM and POEM.

Materials and Methods:

A search of PubMed, Cochrane database, Medline, Embase, Science Citation Index, and current contents for English-language articles comparing LHM and POEM between 2007 and 2016 was performed. Variables analyzed included prior endoscopic treatment, prior medical treatment, prior Heller myotomy, operative time, overall complications rate, postoperative gastroesophageal reflux disease (GERD), length of hospital stay, postoperative pain score, and long-term GERD.

Results:

Seven trials consisting of 483 (LHM=250, POEM=233) patients were analyzed. Preoperative variables, for example, prior endoscopic treatment [odds ratio (OR), 1.32; 95% confidence interval (CI), 0.23-4.61; P=0.96], prior medical treatment [weighted mean difference (WMD), 1.22; 95% CI, 0.52-2.88; P=0.65], and prior Heller myotomy (WMD, 0.47; 95% CI, 0.13-1.67; P=0.25) were comparable. Operative time was 26.28 minutes, nonsignificantly longer for LHM (WMD, 26.28; 95% CI, −11.20 to 63.70; P=0.17). There was a comparable overall complication rate (OR, 1.25; 95% CI, 0.56-2.77; P=0.59), postoperative GERD rate (OR, 1.27; 95% CI, 0.70-2.30; P=0.44), length of hospital stay (WMD, 0.30; 95% CI, −0.24 to 0.85; P=0.28), postoperative pain score (WMD, −0.26; 95% CI, −1.58 to 1.06; P=0.70), and long-term GERD (WMD, 1.06; 95% CI, 0.27-4.1; P=0.08) for both procedures. There was a significantly higher short-term clinical treatment failure rate for LHM (OR, 9.82; 95% CI, 2.06-46.80; P<0.01).

Conclusions:

POEM compares favorably to LHM for achalasia treatment in short-term perioperative outcomes. However, there was a significantly higher clinical treatment failure rate for LHM on short-term postoperative follow-up. Presently long-term postoperative follow-up data for POEM beyond 1 year are unavailable and eagerly awaited.
Laparoscopic Appendectomy in Children With Perforated Appendicitis: A Meta-Analysis
Authors: Zhang Shun , Du Tao , Jiang Xiaohua , Song Chun
Published: May 2017

Background:

The purpose of this meta-analysis was to compare the influence of different surgical procedures on perforated appendicitis in pediatric population.

Materials and Methods:

Studies were identified through a computerized literature search of Pubmed, Embase, Ovid, the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials, the Cochrane Library database, and Web of Science. Two reviewers independently assessed the quality of each study and abstracted outcome data. Data were extracted comparing laparoscopic appendectomy (LA) and open appendectomy (OA) in pediatric population with regard to several postoperative variables. We synthesized published data using fixed-effect models, expressing results as relative risk (RR).

Results:

Nine eligible studies were included which came from various medical centers all over the world. Statistically significant differences between “LA” and “OA” groups were found for wound infection (RR=0.88), intra-abdominal abscess (RR=1.38), and bowel obstruction (RR=0.79).

Conclusions:

Our meta-analysis found that LA is associated with lower incidence of wound infections and bowel obstruction, but the rate of intra-abdominal abscess was higher than OA.
Reexamining the Role of Electroconvulsive Therapy in Anorexia Nervosa in Adolescents
Authors: Andersen Laura , LaRosa Christina , Gih Daniel E.
Published: May 2017

Electroconvulsive therapy (ECT) is rarely, if ever, considered for the treatment of severe anorexia nervosa (AN) or other eating disorders comorbid with an affective illness. Mood disorders are common in these patients, and psychotropic medications, although frequently used, have limited evidence of benefit in AN or copresenting depressive symptoms. Even when the illness is life threatening, ECT as a treatment may be overlooked. We present a case of an adolescent girl with severe AN and comorbid major depressive disorder with suicidality. This patient failed multiple medication trials but went on to experience complete remission from both the symptoms of her AN and major depressive disorder after undergoing a course of bilateral ECT. Electroconvulsive therapy may prove to be a fast and effective treatment strategy for mood disorders and suicidality in the setting of comorbid AN in adolescents.
Lisa Jardine CBE. 12 April 1944 — 25 October 2015
Authors: Hunter Michael
Published: May 2017

After completing a PhD on Francis Bacon, which was published as a book in 1974, Lisa Jardine became a leading expert on Renaissance humanism and particularly on Desiderius Erasmus, her monograph on whom was published in 1993. Meanwhile, she had become the first woman Fellow of Jesus College, Cambridge, later holding chairs at Queen Mary and at University College London. In the early 1990s she became a notable broadcaster and public intellectual, while her
Worldly Goods: A New History of the Renaissance
(1996) made her a best-selling author. In the following decade, she published various significant books, including biographies of Francis Bacon, Sir Christopher Wren and Robert Hooke, and
Going Dutch
, a perceptive study of Anglo-Dutch relations in the seventeenth century. She was also instrumental in founding the Centre for Editing Lives and Letters in 2002, while associated initiatives included the publication of the ‘Hooke Folio’ after its return to the Royal Society in 2006. In her later years, she took on a number of important public responsibilities, perhaps most notably her chairmanship of the Human Fertilisation and Embryology Authority from 2008 to 2014. Lisa Jardine will be remembered as a lively and charismatic figure, who championed the causes that she adopted with vigour and who brought enthusiasm and panache to all the activities in which she engaged.
Three-dimensional midwater camouflage from a novel two-component photonic structure in hatchetfish skin
Authors: Rosenthal Eric I. , Holt Amanda L. , Sweeney Alison M.
Published: May 2017

The largest habitat by volume on Earth is the oceanic midwater, which is also one of the least understood in terms of animal ecology. The organisms here exhibit a spectacular array of optical adaptations for living in a visual void that have only barely begun to be described. We describe a complex pattern of broadband scattering from the skin of
Argyropelecus
sp., a hatchetfish found in the mesopelagic zone of the world's oceans. Hatchetfish skin superficially resembles the unpolished side of aluminium foil, but on closer inspection contains a complex composite array of subwavelength-scale dielectric structures. The superficial layer of this array contains dielectric stacks that are rectangular in cross-section, while the deeper layer contains dielectric bundles that are elliptical in cross-section; the cells in both layers have their longest dimension running parallel to the dorsal–ventral axis of the fish. Using the finite-difference time-domain approach and photographic radiometry, we explored the structural origins of this scattering behaviour and its environmental consequences. When the fish's flank is illuminated from an arbitrary incident angle, a portion of the scattered light exits in an arc parallel to the fish's anterior–posterior axis. Simultaneously, some incident light is also scattered downwards through the complex birefringent skin structure and exits from the ventral photophores. We show that this complex scattering pattern will provide camouflage simultaneously against the horizontal radially symmetric solar radiance in this habitat, and the predatory bioluminescent searchlights that are common here. The structure also directs light incident on the flank of the fish into the downwelling, silhouette-hiding counter-illumination of the ventral photophores.
Dopamine disruption increases cleanerfish cooperative investment in novel client partners
Authors: Soares Marta C. , Santos Teresa P. , Messias João P. M.
Published: May 2017

Social familiarization is a process of gaining knowledge that results from direct or indirect participation in social events. Cooperative exchanges are thought to be conditional upon familiarity with others. Indeed, individuals seem to prefer to engage with those that have previously interacted with them, which are more accurate predictors of reward than novel partners. On the other hand, highly social animals do seek novelty. Truth is that the physiological bases underlying how familiarity and novelty may affect cooperative decision-making are still rather obscure. Here, we provide the first experimental evidence that the level of the dopaminergic influence in cooperative exchanges is constrained to mechanisms of social familiarization and novelty in a cleanerfish,
Labroides dimidiatus
. Cleaners were tested against familiar and novel
Ctenochaetus striatus
surgeonfish (a common client species) in laboratorial conditions, and were found to spend more time providing physical contact (also referred to as tactile stimulation) to familiar fish clients. Cleaners use tactile stimulation as a way to reduce the risk of a non-rewarding outcome, a behavioural response that is even more pronounced when blocking dopamine (DA) D1 receptors. We discovered that the influence of DA disruption on cleaners' provision of physical contact was dependent on the level of familiarity with its partner, being highly exacerbated whenever the client is novel, and unnoticed when dealing with a familiar one. Our findings demonstrate that DA mediation influences the valuation of partner stimuli and the enhancing investment in novel partners, mechanisms that are similar to other vertebrates, including humans.
Early social environment influences the behaviour of a family-living lizard
Authors: Riley Julia L. , Noble Daniel W. A. , Byrne Richard W. , Whiting Martin J.
Published: May 2017

Early social environment can play a significant role in shaping behavioural development. For instance, in many social mammals and birds, isolation rearing results in individuals that are less exploratory, shyer, less social and more aggressive than individuals raised in groups. Moreover, dynamic aspects of social environments, such as the nature of relationships between individuals, can also impact the trajectory of development. We tested if being raised alone or socially affects behavioural development in the family-living tree skink,Egernia striolata. Juveniles were raised in two treatments: alone or in a pair. We assayed exploration, boldness, sociability and aggression repeatedly throughout each juvenile's first year of life, and also assessed social interactions between pairs to determine if juveniles formed dominant–subordinate relationships. We found that male and/or the larger skinks within social pairs were dominant. Developing within this social environment reduced skink growth, and subordinate skinks were more prone to tail loss. Thus, living with a conspecific was costly forE. striolata. The predicted negative effects of isolation failed to materialize. Nevertheless, there were significant differences in behavioural traits depending on the social environment (isolated, dominant or subordinate member of a pair). Isolated skinks were more social than subordinate skinks. Subordinate skinks also became more aggressive over time, whereas isolated and dominant skinks showed invariable aggression. Dominant skinks became bolder over time, whereas isolated and subordinate skinks were relatively stable in their boldness. In summary, our study is evidence that isolation rearing does not consistently affect behaviour across all social taxa. Our study also demonstrates that the social environment plays an important role in behavioural development of a family-living lizard.
A supervised statistical learning approach for accurateLegionella pneumophilasource attribution during outbreaks
Authors: Buultjens Andrew H. , Chua Kyra Y. L. , Baines Sarah L. , Kwong Jason , Gao Wei , Cutcher Zoe , Adcock Stuart , Ballard Susan , Schultz Mark B. , Tomita Takehiro , Subasinghe Nela , Carter Glen P. , Pidot Sacha J. , Franklin Lucinda , Seemann Torsten , Da Silva Anders Gonçalves , Howden Benjamin P. , Stinear Timothy P.
Published: May 2017

Public health agencies are increasingly relying on genomics during Legionnaires’ disease investigations. However, the causative bacterium (Legionella pneumophila) has an unusual population structure with extreme temporal and spatial genome sequence conservation. Furthermore, Legionnaires’ disease outbreaks can be caused by multipleL. pneumophilagenotypes in a single source. These factors can confound cluster identification using standard phylogenomic methods. Here, we show that a statistical learning approach based on

L. pneumophilacore genome single nucleotide polymorphism (SNP) comparisons eliminates ambiguity for defining outbreak clusters and accurately predicts exposure sources for clinical cases. We illustrate the performance of our method by genome comparisons of 234L. pneumophilaisolates obtained from patients and cooling towers in Melbourne, Australia between 1994 and 2014. This collection included one of the largest reported Legionnaires’ disease outbreaks, involving 125 cases at an aquarium. Using only sequence data fromL. pneumophilacooling tower isolates and including all core genome variation, we built a multivariate model using discriminant analysis of principal components (DAPC) to find cooling tower-specific genomic signatures, and then used it to predict the origin of clinical isolates. Model assignments were 93% congruent with epidemiological data, including the aquarium Legionnaires’ outbreak and three other unrelated outbreak investigations. We applied the same approach to a recently described investigation of Legionnaires’ disease within a UK hospital and observed model predictive ability of 86%. We have developed a promising means to breachL. pneumophilagenetic diversity extremes and provide objective source attribution data for outbreak investigations.
Glioma grade map: a machine-learning based imaging biomarker for tumor characterization
Authors: Jakab András , Molnár Péter , Emri Miklós , Berényi Ervin
Published: May 2017

Purpose

To use T1-, T2-weighted and diffusion tensor MR images to portray glioma grade by employing a voxel-wise supervised machine learning approach, and to assess the feasibility of this tool in preoperative tumor characterization.

Materials and Methods

Conventional MRI, DTI datasets and histopathological evaluations of 40 patients with WHO grade II-IV gliomas were retrospectively analyzed. Databases were construed incorporating preoperative images, tumor delineation and grades. This data was used to train a multilayer perceptron based artificial neural network that performed voxel-by-voxel correlation of tumor grade and the feature vector. Results were mapped to grayscale images, whereas grade map was defined as a composite image that depicts grade assignments for intra-tumoral regions. The voxel-wise probability for high grade tumor classification was calculated for the entire tumor volumes, defined as the grade index.

Results

The color hue on glioma grade maps allowed the discrimination of low and high grade cases. This method revealed connection between the heterogeneous appearance of tumors and the histopathological findings. Classification by the grade index had 92.31% specificity, 85.71% sensitivity.

Conclusion

Glioma grade maps are advantageous in the visualization of the heterogeneous nature of intra-tumoral diffusion and relaxivity and can further enhance the characterization of tumors by providing a preoperative modality that expands information available for clinicians.

ABBREVIATIONS

ADC

apparent diffusion coefficient;

ANN

artificial neural networks;

DWI

diffusion weighted imaging;

DTI

diffusion tensor imaging;

FA

fractional anisotropy;

HGPM

high grade probability map;

LGPM

low grade probability map;

TPM

tumor probability map;

WHO

World Health Organization
A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy
Authors: Noorani Ayesha , Bornschein Jan , Lynch Andy G. , Secrier Maria , Achilleos Achilleas , Eldridge Matthew , Bower Lawrence , Weaver Jamie M.J. , Crawte Jason , Ong Chin-Ann , Shannon Nicholas , MacRae Shona , Grehan Nicola , Nutzinger Barbara , O'Donovan Maria , Hardwick Richard , Tavaré Simon , Fitzgerald Rebecca C. ,   on behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Published: May 2017

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.
The Largest Subunit of Human RNA Polymerase III Is Closely Related to the Largest Subunit of Yeast and Trypanosome RNA Polymerase III
Authors: Sepehri Setareh , Hernandez Nouria
Published: May 2017

In both yeast and mammalian systems, considerable progress has been made toward the characterization of the transcription factors required for transcription by RNA polymerase III. However, whereas in yeast all of the RNA polymerase III subunits have been cloned, relatively little is known about the enzyme itself in higher eukaryotes. For example, no higher eukaryotic sequence corresponding to the largest RNA polymerase III subunit is available. Here we describe the isolation of cDNAs that encode the largest subunit of human RNA polymerase III, as suggested by the observations that (1) antibodies directed against the cloned protein immunoprecipitate an active enzyme whose sensitivity to different concentrations of α-amanitin is that expected for human RNA polymerase III; and (2) depletion of transcription extracts with the same antibodies results in inhibition of transcription from an RNA polymerase III, but not from an RNA polymerase II, promoter. Sequence comparisons reveal that regions conserved in the RNA polymerase I, II, and III largest subunits characterized so far are also conserved in the human RNA polymerase III sequence, and thus probably perform similar functions for the human RNA polymerase III enzyme.

[The sequence data described in this paper have been submitted to the GenBank data library under accession no. AF021351.]
Evolutionary Features of the 4-Mb Xq21.3 XY Homology Region Revealed by a Map at 60-kb Resolution
Authors: Mumm Steven , Molini Barbara , Terrell Jennifer , Srivastava Anand , Schlessinger David
Published: May 2017

Forty-three yeast artificial chromosomes (YACs) from the X chromosome have been overlapped across the 4-Mb Xq21.3 region, which is homologous to a segment in Yp11.1. The region is formatted to 60-kb resolution with 57 STSs and is merged at its edges with contigs specific for X. This allows a direct comparison of marker orders and distances on X and Y. In addition to some sequence variation and possible differences in marker order, two larger evolutionary divergencies between the X and Y homologs were revealed: (1) The X homolog is interrupted by a small X-specific region detected by a 3-kb plasmid probe for locus DXS214. An STS was developed from one end of the probe, but the sequence at the other end was highly homologous to an L1 repetitive element. This suggests that the interpolation of the X-specific segment may have involved an L1-mediated event. (2) A 250-kb portion containing DXYS1 is several megabases away from the rest of the homologous DNA on the Y but is contiguous with the remainder of the homologous region on X. Marker orders are consistent with the origin of the Y-specific 250-kb region in a paracentric inversion after the initial transfer of X DNA to the Y chromosome.

[All sequence data for the STSs are in the Genome Database and on the Washington University web site at http://genome.wustl.edu/cgm/cgm.html.]
The Structure of the Human Multiple Exostoses 2 Gene and Characterization of Homologs in Mouse andCaenorhabditis elegans
Authors: Clines Gregory A. , Ashley Jennifer A. , Shah Sangeeta , Lovett Michael
Published: May 2017

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by multiple cartilage-capped outgrowths from the epiphyses of long bones. In some cases, these osteochondromas progress to malignant chondrosarcomas. Alterations in at least three genes (EXT1, EXT2, and EXT3) can cause this disorder. Two of these have been isolated (EXT1 andEXT2) and encode related members of a putative tumor suppressor family. We report here the genomic structure of the humanEXT2 gene consisting of 14 exons (plus 2 alternative exons) covering an estimated 108 kb of chromosome 11p11–13. We have derived the DNA sequences at all exon/intron boundaries throughout this gene—information that is important for the detailed study of mutations in EXT2. We have also characterized the mouse EXT2cDNA and have mapped the mouse locus to chromosome 2 betweenD2Mit15 and Pax6. This mouse homolog should enable transgenic knockout experiments to be initiated to further elucidate gene function. Interestingly, sequence comparisons reveal that the human and mouse EXT genes have at least two homologs in the invertebrate Caenorhabditis elegans, indicating that they do not function exclusively as regulators of bone growth. This observation opens the way for a functional analysis of these genes in nematodes and other lower organisms.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. U67353–U67368 and U67837.]
The E6–AP Ubiquitin–Protein Ligase (UBE3A) Gene Is Localized within a Narrowed Angelman Syndrome Critical Region
Authors: Sutcliffe James S. , Jiang Yong-hui , Galjaard Robert-Jan , Matsuura Toshinobu , Fang Ping , Kubota Takeo , Christian Susan L. , Bressler Jan , Cattanach Bruce , Ledbetter David H. , Beaudet Arthur L.
Published: May 2017

Angelman syndrome (AS) and Prader–Willi syndrome (PWS) are distinct clinical phenotypes resulting from maternal and paternal deficiencies, respectively, in human chromosome 15q11–q13. Although several imprinted, paternally expressed transcripts have been identified within the PWS candidate region, no maternally expressed gene has yet been identified within the AS candidate region. We have developed an integrated physical map spanning the PWS and AS candidate regions and localized two breakpoints, including a cryptic t(14;15) translocation associated with AS and a non-AS 15q deletion, which substantially narrow the AS candidate region to ∼250 kb. Mapping data indicate that the entire transcriptional unit of the E6–AP ubiquitin–protein ligase (UBE3A) gene lies within the AS region. TheUBE3Alocus expresses a transcript of ∼5 kb at low to moderate levels in all tissues tested. The mouse homolog ofUBE3Awas cloned and sequenced revealing a high degree of conservation at nucleotide and protein levels. Northern and RT–PCR analysis ofUbe3aexpression in mouse tissues from animals with segmental, paternal uniparental disomy failed to detect substantially reduced or absent expression compared to control animals, failing to provide any evidence for maternal-specific expression from this locus. Recent identification of de novo truncating mutations inUBE3Ataken with these observations indicates that mutations inUBE3Acan lead to AS and suggests that this locus may encode both imprinted and biallelically expressed products.

[The sequence data described in this paper have been submitted to the GenBank data library under accession no.U82122.]
Single-Nucleotide Polymorphism Identification Assays Using a Thermostable DNA Polymerase and Delayed Extraction MALDI-TOF Mass Spectrometry
Authors: Haff Lawrence A. , Smirnov Igor P.
Published: May 2017

We report a simple method, the PinPoint assay, for detecting and identifying single-base variations (polymorphisms) at specific locations within DNA sequences. An oligonucleotide primer is annealed to the target DNA immediately upstream of the polymorphic site and is extended by a single base in the presence of all four dideoxynucleotide triphosphates and a thermostable DNA polymerase. The extension products are desalted, concentrated, and subjected to delayed-extraction MALDI-TOF mass spectrometry. The base at the polymorphic site is identified by the mass added onto the primer. Heterozygous targets produce two mass-resolved species that represent the addition of both bases complementary to those at the polymorphic site. The assay is suitable for double-stranded PCR products without purification or strand separation. More than one primer can be simultaneously extended and then mass-analyzed. The mass spectrometric method thus shows promise for high-volume diagnostic or genotyping applications.
Sequence Mapping by Electronic PCR
Authors: Schuler Gregory D.
Published: May 2017

The highly specific and sensitive PCR provides the basis for sequence-tagged sites (STSs), unique landmarks that have been used widely in the construction of genetic and physical maps of the human genome. Electronic PCR (e-PCR) refers to the process of recovering these unique sites in DNA sequences by searching for subsequences that closely match the PCR primers and have the correct order, orientation, and spacing that they could plausibly prime the amplification of a PCR product of the correct molecular weight. A software tool was developed to provide an efficient implementation of this search strategy and allow the sort of en masse searching that is required for modern genome analysis. Some sample searches were performed to demonstrate a number of factors that can affect the likelihood of obtaining a match. Analysis of one large sequence database record revealed the presence of several microsatellite and gene-based markers and allowed the exact base-pair distances among them to be calculated. This example provides a demonstration of how e-PCR can be used to integrate the growing body of genomic sequence data with existing maps, reveal relationships among markers that existed previously on different maps, and correlate genetic distances with physical distances.
Genomic Organization of the Human PEX Gene Mutated in X-Linked Dominant Hypophosphatemic Rickets
Authors: Francis Fiona , Strom Tim M. , Hennig Steffen , Böddrich Annett , Lorenz Bettina , Brandau Oliver , Mohnike Klaus L. , Cagnoli Michele , Steffens Christina , Klages Sven , Borzym Katja , Pohl Thomas , Oudet Claudine , Econs Michael J. , Rowe Peter S.N. , Reinhardt Richard , Meitinger Thomas , Lehrach Hans
Published: May 2017

X-linked dominant hypophosphatemic rickets (HYP) is the most common form of hereditary rickets. Recently we have cloned thePEX gene and shown it to be mutated and deleted in HYP individuals. We have now completely sequenced a 243-kb genomic region containing PEX and have identified all intron–exon boundary sequences. We show that PEX, homologous to members of a neutral endopeptidase family, has an exon organization that is very similar to neprilysin. We have performed an extensive mutation analysis examining all 22 PEX coding exons in 29 familial and 14 sporadic cases of hypophosphatemia. Sequence changes include missense, frameshift, nonsense, and splice site mutations and intragenic deletions. A mutation was found in 25 (86%) of the 29 familial cases and 8 (57%) of the 14 sporadic cases. Our data provide the first evidence that most of the familial and also a large number of the sporadic cases of hypophosphatemia are caused by loss-of-function mutations in PEX.

[The sequence data described in this paper have been submitted to GenBank under accession nos.Y08111–Y08132 and Y10196.]
Ataxia-Telangiectasia Locus: Sequence Analysis of 184 kb of Human Genomic DNA Containing the Entire ATM Gene
Authors: Platzer Matthias , Rotman Galit , Bauer David , Uziel Tamar , Savitsky Kinneret , Bar-Shira Anat , Gilad Shlomit , Shiloh Yosef , Rosenthal André
Published: May 2017

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity, and cancer predisposition. The genomic organization of the A-T gene, designatedATM, was established recently. To date, more than 100 A-T-associated mutations have been reported in the ATM gene that do not support the existence of one or several mutational hotspots. To allow genotype/phenotype correlations it will be important to find additional ATM mutations. The nature and location of the mutations will also provide insights into the molecular processes that underly the disease. To facilitate the search for ATMmutations and to establish the basis for the identification of transcriptional regulatory elements, we have sequenced and report here 184,490 bp of genomic sequence from the human 11q22–23 chromosomal region containing the entire ATM gene, spanning 146 kb, and 10 kb of the 5′-region of an adjacent gene named E14/NPAT.The latter shares a bidirectional promoter with ATM and is transcribed in the opposite direction. The entire region is transcribed to ∼85% and translated to 5%. Genome-wide repeats were found to constitute 37.2%, with LINE (17.1%) and Alu (14.6%) being the main repetitive elements. The high representation of LINE repeats is attributable to the presence of three full-length LINE-1s, inserted in the same orientation in introns 18 and 63 as well as downstream of the ATM gene. Homology searches suggest that ATM exon 2 could have derived from a mammalian interspersed repeat (MIR). Promoter recognition algorithms identified divergent promoter elements within the CpG island, which lies between the ATM andE14/NPAT genes, and provide evidence for a putative secondATM promoter located within intron 3, immediately upstream of the first coding exon. The low G + C level (38.1%) of theATM locus is reflected in a strongly biased codon and amino acid usage of the gene.

[The sequence data described in this paper have been submitted to the GenBank data library under accession no. U82828.]
Genomic Organization of the Murine Miller–Dieker/Lissencephaly Region: Conservation of Linkage with the Human Region
Authors: Hirotsune Shinji , Pack Svetlana D. , Chong Samuel S. , Robbins Christiane M. , Pavan William J. , Ledbetter David H. , Wynshaw-Boris Anthony
Published: May 2017

Several human syndromes are associated with haploinsufficiency of chromosomal regions secondary to microdeletions. Isolated lissencephaly sequence (ILS), a human developmental disease characterized by a smooth cerebral surface (classical lissencephaly) and microscopic evidence of incomplete neuronal migration, is often associated with small deletions or translocations at chromosome 17p13.3. Miller–Dieker syndrome (MDS) is associated with larger deletions of 17p13.3 and consists of classical lissencephaly with additional phenotypes including facial abnormalities. We have isolated the murine homologs of three genes located inside and outside the MDS region: Lis1, Mnt/Rox, and14-3-3ε. These genes are all located on mouse chromosome 11B2, as determined by metaphase FISH, and the relative order and approximate gene distance was determined by interphase FISH analysis. The transcriptional orientation and intergenic distance ofLis1 and Mnt/Rox were ascertained by fragmentation analysis of a mouse yeast artificial chromosome containing both genes. To determine the distance and orientation of 14-3-3ε with respect to Lis1 and Mnt/Rox, we introduced a super-rare cutter site (VDE) that is unique in the mouse genome into 14-3-3ε by gene targeting. Using the introducedVDE site, the orientation of this gene was determined by pulsed field gel electrophoresis and Southern blot analysis. Our results demonstrate that the MDS region is conserved between human and mouse. This conservation of linkage suggests that the mouse can be used to model microdeletions that occur in ILS and MDS.
Sequencing and Functional Analysis of the SNRPN Promoter: In Vitro Methylation Abolishes Promoter Activity
Authors: Huq A.H.M. Mahbubul , Sutcliffe James S. , Nakao Mitsuyoshi , Shen Ying , Gibbs Richard A. , Beaudet Arthur L.
Published: May 2017

The gene encoding the small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) maps to the Prader–Willi syndrome critical region on chromosome 15 and is expressed preferentially from the paternal allele. A CpG island encompassing the first exon ofSNRPN is methylated on the inactive maternal allele. DNA sequence was determined for a cosmid containing the first three exons of SNRPN and extending 20 kb upstream and 15 kb downstream from the CpG island. This region is extremely rich in Aluelements and other repetitive sequences and contains a single CpG island, which includes numerous short direct repeat sequences. Functional analysis of the first exon revealed strong promoter activity for a 260-bp fragment extending 207 bp upstream from the exon. In vitro methylation of this 260-bp fragment abolished promoter activity completely, suggesting that the silencing of the maternalSNRPN allele may be a direct consequence of methylation of the promoter region.

[The sequence data described in this paper have been submitted to the GenBank data library under accession no.U41384.]
Centromeric and Noncentromeric ADE2-Selectable Fragmentation Vectors for Yeast Artificial Chromosomes in AB1380
Authors: Heus Joris J. , de Winther Menno P.J. , van de Vosse Esther , van Ommen Gert-Jan B. , den Dunnen Johan T.
Published: May 2017

We have constructed a set of fragmentation vectors for the truncation of either the centromeric or the noncentromeric end of YACs containing a human DNA insert. These vectors carry ADE2 orHIS5 as the selectable marker, enabling direct use in AB1380, the host strain of most publicly available YAC libraries. Centromeric fragmentation vectors for AB1380 have not been reported previously; the noncentromeric vectors show high frequencies of fragmentation.