bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Cervical Sagittal Alignment on Axial Neck Pain and Health-related Quality of Life After Cervical Laminoplasty in Patients With Cervical Spondylotic Myelopathy or Ossification of the Posterior Longitudinal Ligament
Authors: Fujiwara Hiroyasu , Oda Takenori , Makino Takahiro , Moriguchi Yu , Yonenobu Kazuo , Kaito Takashi
Published: March 2018

Study Design:

This is prospective observational study.

Objective:

To prospectively investigate the correlation among axial neck pain; a newly developed patient-based quality of life outcome measure, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ); and cervical sagittal alignment after open-door laminoplasty for cervical myelopathy.

Summary of Background Data:

Many studies have focused on postoperative axial neck pain after laminoplasty. However, the correlation among cervical sagittal alignment, neck pain, and JOACMEQ has not been investigated.

Materials and Methods:

In total, 57 consecutive patients treated by open-door laminoplasty for cervical myelopathy were included (mean age, 63.7 y; 15 women and 42 men) and divided into 2 groups according to diagnosis [cervical spondylotic myelopathy (CSM) group: 35 patients, and ossification of the posterior longitudinal ligament (OPLL) group: 22 patients]. JOA score, a subdomain of cervical spine function (CSF) in the JOACMEQ, and the visual analog scale for axial neck pain were assessed preoperatively and 12 months postoperatively. Radiographic cervical sagittal parameters were measured by C2 sagittal vertical axis (C2 SVA), C2–C7 lordosis, C7 sagittal slope (C7 slope), and range of motion.

Results:

C2 SVA values in both groups shifted slightly anteriorly between preoperative and 12-month postoperative measurements (CSM: +19.7±10.9 mm; OPLL: +22.1±13.4 mm vs. CSM: +23.2±16.1 mm; OPLL: +28.7±15.4 mm, respectively). Postoperative axial neck pain in the OPLL group showed strong negative correlations with C2 SVA and C7 slope. Strong negative correlations were found between axial neck pain and CSF in both the preoperative CSM and OPLL groups (CSM: r=−0.45, P=0.01; OPLL: r=−0.61, P<0.01) and between axial neck pain and CSF in the postoperative OPLL group (r=−0.51, P=0.05).

Conclusions:

This study demonstrated a significant negative correlation between neck pain and CSF in both the CSM and OPLL groups preoperatively and in the OPLL group postoperatively. Radiographic cervical sagittal alignment did not significantly correlate with preoperative or postoperative axial neck pain.
A Prospective Single-blind Randomized Controlled Trial of Chewing Gum on Bowel Function Recovery After Posterior Spinal Fusion Surgery for Adolescent Idiopathic Scoliosis
Authors: Meng Yichen , Lin Tao , Shao Wei , Jiang Heng , Li Tangbo , Gao Rui , Zhou Xuhui
Published: March 2018

Purpose:

To evaluate the effectiveness of chewing gum on promoting bowel function recovery in adolescent idiopathic scoliosis patients undergoing surgical correction.

Materials and Methods:

Adolescent idiopathic scoliosis patients scheduled for posterior spinal fusion surgery at our institution were randomized to either group 1 (chewing gum) or group 2 (control). The primary endpoints were time to flatus, time to bowel movement, length of hospital stay, and time to liquid or solid. The secondary endpoints were postoperative opioid consumption, incidence of complications, pain scores, and nausea scores. In addition, a meta-analysis of available data from the literature was performed identifying 2 studies with quantitative data on the efficacy of gum chewing after scoliosis correction surgery.

Results:

In total, 125 patients (63 gum; 62 control) were included in our analysis after randomization. There was no significant difference in time to first flatus (P=0.087), time to bowel movement (P=0.307), time to liquid or solid, length of postoperative hospital stay (P=0.954), postoperative complications, opioid consumption, and postoperative nausea scores between the 2 groups. The postoperative pain scores on postoperative day 1 were significantly lower (P=0.027). There was a significant decrease in the time to the first flatus for patients having selective thoracic fusion in both groups than those having fusion to lumbar spine. Meta-analysis also indicated there was no significant difference in outcomes of bowel function between the 2 groups.

Conclusions:

Our institutional data and meta-analysis collaboratively suggested that chewing gum did not hasten the return of bowel function.
Incidence and Risk Factors for Proximal Junctional Kyphosis
Authors: Sebaaly Amer , Sylvestre Clément , El Quehtani Yehya , Riouallon Guillaume , Larrieu Daniel , Boussiere Louis , Steib Jean Paul , Roussouly Pierre , Wolff Stéphane , Obeid Ibrahim
Published: March 2018

Study Design:

This was a retrospective multicentric study.

Objective:

The objective of this study was to determine the different risk factors for development of proximal junctional kyphosis (PJK) in patients with adult scoliosis.

Summary of Background Data:

This study was conducted as the reasons for development of PJK in adult scoliosis are still not clear.

Materials and Methods:

In total, 314 patients met the inclusion criteria. The main outcome measure was the PJK, as described by Glattes and colleagues. Extent of the instrumentation, operative time, bleeding, and the use of an osteotomy as well as the type of proximal anchorage were collected. Radiologic variables included preoperative Cobb angles of the lumbar and the thoracic curvatures, pelvic parameters, lumbar lordosis, thoracic kyphosis, and sagittal vertical axis. All measures were performed using the KEOPS software.

Results:

The mean follow-up of this series was 2.5 years with a female to male ratio of 6.6/1 and a mean age of 56.66 years. The incidence of PJK was 25%. Proximal fixation extended to the proximal thoracic spine (TS) in 39%, to the middle TS in 39.5% of cases, and to the thoracolumbar junction in 20.4%, with a higher incidence of PJK noted in the first group. The proximal anchors had no effect on PJK incidence. Age as well as body mass index had a positive correlation to the incidence of PJK. The association, fusion to sacrum and fusion to the upper TS, is associated with the highest incidence of PJK. Preoperative pelvic tilt had a positive correlation with PJK occurrence. Finally, revision for PJK occurred in 2.3% of all patients and accounted for 15% of revisions.

Conclusions:

Increased age, as well as increased body mass index, is a risk factor for the development of PJK. The proximal extent of the construct is also shown to be a risk factor for PJK, but fusion to the sacrum is a risk factor only if fusion extends to the proximal TS. Moderate PJK was observed with undercorrection of the sagittal balance and severe PJKs with overcorrection of the sagittal balance.

Level of Evidence:

Level IV.
Extradural Arachnoid Cyst Excision
Authors: Boody Barrett , Lucasti Christopher J. , Schroeder Gregory D. , Heller Joshua E. , Vaccaro Alexander R.
Published: March 2018

Arachnoid cysts are an uncommon postoperative complication and can result in back pain, radiculopathy, and/or cauda equina syndrome. For symptomatic postoperative arachnoid cysts, surgical management is the accepted treatment. While excision of arachnoid cysts is the preferred surgical method, cysts with adhesions to nerve roots and/or dura can be treated with cyst fenestration to reduce morbidity of excision. Surgeons should be prepared for dural defects after cyst excision, which can require dural grafting and lumbar drains for cerebrospinal fluid diversion.
The Extensile Medial Parapatellar Approach to the Distal Femur and Knee: Anatomic Landmarks and Surgical Technique
Authors: Stevens Jarrad , Clement Nicholas D. , Patton James T.
Published: March 2018

This paper describes an extensile surgical approach to the distal femur, which incorporates the medial parapatellar arthrotomy. This extensile exposure serves as an anterior utility approach to the knee, allowing the surgeon access to all aspects of the anterior knee and near circumferential access to the distal femur. Reported indications for access to this region include: tumor resection, difficult primary arthroplasty and revision arthroplasty of the knee, and intra-articular and extra-articular fractures of the distal femur. Despite adequate working knowledge of the standard medial parapatellar approach to the knee, the extensile approach is seldom required and, as a result, orthopedic trainees and practising orthopedic surgeons may not be familiar with the musculotendonous junctions that occur in the quadriceps tendon. This report describes a novel surgical approach and the relevant anatomy through a series of detailed clinical and fresh cadaveric dissections. A previously undescribed anatomic landmark is demonstrated through photographs and cadaveric variation studies, which may help guide the surgeon in defining crucial planes.
The Role of the Electronic Medical Record in the Intensive Care Unit Nurse's Detection of Patient Deterioration
Authors: Despins Laurel A. , Wakefield Bonnie J.
Published: March 2018

Failure to detect patient deterioration signals leads to longer stays in the hospital, worse functional outcomes, and higher hospital mortality rates. Surveillance, including ongoing acquisition, interpretation, and synthesis of patient data by the nurse, is essential for early risk detection. Electronic medical records promote accessibility and retrievability of patient data and can support patient surveillance. A secondary analysis was performed on interview data from 24 intensive care unit nurses, collected in a study that examined factors influencing nurse responses to alarms. Six themes describing nurses' use of electronic medical record information to understand the patients' norm and seven themes describing electronic medical record design issues were identified. Further work is needed on electronic medical record design to integrate documentation and information presentation with the nursing workflow. Organizations should involve bedside nurses in the design of handoff formats that provide key information common to all intensive care unit patient populations, as well as population-specific information.
Representations of Young Cancer Survivorship
Authors: Lewis Peter , Weston Kathryn M.
Published: March 2018

Background

More young people are surviving treatment for cancer than ever before. Survival can have an adverse impact on their transition to adulthood. Discourses of cancer are applied to cancer survivors of all ages, but they manifest differently for young people.

Objective

The aim of this study was to describe practices of self-representation in an online Web site that supports young Australian cancer survivors.

Method

We conducted a discourse analysis of images and text produced by young cancer survivors (aged 18–35 years) on a public cancer charity Web site.

Results

The dominant subject position of participants published on this web site is one of empowered, beautiful cancer survivor. This applies to young people who have learned to embrace their cancer as providing a positive influence on their lives. However, this discourse can marginalize those whose cancer experience remains a source of distress or shame.

Conclusion

Web based media can provide a valuable forum for some young people to celebrate their cancer survival and to affirm the constructive influence that their cancer experience has had on their lives. However, we ponder the apparent unsuitability of some forums for young cancer survivors who have not yet found cause for celebration.

Implications for Practice

Nurses have the opportunity to contribute to the development of supportive structures that meet the specific needs of different groups of young cancer survivors. This might mean assisting young cancer survivors who are struggling to find meaning in their cancer experience to negotiate the establishment of a new normal that they can embrace.
How Interdisciplinary Teamwork Contributes to Psychosocial Cancer Support
Authors: Daem Michiel , Verbrugghe Mathieu , Schrauwen Wim , Leroux Silvian , Van Hecke Ann , Grypdonck Maria
Published: March 2018

Background

The organization of psychosocial care is rather complex, and its provision diverse. Access is affected by the acceptance and attitude of patients and professional caregivers toward psychosocial care.

Objectives

The aims of this study were to examine when patients with cancer experience quality psychosocial care and to identify circumstances in collaboration that contribute to patient-perceived positive psychosocial care.

Methods

This study used a qualitative design in which semistructured interviews were conducted with patients, hospital workers, and primary health professionals.

Results

Psychosocial care is often requested but also refused by patients with cancer. Based on this discrepancy, a distinction is made between psychosocial support and psychosocial interventions. Psychosocial support aims to reduce the chaos in patients' lives caused by cancer and is not shunned by patients. Psychosocial interventions comprise the formal care offered in response to psychosocial problems. Numerous patients are reluctant to use psychosocial interventions, which are often provided by psychologists.

Conclusion

Psychosocial care aims to assist patients in bearing the difficulties of cancer and its treatment. Patients prefer informal support, given often in conjunction with physical care.

Implications for Practice

This study confirms the important role of nurses in promoting psychosocial care. Patients perceive much support from nurses, although nurses are not considered to be professional psychosocial caregivers. Being perceived as approachable and trustworthy offers nurses a significant opportunity to bring more intense psychosocial interventions within reach of cancer patients.
Predicting Risk Factors for 30-Day Readmissions Following Discharge From Post-Acute Care
Authors: Flanagan Nina M. , Rizzo Victoria M. , James Gary D. , Spegman Adele , Barnawi Najla A.
Published: March 2018

Purpose of Study:

The specific aims of this descriptive study were to (1) examine the relationships between individual-level determinants of health using standard care admission assessments of residents admitted to a skilled nursing facility (SNF) and those residents readmitted to the hospital within 30 days from discharge from the same SNF; (2) identify and describe the risk factors of the residents readmitted to the hospital within 30 days; and (3) use the findings to inform and refine current practice to target the mutable risk factors correlated with 30-day hospital readmission.

Primary Practice Setting:

A 180-bed skilled nursing center in Northeastern Pennsylvania.

Methodology and Sample:

A retrospective paper medical record review of patients discharged from an SNF to community living was conducted to examine the relationship between individual determinants of health behaviors and 30-day hospital readmissions. The study sample (N = 221) included adults 65 years and older who were admitted to the SNF from January to December 2014 for subacute physical rehabilitation following an acute care hospital stay with a discharge plan to community living.

Results:

The 30-day readmission rate was 11%. The results of the logistic regression including diagnosis at readmission showed that the odds of readmission before 30 days were nearly three times greater in patients who had congestive heart failure (p < .02). Patients who were at “very high risk” on the Braden Scale were 20 times more likely to be readmitted before 30 days compared with those at low risk. Age and gender were not predictors. None of the other standard screening assessments for delirium, depression, functional status, and fall risk were predictive of 30-day readmission.

Implications for Case Management Practice:

(1) Care coordination and communication with residents, caregivers, and home health can have an impact on 30-day readmissions post-SNF discharge. (2) Chronic respiratory diseases continue to be a challenge in prevention of hospital readmissions.
Pediatric Forefoot Fractures
Authors: Lim Rodrick K. , Gerson Bridgette , Seabrook Jamie A. , Reardon Jaime , Poonai Naveen
Published: March 2018

Background

Forefoot fractures account for 6% to 10% of fractures in children, and although the majority heals with supportive treatment, complications may lead to pain and disability. No previous study in children has evaluated complication risk in the emergency department based on initial assessment characteristics.

Study Objectives

The study aim was to identify the radiological and clinical variables that increase the complication rate of pediatric forefoot fractures. This may help emergency physicians refer patients who require more thorough follow-up or surgical intervention.

Methods

We evaluated 497 forefoot fractures on initial presentation to a pediatric emergency department at the Children’s Hospital at London Health Science Centre over a 6-year period. We collected variables such as degree of angulation, displacement, number of concurrent fractures, and demographic data such as age and sex. We then determined the variables associated with complications by reviewing each patient's chart.

Results

Overall, there was a 6.4% complication rate. Analysis identified sex as an important predictor of complications. Females, although representing approximately one third of the sample, represented nearly two thirds of the cases with complicated outcomes (P = 0.001; odds ratio [OR], 4.67). Increased number of fractures was also significant (P = 0.01; OR, 2.41) as was increasing age (P = 0.01; OR, 1.17) and patients who chose to return to the emergency department (P < 0.05; OR, 5.282). Lateral angulation/displacement and anteroposterior angulation/displacement were not associated with increased complications.

Conclusion

Identifying features, such as female sex, increasing age, multiple fractures, and return to emergency departments for repeat visits, may help guide the emergency physician on whom to refer for specialized care.
Optimal Use of Surgical Drains: Evidence-Based Strategies
Authors: Khansa Ibrahim , Khansa Lara , Meyerson Joseph , Janis Jeffrey E.
Published: March 2018

Background:

Closed-suction drains are widely used to reduce the incidence of seroma whenever potential spaces are surgically created. However, few studies have examined the parameters that affect drain efficacy.

Methods:

An in vitro model was created to assess the effects of tubing length, tubing size, tubing type, fluid viscosity, fluid clotting, evacuator type, evacuator squeeze method, evacuator fill, and evacuator pressure on the performance of closed-suction drains.

Results:

Fluid flow rate through the drain increases with increasing intracavitary tubing length, decreasing extracavitary tubing length, increasing tubing diameter, increasing negative pressure, decreasing fluid viscosity, and the use of perforated rather than fluted drains. Bulbs generate more effective suction when squeezed “side-to-side” than when squeezed “bottom-up,” and evacuators were only able to generate half the maximal negative pressure when 25 percent full or greater. Stripping the drain tubing helped relieve obstruction caused by clotting.

Conclusions:

The authors’ findings have practical clinical implications for surgeons hoping to maximize the efficacy of closed-suction drains. Through this comprehensive review of the literature and in vitro analysis of relevant variables that affect drain function, the performance of closed-suction drains can be optimized by increasing intracavitary tubing length, decreasing extracavitary tubing length, increasing tubing diameter, increasing the pressure differential, using perforated drains, squeezing bulbs side-to-side, stripping drain tubing frequently, and evacuating containers whenever they are 25 percent full.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Flux-dependent graphs for metabolic networks
Authors: Beguerisse-Díaz Mariano , Bosque Gabriel , Oyarzún Diego , Picóo Jesús , Barahona Mauricio
Published: March 2018

Cells adapt their metabolic fluxes in response to changes in the environment. We present a frame-work for the systematic construction of flux-based graphs derived from organism-wide metabolic networks. Our graphs encode the directionality of metabolic fluxes via edges that represent the flow of metabolites from source to target reactions. The methodology can be applied in the absence of a specific biological context by modelling fluxes probabilistically, or can be tailored to different environ-mental conditions by incorporating flux distributions computed through constraint-based approaches such as Flux Balance Analysis. We illustrate our approach on the central carbon metabolism ofEscherichia coliand on a metabolic model of human hepatocytes. The flux-dependent graphs under various environmental conditions and genetic perturbations exhibit systemic changes in their topo-logical and community structure, which capture the re-routing of metabolic fluxes and the varying importance of specific reactions and pathways. By integrating constraint-based models and tools from network science, our framework allows the study of context-specific metabolic responses at a system level beyond standard pathway descriptions.
A deep learning approach for uncovering lung cancer immunome patterns
Authors: Hess Moritz , Lenz Stefan , Binder Harald
Published: March 2018

Tumor immune cell infiltration is a well known factor related to survival of cancer patients. This has led to deconvolution approaches that can quantify immune cell proportions for each individual. What is missing, is an approach for modeling joint patterns of different immune cell types. We adapt a deep learning approach, deep Boltzmann machines (DBMs), for modeling immune cell gene expression patterns in lung adenocarcinoma. Specifically, a partially partitioned training approach for dealing with a relatively large number of genes. We also propose a sampling-based approach that smooths the original data according to a trained DBM and can be used for visualization and clustering. The identified clusters can subsequently be judged with respect to association with clinical characteristics, such as tumor stage, providing an external criterion for selecting DBM network architecture and tuning parameters for training. We show that the hidden nodes of the trained networks cannot only be linked to clinical characteristics but also to specific genes, which are the visible nodes of the network. We find that hidden nodes that are linked to tumor stage and survival represent expression of T-cell and mast cell genes among others, probably reflecting specific immune cell infiltration patterns. Thus, DBMs, trained and selected by the proposed approach, might provide a useful tool for extracting immune cell gene expression patterns. In the case of lung adenocarcinomas, these patterns are linked to survival as well as other patient characteristics, which could be useful for uncovering the underlying biology.
Simultaneous detection of invasive signal crayfish, endangered white-clawed crayfish and the crayfish plague pathogen using environmental DNA
Authors: Robinson Chloe Victoria , Webster Tamsyn M. Uren , Cable Joanne , James Joanna , Consuegra Sofia
Published: March 2018

Aquatic Invasive Species (AIS) are important vectors for the introduction of novel pathogens which can, in turn, become drivers of rapid ecological and evolutionary change, compromising the persistence of native species. Conservation strategies rely on accurate information regarding presence and distribution of AIS and their associated pathogens to prevent or mitigate negative impacts, such as predation, displacement or competition with native species for food, space or breeding sites. Environmental DNA is increasingly used as a conservation tool for early detection and monitoring of AIS. We used a novel eDNA high-resolution melt curve (HRM) approach to simultaneously detect the UK endangered native crayfish (Austropotamobius pallipes), the highly invasive signal crayfish (Pacifastacus leniusculus) and their dominant pathogen, Aphanomyces astaci, (causative agent of crayfish plague). We validated the approach with laboratory and field samples in areas with known presence or absence of both crayfish species as well as the pathogen, prior to the monitoring of areas where their presence was unknown. We identified the presence of infected signal crayfish further upstream than previously detected in an area where previous intensive eradication attempts had taken place, and the coexistence of both species in plague free catchments. We also detected the endangered native crayfish in an area where trapping had failed. With this method, we could estimate the distribution of native and invasive crayfish and their infection status in a rapid, cost effective and highly sensitive way, providing essential information for the development of conservation strategies in catchments with populations of endangered native crayfish.
Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children
Authors: Zinter MS , Dvorak CC , Mayday MY , Iwanaga K , Ly NP , McGarry ME , Church GD , Faricy LE , Rowan CM , Hume JR , Steiner ME , Crawford ED , Langelier C , Kalantar K , Chow ED , Miller S , Shimano K , Melton A , Yanik GA , Sapru A , DeRisi JL
Published: March 2018

RATIONALE

Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant morbidity and mortality.

OBJECTIVES

To develop a highly sensitive metagenomic next generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.

METHODS

We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014-2016. Samples underwent mechanical homogenization, paired RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the NCBI nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.

MEASUREMENTS & MAIN RESULTS

We identified a rich cross-domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median 0.58, IQR 0.33-0.62 vs. median 0.94, IQR 0.93-0.95, p<0.001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (p<0.001).

CONCLUSIONS

An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.
Structural disruption of exonic stem-loops immediately upstream of the intron regulates mammalian splicing
Authors: Saha Kaushik , England Whitney , Fernandez Mike Minh , Biswas Tapan , Spitale Robert C. , Ghosh Gourisankar
Published: March 2018

Recognition of highly degenerate mammalian splice sites by the core spliceosomal machinery is regulated by several protein factors that predominantly bind exonic splicing motifs. These are postulated to be single-stranded in order to be functional, yet knowledge of secondary structural features that regulate the exposure of exonic splicing motifs across the transcriptome is not currently available. Using transcriptome-wide RNA structural information we show that retained introns in mouse are commonly flanked by a short (≲70 nucleotide), highly base-paired segment upstream and a predominantly single-stranded exonic segment downstream. Splicing assays with select pre-mRNA substrates demonstrate that loops immediately upstream of the introns contain pre-mRNA-specific splicing enhancers, the substitution or hybridization of which impedes splicing. Additionally, the exonic segments flanking the retained introns appeared to be more enriched in a previously identified set of hexameric exonic splicing enhancer (ESE) sequences compared to their spliced counterparts, suggesting that base-pairing in the exonic segments upstream of retained introns could be a means for occlusion of ESEs. The upstream exonic loops of the test substrate promoted recruitment of splicing factors and consequent pre-mRNA structural remodeling, leading up to assembly of the early spliceosome. These results suggest that disruption of exonic stem-loop structures immediately upstream (but not downstream) of the introns regulate alternative splicing events, likely through modulating accessibility of splicing factors.
Non-parametric and semi-parametric support estimation using SEquential RESampling random walks on biomolecular sequences
Authors: Wang Wei , Smith Jack , Hejase Hussein A. , Liu Kevin J.
Published: March 2018

Non-parametric and semi-parametric resampling procedures are widely used to perform support estimation in computational biology and bioinformatics. Among the most widely used methods in this class is the standard bootstrap method, which consists of random sampling with replacement. While not requiring assumptions about any particular parametric model for resampling purposes, the bootstrap and related techniques assume that sites are independent and identically distributed (i.i.d.). The i.i.d. assumption can be an over-simplification for many problems in computational biology and bioinformatics. In particular, sequential dependence within biomolecular sequences is often an essential biological feature due to biochemical function, evolutionary processes such as recombination, and other factors.

To relax the simplifying i.i.d. assumption, we propose a new non-parametric/semi-parametric sequential resampling technique that generalizes “Heads-or-Tails” mirrored inputs, a simple but clever technique due to Landan and Graur. The generalized procedure takes the form of random walks along either aligned or unaligned biomolecular sequences. We refer to our new method as the SERES (or “SEquential RESampling”) method.

To demonstrate the flexibility of the new technique, we apply SERES to two different applications – one involving aligned inputs and the other involving unaligned inputs. Using simulated and empirical data, we show that SERES-based support estimation yields comparable or typically better performance compared to state-of-the-art methods for both applications.
Discovery of a pre-mRNA structural scaffold as a contributor to the mammalian splicing code
Authors: Saha Kaushik , Fernandez Mike Minh , Biswas Tapan , Joseph Simpson , Ghosh Gourisankar
Published: March 2018

The specific recognition of splice signals at or near exon-intron junctions is not explained by their weak conservation and instead is postulated to require a multitude of features embedded in the pre-mRNA strand. We explored the possibility of three-dimensional structural scaffold of AdML – a model pre-mRNA substrate – guiding early spliceosomal components to the splice signal sequences. We find that mutations in the non-cognate splice signal sequences impede recruitment of early spliceosomal components due to disruption of the global structure of the pre-mRNA. We further find that the pre-mRNA segments potentially interacting with the early spliceosomal component U1 snRNP are distributed across the intron, that there is a spatial proximity of 5′ and 3′ splice sites within the pre-mRNA scaffold, and that an interplay exists between the structural scaffold and splicing regulatory elements in recruiting early spliceosomal components. These results suggest that early spliceosomal components can recognize a three-dimensional structural scaffold beyond the short splice signal sequences, and that in our model pre-mRNA, this scaffold is formed across the intron involving the major splice signals. This provides a conceptual basis to analyze the contribution of recognizable three-dimensional structural scaffolds to the splicing code across the mammalian transcriptome.
Whole-exome sequencing identifies germline mutation in TP53 and ATRX in a child with genomically aberrant AT/RT and her mother with anaplastic astrocytoma
Authors: Nordfors Kristiina , Haapasalo Joonas , Afyounian Ebrahim , Tuominen Joonas , Annala Matti , Häyrynen Sergei , Karhu Ritva , Helén Pauli , Lohi Olli , Nykter Matti , Haapasalo Hannu , Granberg Kirsi J.
Published: March 2018

Brain tumors typically arise sporadically and do not affect several family members simultaneously. In the present study, we describe clinical and genetic data from two patients, a mother and her daughter, with familial brain tumors. Exome sequencing revealed a germline missense mutation in the TP53 and ATRX genes in both cases, and a somatic copy-neutral loss of heterozygosity (LOH) in TP53 in both atypical teratoid/rhabdoid tumor (AT/RT) and astrocytoma tumors. ATRX mutation was associated with the loss of ATRX protein expression. In the astrocytoma case, R132C missense mutation was found in the known hotspot site in isocitrate dehydrogenase 1 (IDH1) and LOH was detected in TP53. The mother carried few other somatic alterations, suggesting that the IDH1 mutation and LOH in TP53 were sufficient to drive tumor development. The genome in the AT/RT tumor was atypically aneuploid: Most chromosomes had experienced copy-neutral LOH or whole-chromosome gains. Only Chromosome 18 had normal diploid status. INI1/hSNF5/SMARCB1 was homozygously deleted in the AT/RT tumor. This report provides further information about tumor development in a predisposed genetic background and describes two special Li–Fraumeni cases with a familial brain tumor.
A Preliminary Analysis of the Age of Full Expression of Sexually Dimorphic Cranial Traits
Authors: Stock Michala K.
Published: March 2018

Although high accuracy rates have been achieved for adult skeletal sex estimation, it is unclear at what age sexually dimorphic traits of the skull become fully developed and useful in subadults. Four linear distances that capture sexual dimorphism—the nuchal crest, mastoid process, glabella, and mental eminence—were measured in a longitudinal sample of lateral cranial radiographs from 10 males and 10 females in the Denver Growth Study (total n = 190). The age full trait expression was attained was compared to that of dental maturity (i.e., third molar eruption). The mental eminence reached full expression significantly earlier than dental maturity (p < 0.001), although a high degree of variability was observed. Ages of expression of the other traits did not differ significantly from dental maturity. These results suggest that in forensic cases, where misclassification can have substantial impacts, cranial traits cannot yet be used reliably for sex estimation prior to third molar eruption.
Long‐term survival in locally advanced non‐small cell lung cancer invading the great vessels and heart
Authors: Park Byungjoon , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Zo Jae Il , Shim Young Mog , Kim Jhingook
Published: March 2018

Background

The aim of this study was to analyze the surgical outcomes of locally advanced lung cancer invading the great vessels or heart, according to the extension of cancer invasion.

Methods

From 1995 to 2015, 59 patients who were surgically treated and pathologically diagnosed with T4N0–1 non‐small cell lung cancer with invasion to the great vessels or heart were enrolled. Surgical outcomes were compared between patient groups with and without intrapericardial invasion.

Results

The median age was 64 years (interquartile range [IQR] 57–68) and 56 patients (95%) were male. In‐hospital mortality was 9% and median overall survival was 30 months (IQR 12–83). One and five‐year overall survival rates were 75% and 44%, respectively. The median overall survival in patients with lung cancer invasion to the intrapericardial space (n = 45) was 27 months (IQR 10–63), while it was 42 months (IQR 18–104) in patients without intrapericardial invasion (n = 14). Median disease‐free survival was significantly poorer in patients with intrapericardial invasion (12 months; IQR 6–55), especially in patients with heart invasion (n = 11, 7 months, IQR 5–27), than in patients without intrapericardial invasion (30 months, IQR 13–103).

Conclusion

Patients with lung cancer invading the intrapericardial space showed worse surgical outcomes in both overall and disease‐free survival. Therefore, surgical management should be carefully considered in patients with intrapericardial invasion.
Ethanol Exposure History and Alcoholic Reward Differentially Alter Dopamine Release in the Nucleus Accumbens to a Reward‐Predictive Cue
Authors: Fiorenza Amanda M. , Shnitko Tatiana A. , Sullivan Kaitlin M. , Vemuru Sudheer R. , Gomez‐A Alexander , Esaki Julie Y. , Boettiger Charlotte A. , Da Cunha Claudio , Robinson Donita L.
Published: March 2018

Background

Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called “goal‐tracking”) or to the CS itself (called “sign‐tracking”). Previous research has linked sign‐tracking in particular to impulsivity and drug self‐administration, and addictive drugs may promote the expression of sign‐tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign‐tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign‐tracking while acute administration of naltrexone (NTX) would reduce it.

Methods

Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast‐scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach.

Results

Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign‐tracking, as both CIE and alcoholic reward shifted conditioned approach from sign‐tracking behavior to goal‐tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal‐tracking behavior.

Conclusions

While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign‐tracking under the current conditions. These findings are consistent with the interpretation that EtOH can stimulate conditioned approach, but indicate that the conditioned response may manifest as goal‐tracking.
Blackouts as a Moderator of Young Adult Veteran Response to Personalized Normative Feedback for Heavy Drinking
Authors: Miller Mary Beth , DiBello Angelo M. , Carey Kate B. , Pedersen Eric R.
Published: March 2018

Background

Blackouts—or periods of alcohol‐induced amnesia for all or part of a drinking event—have been identified as independent predictors of alcohol‐related harm that may be used to identify individuals who would benefit from intervention. However, little is known about the prevalence and impact of blackouts among Veterans. This study examined blackouts as a moderator of young adult veteran response to a brief, online personalized normative feedback (PNF) intervention for heavy drinking.

Methods

Veterans scoring ≥3/4 (women/men) on the Alcohol Use Disorders Identification Test completed a baseline and 1‐month assessment as part of a larger intervention trial (N = 571; 83% male; age M = 28.9, SD = 3.3). Participants were randomized to alcohol PNF (n = 285) or a video game attention control (n = 286). Hierarchical regression was used to examine the interaction between intervention condition and blackouts on alcohol‐related outcomes at 1‐month follow‐up.

Results

At baseline, 26% of participants reported loss of memory for drinking events in the past 30 days. The interaction between condition and blackouts was significant, such that PNF participants who had experienced blackouts at baseline reported greater decreases in drinking quantity at 1 month than those who had not, and only PNF participants who had experienced baseline blackouts reported a decrease in alcohol problems at follow‐up.

Conclusions

PNF appears to be particularly effective for individuals who have experienced alcohol‐induced blackout, perhaps because blackouts prime them for feedback on their alcohol use. While other negative consequences may also prime individuals for behavior change, blackouts are posited as a particularly useful screening tool because they are prevalent among young adults, have a strong association with alcohol‐related harm, and are assessed in widely used clinical measures.
No differences in olanzapine‐ and risperidone‐related weight gain between women and men: a meta‐analysis of short‐ and middle‐term treatment
Authors: Schoretsanitis G. , Drukker M. , Van Os J. , Schruers K. R. J. , Bak M.
Published: March 2018

Objective

A plethora of data deriving from single studies as well as meta‐analyses demonstrates that weight gain is associated with the exposure to the majority of antipsychotics (AP). However, potential sex differences have widely evaded the attention of AP treatment trials. It is hypothesised that female patients gain more weight compared with male patients due to their enhanced susceptibility to adverse drug reactions.

Method

A meta‐analysis was conducted using clinical trials of AP that reported weight change separately for female and male patients. Duration of AP use was stratified in four categories: <6 weeks, 6–16 weeks, 16–38 weeks and >38 weeks. Forest plots were generated for men and women separately, stratified by AP as well as by duration of use. Sex differences were tested by performing meta‐regression.

Results

Data of 26 studies were used in the present analysis because sufficient data were available only for olanzapine, risperidone and the no‐medication group. Both female and male patients showed considerable weight gain after switch or initiate of olanzapine or risperidone, but meta‐regression analyses did not show significant sex differences.

Conclusion

The present meta‐analysis revealed that sex differences in AP‐related weight gain have been under investigated hampering the detection of sex‐specific patterns. In chronic patients switching to olanzapine or risperidone receiving short‐or middle‐term treatment, AP were associated with weight gain in both sex subgroups and no significant differences were reported.
Soil microarthropod communities reduceHeterorhabditis bacteriophora(Nematoda: Heterorhabditidae) host infection
Authors: Helmberger Maxwell S. , Shields Elson J. , Wickings Kyle G.
Published: March 2018

Biological control agents applied to soil, such as entomopathogenic nematodes (EPNs), are exposed to a wide variety of organisms other than the pest that they are utilized against. Interactions with these other organisms may positively or negatively affect EPN performance and may be important for managers to take into account when using EPNs to control pests.

The present study assessed the effect of soil microarthropods on the EPNHeterorhabditis bacteriophorawith respect to establishment within and infection of wax mothGalleria mellonellalarvae in soil arenas.

The presence of soil microarthropods at typical field densities significantly reduced the establishment ofH. bacteriophoraadults withinG. mellonellalarvae and also reduced the percentage of hosts infected in one of two replicated trials. Specifically, adult EPN establishment was negatively correlated with the abundance of mesostigmatid mites.

The results of the present study indicate that soil microarthropods at natural abundances can reduce EPN establishment even within the structurally complex environment of soil, although this does not always lead to reductions in insect infection rates.
Structural Model for Viscoelastic Properties of Pericardial Bioprosthetic Valves
Authors: Rassoli Aisa , Fatouraee Nasser , Guidoin Robert
Published: March 2018

The benefit of bioprosthetic aortic valve over mechanical valve replacements is the release of thromboembolism and digression of long‐term anticoagulation treatment. The function of bioprostheses and their efficiency is known to depend on the mechanical properties of the leaflet tissue. So it is necessary to select a suitable tissue for the bioprosthesis. The purpose of the present study is to clarify the viscoelastic behavior of bovine, equine, and porcine pericardium. In this study, pericardiums were compared mechanically from the viscoelastic aspect. After fixation of the tissues in glutaraldehyde, first uniaxial tests with different extension rates in the fiber direction were performed. Then, the stress relaxation tests in the fiber direction were done on these pericardial tissues by exerting 20, 30,40, and 50% strains. After evaluation of viscoelastic linearity, the Prony series, quasilinear viscoelastic (QLV) and modified superposition theory were applied to the stress relaxation data. Finally, the parameters of these constitutive models were extracted for each pericardium tissue. All three tissues exhibited a decrease in relaxation rate with elevating strain, indicating the nonlinear viscoelastic behavior of these tissues. The three‐term Prony model was selected for describing the linear viscoelasticity. Among different models, the QLV model was best able to capture the relaxation behavior of the pericardium tissues. More stiffness of porcine pericardium was observed in comparison to the two other pericardium tissues. The relaxation percentage of porcine pericardium was less than the two others. It can be concluded that porcine pericardium behaves more as an elastic and less like a viscous tissue in comparison to the bovine and equine pericardium.