bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of an Alternative Surgical Corridor in Oblique Lateral Interbody Fusion at the L5–S1 Segment
Authors: Chung Nam-Su , Jeon Chang-Hoon , Lee Han-Dong
Published: March 2018

Study Design:

Technical report.

Objective:

To demonstrate the use of an alternative surgical corridor in oblique lateral interbody fusion (OLIF) at the L5–S1 segment.

Summary of Background Data:

OLIF L5–S1 is essentially performed through the central disk space between the bifurcations of the iliac vessels, which is sometimes difficult due to the vascular structures that obstruct the surgical field. Another concern is retrograde ejaculation following superior hypogastric plexus injury in male patients.

Materials and Methods:

The alternative surgical corridor involves the lateral disk space external to the left iliac vessels. The patient position and the retroperitoneal approach are similar to those used in the conventional OLIF L5–S1. The left iliac vessels are identified and mobilized medially to the midline of the L5–S1 disk space. The vascular structures are then protected using the conventional OLIF 51 retractor system.

Results:

Six patients underwent OLIF L5–S1 through the alternative lateral surgical corridor. The L5–S1 disk spaces were always exposed sufficiently for disk preparation and cage insertion. The postoperative radiographs showed a satisfactory L5–S1 reconstruction with good cage position. There were no perioperative complications during the surgical access and reconstruction procedures.

Conclusions:

When the central approach to the L5–S1 disk space poses a risk of vascular or superior hypogastric plexus injury, use of a lateral approach external to the left iliac vessels can be an alternative method to perform OLIF L5–S1.
Meralgia Paresthetica After Spine Surgery on the Jackson Table
Authors: Agarwal Nitin , Mistry Jaydev B. , Khandge Preeya V. , Hansberry David R. , Goldstein Ira M.
Published: March 2018

Meralgia paresthetica is a non–life-threatening neurological disorder characterized by numbness, tingling, and burning pain over the anterolateral thigh due to impingement of the lateral femoral cutaneous nerve. This disorder has been seen in patients with diabetes mellitus and obesity, but has also been observed in patients after procedures such as posterior spine surgery, iliac crest bone grafts, lumbar disk surgery, hernia repair, appendectomies, and pelvic osteotomies that ultimately lead to compression or damage to the lateral femoral cutaneous nerve. Overall, permanent sequelae of meralgia paresthetica are rare, however, some cases do require intervention.
Ethnic Variations in Radiographic Parameters and SRS-22 Scores in Adult Spinal Deformity
Authors: Hosogane Naobumi , Ames Christopher , Matsumoto Morio , Yagi Mitsuru , Matsuyama Yukihiro , Taneichi Hiroshi , Yamato Yu , Takeuchi Daisaku , Schwab Frank , Shaffrey Christopher , Smith Justin S. , Bess Shay , Lafage Virginie
Published: March 2018

Study Design:

Retrospective review of North American and Japanese adult spinal deformity (ASD) database.

Objective:

To investigate the ethnical differences in radiographic parameters and Scoliosis Research Society (SRS)-22 between North American and Japanese ASD.

Summary of Background Data:

Previous comparison study between North American and Japanese ASD patients has revealed Japanese patients had marked pelvic tilt deformity and had lower Oswestry Disability Index scores corresponding to established thresholds of radiographic deformity. However, the subjects of the previous study included relatively younger ASD patients (above 18 y) of idiopathic origin.

Materials and Methods:

Total 282 ASD patients older than 50 years, 211 patients from North America (United States) and 71 patients from Japan (JP), with minimum 2-year follow-up postoperatively were included in the study. Radiologic parameters were compared at the baseline and at 2-year follow-up. SRS-22 score was used for the comparison of clinical outcome.

Results:

At baseline, Japan showed significantly worse sagittal alignment such as smaller lumbar lordosis (LL), larger pelvic incidence (PI), and larger sagittal vertical axis than United States. However, Japan had significantly fewer levels fused than United States (US, 12.66±4.6; JP, 8.49±2.7). At 2 years after the surgery, Japan still had significantly worse residual sagittal deformity. Comparison of SRS-22 scores revealed Japan had better pain but worse functional domain scores at baseline which improved to comparable levels to the United States at 2 years. Self-image and mental health scores in Japan were significantly worse both at baseline and at 2 years. Analysis of factors affecting SRS-22 satisfaction score at 2 years revealed that previous spinal fusion surgery in the United States and LL, PI-LL, and sagittal vertical axis at 2 years in Japan had significant correlation.

Conclusions:

These similarities and discrepancies may be influenced by the cultural or lifestyle differences between both nations and should be considered when interpreting the results of ASD studies among different ethnicities.
Distribution and Determinants of 90-Day Payments for Multilevel Posterior Lumbar Fusion
Authors: Jain Nikhil , Phillips Frank M. , Khan Safdar N.
Published: March 2018

Study Design:

A retrospective, economic analysis.

Objective:

The objective of this article is to analyze the distribution of 90-day payments, sources of variation, and reimbursement for complications and readmissions for primary ≥3-level posterior lumbar fusion (PLF) from Medicare data. A secondary objective was to identify risk factors for complications.

Summary of Background Data:

Bundled payments represent a single payment system to cover all costs associated with a single episode of care, typically over 90 days. The dollar amount spent on different health service providers and the variation in payments for ≥3-level PLF have not been analyzed from a bundled perspective.

Materials and Methods:

Administrative claims data were used to study 90-day Medicare (2005–2012) reimbursements for primary ≥3-level PLF for deformity and degenerative conditions of the lumbar spine. Distribution of payments, sources of variation, and reimbursements for managing complications were studied using linear regression models. Risk factors for complications were studied by stepwise multiple-variable logistic regression analysis.

Results:

Hospital payments comprised 73.8% share of total 90-day payment. Adjusted analysis identified several factors for variation in index hospital payments. The average 90-day Medicare payment for all multilevel PLFs without complications was $35,878 per patient. The additional average cost of treating complications with/without revision surgery within 90 days period ranged from $17,284 to $68,963. A 90-day bundle for ≥3-level PLF with readmission ranges from $88,648 (3 levels) to $117,215 (8+ levels). Rates and risk factors for complications were also identified.

Conclusions:

The average 90-day payment per patient from Medicare was $35,878 with several factors such as levels of surgery, comorbidities, and development of complications influencing the cost. The study also identifies the risks and costs associated with complications and readmissions and emphasize the significant effect these would have on bundled payments (additional burden of up to 192% the cost of an average uncomplicated procedure over 90 days).

Level of Evidence:

Level 3.
Discrepancies in the Definition of “Outpatient” Surgeries and Their Effect on Study Outcomes Related to ACDF and Lumbar Discectomy Procedures
Authors: Bovonratwet Patawut , Webb Matthew L. , Ondeck Nathaniel T. , Gala Raj J. , Nelson Stephen J. , McLynn Ryan P. , Cui Jonathan J. , Grauer Jonathan N.
Published: March 2018

Study Design:

This is a retrospective study.

Objective:

To study the differences in definition of “inpatient” and “outpatient” [stated status vs. actual length of stay (LOS)], and the effect of defining populations based on the different definitions, for anterior cervical discectomy and fusion (ACDF) and lumbar discectomy procedures in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database.

Summary of Background Data:

There has been an overall trend toward performing ACDF and lumbar discectomy in the outpatient setting. However, with the possibility of patients who underwent outpatient surgery staying overnight or longer at the hospital under “observation” status, the distinction of “inpatient” and “outpatient” is not clear.

Materials and Methods:

Patients who underwent ACDF or lumbar discectomy in the 2005–2014 ACS-NSQIP database were identified. Outpatient procedures were defined in 1 of 2 ways: either as being termed “outpatient” or hospital LOS=0. Differences in definitions were studied. Further, to evaluate the effect of the different definitions, 30-day outcomes were compared between “inpatient” and “outpatient” and between LOS>0 and LOS=0 for ACDF patients.

Results:

Of the 4123 “outpatient” ACDF patients, 919 had LOS=0, whereas 3204 had LOS>0. Of the 13,210 “inpatient” ACDF patients, 337 had LOS=0, whereas 12,873 had LOS>0. Of the 15,166 “outpatient” lumbar discectomy patients, 8968 had LOS=0, whereas 6198 had LOS>0. Of the 12,705 “inpatient” lumbar discectomy patients, 814 had LOS=0, whereas 11,891 had LOS>0. On multivariate analysis of ACDF patients, when comparing “inpatient” with “outpatient” and “LOS>0” with “LOS=0” there were differences in risks for adverse outcomes based on the definition of outpatient status.

Conclusions:

When evaluating the ACS-NSQIP population, ACDF and lumbar discectomy procedures recorded as “outpatient” can be misleading and often did not correlate with same day discharge. These findings have significant impact on the interpretation of existing studies and define an area that needs clarification for future studies.

Level of Evidence:

Level 3.
Long Fusion Arthrodesis Stopping at L5 for Adult Scoliosis
Authors: Gao Xianda , Wang Linfeng , Zhang Jingtao , Wang Peng , Shen Yong
Published: March 2018

Study Design:

This is retrospective study.

Objective:

Our purpose is to examine the state of the L5–S1 disk after long fusion arthrodesis stopping at L5 in adult scoliosis, and to identify the risk factors for disk degeneration.

Summary of Background Data:

The long fusion arthrodesis surgery for adult scoliosis has shown to have good clinical results. However, there is still some controversy with reference to the potential caudal extents of the fusion, that is, L5 or S1. One of the most common problems related to the L5 fusion is whether subsequent L5–S1 disk degenerations occurs because of stress concentration. In this study, 1.5-T MRI was used to evaluate the L5–S1 disk degeneration according to Pfirrmann classification.

Materials and Methods:

In total, 43 patients with adult scoliosis after posterior long fusions arthrodesis surgery were reviewed retrospectively with the average follow-up period of 4.17±1.55 years (range, 2–9 y). The 1.5 T MRI and standing long x-ray were performed preoperatively and at last follow-up visit. Clinical outcomes were evaluated according to Japanese Orthopedic Association (JOA) scores and Oswestry Disability Index (ODI).

Results:

Subsequent L5–S1 disk degeneration was observed in 33 patients (51.56%). Preoperative average Pfirrmann grade was 1.98±0.58, whereas during last follow-up average Pfirrmann grade was 2.63±0.83 (P<0.001). Preoperative Pfirrmann grade in patients with subsequent disk degeneration was 1.94±0.66, and in patients without subsequent disk degeneration was 2.06±0.51 (P=0.278). Greater ODI showed in patients with subsequent degeneration (P=0.008). Multivariate logistic regression analysis revealed that long follow-up period, heavy labor, and preoperative imbalance were the risk factors.

Conclusions:

Subsequent L5–S1 disk degeneration was common after long fusions arthrodesis was stopped at L5. The recovery of neurological status was similar in patients with or without subsequent L5–S1 disk degeneration, whereas patients with subsequent degeneration complained more about low back pain. Patients with long follow-up period, heavy labor, and preoperative imbalance were more likely to suffer subsequent L5–S1 disk degeneration.
Natural History and Prognostic Factors of Cholangiocarcinoma With Spinal Metastasis
Authors: Sangsin Apiruk , Saiudom Dew , Pongmanee Suthipas , Saengsin Jirawat , Leerapun Taninnit , Murakami Hideki
Published: March 2018

Study Design:

This is a retrospective analysis.

Objective:

The aim of this study was to determine the epidemiology, survival, and prognostic factors for cholangiocarcinoma (CCA) with spinal metastasis.

Summary of Background Data:

CCA is an epithelial cell malignancy of the bile duct, and a frequent site for its metastasis is the spine. Many areas of Asia are endemic for CCAs. To date, there is limited data on the epidemiology, natural history, and prognostic factors of CCA with spinal metastasis, which is crucial for better management and treatment of the disease.

Materials and Methods:

Patients diagnosed with CCA were recruited to our study, in order to identify cases with spinal metastasis. The survival rate was estimated by the Kaplan-Meier method. The univariate and multivariate analyses of tumor-specific and spinal metastatic factors were performed to identify the independent factors that affect survival.

Results:

From 2006 to 2015, 4585 CCA patients were identified and 182 of these patients had spinal metastasis. The overall median survival of patients with spinal metastasis was 88 days. Serum carcinoembryonic antigen <5 ng/mL, carbohydrate antigen 19-9 <39 U/mL, albumin ≥3.5 g/L, and Frankel score D–E were found to be independent factors that resulted in better survival in a multivariate Cox regression analysis. CCA resection or spinal surgery did not prolong the survival of patients with spinal metastasis.

Conclusion:

Spinal surgery should be considered for CCA patients with spinal metastasis, who have a favorable prognosis, and are likely to live long enough to benefit from surgery. The aim is to palliate the symptoms and not as much to improve the survival.
Hidden Blood Loss in Posterior Lumbar Fusion Surgery
Authors: Wen Longfei , Jin Daxiang , Xie Weixing , Li Yue , Chen Weijian , Ding Jinyong , Xu Jixi , Ren Dongcheng
Published: March 2018

Study Design:

Descriptive study.

Objectives:

This study aimed to evaluate the hidden blood loss (HBL) of patients who underwent lumbar fusion surgery for degenerative spine and to analyze its risk factors.

Summary of Background Data:

When planning transfusion strategies, blood loss calculation is important. However, in clinical practice, spine surgeons usually ignore the possibility that a large amount of HBL may occur after lumbar fusion surgery.

Materials and Methods:

We studied the patients who underwent posterior lumbar fusion (PLF) surgery for degenerative spine from 2014 to 2015 in one institution. The patient’s demographics, comorbid conditions, coagulation panel value, surgical time, number of levels fused, American Society of Anesthesiologists (ASA) classification, cell saver, preoperative hematocrit level, preoperative hemoglobin level, and postoperative complications were collected retrospectively. Pearson correlation analyses were used to find an association between patient characteristics and HBL. Multivariate linear analysis was used to determine independent risk factors of HBL.

Results:

We reviewed 169 consecutive patients who underwent PLF surgery for degenerative spine in one institution. The mean amount of HBL was 588 mL, which was 39% of the total blood loss. On the basis of the model of multiple linear regression analysis, the multilevel fusion (P=0.001), surgical time (P=0.034), and fibrinogen level (P=0.027) were independent risk factors that contributed to HBL, but age of 60 years or above (P=0.110), postoperative complications (P=0.278), and cell saver were not (P=0.739).

Conclusions:

We conclude that a large amount of HBL may occur in patients who underwent PLF surgery for degenerative spine. In addition, significant hidden loss may have a correlation with postoperative mortality. Multilevel fused, surgical time, and fibrinogen level should be paid close attention when considering strategies of fluid infusion and blood transfusion.
Thoracolumbar Burst Fractures
Authors: Rosenthal Brett D. , Boody Barrett S. , Jenkins Tyler J. , Hsu Wellington K. , Patel Alpesh A. , Savage Jason W.
Published: March 2018

Thoracolumbar burst fractures are high-energy vertebral injuries, which commonly can be treated nonoperatively. Consideration of the injury pattern, extent of comminution, neurological status, and integrity of the posterior ligamentous complex may help determine whether operative management is appropriate. Several classification systems are contingent upon these factors to assist with clinical decision-making. A multitude of operative procedures have been shown to have good radiographic and clinical outcomes with extended follow-up, and treatment choice should be based on the individual’s clinical and radiographic presentation.
The Anterolateral Ligament is Not the Whole Story: Reconsidering the Form and Function of the Anterolateral Knee and its Contribution to Rotatory Knee Instability
Authors: Sheean Andrew J. , Shin Jason , Patel Neel K. , Lian Jayson , Guenther Daniel , Musahl Volker
Published: March 2018

The heterogeneity of available cadaveric, histologic, and radiographic results related to the anterolateral ligament (ALL) does not support its existence as a discrete anatomic structure. Moreover, focusing narrowly on the ALL in isolation, what has previously been referred to as “ALL myopia,” obscures a thorough appreciation for the stability contributions of both capsular and extracapsular structures. We consider injury to the soft tissues of the anterolateral knee–the anterolateral complex—just one component of what is frequently found to be a spectrum of pathology observed in the rotationally unstable, anterior cruciate ligament (ACL)-deficient knee. Increased lateral tibial slope, meniscal root tears, and “ramp” lesions of the medial meniscocapsular junction have all been implicated in persistent rotatory knee instability, and the restoration of rotational stability requires a stepwise approach to the assessment of each of these entities. Through an appreciation for the multifactorial nature of rotatory knee instability, surgeons will be better equipped to perform durable ACL reconstructions that maximize the likelihood of optimal clinical outcomes for patients. The purposes of this review are to provide an update on the relevant anatomy of the anterolateral knee soft tissues and to explain the multifactorial nature of rotatory knee instability in the setting of ACL deficiency.
Feeling Safe and Taking on Responsibilities: Newly Graduated Nurses' Perceptions and Evaluations of Their Transition Into a Forensic Mental Health Inpatient Setting
Authors: Sørensen Tanja , Tingleff Ellen B. , Gildberg Frederik A.
Published: March 2018

Forensic mental health care is faced with serious problems in the recruitment and retention of newly graduated nurses (NGNs). Research into NGNs' experiences of their transition to and evaluations of transition programs in forensic care is sparse, and more studies are called for. This study aimed to investigate the characteristics of NGNs' experiences and perceptions of their transition into a forensic setting and their evaluations of the introduction period. Three focus group interviews were carried out, involving 13 NGNs, lasting 79.68 minutes on average. They were analyzed using thematic analysis. Results show two main themes: “feeling safe” and “taking on responsibilities.” If NGNs felt overburdened with clinical responsibilities during their transition, their feeling of safety reduced. The converse also applied; theThe safer they felt, the greater clinical responsibility they felt capable of handling. The more difficult the NGNs perceived the informal transition, the more unsafe they felt, and the more negatively they perceived the responsibilities placed upon them. Tailored programs designed to support both the informal and formal transitions are recommended, along with preceptorship, theoretical training, and role-based support, such as a shift manager, along with early introduction to conflict management and security measures.
Managing the Social Determinants of Health: Part I
Authors: Fink-Samnick Ellen
Published: March 2018

Objectives:

This article will:

Define the social determinants of health (SDH)

Provide industry evidence on the SDH from a population health perspective

Discuss current sociopolitical drivers to impact the progression of SDH

Discuss career implications for the professional case management workforce

Primary Practice Setting(s):

Applicable to health and behavioral health settings, wherever case management is practiced.

Finding/Conclusion:

The SDH pose major challenges to the health care workforce in terms of effective resource provision, health and behavioral health treatment planning plus adherence, and overall coordination of care. Obstacles and variances to needed interventions easily lead to less than optimal outcomes for case managers and their health care organizations. Possessing sound knowledge and clear understanding of each SDH, the historical perspectives, main theories, and integral dynamics, as well as creative resource solutions, all support a higher level of intentional and effective professional case management practice.

Implications for Case Management Practice:

Those persons and communities impacted most by the SDH comprise every case management practice setting. These clients can be among the most vulnerable and disenfranchised members of society, which can easily engender biases on the part of the interprofessional workforce. They are also among the costliest to care for with 50% of costs for only 5% of the population. Critical attention to knowledge about managing the SDH leverages and informs case management practice, evolves more effective programming, and enhances operational outcomes across practice settings.
To Exist as a Case Manager Is to Constantly Change; to Be Successful, You Must Constantly Adapt
Authors: Tahan Hussein M.
Published: March 2018

Change is inevitable whether in personal or professional lives. Case management practice is always evolving on the basis of the dynamic nature of the U.S. health care environment. Effective case managers are those who possess an adaptive mind-set, recognize the importance to change to maintain success, and remain relevant. They also demonstrate a sense of accountability and responsibility for own learning, professional development, and acquisition of new skills and knowledge. This editorial discusses the nature of change and adaptation and presents key strategies for case managers to remain relevant and effective in dynamic practice environments.
Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding
Authors: Pannucci Christopher J. , Fleming Kory I. , Momeni Arash , Prazak Ann Marie , Agarwal Jayant , Rockwell W. Bradford
Published: March 2018

Background:

Low anti–factor Xa level, indicative of inadequate enoxaparin dosing, has a significant association with 90-day venous thromboembolism events. The authors examined the pharmacodynamics of enoxaparin 40 mg twice daily and its correlation with anti–factor Xa level, postoperative venous thromboembolism, and bleeding.

Methods:

Adult patients were admitted after plastic and reconstructive surgery and received enoxaparin 40 mg twice daily. Peak anti–factor Xa levels, which quantify enoxaparin’s antithrombotic effect, were drawn, with a goal level of 0.2 to 0.4 IU/ml. Ninety-day symptomatic venous thromboembolism and clinically relevant bleeding were identified.

Results:

The authors enrolled 118 patients who received enoxaparin 40 mg twice daily. Of these patients, 9.6 percent had low peak anti–factor Xa levels (<0.2 IU/ml), 62.6 percent had in-range peak anti–factor Xa levels (0.2 to 0.4 IU/ml), and 27.8 percent had high anti–factor Xa levels (>0.4 IU/ml). With enoxaparin 40 mg twice daily, 90.4 percent of patients received at least adequate prophylaxis. Patient weight predicted the rapidity of enoxaparin metabolism. Zero acute 90-day venous thromboembolism occurred. Eight patients (6.8 percent) had clinically relevant 90-day bleeding: clinical consequences ranged from cessation of enoxaparin prophylaxis to transfusion to operative hematoma evacuation.

Conclusions:

When enoxaparin 40 mg twice daily is provided, 90 percent of patients receive at least adequate venous thromboembolism prophylaxis (anti–factor Xa level >0.2 IU/ml). However, 27 percent of the overall population is overtreated (anti–factor Xa level >0.4 IU/ml). These pharmacodynamics data likely explain the low rate of 90-day acute venous thromboembolism (0 percent) and the high rate of clinically relevant bleeding (6.8 percent) observed. Future studies are needed to better optimize the risks and benefits of enoxaparin prophylaxis in plastic and reconstructive surgery patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language
Authors: Hoyt Charles Tapley , Domingo-Fernández Daniel , Hofmann-Apitius Martin
Published: March 2018

The rapid accumulation of knowledge in the field of systems and networks biology during recent years requires complex, but user-friendly and accessible web applications that allow from visualization to complex algorithmic analysis. While several web applications exist with various focuses on creation, revision, curation, storage, integration, collaboration, exploration, visualization, and analysis, many of these services remain disjoint and have yet to be packaged into a cohesive environment.

Here, we present BEL Commons; an integrative knowledge discovery environment for networks encoded in the Biological Expression Language (BEL). Users can upload files in BEL to be parsed, validated, compiled, and stored with fine-granular permissions. After, users can summarize, explore, and optionally shared their networks with the scientific community. We have implemented a query builder wizard to help users find the relevant portions of increasingly large and complex networks and a visualization interface that allows them to explore their resulting networks. Finally, we have included a dedicated analytical service for performing data-driven analysis of knowledge networks to support hypothesis generation.

This web application can be freely accessed athttps://bel-commons.scai.fraunhofer.de.
Leaps and bounds: geographical and ecological distance constrained the colonisation of the Afrotemperate by Erica
Authors: Pirie M.D. , Kandziora M. , Nürk N.M. , Le Maitre N.C. , Mugrabi de Kuppler A. , Gehrke B. , Oliver E.G.H. , Bellstedt D.U.
Published: March 2018

The coincidence of long distance dispersal and biome shift is assumed to be the result of a multifaceted interplay between geographical distance and ecological suitability of source and sink areas. Here, we test the influence of these factors on the dispersal history of the flowering plant genus Erica (Ericaceae) across the Afrotemperate. We quantify similarity of Erica climate niches per biogeographic area using direct observations of species, and test various colonisation scenarios while estimating ancestral areas for the Erica clade using parametric biogeographic model testing. We infer that the overall dispersal history of Erica across the Afrotemperate is the result of infrequent colonisation limited by geographic proximity and niche similarity. However, the Drakensberg Mountains represent a colonisation sink, rather than acting as a “stepping stone” between more distant and ecologically dissimilar Cape and Tropical African regions. Strikingly, the most dramatic examples of species radiations in Erica were the result of single unique dispersals over longer distances between ecologically dissimilar areas, contradicting the rule of phylogenetic biome conservatism. These results highlight the importance of rare biome shifts, in which a unique dispersal event fuels evolutionary radiation.
Rapid Turnover of Life-Cycle-Related Genes in the Brown Algae
Authors: Lipinska A.P. , Serrano-Serrano M.L. , Peters Akira F. , Kogame K. , Cock J Mark , Coelho Susana M.
Published: March 2018

Background

Sexual life cycles in eukaryotes involve a cyclic alternation between haploid and diploid phases. While most animals possess a diploid life cycle, plants and algae alternate between multicellular haploid (gametophyte) and diploid (sporophyte) generations. In many algae, gametophytes and sporophytes are independent and free living, and may present dramatic phenotypic differences. The same shared genome can therefore be subject to different, even conflicting, selection pressures in each of the life cycle generations. Here, we have analysed the nature and extent of genome-wide generation-biased gene expression in four species of brown algae with contrasting levels of dimorphism between life cycle generations, in order to assess the potential role of generation-specific selection in shaping patterns of gene expression and divergence.

Results

We show that the proportion of the transcriptome that is generation-biased is associated with the level of phenotypic dimorphism between the life cycle stages. Importantly, our data reveals a remarkably high turnover rate for life-cycle-related gene sets across the brown algae and highlights the importance not only of co-option of regulatory programs from one generation to the other but also a key role for newly emerged, lineage-specific genes in the evolution of the gametophyte and sporophyte developmental programs in this major eukaryotic group. Moreover, we show that generation-biased genes display distinct evolutionary modes, with gametophyte-biased genes evolving rapidly at the coding sequence level whereas sporophyte-biased genes exhibit changes in their patterns of expression.

Conclusion

Our analysis uncovers the characteristics, expression patterns and evolution of generation-biased genes and underline the selective forces that shape this previously underappreciated source of phenotypic diversity.
Combining high resolution and exact calibration to boost statistical power: A well-calibrated score function for high-resolution MS2 data
Authors: Lin Andy , Howbert J. Jeffry , Noble William Stafford
Published: March 2018

To achieve accurate assignment of peptide sequences to observed fragmentation spectra, a shotgun proteomics database search tool must make good use of the very high resolution information produced by state-of-the-art mass spectrometers. However, making use of this information while also ensuring that the search engine’s scores are well calibrated—i.e., that the score assigned to one spectrum can be meaningfully compared to the score assigned to a different spectrum—has proven to be challenging. Here, we describe a database search score function, the “residue evidence” (res-ev) score, that achieves both of these goals simultaneously. We also demonstrate how to combine calibrated res-ev scores with calibrated XCorr scores to produce a “combined p-value” score function. We provide a benchmark consisting of four mass spectrometry data sets, which we use to compare the combined p-value to the score functions used by several existing search engines. Our results suggest that the combined p-value achieves state-of-the-art performance, generally outperforming MS Amanda and Morpheus and performing comparably to MS-GF+. The res-ev and combined p-value score functions are freely available as part of the Tide search engine in the Crux mass spectrometry toolkit (http://crux.ms).
Spatial and Temporal Cortical Variability Track with Age and Affective Experience During Emotion Regulation in Youth
Authors: Moreira João F. Guassi , McLaughlin Katie A. , Silvers Jennifer A.
Published: March 2018

Variability is a fundamental feature of human brain activity that is particularly pronounced during development. However, developmental neuroimaging research has only recently begun to move beyond characterizing brain function exclusively in terms of magnitude of neural activation to incorporate estimates of variability. No prior neuroimaging study has done so in the domain of emotion regulation. We investigated how age and affective experiences relate to spatial and temporal variability in neural activity during emotion regulation. In the current study, 70 typically developing youth aged 8-17 years completed a cognitive reappraisal task of emotion regulation while undergoing functional magnetic resonance imaging. Estimates of spatial and temporal variability during regulation were calculated across a network of brain regions, defineda priori, and were then related to age and affective experiences. Results showed that increasing age was associated with reduced spatial and temporal variability in a set of frontoparietal regions (e.g., dorsomedial prefrontal cortex, superior parietal lobule) known to be involved in effortful emotion regulation. In addition, youth who reported less negative affect during regulation had less spatial variability in the ventrolateral prefrontal cortex, which has previously been linked to cognitive reappraisal. We interpret age-related reductions in spatial and temporal variability as implying neural specialization. These results suggest that the development of emotion regulation is undergirded by a process of neural specialization and open up a host of possibilities for incorporating neural variability into the study of emotion regulation development.
Cancer therapy with a CRISPR-assistant telomerase-activating gene expression system
Authors: Dai Wei , Xu Xinhui , Wang Danyang , Wu Jian , Wang Jinke
Published: March 2018

Telomerase is silent in most normal somatic cells while active in 90% of tumor cells. Various telomerase activity inhibitors have been developed to treat cancer but all failed due to side effects. Here we acted oppositely to develop a cancer therapy named telomerase-activating gene expression (Tage) by utilizing the telomerase activity in tumor cells. By using CRISPR/Cas9 functions, the Tage system can effectively kill various cancer cells, including HepG2, HeLa, PANC-1, MDA-MB-453, A549, HT-29, SKOV-3, Hepa1-6, and RAW264.7, without effecting normal cells. By using homothallic switching endonuclease and adeno-associated virus, the Tage system realizes its in vivo application. The virus-loaded Tage system can significantly and specifically kill the cancer cells in mice by intravenous drug administration without side effects or toxicity.

One Sentence Summary: Killing cancer cells in body with a gene therapy missile detonated by telomerase.
GPRIN1 modulates neuronal signal transduction and affects mouse-learning behavior
Authors: Savoia Claudia , Pujol Julien B , Vaucher Angelique , Marchi Umberto De , Rieker Claus , Heikkilä Eija , Núñez Galindo Antonio , Dayon Loïc , Dioum Elhadji M
Published: March 2018

In the adult and developing brain, G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) is a downstream effector for Gαo/i/z proteins that promotes neurite outgrowth. However, so far, the physiological role of GPRIN1 in brain health has not been reported. We generated a viable GPRIN1 whole-body knockout mouse to assess its physiological role in synaptic function both ex vivo and in vivo. In adult neurons, GPRIN1 is highly localized to the plasma membrane and synapses where it regulates neuronal signal transduction and Ca2+ homeostasis. Our results reveal that GPRIN1 might be a novel protein involved in agonist-stimulated cytoskeletal reorganization, which is crucial for early neuronal network development and in functionally mature neurons. Finally, we show that loss of GPRIN1 leads to a learning deficit in vivo and sensitizes neurons to stress, suggesting a modulatory role in brain health and disease.
Coding and non-coding RNA dysregulation in bipolar disorder
Authors: Luykx Jurjen J. , Giuliani F. , Giuliani G. , Veldink J.H.
Published: March 2018

The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. We found twenty genes, some of which not previously implicated in BPD, differentially expressed. PCR validation and replication confirmed the implication of these DE genes. Functional analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, we detected an overall increased number of alternative splicing events in BPD, as well as an increase in the number of genes carrying alternative splicing events. Finally, we report altered levels of two circular transcripts, cNEBL and cEPHA3. In conclusion, our non-coding RNA findings demonstrate that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.
A fungal ribonuclease-like effector protein inhibits plant host ribosomal RNA degradation
Authors: Pennington Helen G. , Jones Rhian , Kwon Seomun , Bonciani Giulia , Thieron Hannah , Chandler Thomas , Luong Peggy , Morgan Sian , Przydacz Michal , Bozkurt Tolga , Bowden Sarah , Craze Melanie , Wallington Emma , Garnett James , Kwaaitaal Mark , Panstruga Ralph , Cota Ernesto , Spanu Pietro D.
Published: March 2018

The biotrophic fungal pathogenBlumeria graminiscauses the powdery mildew disease of cereals and grasses. Proteins with a predicted ribonuclease (RNase)-like fold (termed RALPHs) comprise the largest set of secreted effector candidates within theB. graminisf. sp.hordeigenome. Their exceptional abundance suggests they play crucial functions during pathogenesis. We show that transgenic expression of RALPH CSEP0064/BEC1054 increases susceptibility to infection in monocotyledenous and dicotyledonous plants. CSEP0064/BEC1054 interactsin plantawith five host proteins: two translation elongation factors (eEF1α and eEF1γ), two pathogenesis-related proteins (PR5 and PR10) and a glutathione-S-transferase. We present the first crystal structure of a RALPH, CSEP0064/BEC1054, demonstrating it has an RNase-like fold. The protein interacts with total RNA and weakly with DNA. Methyl jasmonate levels modulate susceptibility to aniline-induced host RNA fragmentation.In plantaexpression of CSEP0064/BEC1054 reduces the formation of this RNA fragment. We propose that CSEP0064/BEC1054 is a pseudoenzyme that binds to host ribosomes, thereby inhibiting the action of plant ribosome-inactivating proteins that would otherwise lead to host cell death, an unviable interaction and demise of the fungus.
Hippocampal signature of associative memory measured by chronic ambulatory intracranial EEG
Authors: Henin Simon , Shankar Anita , Hasulak Nicolas , Friedman Daniel , Dugan Patricia , Melloni Lucia , Flinker Adeen , Sarac Cansu , Fang May , Doyle Werner , Tcheng Thomas , Devinsky Orrin , Davachi Lila , Liu Anli
Published: March 2018

Some patients with medically refractory focal epilepsy are chronically implanted with a brain-responsive neurostimulation device (the RNS® System), permitting neurophysiological measurements at millisecond resolution. This clinical device can be adapted to measure hippocampal dynamics time-locked to cognitive tasks. We illustrate the technique with a proof of concept in three patients previously implanted with the RNS System as they engage in an associative memory task, measured months apart. Hippocampal activity measured in successful encoding in RNS System patients mirrors that in surgical patients during intracranial electroencephalography (iEEG), suggesting that chronic iEEG allows sensitive measurements of hippocampal physiology over prolonged timescales.
Age dependence of systemic bone loss and recovery following femur fracture in mice
Authors: Emami Armaun J. , Toupadakis Chrisoula A. , Telek Stephanie M. , Fyhrie David P. , Yellowley Clare E. , Christiansen Blaine A.
Published: March 2018

The most reliable predictor of future fracture risk is a previous fracture of any kind. The etiology of this increased fracture risk is not fully known, but it is possible that fracture initiates systemic bone loss leading to greater fracture risk at all skeletal sites. In this study we investigated systemic bone loss and recovery following femoral fracture in young (3 month old) and middle-aged (12 month old) mice. Transverse femur fractures were created using a controlled impact, and whole-body bone mineral density (BMD), trabecular and cortical microstructure, bone mechanical properties, bone formation and resorption rates, mouse voluntary movement, and systemic inflammation were quantified at multiple time points post-fracture. We found that fracture led to decreased whole-body BMD in both young and middle-aged mice 2 weeks post-fracture; this bone loss was recovered by 6 weeks in young, but not middle-aged mice. Similarly, trabecular bone volume fraction (BV/TV) of the L5 vertebral body was significantly reduced in fractured mice relative to control mice 2 weeks post-fracture (−11% for young mice, −18% for middle-aged mice); this bone loss was fully recovered by 6 weeks post-fracture in young mice. At 3 days post-fracture we observed significant increases in serum levels of interleukin-6 and significant decreases in voluntary movement in fractured mice compared to control mice, with considerably greater changes in middle-aged mice than in young mice. At this time point we also observed increased osteoclast number on L5 vertebral body trabecular bone of fractured mice compared to control mice. These data show that systemic bone loss occurs after fracture in both young and middle-aged mice, and recovery from this bone loss may vary with age. This systemic response could contribute to increased future fracture risk following fracture, and these data may inform clinical treatment of fractures with respect to improving long-term skeletal health.
Cryptic selection forces and dynamic heritability in generalized phenotypic evolution
Authors: Gilpin William , Feldman Marcus W.
Published: March 2018

Individuals with different phenotypes can have widely-varying responses to natural selection, yet many classical approaches to evolutionary dynamics emphasize how a population’s average phenotype increases in fitness over time. However, recent experimental results have produced examples of populations that have multiple fitness peaks, or that experience frequency-dependence that affects the direction and strength of selection on certain individuals. Here, we extend classical fitness gradient formulations of natural selection in order to describe the dynamics of a phenotype distribution in terms of its moments—such as the mean, variance, skewness, etc. The number of governing equations in our model can be adjusted in order to capture different degrees of detail about the population. We compare our simplified model to direct Wright-Fisher simulations of evolution in several canonical fitness landscapes, we find that our model provides a low-dimensional description of complex dynamics not typically explained by classical theory, such as cryptic selection forces due to selection on trait ranges, time-variation of the heritability, and nonlinear responses to stabilizing or disruptive selection due to asymmetric trait distributions. In addition to providing a framework for extending general understanding of common qualitative concepts in phenotypic evolution—such as fitness gradients, selection pressures, and heritability—our approach has practical importance for studying evolution in contexts in which genetic analysis is infeasible.
Bayesian Inference for a Generative Model of Transcriptome Profiles from Single-cell RNA Sequencing
Authors: Lopez Romain , Regier Jeffrey , Cole Michael , Jordan Michael , Yosef Nir
Published: March 2018

Transcriptome profiles of individual cells reflect true and often unexplored biological diversity, but are also affected by noise of biological and technical nature. This raises the need to explicitly model the resulting uncertainty and take it into account in any downstream analysis, such as dimensionality reduction, clustering, and differential expression. Here, we introduce Single-cell Variational Inference (scVI), a scalable framework for probabilistic representation and analysis of gene expression in single cells. Our model uses variational inference and stochastic optimization of deep neural networks to approximate the parameters that govern the distribution of expression values of each gene in every cell, using a non-linear mapping between the observations and a low-dimensional latent space.

By doing so, scVI pools information between similar cells or genes while taking nuisance factors of variation such as batch effects and limited sensitivity into account. To evaluate scVI, we conducted a comprehensive comparative analysis to existing methods for distributional modeling and dimensionality reduction, all of which rely on generalized linear models. We first show that scVI scales to over one million cells, whereas competing algorithms can process at most tens of thousands of cells. Next, we show that scVI fits unseen data more closely and can impute missing data more accurately, both indicative of a better generalization capacity. We then utilize scVI to conduct a set of fundamental analysis tasks – including batch correction, visualization, clustering and differential expression – and demonstrate its accuracy in comparison to the state-of-the-art tools in each task. scVI is publicly available, and can be readily used as a principled and inclusive solution for multiple tasks of single-cell RNA sequencing data analysis.
Analysis of genome-wide differentiation between native and introduced populations of the cupped oystersCrassostrea gigasandCrassostrea angulata
Authors: Gagnaire Pierre-Alexandre , Lamy Jean-Baptiste , Cornette Florence , Heurtebise Serge , Dégremont Lionel , Flahauw Emilie , Boudry Pierre , Bierne Nicolas , Lapègue Sylvie
Published: March 2018

The Pacific cupped oyster is genetically subdivided into two sister taxa,Crassostrea gigasandC. angulata, which are in contact in the north-western Pacific. The nature and origin of their genetic and taxonomic differentiation remains controversial due the lack of known reproductive barriers and morphologic similarity. In particular, whether ecological and/or intrinsic isolating mechanisms participate to species divergence remains unknown. The recent co-introduction of both taxa into Europe offers a unique opportunity to test how genetic differentiation maintains under new environmental and demographic conditions. We generated a pseudo-chromosome assembly of the Pacific oyster genome using a combination of BAC-end sequencing and scaffold anchoring to a new high-density linkage map. We characterized genome-wide differentiation betweenC. angulataandC. gigasin both their native and introduced ranges, and showed that gene flow between species has been facilitated by their recent co-introductions in Europe. Nevertheless, patterns of genomic divergence between species remain highly similar in Asia and Europe, suggesting that the environmental transition caused by the co-introduction of the two species did not affect the genomic architecture of their partial reproductive isolation. Increased genetic differentiation was preferentially found in regions of low recombination. Using historical demographic inference, we show that the heterogeneity of differentiation across the genome is well explained by a scenario whereby recent gene flow has eroded past differentiation at different rates across the genome after a period of geographical isolation. Our results thus support the view that low-recombining regions help in maintaining intrinsic genetic differences between the two species.