bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining Autologous and Prosthetic Techniques: The Breast Reconstruction Scale Principle
Authors: Taglialatela Scafati Salvatore , Cavaliere Annachiara , Aceto Bianca , Somma Francesco , Cremone Luigi
Published: January 2018

Background:

The latissimus dorsi (LD) flap remains a good option for immediate or delayed breast reconstruction. The main limitation of this flap is the small volume provided. To improve the reconstructed breast volume, the LD flap is usually combined with a breast implant. Recently, fat grafting to the LD flap was described to maximize flap volume and obtain a totally autologous breast reconstruction. We report our experience with hybrid breast reconstruction using both breast implants and fat-enriched latissimus dorsi (FELD) flaps.

Methods:

Between 2013 and 2016, 74 patients underwent breast reconstruction with FELD flaps only or FELD flaps combined with a breast implant. The LD flap was harvested as previously described. Donor sites for fat harvesting were chosen according to each patient’s natural fat distribution. Fat was harvested, centrifuged, and injected into the LD flap. After fat grafting, breast sizers were employed to determine the final breast volume when the addition of an implant was indicated.

Results:

Good cosmetic outcomes were achieved in all cases, with a mean follow-up of 2.1 years. No patients had cancer reoccurrences. Four patients experienced a seroma of the LD donor site, 1 had a breast hematoma, and 1 developed Baker grade III capsular contracture. One year postoperatively, a clinically relevant area of fat necrosis was observed in 1 patient and was surgically treated. Additional fat grafting sessions were required in 3 cases.

Conclusion:

In elected cases, a FELD flap alone or in combination with a small implant is a valuable technique for breast reconstruction surgery.
HIV Infection: Antepartum Treatment and Management
Authors: BERNSTEIN HELENE B. , WEGMAN ADAM D.
Published: January 2018

Human immunodeficiency virus (HIV) is a retrovirus which became pandemic in the early 1980s. Since its initial characterization, advancements in diagnosis and management have transformed HIV infection from a terminal diagnosis to a chronic, manageable condition. Effective antiretroviral therapy, acting at multiple steps in the viral lifecycle, durably suppresses viral replication, preserves maternal health and prevents mother to child HIV transmission. Here, we review the salient clinical and ethical considerations of managing HIV infection during pregnancy and delivery.
Impact of relational coordination on staff and patient outcomes in outpatient surgical clinics
Authors: Gittell Jody Hoffer , Logan Caroline , Cronenwett Jack , Foster Tina C. , Freeman Richard , Godfrey Marjorie , Vidal Dale Collins
Published: January 2018

Background:

Pressures are increasing for clinicians to provide high-quality, efficient care, leading to increased concerns about staff burnout.

Purpose:

This study asks whether staff well-being can be achieved in ways that are also beneficial for the patient’s experience of care. It explores whether relational coordination can contribute to both staff well-being and patient satisfaction in outpatient surgical clinics where time constraints paired with high needs for information transfer increase both the need for and the challenge of achieving timely and accurate communication.

Methodology/Approach:

We studied relational coordination among surgeons, nurses, residents, administrators, technicians, and secretaries in 11 outpatient surgical clinics. Data were combined from a staff and a patient survey to conduct a cross-sectional study. Data were analyzed using ordinary least squares and random effects regression models.

Results:

Relational coordination among all workgroups was significantly associated with staff outcomes, including job satisfaction, work engagement, and burnout. Relational coordination was also significantly associated with patients’ satisfaction with staff and their overall visit, though the association between relational coordination and patients’ satisfaction with their providers did not reach statistical significance.

Practice Implications:

Even when patient–staff interactions are relatively brief, as in outpatient settings, high levels of relational coordination among interdependent workgroups contribute to positive outcomes for both staff and patients, and low levels tend to have the opposite effect. Clinical leaders can increase the expectation of positive outcomes for both staff and their patients by implementing interventions to strengthen relational coordination.
Efficacy and Safety of Intensive Transcranial Magnetic Stimulation
Authors: Sverak Tomas , Ustohal Libor
Published: January 2018

Repetitive transcranial magnetic stimulation (rTMS) is customarily applied on a daily basis for prolonged periods of time for the treatment of psychiatric diseases. The process is demanding in terms of staff and patient time, and the onset of the effect is slow. Recently, intensive rTMS protocols have been introduced in which stimulation is applied to the same area more than once a day with a higher than standard number of pulses. This article reviews 16 articles to determine the safety and efficacy of such protocols. Intensive rTMS seems to be effective in various mental disorders. It appears to have, in general, the same adverse events as classic, long-term, daily rTMS, and it is largely well tolerated by the patients. One episode of depersonalization, one of increased suicidal thoughts, and two of induced mania were observed in the 16 studies reviewed. The advantages of intensive rTMS are in the possible acute effect of the stimulation and in the possible reduction in the time required to achieve remission in depression (and potentially other disorders). It remains uncertain whether intensive rTMS is more effective than sham stimulation or once-daily, long-term rTMS.
Dry Eye Assessment in Patients With Vitiligo
Authors: Erdur Sevil Karaman , Aydin Rukiye , Balevi Ali , Ozsutcu Mustafa , Kocabora Mehmet Selim
Published: January 2018

Purpose:

To evaluate tear osmolarity and tear film parameters in patients with vitiligo.

Methods:

A total of 25 eyes of 25 patients with vitiligo with periocular involvement (group 1), 30 eyes of 30 patients with vitiligo without periocular involvement (group 2), and 20 eyes of 20 controls (group 3) were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, tear film breakup time, scoring of ocular surface fluorescein staining using a modified Oxford scale, and tear osmolarity.

Results:

Mean tear osmolarity was 332 ± 16.3 mOsm/L in group 1, 308.8 ± 19.5 mOsm/L in group 2, and 286.3 ± 23.4 mOsm/L in group 3 (P < 0.001). There was no significant difference in Schirmer I test results among the 3 groups (16.5 ± 3.2 mm in group 1, 16.3 ± 4.7 mm in group 2, and 17.4 ± 4.2 mm in group 3) (P = 0.175). Tear film breakup time measurements in groups 1 (9.8 ± 3.5 seconds) and 2 (10.1 ± 4.3 seconds) were significantly lower than those in group 3 (18.5 ± 4.0 seconds) (P < 0.001). There was no significant difference among the 3 groups on the Oxford scale (0.04 ± 0.70 in group 1, 0.03 ± 0.33 in group 2, and 0.03 ± 0.20 in group 3) (P = 0.865). The mean Ocular Surface Disease Index score was significantly higher in groups 1 and 2 than in group 3 (42.1 ± 16.5 in group 1, 39.9 ± 17.3 in group 2, and 12.3 ± 11.6 in group 3) (P < 0.001).

Conclusions:

This study showed that vitiligo is associated with tear hyperosmolarity and tear film dysfunction. Patients with vitiligo with periocular involvement may be more prone to dry eye than those without ocular involvement.
The first episode of spontaneous bacterial peritonitis is a threat event in children with end-stage liver disease
Authors: Vieira Sandra M.G. , Schwengber Fernando P. , Melere Melina , Ceza Marília R. , Souza Melina , Kieling Carlos O.
Published: January 2018

Objective

Studies on native liver survival (NLS) after the first episode of spontaneous bacterial peritonitis (SBP) are rare. Our objective was to evaluate NLS in children up to 1 year after SBP.

Methods

A historical cohort study of 18 children followed after the first episode of SBP was conducted. NLS, in-hospital mortality, causes of death, and rate of multidrug-resistant organisms were reported.

Results

Biliary atresia was the most prevalent diagnosis (72.2%); all were Child–Pugh C, and the median age was 1.0 year. The probability of NLS was 77.8, 27.8, and 11.1% at 1, 3 and 6 months, respectively. At 9 months, no child had the native liver. In-hospital mortality was 38.9%, and the main causes of death were septic shock and acute-on-chronic liver failure. Escherichia coli was the predominant organism cultured. Multidrug-resistant organisms were not detected. The cumulative probability of NLS was 77.8% at 1 month, 27.8% at 3 months, and 11.1% at 6 months. At 9-month follow-up, none of children had their native liver. Ascites PMN count cell more than 1000 cells/mm3, positive ascites culture, and prolonged international normalized ratio reached a significant value as predictive factors of NLS and were selected for multivariate analysis. We did not identify independent predictors of survival.

Conclusion

Development of SBP was a late event in children and had a high effect on NLS.
The association of fatty pancreas with subclinical atherosclerosis in nonalcoholic fatty liver disease
Authors: Ozturk Kadir , Dogan Tolga , Celikkanat Serhat , Ozen Alptug , Demirci Hakan , Kurt Omer , Turker Turker , Yilmaz Yusuf , Uygun Ahmet
Published: January 2018

Introduction

Ectopic fat accumulation in many tissues has been shown to be a risk factor for developing cardiovascular disease. No study to date has investigated whether fatty pancreas plays a role in the development of subclinical atherosclerosis. We aimed to assess the relationship between fatty pancreas and subclinical atherosclerosis in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) and healthy controls.

Patients and methods

One hundred patients with biopsy-proven NAFLD and 38 healthy controls were included. Transabdominal ultrasonography examination was performed on all the cases with high-resolution ultrasonography (Acuson S3000) using 6 mHz convex probes. The measurements of carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) were performed to investigate the relationship between fatty pancreas and atherosclerosis.

Results

The rate of newly diagnosed DM and prediabetes in the NAFLD patients was 6 and 21%, respectively. Most of the patients with NAFLD (97%) were found to have an increased echogenicity of the pancreas at ultrasound examination. Grade of fatty pancreas was correlated positively with cf-PWV levels (P<0.05), whereas no correlation was found with CIMT (P>0.05). The presence of fatty pancreas was associated significantly with higher CIMT and cf-PWV levels (P<0.05). The results for cf-PWV and CIMT did not remain significant after adjustment for confounding factors. Although the levels of cf-PWV and CIMT increased with increasing grade of fatty pancreas, there was no significant association.

Conclusion

We have shown for the first time that fatty pancreas is a contributing factor for the development of atherosclerosis in patients with NAFLD. This study also confirms the strong association between NAFLD and fatty pancreas.
Progression of Chronic Pancreatitis to Pancreatic Cancer
Authors: Rashid Sumaira , Singh Nidhi , Gupta Surabhi , Rashid Safoora , Nalika Nandini , Sachdev Vikas , Bal Chandra Sekhar , Datta Gupta Siddhartha , Chauhan Shyam S. , Saraya Anoop
Published: January 2018

Objectives

Early detection of pancreatic ductal adenocarcinoma still remains a challenge. Patients with chronic pancreatitis (CP) have a markedly increased risk of pancreatic cancer. Mutations in oncogenes and/or tumor suppressor genes play a role in development of pancreatic ductal adenocarcinoma. This study assessed mutations in KRAS and p53 gene in blood as a screening tool for malignant transformation in CP patients.

Methods

This was a cohort, single-center study including 294 CP patients. DNA was isolated from plasma of CP patients, and KRAS mutations were identified using polymerase chain reaction–restriction fragment length polymorphism. Patients with positive KRAS mutation were screened for malignancy using positron emission tomography or endoscopic ultrasound. Mutations in p53 gene were analyzed by sequencing. Tissue samples from CP and pancreatic cancer patients were also tested for mutations in KRAS and p53 genes.

Results

The plasma samples of 64 CP patients were positive for KRAS mutation, and 4 had mutation in p53 gene also. No patient positive for KRAS mutation and/or p53 mutation was found to have malignant transformation.

Conclusion

Detection of KRAS or p53 mutation in plasma is not an effective screening tool for pancreatic cancer because accumulation of multiple mutations is required for malignant transformation in the pancreas.
The Case for Utilizing RNs in Medicare Annual Wellness Visits
Authors: Bogrett Heather , Carriel Maura
Published: January 2018

RNs in ambulatory practice must expand their role to assist primary care physicians meet the growing demands of the aging American population. This article explores the benefits of RNs performing annual wellness visits (AWVs) for Medicare patients. Having RNs conduct AWVs can decrease the workload of primary care providers, improve patient outcomes, contribute to the revenue of the practice, and elevate nursing standards in the ambulatory setting.
Patient Perception and Satisfaction Questionnaire for Microtia Reconstruction: A New Clinical Tool to Improve Patient Outcome
Authors: Cui Chunxiao , Li Yiyuan , Zhang Ruhong , Zhang Qun , Xu Zhicheng , Chiu Ernest S. , Xu Feng , Li Datao , Li Tianya , Chen Wei
Published: January 2018

Background:

Patients’ satisfaction is an increasingly important indicator for successful ear reconstruction surgeries. However, there is no scientifically sound patient-based outcome instrument in this field. This study aims at developing a patient-reported outcome measure for microtia reconstruction for investigating patients’ satisfaction and perception of reconstructed ear and clinical researches.

Methods:

The development of questionnaire included 3 stages. Traditional psychometric tests were used for analysis. At first stage, a preliminary version of the questionnaire was developed using qualitative methods, including interviews with 10 patients. At second stage, the questionnaire was field tested by survey of 76 patients. Redundant items were deleted; acceptability, reliability, and responsiveness were examined. At third stage, survey was conducted to another 94 patients with the shortened questionnaire to further evaluate the acceptability, reliability, and validity.

Results:

A questionnaire of 12 items for microtia reconstruction was developed. Results demonstrated the instrument satisfied the current criteria. The acceptability (missing data <1%, largest endorsement frequencies <60%), reliability (Cronbach alphas >0.80, item-total correlations >0.7, interitem correlation <0.8), validity (scale intercorrelations r = 0.59, low correlations with age and sex) of the questionnaire.

Conclusions:

The questionnaire is an acceptable, reliable, and validated outcome measure for evaluation of ear reconstruction esthetic outcomes in microtia patients. It could be used for further comparison studies and effectiveness studies.
Surgical Treatment of Synovial Chondromatosis in the Inferior Compartment of the Temporomandibular Joint With Articular Disc Involvement
Authors: Leite Pablo Cornelius Comelli , Tolentino Elen de Souza , Yamashita Amanda Lury , Iwaki Lilian Cristina Vessoni , Iwaki Filho Liogi
Published: January 2018

The authors report an unusual case of painful synovial chondromatosis originated in the inferior compartment of the temporomandibular joint (TMJ) with articular disc involvement in a 56-year-old woman with complaint of severe pain in the right preauricular region. Magnetic resonance images showed advanced destruction of the right articular disc anteriorly displaced, condylar erosion, and distinct nodules within an extremely expanded inferior joint compartment with large amount of fluid, as well as a large TMJ effusion. A scintigraphy showed elevated bone uptake in the right TMJ, demonstrating intense bone remodeling activity in the region. After a right internal maxillary artery embolization, the patient underwent open surgery. The intraoperative procedures, including articular disc removal, condylar remodeling, and replacement of the articular disc, are described in detail. Synovial chondromatosis of the TMJ is a rare disease, especially when it affects the inferior compartment and the articular disc. Initial diagnosis is challenging and imaging techniques (magnetic resonance imaging and scintigraphy) play an important role in identifying signs, making accurate diagnosis, and offering additional information not available with conventional imaging, such as TMJ inflammation or remodeling. In these patients, open surgery may be considered a definitive treatment, since the postoperative recurrence rate is very low.
Unusual Craniofacial Distraction
Authors: Greig Aina V.H. , Cutting Court B. , Levine Jamie , Grayson Barry , McCarthy Joseph G.
Published: January 2018

A retrospective Institutional Review Board-approved review was performed at the Institute of Reconstructive Plastic Surgery, NYU Langone Medical Center, of patients undergoing craniofacial distraction osteogenesis procedures using the rigid external distractor device between 2000 and 2010. Three particularly challenging cases were identified and are presented here.
Facing a New Face: An Interpretative Phenomenological Analysis of the Experiences of a Blind Face Transplant Patient and His Partner
Authors: Hendrickx Hannelore , Blondeel Phillip N. , Van Parys Hanna , Roche Nathalie A. , Peeters Patrick C. , Vermeersch Hubert F. , Rogiers Xavier , Van Lierde Kristiane , Lemmens Gilbert M. D.
Published: January 2018

Increasing evidence points to good functional, aesthetic, and psychosocial outcomes after face transplantation. However, research investigating how patients and their families subjectively experience the transplantation process is lacking thus far. This study aims to investigate the personal experiences of a blind face transplant patient and his partner. In-depth interviews exploring different experiences were conducted with both partners separately 20 months after face transplantation. The interviews were analyzed using interpretative phenomenological analysis. Seven themes were identified in both interviews: coping with the facial trauma, motivation for the face transplantation, outcomes of the face transplantation, acceptance of the new face, gratitude toward the donor family, relation to the medical team, and dealing with the media. Two further themes were only mentioned by the patient (coping with complications and coping with blindness) and one theme only by the partner (loss of choices). The results of this study increase our understanding of the transplantation process as experienced by a face transplant recipient and his partner. They may help to better inform professionals to optimize transplantation procedures or supportive interventions.
No Gains in Long-term Survival After Liver Transplantation Over the Past Three Decades
Authors: Rana Abbas , Ackah Ruth L. , Webb Gwilym J. , Halazun Karim J. , Vierling John M. , Liu Hao , Wu Meng-Fen , Yoeli Dor , Kueht Michael , Mindikoglu Ayse L. , Sussman Norman L. , Galván Nhu T. , Cotton Ronald T. , O’Mahony Christine A. , Goss John A.
Published: January 2018

Objective:

The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year.

Summary of Background Data:

Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success.

Methods:

We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression.

Results:

There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28–1.42] and 1991 to 1995 (HR 1.17, CI 1.13–1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P < 0.001).

Conclusion:

In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.
Mapping and dynamics of regulatory DNA in maturing seeds
Authors: Sullivan Alessandra M. , Arsovski Andrej A. , Thompson Agnieszka , Sandstrom Richard , Thurman Robert E. , Neph Shane , Johnson Audra K. , Sullivan Shawn T. , Sabo Peter J. , Neri Fidencio V. , Weaver Molly , Diegel Morgan , Nemhauser Jennifer L. , Stamatoyannopoulos John A. , Bubb Kerry L. , Queitsch Christine
Published: January 2018

The genome is reprogrammed during development to produce diverse cell types, largely through altered expression and activity of key transcription factors. The accessibility and critical functions of epidermal cells have made them a model for connecting transcriptional events to development in a range of model systems. In Arabidopsis thaliana and many other plants, fertilization triggers differentiation of specialized epidermal seed coat cells that have a unique morphology caused by large extracellular deposits of pectin. Here, we used DNase I-seq to generate regulatory landscapes of A. thaliana seeds at two critical time points in seed coat maturation, enriching for seed coat cells with the INTACT method. We found over 3000 developmentally dynamic regulatory DNA elements and explored their relationship with nearby gene expression. The dynamic regulatory elements were enriched for motifs for several transcription factors families; most notably the TCP family at the earlier time point and the MYB family at the later one. To assess the extent to which the observed regulatory sites in seeds added to previously known regulatory sites in A. thaliana, we compared our data to 11 other data sets generated with seven-day-old seedlings for diverse tissues and conditions. Surprisingly, over a quarter of the regulatory, i.e. accessible, bases observed in seeds were novel. Notably, in this comparison, development exerted a stronger effect on the plant regulatory landscape than extreme environmental perturbations, highlighting the importance of extending studies of regulatory landscapes to other tissues and cell types during development.
Genome-wide association study of 1 million people identifies 111 loci for atrial fibrillation
Authors: Nielsen Jonas B. , Thorolfsdottir Rosa B. , Fritsche Lars G. , Zhou Wei , Skov Morten W. , Graham Sarah E. , Herron Todd J. , McCarthy Shane , Schmidt Ellen M. , Sveinbjornsson Gardar , Surakka Ida , Mathis Michael R. , Yamazaki Masatoshi , Crawford Ryan D. , Gabrielsen Maiken E. , Skogholt Anne Heidi , Holmen Oddgeir L. , Lin Maoxuan , Wolford Brooke N. , Dey Rounak , Dalen Håvard , Sulem Patrick , Chung Jonathan H. , Backman Joshua D. , Arnar David O. , Thorsteinsdottir Unnur , Baras Aris , O’Dushlaine Colm , Holst Anders G. , Wen Xiaoquan , Hornsby Whitney , Dewey Frederick E. , Boehnke Michael , Kheterpal Sachin , Lee Seunggeun , Kang Hyun M. , Holm Hilma , Kitzman Jacob , Shavit Jordan A. , Jalife José , Brummett Chad M. , Teslovich Tanya M. , Carey David J. , Gudbjartsson Daniel F. , Stefansson Kari , Abecasis Goncalo R. , Hveem Kristian , Willer Cristen J.
Published: January 2018

To understand the genetic variation underlying atrial fibrillation (AF), the most common cardiac arrhythmia, we performed a genome-wide association study (GWAS) of > 1 million people, including 60,620 AF cases and 970,216 controls. We identified 163 independent risk variants at 111 loci and prioritized 165 candidate genes likely to be involved in AF. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans or mice (MYH6, NKX2-5, PITX2, TBC1D32, TBX5),1,2 or near genes important for striated muscle function and integrity (e.g. MYH7, PKP2, SSPN, SGCA). Experiments in rabbits with heart failure and left atrial dilation identified a heterogeneous distributed molecular switch from MYH6 to MYH7 in the left atrium, which resulted in contractile and functional heterogeneity and may predispose to initiation and maintenance of atrial arrhythmia.
The Tudor protein Veneno assembles the ping-pong amplification complex that 1 produces viral piRNAs in Aedes mosquitoes
Authors: Joosten Joep , Miesen Pascal , Pennings Bas , Jansen Pascal W.T.C. , Huynen Martijn A. , Vermeulen Michiel , Van Rij Ronald P.
Published: January 2018

TUDOR-domain containing proteins facilitate PIWI interacting (pi)RNA biogenesis in Drosophila melanogaster and other model organisms. In Aedes aegypti mosquitoes, a somatically active piRNA pathway generates piRNAs from viral RNA during acute infection with cytoplasmic RNA viruses. Viral piRNA biogenesis requires ping-pong amplification by the PIWI proteins Ago3 and Piwi5. We hypothesized that Tudor proteins are required for viral piRNA production and performed a knockdown screen targeting all Ae. aegypti Tudor genes. Knockdown of several Tudor genes resulted in reduced viral piRNA levels, with silencing of AAEL012437 having the strongest effect. This protein, which we named Veneno, associates directly with Ago3 in an sDMA-dependent manner and localizes in cytoplasmic foci reminiscent of piRNA processing granules of Drosophila. Veneno-interactome analyses reveal a network of co-factors including the orthologs of the Drosophila piRNA pathway components Vasa and Yb, which in turn interacts directly with Piwi5. We propose that Veneno assembles a multi-protein complex for ping-pong dependent piRNA production from exogenous viral RNA.
Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients
Authors: Rosanova M. , Fecchio M. , Casarotto S. , Sarasso S. , Casali A.G. , Pigorini A. , Comanducci A. , Seregni F. , Devalle G. , Bodart O , Boly M. , Gosseries O. , Laureys S. , Massimini M.
Published: January 2018

Unresponsiveness Wakefulness Syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and responsive to sensory stimuli. In these patients, Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) also reveals preserved cortical reactivity, but in most cases, the residual thalamocortical circuits fail to engage complex causal interactions, as assessed by the perturbational complexity index (PCI).

Another condition during which thalamocortical circuits are intact, active and reactive, yet unable to generate complex responses, is physiological non-rapid eye movement (NREM) sleep. The underlying mechanism is bistability: the tendency of cortical neurons to fall into a silent period (OFF-period) upon receiving an input.

Here we tested whether a pathological form of bistability may be responsible for loss of brain complexity in UWS patients. Time-frequency decomposition analysis of TMS/EEG responses in UWS patients revealed the occurrence of OFF-periods (detected as a transient suppression of high-frequency oscillations in the EEG) similar to the ones evoked by TMS in the cortex of healthy sleeping subjects. Pathological OFF-periods were detected in any cortical area, significantly impaired local causal interactions (as measured by PLF) and prevented the buildup of global complexity (as measured by PCI) in the brain of UWS patients.

Our results draw a first link between neuronal events (OFF-periods) and global brain dynamics (complexity) in UWS patients. To the extent that sleep-like bistability represents the common functional endpoint of loss of complexity, detecting its presence and tracking its evolution over time, may offer a valuable read-out to devise, guide and titrate therapeutic strategies aimed at restoring consciousness.
Unrelated Donor Selection for Stem Cell Transplants using Predictive Modelling
Authors: Sivasankaran Adarsh , Williams Eric , Maiers Martin , Cherkassky Vladimir
Published: January 2018

Unrelated Donor selection for a Hematopoietic Stem Cell Transplant is a complex multi-stage process. Choosing the most suitable donor from a list of Human Leukocyte Antigen (HLA) matched donors can be challenging to even the most experienced physicians and search coordinators. The process involves experts sifting through potentially thousands of genetically compatible donors based on multiple factors. We propose a Machine Learning approach to donor selection based on historical searches performed and selections made for these searches. We describe the process of building a computational model to mimic the donor selection decision process and show benefits of using the proposed model in this study.
Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits
Authors: Wang Min , Hancock Timothy P , Chamberlain Amanda J. , Vander Jagt Christy J. , Pryce Jennie E , Cocks Benjamin G , Goddard Mike E , Hayes Benjamin J
Published: January 2018

Background

Topological association domains (TADs) are chromosomal domains characterised by frequent internal DNA-DNA interactions. The transcription factor CTCF binds to conserved DNA sequence patterns called CTCF binding motifs to either prohibit or facilitate chromosomal interactions. TADs and CTCF binding motifs control gene expression, but they are not yet well defined in the bovine genome. In this paper, we sought to improve the annotation of bovine TADs and CTCF binding motifs, and assess whether the new annotation can reduce the search space for cis-regulatory variants.

Results

We used genomic synteny to map TADs and CTCF binding motifs from humans, mice, dogs and macaques to the bovine genome. We found that our mapped TADs exhibited the same hallmark properties of those sourced from experimental data, such as housekeeping gene, tRNA genes, CTCF binding motifs, SINEs, H3K4me3 and H3K27ac. Then we showed that runs of genes with the same pattern of allele-specific expression (ASE) (either favouring paternal or maternal allele) were often located in the same TAD or between the same conserved CTCF binding motifs. Analyses of variance showed that when averaged across all bovine tissues tested, TADs explained 14% of ASE variation (standard deviation, SD: 0.056), while CTCF explained 27% (SD: 0.078). Furthermore, we showed that the quantitative trait loci (QTLs) associated with gene expression variation (eQTLs) or ASE variation (aseQTLs), which were identified from mRNA transcripts from 141 lactating cows’ white blood and milk cells, were highly enriched at putative bovine CTCF binding motifs. The most significant aseQTL and eQTL for each genic target were located within the same TAD as the gene more often than expected (Chi-Squared test P-value ≤ 0.001).

Conclusions

Our results suggest that genomic synteny can be used to functionally annotate conserved transcriptional components, and provides a tool to reduce the search space for causative regulatory variants in the bovine genome.
Efficient neural decoding of self-location with a deep recurrent network
Authors: Tampuu Ardi , Matiisen Tambet , Ólafsdóttir H. Freyja , Barry Caswell , Vicente Raul
Published: January 2018

Place cells in the mammalian hippocampus signal self-location with sparse spatially stable firing fields. Based on observation of place cell activity it is possible to accurately decode an animal’s location. The precision of this decoding sets a lower bound for the amount of information that the hippocampal population conveys about the location of the animal. In this work we use a novel recurrent neural network (RNN) decoder to infer the location of freely moving rats from single unit hippocampal recordings. RNNs are biologically plausible models of neural circuits that learn to incorporate relevant temporal context without the need to make complicated assumptions about the use of prior information to predict the current state. When decoding animal position from spike counts in 1D and 2D-environments, we show that the RNN consistently outperforms a standard Bayesian model with flat priors. In addition, we also conducted a set of sensitivity analysis on the RNN decoder to determine which neurons and sections of firing fields were the most influential. We found that the application of RNNs to neural data allowed flexible integration of temporal context, yielding improved accuracy relative to a commonly used Bayesian approach and opens new avenues for exploration of the neural code.

Author summary

Being able to accurately self-localize is critical for most motile organisms. In mammals, place cells in the hippocampus appear to be a central component of the brain network responsible for this ability. In this work we recorded the activity of a population of hippocampal neurons from freely moving rodents and carried out neural decoding to determine the animals’ locations. We found that a machine learning approach using recurrent neural networks (RNNs) allowed us to predict the rodents’ true positions more accurately than a standard Bayesian method with flat priors. The RNNs are able to take into account past neural activity without making assumptions about the statistics of neuronal firing. Further, by analyzing the representations learned by the network we were able to determine which neurons, and which aspects of their activity, contributed most strongly to the accurate decoding.
Mutational landscape of a chemically-induced mouse model of liver cancer
Authors: Connor Frances , Rayner Tim F. , Feig Christine , Aitken Sarah J. , Lukk Margus , Odom Duncan T.
Published: January 2018

Carcinogen-induced mouse models of liver cancer are used extensively to study the pathogenesis of the disease and have a critical role in validating candidate therapeutics. These models can recapitulate molecular and histological features of human disease. However, it is not known if the spectra of genomic alterations driving these mouse tumour genomes are comparable to those found in humans. Here, we provide a detailed characterisation of the exome-wide pattern of mutations in tumours from mice exposed to diethylnitrosamine (DEN), a commonly used model of hepatocellular carcinoma (HCC). DEN-initiated tumours had a high, uniform number of somatic single nucleotide variants (SNVs), with very few insertions, deletions or copy number alterations, consistent with the known genotoxic action of DEN. Exposure of hepatocytes to DEN left a reproducible mutational imprint in resulting tumour exomes which we could computationally reconstruct using six known COSMIC mutational signatures. The tumours carried a high diversity of low-incidence, non-synonymous point mutations in many oncogenes and tumour suppressors, reflecting the stochastic introduction of SNVs into the hepatocyte genome by the carcinogen. We identified four recurrently mutated genes that were putative oncogenic drivers of HCC in this model. Every neoplasm carried activating hotspot mutations either in codon 61 of Hras, in codon 584 of Braf or in codon 254 of Egfr. Truncating mutations of Apc occurred in 21% of neoplasms, which were exclusively carcinomas supporting a role for deregulation of Wnt/β-catenin signalling in cancer progression. Conclusion: Our study provides detailed insight into the mutational landscape of tumours arising in a commonly-used carcinogen model of hepatocellular carcinoma, facilitating the future use of this model to understand the human disease.
Long Noncoding RNA- Maternally Expressed Gene 3 Contributes to Hypoxic Pulmonary Hypertension
Authors: Xing Yan , Zheng Xiaodong , Fu Yao , Qi Jing , Li Minghui , Peng Haisheng , Wang Shuang , Li Shuzhen , Zhu Daling
Published: January 2018

The expression and function of long noncoding RNAs (lncRNAs) in the development of hypoxic pulmonary hypertension, especially in the proliferation of pulmonary artery smooth muscle cells (PASMCs) are largely unknown. Here, we characterized the expression of lncRNA-maternally expressed gene 3 (lncRNA-MEG3) was significantly increased and primarily located in the cytoplasm of PASMCs by hypoxia. LncRNA-MEG3 knockdown by lung-specific delivery of small interfering RNAs (siRNAs) significantly prevented the development of hypoxic pulmonary hypertension in vivo. Silencing of lncRNA-MEG3 by siRNAs and gapmers attenuated PASMC responses to hypoxia in vitro. Mechanically, we found that lncRNA-MEG3 acts as a molecular sponge of microRNA-328 (miR-328); upon hypoxia, lncRNA-MEG3 interacts and sequesters miR-328, leading to the upregulation of insulin-like growth factor 1 receptor (IGF1R). Additionally, higher expression of lncRNA-MEG3 and IGF1R, and lower expression of miR-328 were observed in PASMCs of iPAH patients. These data provide insight into the contribution of lncRNA-MEG3 in hypoxia pulmonary hypertension. Upregulation of lncRNA-MEG3 sequesters cytoplasmic miR-328, eventually leading to the expression of IGF1R, revealing a regulatory mechanism by lncRNAs in hypoxia-induced PASMC proliferation.
PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
Authors: Ronson George E. , Piberger Ann Liza , Higgs Martin R. , Olsen Anna L. , Stewart Grant S. , McHugh Peter J. , Petermann Eva , Lakin Nicholas D.
Published: January 2018

PARP1 regulates the repair of DNA single strand breaks (SSBs) generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whilst PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication associated DNA damage due to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and through stabilising replication forks that encounter BER intermediates.
Target Control in Logical Models Using the Domain of Influence of Nodes
Authors: Yang Gang , Zañudo Jorge G. T. , Albert Réka
Published: January 2018

Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control, and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system’s state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in logical models of biomolecular networks. Specifically, we define the domain of influence of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose domain of influence can cover the desired target node states. We perform greedy randomized adaptive search in state space to find such solutions. We apply our strategy to several biological networks to demonstrate its effectiveness.
Exhibition and preservation of non-fiction interactive and transmedia forms of expression
Authors: Gifreu-Castells Arnau
Published: January 2018

Purpose

The constant updating and unstoppable advance of technologies, mixing of platforms, programs and codes and the new trends in funding, among other factors, have led us to a present-future full of interactive, collaborative, participatory and co-creative digital artefacts and works. Games, experimental projects, short films and interactive video clips, in relation to fictional and non-fictional narrative, like documentary and journalism mainly, generate a complex body of works that depend on a series of compatibilities between technologies and languages to work properly and keep up with the times. The main purpose of this article is to analyse how the expression forms of interactive nonfiction narrative can be exhibited and preserved, looking at four main genres: documentary, journalism, museums and education.

Design/methodology/approach

At the methodological level, a study of analogue and digital forms in the proposed areas was performed, and a series of projects as case studies were analysed. In addition, a series of initiatives and institutions developing preservation methods are listed and ten effective strategies have been proposed to preserve interactive and transmedia nonfiction works.

Findings

The results make it possible to propose new ways of exhibiting and preserving valuable digital non-fiction works that need to be catalogued and safeguarded for the future.

Originality/value

For non-digital artistic forms of expression, copies were the main way of ensuring their preservation, but how does this process work for digital art forms? This area is a virgin field that urgently needs to be studied to determine and generate structures for preserving these types of works.
The obsessive and harmonious nature of entrepreneurial passion
Authors: Fisher Rosemary , Merlot Elizabeth , Johnson Lester W.
Published: January 2018

Purpose

The purpose of this paper is to examine the nature of entrepreneurial passion and in doing so explores the relationship between harmonious and obsessive passion (OP) and resilience. A pathway between passion and entrepreneurial success (ES) that is mediated by sustained entrepreneurial commitment (SEC) and resilience is tested.

Design/methodology/approach

An online questionnaire survey was completed by (n=215) Australian entrepreneurs. Results were based on structural equation modelling analysis.

Findings

Harmonious passion contributes directly and indirectly to perceptions of ES through resilience; OP contributes to SEC which contributes to success through resilience.

Research limitations/implications

Limitations stem from the survey methodology used. Implications for incorporating harmonious and OP into training to ensure well developed entrepreneurs are raised.

Originality/value

This study is one of the few studies to test the theoretical constructs of passion and resilience in the entrepreneurship context, and seemingly the first to do so on an Australian sample of entrepreneurs. This research finds that both types of passion are important to individual level resilience and ultimately to ES. An OP for one’s venture is an important contributor to persisting with the venture.
Identifying groups of entrepreneurial activities at universities
Authors: Fuller Daniel , Pickernell David
Published: January 2018

Purpose

The purpose of this paper is to identify whether the entrepreneurial activities of universities in the UK can be statistically grouped together.

Design/methodology/approach

This paper is performing a principal component analysis (PCA) of the 2009/2010 UK Higher Education Business and Community Interaction Survey (HE-BCIS) data for the third stream activities of universities in the UK.

Findings

The PCA of the 144 included institutions identified four groups of entrepreneurial activities being engaged in by universities in the UK. Three of the four groups were related to spin-offs, labelled as “Staff Spin-off Activity”, “Non-HEI Owned Spin-Off Activity” and “Graduate Start-up Activity”. The remaining factor has been named “University Knowledge Exploitation Activity (UKEA)” and encompasses a wide range of university knowledge creation, exchange and exploitation activities.

Research limitations/implications

The research indicates, through a ranking system for each university for the various groups of entrepreneurial activities, that universities are often entrepreneurial in just one or two of the groups of entrepreneurial activities identified by the PCA. Identifying what is causing those differences is required to further understand why we see this variation across the HE sector.

Originality/value

The use of a PCA to identify groups of entrepreneurial activities is a novel approach. Typically studies use a select few indicators, such as spin-offs or patents to analyse the entrepreneurial activities of universities. This study uses PCA to group together statistically related activities which can then be used to identify what is driving these groups of activities in future studies.
The power of peers
Authors: Bellò Benedetta , Mattana Veronica , Loi Michela
Published: January 2018

Purpose

Although the role of creativity in the entrepreneurial process has long been analysed, only recently scholars have begun addressing its influence on entrepreneurial intentions, showing that complex dynamics characterise this relationship. The purpose of this paper is to understand the surrounding mechanisms (moderation and mediation) that connect creativity to entrepreneurial intentions, with a focus on social context and entrepreneurial self-efficacy.

Design/methodology/approach

A structured questionnaire was administered to a sample of 507 students from 17 to 21 years old. The effect of creativity on entrepreneurial intentions and the moderating role of social context were tested with a three-step hierarchical regression, while the mediating effect of self-efficacy was tested by a multiple regression analysis based on the bootstrapping method.

Findings

The results reveal that: peers who encourage entrepreneurship moderate the relationship between creativity and entrepreneurial intentions by strengthening this relationship, and entrepreneurial self-efficacy mediates the relationship between creativity and entrepreneurial intentions.

Research limitations/implications

In light of these results, institutions should draw attention to how creative potential in students differs in order to provide new educational programmes to strengthen self-efficacy in entrepreneurial students and support encouraging social context of peers in which entrepreneurial intentions can be fostered.

Originality/value

The study, by responding to the suggestions of conducting research on the interface between creativity and entrepreneurship (Shane and Nicolaou, 2015), brings new empirical details regarding the mechanisms that link creativity to entrepreneurial intentions. Furthermore, it casts light on the interaction between dispositional and social variables, showing the crucial role of peers in enhancing the interaction between creativity and intentions.