bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast Cleavage Remodeling with Fat Grafting: A Safe Way to Optimize Symmetry and to Reduce Intermammary Distance
Authors: Serra-Mestre José Maria , Fernandez Peñuela Randolfo , Foti Vanessa , D’Andrea Francesco , Serra-Renom José Maria
Published: October 2017

Background:

In their descriptions of the ideal breast, most studies have focused primarily on the dimensions, shape, and proportions. The distance between the breasts has only very rarely been considered. The intermammary distance and the medial symmetry between the breasts are important parts of the outcome of surgery and have a strong bearing on patient satisfaction. However, the control surgeons have over these factors is only relative, and depends heavily on the underlying anatomical characteristics of the patients.

Methods:

Eighty-six patients undergoing breast augmentation, breast reduction, or mastopexy and breast reconstruction with separated or asymmetric breasts underwent fat grafting in the medial quadrants. Intermammary distances were measured before fat grafting and 12 months later. Complications were also recorded.

Results:

This technique obtained a statistically significant reduction in the mean intermammary distance (p < 0.0001) from 3 ± 0.6 cm (range, 1.6 to 5 cm) to 1.7 ± 0.4 cm (range, 1 to 2.8 cm) at 12-month follow-up. There were no major complications: one capsular contracture in a breast reconstruction requiring capsulotomy and an oil cyst requiring aspiration were reported.

Conclusion:

The authors’ technique allows safe remodeling of the medial cleavage of the breast, reducing the intermammary distance and optimizing the symmetry between the breasts.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Mixed Reality with HoloLens: Where Virtual Reality Meets Augmented Reality in the Operating Room
Authors: Tepper Oren M. , Rudy Hayeem L. , Lefkowitz Aaron , Weimer Katie A. , Marks Shelby M. , Stern Carrie S. , Garfein Evan S.
Published: October 2017

Virtual reality and augmented reality devices have recently been described in the surgical literature. The authors have previously explored various iterations of these devices, and although they show promise, it has become clear that virtual reality and/or augmented reality devices alone do not adequately meet the demands of surgeons. The solution may lie in a hybrid technology known as mixed reality, which merges many virtual reality and augmented realty features. Microsoft’s HoloLens, the first commercially available mixed reality device, provides surgeons intraoperative hands-free access to complex data, the real environment, and bidirectional communication. This report describes the use of HoloLens in the operating room to improve decision-making and surgical workflow. The pace of mixed reality–related technological development will undoubtedly be rapid in the coming years, and plastic surgeons are ideally suited to both lead and benefit from this advance.
Injection of Compressed Diced Cartilage in the Correction of Secondary and Primary Rhinoplasty: A New Technique with 12 Years’ Experience
Authors: Erol O. Onur
Published: October 2017

Background:

There are instances where small or large pockets are filled with diced cartilage in the nose, without use of wrapping materials. For this purpose, 1-cc commercial syringes were used. The obtained results were partial and incomplete. For better and improved results, the author designed new syringes, with two different sizes, which compress the diced cartilage for injection.

Methods:

The author presents his experience accrued over the past 12 years with 2366 primary, 749 secondary, 67 cleft lip and nose, and a total of 3182 rhinoplasties, using his new syringe design, which compresses diced cartilage and injects the diced cartilages as a conglutinate mass, simulating carved costal cartilage, but a malleable one.

Results:

In 3125 patients, the take of cartilage graft was complete (98.2 percent) and a smooth surface was obtained, giving them a natural appearance. In 21 patients (0.65 percent), there was partial resorption of cartilage. Correction was performed with touch-up surgery by reinjection of a small amount of diced cartilage. In 36 patients (1.13 percent), there was overcorrection that, 1 year later, was treated by simple rasping.

Conclusions:

Compared with diced cartilage wrapped with Surgicel or fascia, the amount of injected cartilage graft is predictable because it consists purely of cartilage. The injected diced cartilage, because it is compressed and becomes a conglutinated mass, resembles a wood chip and simulates carved cartilage. It is superior to carved cartilage in that it is moldable, time saving, and gives a good result with no late show or warping. The injection takes only a few minutes.
Intimate Partner Violence and Self-Reported Pre-exposure Prophylaxis Interruptions Among HIV-Negative Partners in HIV Serodiscordant Couples in Kenya and Uganda
Authors: Cabral Alejandra , M. Baeten Jared , Ngure Kenneth , Velloza Jennifer , Odoyo Josephine , E. Haberer Jessica , Celum Connie , Muwonge Timothy , Asiimwe Stephen , Heffron Renee ,   for the Partners Demonstration Project Team
Published: October 2017

Background:

Oral pre-exposure prophylaxis (PrEP) is effective for HIV prevention, and PrEP delivery studies are investigating ways to deliver PrEP with high adherence. However, in many settings with high HIV burden, intimate partner violence (IPV) is reported often and could be a barrier to the effective PrEP use. We examined the association between IPV and interruptions in PrEP use.

Methods:

We analyzed data from 1013 serodiscordant heterosexual couples enrolled in a large PrEP demonstration project in Kenya and Uganda, the Partners Demonstration Project. At quarterly study visits, HIV-negative participants receiving PrEP were asked about interruptions in their PrEP use and experiences with IPV. The association between IPV and PrEP interruptions was analyzed using multivariable generalized estimating equations.

Results:

At baseline and follow-up, there were 53 visits with reports of abuse by 49 HIV-negative partners, including physical, economic, and verbal IPV. Interruptions in PrEP use were reported at 328 visits (7.1% of all visits) by 249 people. The median length of PrEP interruption was 28 days (interquartile range: 7–45). The frequency of PrEP interruptions among those reporting IPV was 23.8% and those without IPV was 6.9%. PrEP interruption was significantly associated with IPV after adjustment for age and frequency of sexual intercourse (adjusted odds ratio = 2.6, 95% confidence interval: 1.2 to 6.0).

Conclusions:

IPV was more likely to be reported at visits when PrEP interruptions were also reported, which may have implications for sustained adherence to PrEP. Within PrEP delivery programs, there may be opportunities to assess individual safety and well-being to bolster adherence.
Unexpected Pyelonephritis Incidentally Revealed on 99mTc MDP Bone Scintigraphy
Authors: Zhao Xiaofei , Zhao Ruifang , Wu Ha
Published: October 2017

A 5-year-old girl had intermittent fever for 4 months. A 99mTc MDP bone scintigraphy was performed to evaluate possible occult osteomyelitis, which revealed no bone lesion. However, abnormal MDP activity in the upper poles of both kidneys was noted, which was confirmed as pyelonephritis subsequently.
Focal Pulmonary Uptake on 99mTc-Sestamibi Parathyroid Scintigraphy Due to Iatrogenic Microembolism
Authors: Kou Ying , Shen Guohua , Ou Xiaohong , Huang Rui , Kuang Anren
Published: October 2017

A middle-aged woman underwent 99mTc-sestamibi parathyroid scintigraphy because of parathyroid disease, and a focal pulmonary uptake of 99mTc-sestamibi was incidentally found on both planar and SPECT/CT images without corresponding pulmonary abnormality on the CT images. After 10 days, a subsequent parathyroid scintigraphy revealed no pulmonary accumulation. Therefore, the pulmonary intense 99mTc-sestamibi focus that once appeared in the first scan might be an artifact of iatrogenic microembolism from injection site.
Aspiration Incidentally Detected by a Meckel Scintigraphy
Authors: Bai Xia , Fostitsch Johannes C. , Zhuang Hongming
Published: October 2017

Meckel scintigraphy with 99mTc-pertechnetate was performed in a 5-year-old boy to determine whether a Meckel diverticulum containing ectopic gastric mucosa caused bleeding. The images did not reveal focal activity characteristic of a Meckel diverticulum. Unexpectedly, activity in the tracheobronchial tree was visualized, consistent with aspiration of the radioactive saliva.
AIDS-Related Central Nervous System Toxoplasmosis With Increased 18F-Fluoroethyl-l-Tyrosine Amino Acid PET Uptake Due to LAT1/2 Expression of Inflammatory Cells
Authors: Hutterer Markus , Bumes Elisabeth , Riemenschneider Markus J. , Grosse Jirka , Hellwig Dirk , Galldiks Norbert , Langen Karl-Josef , Hau Peter
Published: October 2017

We report the case of a 40-year-old woman with a progressive right-sided hemiparesis. Standard MRI revealed a contrast-enhancing brain lesion within the left basal ganglia. 18Ffluoroethyl-l-tyrosine (18F-FET) PET showed a distinct tracer uptake (lesion-to-brain ratio [LBR]: LBRmax = 2.03, LBRmean = 1.68) with a significant larger metabolic lesion volume than contrast-enhancement in MRI, indicating cerebral glioma. Surprisingly, histopathologic analysis demonstrated central nervous system toxoplasmosis with pronounced inflammatory reaction (reactive astrogliosis, microglia activation, macrophage, and T-lymphocyte infiltration), which was associated with strong LAT1/LAT2/CD98 expression. In conclusion, inflammatory brain lesions, such as cerebral toxoplasmosis, represent a potential pitfall of 18F-FET PET mimicking a brain tumor.
Abdominal Splenosis Mimicking Peritoneal Metastasis in Prostate-Specific Membrane Antigen PET/CT, Confirmed With Selective Spleen SPECT/CT
Authors: Demirci Emre , Has Simsek Duygu , Kabasakal Levent , Mülazimoğlu Mehmet
Published: October 2017

68Ga–prostate-specific membrane antigen (PSMA) PET/CT is a rapidly evolving diagnostic technique to image prostate cancer. In contrast to the name PSMA, various tissues show 68Ga-PSMA uptake in PET/CT imaging. We present a case of a 68-year-old man with prostate cancer who underwent Ga-PSMA PET/CT. Along with metastatic lymph nodes, multiple nodular lesions within the peritoneal spaces of all 4 quadrants of the abdomen showed high PSMA expression. Because of a history of splenic rupture, a 99mTc-labeled heat-denatured erythrocyte scintigraphy and SPECT were performed. Peritoneal lesions showed high uptake, confirming widespread peritoneal splenosis.
Autogenous Partial Bone Chip Grafting on the Exposed Inferior Alveolar Nerve After Cystic Enucleation
Authors: Seo Mi Hyun , Eo Mi Young , Cho Yun Ju , Kim Soung Min , Lee Suk Keun
Published: October 2017

This prospective study evaluated the clinical effectiveness of the new approach of partial autogenous bone chip grafts for the treatment of mandibular cystic lesions related to the inferior alveolar nerve (IAN). A total of 38 patients treated for mandibular cysts or benign tumors were included in this prospective study and subsequently divided into 3 groups depending on the bone grafting method used: cystic enucleation without a bone graft (group 1), partial bone chip graft covering the exposed IAN (group 2), and autogenous bone graft covering the entire defect (group 3). We evaluated the symptoms, clinical signs, and radiographic changes using dental panorama preoperatively, immediate postoperatively, and at 1, 3, 6, and 12 months postoperatively. Radiographic densities were compared using Adobe Photoshop CS5 (Adobe Systems Inc., San Jose, CA). Repeated measures analysis of variance was used for statistical evaluation with SPSS 22.0 (SPSS Inc, Chicago, IL), and P < 0.05 was considered statistically significant.

Radiopacities were the most increased at 1 year postoperative in group 3; groups 2 and 3 did not show statistically significant differences, whereas groups 1 and 3 were statistically significant. In terms of radiographic bone healing with clinical regeneration of the exposed IAN, healing occurred in all patients, although the best healing was achieved in group 2.

This autogenous partial bone chip grafting procedure to cover the exposed IAN is suggested as a new surgical protocol for the treatment of cystic lesions associated with the IAN.
Myoepithelioma of the Soft Palate
Authors: Ata Nurdoğan
Published: October 2017

Myoepitheliomas are extremely rare salivary gland tumors. Myoepithelioma of salivary glands comprised only 1% of all salivary tumors, most commonly occurring in the parotid gland followed by the minor salivary glands in the oral cavity. Involvement of the soft palate is a rare occurrence. This tumor is usually benign, and its treatment is total lesion excision. Here, the author reports a case of myoepithelioma of the soft palate in a 42-year-old Turkish man. The mass was removed by local excision under general anesthesia. There was no recurrence during the follow-up period of 10 months.
Use of Simulation in Multimodal Researcher Training for Observational Studies
Authors: Pecanac Kristen E. , Rainbow Jessica G. , Doherty-King Barbara , Steege Linsey M.
Published: October 2017

Summary Statement

Researchers employing observational studies need to develop a coding scheme that is robust enough to measure behaviors of interest adequately. However, the more intricate the coding scheme, the more difficult it is for observers to code correctly and consistently. The purpose of this article is to describe the use of a simulation suite in a multimodal training approach to accommodate a complex coding structure and achieve observer agreement. The observer training included explanation of codes and technology, coding of simulation video, and observer-trainer hospital practice. The simulation video consisted of hypothetical nurse-patient scenarios filmed in a simulation suite that mimicked the hospital setting. Researchers should consider using simulation suites in their training programs to achieve observer agreement in observational studies of complex behaviors in the ever-changing clinical environment.
Is It safe? Nonoperative management of blunt splenic injuries in geriatric trauma patients
Authors: Trust Marc D. , Teixeira Pedro G. , Brown Lawrence H. , Ali Sadia , Coopwood Ben , Aydelotte Jayson D. , Brown Carlos V.R.
Published: October 2017

BACKGROUND

Because of increased failure rates of nonoperative management (NOM) of blunt splenic injuries (BSI) in the geriatric population, dogma dictated that this management was unacceptable. Recently, there has been an increased use of this treatment strategy in the geriatric population. However, published data assessing the safety of NOM of BSI in this population is conflicting, and well-powered multicenter data are lacking.

METHODS

We performed a retrospective analysis of data from the National Trauma Data Bank (NTDB) from 2014 and identified young (age < 65) and geriatric (age ≥ 65) patients with a BSI. Patients who underwent splenectomy within 6 hours of admission were excluded from the analysis. Outcomes were failure of NOM and mortality.

RESULTS

We identified 18,917 total patients with a BSI, 2,240 (12%) geriatric patients and 16,677 (88%) young patients. Geriatric patients failed NOM more often than younger patients (6% vs. 4%, p < 0.0001). On logistic regression analysis, Injury Severity Score of 16 or higher was the only independent risk factor associated with failure of NOM in geriatric patients (odds ratio, 2.778; confidence interval, 1.769–4.363; p < 0.0001). There was no difference in mortality in geriatric patients who had successful vs. failed NOM (11% vs. 15%; p = 0.22). Independent risk factors for mortality in geriatric patients included admission hypotension, Injury Severity Score of 16 or higher, Glasgow Coma Scale score of 8 or less, and cardiac disease. However, failure of NOM was not independently associated with mortality (odds ratio, 1.429; confidence interval, 0.776–2.625; p = 0.25).

CONCLUSION

Compared with younger patients, geriatric patients had a higher but comparable rate of failed NOM of BSI, and failure rates are lower than previously reported. Failure of NOM in geriatric patients is not an independent risk factor for mortality. Based on our results, NOM of BSI in geriatric patients is safe.

LEVEL OF EVIDENCE

Therapeutic, level IV.
Evidence-Based Interventions for Diabetic Heel Ulcers
Authors: Tiderencel Kelly A. , Brody Rebecca A.
Published: October 2017

Diabetes can increase a patient's risk for the development of a pressure ulcer. Specifically, diabetic heel ulcers require an interprofessional approach that includes nutritional care provided by a dietitian. Assessment of malnutrition risk, along with a review of macro- and micronutrient deficiencies, assists the dietitian in determining the most appropriate intervention for a diabetic patient with a heel ulcer. Standardized nutrition recommendations exist for the management of pressure ulcers; however, a need exists for further evidence to support these guidelines. This case report presents a patient with a diabetic heel ulcer and explores evidence-based nutrition management.
Implementing Evidence-Based Nutrition Practice Guidelines for Type 2 Diabetes Mellitus in Lebanon
Authors: Yahia Najat , Khoury Maya , Salloum Tania , Younes Rita , Saleh Mounzer , Myers Esther
Published: October 2017

Lebanon is a Middle Eastern country experiencing a surge in the prevalence of type 2 diabetes mellitus among adults. This pilot study evaluated the feasibility and outcomes of implementing the Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guidelines (EBNPGs) as part of medical care for patients newly diagnosed with type 2 diabetes mellitus. Seventy-five patients were recruited from 3 Lebanese hospitals, received nutrition care according to EBNPGs, and were followed up for 12 months. Patients achieved significant improvement in clinical outcomes between baseline and 3, 6, and 12 months. Further research is recommended to confirm the benefits of using EBNPGs.
Mechanochemical feedback and control of endocytosis and membrane tension
Authors: Thottacherry Joseph Jose , Kosmalska Anita Joanna , Elosegui-Artola Alberto , Pradhan Susav , Sharma Sumit , Singh Parvinder P. , Guadamillas Marta C. , Chaudhary Natasha , Vishwakarma Ram , Trepat Xavier , del Pozo Miguel A. , Parton Robert G. , Pullarkat Pramod , Roca-Cusachs Pere , Mayor Satyajit
Published: October 2017

Plasma membrane tension is an important factor that regulates many key cellular processes. Membrane trafficking is tightly coupled to membrane tension and can modulate the latter by addition or removal of the membrane. However, the cellular pathway(s) involved in these processes are poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin and clathrin-independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon reduction of tension. On the other hand, inhibition of the CG pathway results in lower membrane tension, while up regulation significantly enhances membrane tension. We find that vinculin, a well-studied mechanotransducer, mediates the tension-dependent regulation of the CG pathway. Vinculin negatively regulates a key CG pathway regulator, GBF1, at the plasma membrane in a tension dependent manner. Thus, the CG pathway operates in a negative feedback loop with membrane tension which leads to a homeostatic regulation of membrane tension.
OGT (O-GlcNAc Transferase) selectively modifies multiple residues unique to lamin A
Authors: Simon Dan N. , Wriston Amanda , Fan Qiong , Shabanowitz Jeffrey , Florwick Alyssa , Dharmaraj Tejas , Peterson Sherket B. , Gruenbaum Yosef , Carlson Cathrine R. , Grønning-Wang Line M. , Hunt Donald F , Wilson Katherine L.
Published: October 2017

The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, chromatin organization, and genome integrity. Mutations in LMNA cause >12 diseases, termed laminopathies. Lamins A and C are identical for their first 566 residues. However, they form distinct filaments in vivo with apparently distinct roles. We report that lamin A is O-GlcNAc modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified OGT enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385-646), with no detectable modification of lamin B1, lamin C, or ‘progerin’ (Δ50) tails. Using mass spectrometry, we identified 11 O-GlcNAc sites in a ‘sweet spot’ unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites. By contrast, O-GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson-Gilford progeria syndrome, and greatly reduced by deletion Δ35, suggesting this region is required for substrate recognition or modification by OGT in vitro. These results suggest OGT, an essential protein and master regulator, regulates partners or function(s) unique to lamin A that are lost in progeria.
FERMI: A novel method for sensitive detection of rare mutations in somatic tissue
Authors: Liggett L. Alexander , Sharma Anchal , De Subhajyoti , DeGregori James
Published: October 2017

With growing interest in monitoring mutational processes in normal tissues, tumor heterogeneity, and cancer evolution under therapy, the ability to accurately and economically detect ultra-rare mutations is becoming increasingly important. However, this capability has often been compromised by significant sequencing, PCR and DNA preparation error rates. Here, we describe FERMI (Fast Extremely Rare Mutation Identification) - a novel method designed to eliminate majority of these sequencing and library preparation errors in order to significantly improve rare somatic mutation detection. This method leverages barcoded targeting probes to capture and sequence DNA of interest with single copy resolution. The variant calls from the barcoded sequencing data then further filtered in a position-dependent fashion against an adaptive, context-aware null model in order to distinguish true variants. As a proof of principle, we employ FERMI to probe bone marrow biopsies from leukemia patients, and show that rare mutations and clonal evolution can be tracked throughout cancer treatment, including during historically intractable periods like minimum residual disease. Importantly, FERMI is able to accurately detect nascent clonal expansions within leukemias in a manner that may facilitate the early detection and characterization of cancer relapse.
3D Cell Nuclear Morphology: Microscopy Imaging Dataset and Voxel-Based Morphometry Classification Results
Authors: Kalinin Alexandr A. , Allyn-Feuer Ari , Ade Alex , Fon Gordon-Victor , Meixner Walter , Dilworth David , de Wet Jeffrey R. , Higgins Gerald A. , Zheng Gen , Creekmore Amy , Wiley John W. , Verdone James E. , Veltri Robert W. , Pienta Kenneth J. , Coffey Donald S. , Athey Brian D. , Dinov Ivo D.
Published: October 2017

Cell deformation is regulated by complex underlying biological mechanisms associated with spatial and temporal morphological changes in the nucleus that are related to cell differentiation, development, proliferation, and disease. Thus, quantitative analysis of changes in size and shape of nuclear structures in 3D microscopic images is important not only for investigating nuclear organization, but also for detecting and treating pathological conditions such as cancer. While many efforts have been made to develop cell and nuclear shape characteristics in 2D or pseudo-3D, several studies have suggested that 3D morphometric measures provide better results for nuclear shape description and discrimination. A few methods have been proposed to classify cell and nuclear morphological phenotypes in 3D, however, there is a lack of publicly available 3D data for the evaluation and comparison of such algorithms. This limitation becomes of great importance when the ability to evaluate different approaches on benchmark data is needed for better dissemination of the current state of the art methods for bioimage analysis. To address this problem, we present a dataset containing two different cell collections, including original 3D microscopic images of cell nuclei and nucleoli. In addition, we perform a baseline evaluation of a number of popular classification algorithms using 2D and 3D voxel-based morphometric measures. To account for batch effects, while enabling calculations of AUROC and AUPR performance metrics, we propose a specific cross-validation scheme that we compare with commonly used k-fold cross-validation. Original and derived imaging data are made publicly available on the project web-page: http://www.socr.umich.edu/projects/3d-cell-morphometry/data.html.
Climatic niche dynamics and its role in the insular endemism ofAnolislizards
Authors: Velasco Julian A. , Martinez-Meyer Enrique , Flores-Villela Oscar
Published: October 2017

We evaluated the tempo and mode of climatic niche evolution in the radiation of CaribbeanAnolislizards and the role of climate in shaping their exceptional insular endemism. Using phylogenetic comparative methods, climatic niche data and a calibrated phylogeny, we reconstructed climatic niche dynamics across time and space for CaribbeanAnolislizards. We found evidence of several instances of niche shifts through the CaribbeanAnolisradiation. Caribbean anole species have diversified mainly along a precipitation rather than a temperature gradient. Only a few lineages have colonized both cold and hot conditions. Furthermore, most of the single-island endemic species are climatically restricted to its native islands and a small set of species might the potential to colonize other islands given its climatic niche requirements. Overall, we found evidence that climate niche conservation has played a role structuring current insularAnolisendemism. The observed climatic dissimilarity across the Greater Antilles likely limit successful population establishment of potential exotic insular species.
Differentiable processing of objects, associations and scenes within the hippocampus
Authors: Dalton Marshall A. , Zeidman Peter , McCormick Cornelia , Maguire Eleanor A.
Published: October 2017

The hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive, with some theories emphasising associative processes and another proposing that scene construction is its primary role. To directly compare these accounts of hippocampal function in human males and females, we devised a novel mental imagery paradigm where different tasks were closely matched for associative processing and mental construction, but either did or did not evoke scene representations, and we combined this with high resolution functional MRI. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. The contrasting patterns of neural engagement could not be accounted for by differences in eye movements, mnemonic processing or the phenomenology of mental imagery. These results inform conceptual debates in the field by showing that the hippocampus does not seem to favour one type of process over another; it is not a story of exclusivity. Rather, there may be different circuits within the hippocampus, each associated with different cortical inputs, which become engaged depending on the nature of the stimuli and the task at hand. Overall, our findings emphasise the importance of considering the hippocampus as a heterogeneous structure, and that a focus on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.

Significance statement

The hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive. Here we used a novel mental imagery paradigm and high resolution fMRI to compare accounts of hippocampal function that emphasise associative processes with a theory that proposes scene construction as a primary role. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. We conclude that a greater emphasis on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.
Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression
Authors: Gould Peter D. , Domijan Mirela , Greenwood Mark , Tokuda Isao T. , Rees Hannah , Kozma-Bognar Laszlo , Hall Anthony J.W. , Locke James C.W.
Published: October 2017

The Arabidopsis circadian clock orchestrates gene regulation across the day/night cycle. Although a multiple feedback loop circuit has been shown to generate the 24h rhythm, it remains unclear how robust the clock is in individual cells, or how clock timing is coordinated across the plant. Here we examine clock activity at the single cell level across Arabidopsis seedlings over several days. Our data reveal robust single cell oscillations, albeit desynchronised. In particular, we observe two waves of clock activity; one going down, and one up the root. We also find evidence of cell-to-cell coupling of the clock, especially in the root tip. A simple model shows that cell-to-cell coupling and our measured period differences between cells can generate the observed waves. Our results reveal the spatial structure of the plant circadian clock and suggest that unlike the centralised mammalian clock, the clock has multiple points of coordination in Arabidopsis.
Characterizing the sub-second timescale strategies of fighting in zebrafish
Authors: Laan Andres , Iglesias-Julios Marta , de Polavieja Gonzalo G.
Published: October 2017

Most animals fight by repeating complex stereotypic behaviors, yet the internal structure of these behaviors has rarely been dissected in detail. We characterized the internal structure of fighting behaviors by developing a machine learning pipeline that measures and classifies the behavior of individual unmarked animals on a sub-second timescale. This allowed us to quantify several previously hidden features of zebrafish fighting strategies. We found strong correlations between the velocity of the attacker and the defender indicating a dynamic matching of approach and avoidance efforts consistent with the cumulative assessment model of aggression. While velocity matching was ubiquitous, the spatial dynamics of attacks showed phase-specific differences. Contest phase attacks were characterized by a paradoxical side-ways attraction of the retreating animal towards the attacker suggesting that the defender combines avoidance maneuvers with display maneuvers. Post-resolution attacks lacked display-like features and the the defender was avoidance-focused. From the perspective of the winner, game theory modeling further suggested that highly energetically costly post resolution attacks occurred because the winner was trying to increase its relative dominance over the loser. Overall, the rich structure of zebrafish motor coordination during fighting indicates a greater complexity and layering of strategies than has previously been recognized.
Power, false discovery rate and Winner’s Curse in eQTL studies
Authors: Huang Qin Qin , Ritchie Scott C. , Brozynska Marta , Inouye Michael
Published: October 2017

Investigation of the genetic architecture of gene expression traits has aided interpretation of disease and trait-associated genetic variants, however key aspects of expression quantitative trait (eQTL) study design and analysis remain understudied. We used extensive, empirically-driven simulations to explore eQTL study design and the performance of various analysis strategies. Across multiple testing correction methods, false discoveries of genes with eQTLs (eGenes) were substantially inflated when false discovery rate (FDR) control was applied to all tests, and only appropriately controlled using hierarchical procedures. All multiple testing correction procedures had low power and inflated FDR for eGenes whose causal SNPs had small allele frequencies using small sample sizes (e.g. frequency <10% in 100 samples), indicating that even moderately low frequency eQTL SNPs (eSNPs) in these studies are enriched for false discoveries. In scenarios with ≥80% power, the top eSNP was the true simulated eSNP 90% of the time, but substantially less frequently for very common eSNPs (minor allele frequencies >25%). Overestimation of eQTL effect sizes, so-called “Winner’s Curse”, was common in low and moderate power settings. To address this, we developed a bootstrap method (BootstrapQTL) which led to more accurate effect size estimation. These insights provide a foundation for future eQTL studies, especially those with sampling constraints and subtly different conditions.
ProLIF: a quantitative assay for investigating integrin cytoplasmic protein interactions and synergistic membrane effects on proteoliposomes
Authors: De Franceschi Nicola , Miihkinen Mitro , Hamidi Hellyeh , Alanko Jonna , Mai Anja , Picas Laura , Lévy Daniel , Mattjus Peter , Goult Benjamin T , Goud Bruno , Ivaska Johanna
Published: October 2017

Integrin transmembrane heterodimeric receptors control a wide range of biological interactions by triggering the assembly of large multiprotein complexes at their cytoplasmic interface. A diverse set of methods have been used to investigate cytoplasmic interactions between integrins and intracellular proteins. These predominantly consist of peptide-based pull-downs and biochemical immuno-isolations from detergent-solubilized cell lysates. However, quantitative methods to probe integrin-protein interactions in a more biologically relevant context where the integrin is embedded within a lipid bilayer have been lacking. Here we describe a technique called ProLIF (Protein-Liposome Iinenteractions by Flow cytometry) to reconstitute recombinant integrin transmembrane domain (TMD) and cytoplasmic tail (CT) fragments on liposomes as individual α or β subunits or as αβ heterodimers and, using flow cytometry, to rapidly and quantitatively measure protein interactions with these membrane-embedded integrins. Importantly, the assay can analyse binding of fluorescent proteins directly from cell lysates without further purification steps. By combining integrins with membrane lipids to generate proteoliposomes, the effects of membrane composition such as PI(4,5)P2 presence on protein recruitment to the integrin CTs can be analyzed. ProLIF requires no specific instrumentation, apart from a standard flow cytometer and can be applied to measure a broad range of membrane-dependent protein-protein interactions with the potential for high-throughput/multiplex analyses.
A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer
Authors: Liu Zhixian , Li Mengyuan , Jiang Zehang , Wang Xiaosheng
Published: October 2017

Background

Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed a comprehensive portrait of immunologic landscape of TNBC based on 2 large-scale breast cancer genomic data.

Methods

We compared expression levels of immune-related genes and gene-sets among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. Moreover, we explored the association of immune-related genes or gene-sets expression and survival prognosis in TNBC patients.

Results

We found that almost all analyzed immune-related gene-sets had significantly higher expression levels in TNBC than non-TNBC. These highly expressed gene-sets in TNBC included 15 immune cell type and function, human leukocyte antigen (HLA), cancer testis (CT), tumor-infiltrating lymphocytes (TILs), immune cell infiltrate, regulatory T (Treg) cells, immune checkpoint, cytokine and cytokine receptor, metastasis-promoting, pro-inflammatory and parainflammation (PI) gene-sets. Moreover, TP53-mutated, TNBC had significantly higher expression levels of the immune checkpoint, Treg, PI, and CT gene-sets, and lower expression levels of the immune cell infiltrate gene-set than TP53-wildtype TNBC. Furthermore, we found that elevated expression of most of the immune-related genes in TNBC was associated with the ER-status, while some were associated with both ER-and HER2-status. Elevated expression of the immune-related genes in TNBC was also associated with the high tumor mutation burden (TMB) in TNBC. Finally, elevated expression of the immune-related gene-sets was likely to be associated with better survival prognosis in TNBC.

Conclusions

Our findings suggest that TNBC is a breast cancer subtype with particularly strong immunogenicity, and therefore could be propitious to immunotherapeutic options.
Pathway-based polygenic risk implicates GO: 17144 drug metabolism in recurrent depressive disorder
Authors: Docherty Anna R. , Moscati Arden , Bigdeli T. Bernard , Edwards Alexis K. , Peterson Roseann , Yang Fuzhong , Adkins Daniel E. , Anderson John S. , Flint Jonathan , Kendler Kenneth S. , Bacanu Silviu-Alin
Published: October 2017

The Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic, with any top risk loci conferring a very small proportion of variance in case-control status (1). Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways have proved successful in treating MDD. However, it is possible that with information from PGC analyses, examining specific molecular pathway(s) implicated in MDD can further inform our study of molecular drug targets. Using a large case-control GWAS based on low-coverage whole genome sequencing (N = 10,640), we derived polygenic risk scores for MDD and for MDD specific to each of over 300 molecular pathways. We then used these data to identify sets of scores significantly predictive of case status, accounting for critical covariates. Over and above global polygenic risk for MDD, polygenic risk within the GO: 17144 drug metabolism pathway significantly predicted recurrent depression. In transcriptomic analyses, two pathway genes yielded suggestive signals at FDR q-values = .054: CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1). Because the neuroleptic carbamazepine is a known inducer of CYP2C19, future research might examine whether drug metabolism PRS has any influence on clinical presentation and treatment response. Overall, results indicate that pathway-based risk might inform treatment of severe depression. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
A review of the oxidation–pressure concept (OPC) and extended Zintl–Klemm concept (EZKC), and the emergence of the high-pressure Ni2In-type phase of lithium sulfide (Li2S) rationalized by reference to a newly defined stability enhancement ratio (S)
Authors: Vegas Angel , Jenkins H. Donald Brooke
Published: October 2017

Taking into account new experimental data [Barkalov et al. (2016). Solid State Sci.
61, 220–224] on the pressure-induced Ni2In phase of Li2S, at 30 GPa, three concepts related to high-pressure phase transitions are reviewed here. This paper firstly reviews evidence that chemical oxidation (by inclusion of oxygen atoms) can produce a similar effect to the application of physical high pressure and temperature, in an effect labelled as the oxidation–pressure concept. Secondly, the pressure-induced Ni2In phase of Li2S is the final phase in the double transition antifluorite → anticotunnite → Ni2In, as is observed in other alkali metal sulfides. This new phase for Li2S could be expected after knowledge of the high-pressure Cmcm phase of Li2SO4, which is a distortion of the hexagonal I-Na2SO4 phase, both having M
2S subarrays of the Ni2In-type. Thirdly, in order to clarify these links, a simple methodology is proposed for gauging the level of increased stability (by defining a stability enhancement ratio, S) when the extended Zintl–Klemm concept (EZKC) has been applied. The method uses relative values of the lattice potential energies estimated for Li2S and for the pseudo-lattice Ψ-BeS derived by applying the EZKC to Li2S, after which, Li2S can be reformulated as Li+[LiS]− ≡ Li+[Ψ-BeS].
Conformational and structural diversity of iridium dimethyl sulfoxide complexes
Authors: Ridgway Benjamin M. , Foi Ana , Corrêa Rodrigo S. , Bikiel Damian E. , Ellena Javier , Doctorovich Fabio , Di Salvo Florencia
Published: October 2017

Transition metal complexes containing dimethyl sulfoxide (DMSO) are important precursors in catalysis and metallodrugs. Understanding the solid-state supramolecular structure is crucial for predicting the properties and biological activity of the material. Several crystalline phases of DMSO-coordinated iridium anions with different cations, potassium (1a) and n-butylammonium (1b), were obtained and their structures determined by X-ray crystallography. Compound (1a) is present in two solvatomorphic forms: α and β; the β form contains disordered solvent water. In addition, the structures exhibit different rotamers of the trans-[IrCl4(DMSO)2]− anion with the trans-DMSO ligands being oriented in anti and gauche conformations. In consideration of these various conformers, the effects of the crystallized solvent and intermolecular interactions on the conformational preferences of the anion are discussed. In addition, density functional theory calculations were used to investigate the energies of the anions in the different conformations. It was found that hydrogen bonds between water and the DMSO complex stabilize the gauche conformation which is the least stable form of the trans-DMSO complex. Consequently, by controlling the number of hydrogen-bond donors and acceptors and the amount of water, it may be possible to obtain different solvatomorphs of clinically significant metallodrugs.
2-Amino-N-(2-chloropyridin-3yl)benzamide
Authors: Riad Noura M. , Zlotos Darius P. , Holzgrabe Ulrike
Published: October 2017

The title compound, C12H10ClN3O, is a condensation product of 3-amino-2-chloropyridine and ethyl 2-aminobenzoate in which the aromatic rings are almost coplanar [dihedral angle = 2.28 (9)°] and an intramolecular N—H...O hydrogen bond occurs. In the crystal, N—H...O and N—H...N hydrogen bonds link the molecules into (100) sheets.
Searching to bridge the gaps: a new typology of university-industry interaction
Authors: Schaeffer Paola Rücker , Dullius Andréia Cristina , Maldonado Rodrigues Rodrigo , Zawislak Paulo Antonio
Published: October 2017

Purpose

The purpose of this paper is to propose a new typology to leverage the different knowledge gaps existing between universities and industries. This new typology classifies interactions into training-oriented, diffusion-oriented, service-oriented, development-oriented, and research-oriented.

Design/methodology/approach

The Brazilian 2010 Census data available from the CNPq Research Group Directory were used to test the typology.

Findings

It was found that, among the five types of interactions proposed, the most frequent were the development-oriented (39 per cent), diffusion-oriented (23 per cent), and research-oriented (16 per cent) ones. These findings indicate that it is likely that university-industry (U-I) interactions have improved in terms of quality in an attempt to attain a joint higher technological development.

Originality/value

The paper provides the U-I interaction debate with a new perspective about the kinds of interactions that could effectively bridge the knowledge gaps between universities and industries, especially in a developing country context.
Managing innovation in the Argentinian nuclear sector
Authors: Cantero Javier , Gonzalez Natalia Lorena , Diaz Daiana
Published: October 2017

Purpose

The design, construction, and operation of a nuclear power plant (NPP) pose technological and R&D challenges for the organisations concerned. The purpose of this paper is to analyse the sources of innovation and the technological developments throughout the construction and commissioning processes for Atucha II NPP.

Design/methodology/approach

Studying a high-risk organisation that is reliable in practice poses several research questions the authors consider in this work. What kind of R&D processes can take place in a mature industry like the nuclear sector in Argentina? How have technological challenges been overcome since the restart of the completion phase of Atucha II NPP? Primary data were mostly gathered through semi-structured interviews. Grounded theory was the methodological approach adopted.

Findings

Multiple sources of technological developments arise, an incremental R&D pattern being the most salient. Atucha II NPP seems to be a case of network innovation in a triple helix innovation scheme led by the Argentinian state. In effect, one of the outcomes of the construction of the Atucha II NPP was the development of the Argentinian nuclear sector together with the development of organisational capabilities. In this sense, the third Argentine NPP follows the socio-technical path of the Argentine nuclear industry.

Originality/value

Too little is known about R&D processes in high reliability organisations (HROs), especially in the nuclear sector of a Latin American country such as Argentina as there seem to be no organisational studies analysing HROs’ impact on innovation, reliability, and economic development.