bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyprotein strategy for stoichiometric assembly of nitrogen fixation components for synthetic biology
Authors: Yang Jianguo , Xie Xiaqing , Xiang Nan , Tian Zhe-Xian , Dixon Ray , Wang Yi-Ping
Published: July 2018

Significance

The requirement of maintaining balanced expression of a large number of gene products represents a major challenge to the engineering of nitrogen fixation in cereal crops, necessitating reiterative combinatorial assembly cycles to optimize monocistronic gene expression. In this study, we have explored a “fuse-and-cleave” virus-derived polyprotein strategy to reduce gene numbers and achieve balanced expression of protein components required for nitrogenase biosynthesis and activity. After testing and regrouping assemblies on the basis of expression profiles, cleavage patterns, and activity, 14 essential genes were selectively assembled into 5 giant genes that enable growth on dinitrogen. This strategy has potential advantages, not only for transferring nitrogen fixation to plants, but also for the engineering of other complex systems of profound agronomic and ecological importance.
Inhibition of tumor–microenvironment interaction and tumor invasion by small-molecule allosteric inhibitor of DDR2 extracellular domain
Authors: Grither Whitney R. , Longmore Gregory D.
Published: July 2018

Significance

To effectively prevent cancer spread from primary tumor sites, new treatments need to target tumor cells, the cells and extracellular matrix within the tumor environment, and communicating pathways between these sites simultaneously. The collagen receptor discoidin domain receptor 2 (DDR2) has been implicated as such a target. Here, we describe the identification and characterization of a small molecule inhibitor of DDR2 that uniquely acts in an allosteric manner via the extracellular domain to selectively inhibit the action of DDR2 in tumor cells and tumor stromal cancer-associated fibroblasts. In experimental mouse models of breast cancer, WRG-28 inhibits DDR2 signaling and tumor cell invasion.
Prevalence of tornado-scale vortices in the tropical cyclone eyewall
Authors: Wu Liguang , Liu Qingyuan , Li Yubin
Published: July 2018

Significance

Tornado-scale vortices in the intense tropical cyclone eyewall have been speculated upon for more than two decades, but their small horizontal scale, their fast movement, and the associated severe turbulence make them very difficult to observe directly, except for the case of Hurricane Hugo (1989) in the Atlantic basin. Using the Advanced Weather Research and Forecast large eddy simulation framework with the unprecedented horizontal grid size of 37 m, the numerical experiment in this study confirms the existence of simulated tornado-scale vortices similar to the Hugo case in the turbulent eyewall boundary layer and further suggests that tornado-scale vortices are prevalent at the inner edge of the intense eyewall convection.
Mutations in the
Drosophila
tricellular junction protein M6 synergize with
Ras

V12

to induce apical cell delamination and invasion
Authors: Dunn Brandon S. , Rush Lindsay , Lu Jin-Yu , Xu Tian
Published: July 2018

Significance

Complications from metastasis are responsible for the majority of cancer-related deaths, yet we understand relatively little about how cells initiate metastasis and depart from their original tissues. To uncover the cellular and molecular mechanisms governing departure of a tumor cell from its tissue, we show here that, in a
Drosophila
cancer model, invasion can be initiated through apical delamination. Furthermore, this apical delamination occurs as a result of alterations in the junctions between three neighboring cells, termed “tricellular junctions.” This work provides evidence that apical delamination can initiate invasion in certain contexts and highlights the important role that tricellular junction integrity can play in this process.
Identification of a biologically active fragment of ALK and LTK-Ligand 2 (augmentor-α)
Authors: Reshetnyak Andrey V. , Mohanty Jyotidarsini , Tomé Francisco , Puleo David E. , Plotnikov Alexander N. , Ahmed Mansoor , Kaur Navjot , Poliakov Anton , Cinnaiyan Arul M. , Lax Irit , Schlessinger Joseph
Published: July 2018

Significance

The limited availability of the two ligands of the receptor tyrosine kinases ALK and LTK precluded the elucidation of their physiological roles and mechanism of action. In this report we describe two new approaches to produce full-length ALKAL2/AUG-α and an active variant lacking the N-terminal variable region. Detailed characterization of the primary structure and disulfide bridges using mass spectrometry demonstrates that the N-terminal variable region plays an important role in AUG-α dimerization and provides insight into the structural organization of a previously unknown augmentor fold. A variety of cellular experiments show that both AUG-α and its deletion mutant induce similar activation of ALK and LTK and stimulation neuronal differentiation of human neuroblastoma NB1 and rat pheochromocytoma PC12 cells.
Juvenile hormone-regulated alternative splicing of thetaimangene primes the ecdysteroid response in adult mosquitoes
Authors: Liu Pengcheng , Fu Xiaonan , Zhu Jinsong
Published: July 2018

Significance

Many physiological events in insects are controlled by both juvenile hormone (JH) and 20-hydroxyecdysone (20E). The presence of JH sometimes alters the nature of the 20E action, but the underlying mechanisms have not been fully elucidated. InAedes aegyptimosquitoes, four protein isoforms are generated by thetaimangene, which plays an indispensable role in the action of both JH and 20E. Our study indicates that different hormone responses demand distinct Taiman isoforms. Moreover, JH controls the formation of the Taiman isoforms that are specifically required for 20E-regulated gene expression after blood feeding. Therefore, this study discovers a previously unknown mode of JH action and provides insight into how JH influences cellular responses to 20E in insects.
Reduction of intermetallic compounds in ultrasonic-assisted semi-solid brazing of Al/Mg alloys
Authors: Xu Zhiwu , Li Zhengwei , Xu Lei , Yan Jiuchun
Published: July 2018

An ultrasonic-assisted semi-solid brazing method was used to control Mg/Al intermetallic compounds (IMCs). Zn–20.95Al, which has a large semi-solid temperature range of 60°C, was chosen as filler metal. Oxide films on the Al/Mg surfaces were removed despite the semi-solid state of the filler metal at 430°C. Al–Mg–Zn IMCs were observed inside the joint at 667 W and 5 s. The IMCs was reduced as ultrasonication time was prolonged. At high power of 1000 W, short ultrasonication time was needed to guarantee that no IMCs remained inside the joint. Otherwise, new IMCs formed because of serious cavitation erosion on substrates. Ultrasonication time of 20 s was unable to completely eliminate IMCs and solid phases at 423°C.
GSK3-β promotes calpain-1–mediated desmin filament depolymerization and myofibril loss in atrophy
Authors: Aweida Dina , Rudesky Inga , Volodin Alexandra , Shimko Eitan , Cohen Shenhav
Published: July 2018

Myofibril breakdown is a fundamental cause of muscle wasting and inevitable sequel of aging and disease. We demonstrated that myofibril loss requires depolymerization of the desmin cytoskeleton, which is activated by phosphorylation. Here, we developed a mass spectrometry–based kinase-trap assay and identified glycogen synthase kinase 3-β (GSK3-β) as responsible for desmin phosphorylation. GSK3-β inhibition in mice prevented desmin phosphorylation and depolymerization and blocked atrophy upon fasting or denervation. Desmin was phosphorylated by GSK3-β 3 d after denervation, but depolymerized only 4 d later when cytosolic Ca2+ levels rose. Mass spectrometry analysis identified GSK3-β and the Ca2+-specific protease, calpain-1, bound to desmin and catalyzing its disassembly. Consistently, calpain-1 down-regulation prevented loss of phosphorylated desmin and blocked atrophy. Thus, phosphorylation of desmin filaments by GSK3-β is a key molecular event required for calpain-1–mediated depolymerization, and the subsequent myofibril destruction. Consequently, GSK3-β represents a novel drug target to prevent myofibril breakdown and atrophy.
Aortic Root Dilatation Is Associated With Incident Cardiovascular Events in a Population of Treated Hypertensive Patients: The Campania Salute Network
Authors: Canciello Grazia , Mancusi Costantino , Losi Maria Angela , Izzo Raffaele , Trimarco Bruno , de Simone Giovanni , De Luca Nicola
Published: July 2018

BACKGROUND

Aortic root (AR) dimension (ARD) at the Valsalva sinuses has been associated with incident cardiovascular (CV) events in population-based studies, but this effect could be due to the association with increased left ventricular (LV) mass. There is also uncertainty on how to define clear-cut AR dilatation. Thus, we analyzed the Campania Salute Network (CSN) registry to (i) establish criteria for evaluation of ARD, (ii) propose cut-points for AR dilatation, and (iii) determine whether AR dilatation has prognostic value independent of LV hypertrophy (LVH).

METHODS

We analyzed hypertensive patients with available follow-up, in sinus rhythm and free of prevalent valvular and CV disease (n = 8,573). AR exceeding the 75th percentile of the AR z-score (Ao-Z) obtained by comparison with the value predicted by age, sex, and height (i.e., Ao-Z > 0.80) was considered dilated.

RESULTS

Patients with baseline-dilated ARD by Ao-Z were more likely to be younger, men, and obese and had higher baseline blood pressure (BP; all <0.02) but similar kidney function as those without ARD dilatation. In multivariable Cox regression model, dilated ARD predicted 36% increased rate of CV events, independently of older age, male sex, systolic BP, LVH, and class of antihypertensive medications used during follow-up (95% confidence interval: 1.07–1.71, P = 0.011).

CONCLUSIONS

In the context of a population of treated hypertensive patients, ARD defined by z-score of predicted values is an independent predictor of CV events regardless of LVH and other common confounders.

CLINICAL TRIALS REGISTRATION

Trial Number NCT02211365.
Gatifloxacin Pharmacokinetics/Pharmacodynamics–based Optimal Dosing for Pulmonary and Meningeal Multidrug-resistant Tuberculosis
Authors: Deshpande Devyani , Pasipanodya Jotam G , Srivastava Shashikant , Bendet Paula , Koeuth Thearith , Bhavnani Sujata M , Ambrose Paul G , Smythe Wynand , McIlleron Helen , Thwaites Guy , Gumusboga Mourad , Van Deun Armand , Gumbo Tawanda
Published: July 2018

Background

Gatifloxacin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB). The optimal dose is unknown.

Methods

We performed a 28-day gatifloxacin hollow-fiber system model of tuberculosis (HFS-TB) study in order to identify the target exposures associated with optimal kill rates and resistance suppression. Monte Carlo experiments (MCE) were used to identify the dose that would achieve the target exposure in 10000 adult patients with meningeal or pulmonary MDR-TB. The optimal doses identified were validated using probit analyses of clinical data from 2 prospective clinical trials of patients with pulmonary and meningeal tuberculosis. Classification and regression-tree (CART) analyses were used to identify the gatifloxacin minimum inhibitory concentration (MIC) below which patients failed or relapsed on combination therapy.

Results

The target exposure associated with optimal microbial kill rates and resistance suppression in the HFS-TB was a 0–24 hour area under the concentration-time curve-to-MIC of 184. MCE identified an optimal gatifloxacin dose of 800 mg/day for pulmonary and 1200 mg/day for meningeal MDR-TB, and a clinical susceptibility breakpoint of MIC ≤ 0.5 mg/L. In clinical trials, CART identified that 79% patients failed therapy if MIC was >2 mg/L, but 98% were cured if MIC was ≤0.5 mg/L. Probit analysis of clinical data demonstrated a >90% probability of a cure in patients if treated with 800 mg/day for pulmonary tuberculosis and 1200 mg/day for meningeal tuberculosis. Doses ≤400 mg/day were suboptimal.

Conclusions

Gatifloxacin doses of 800 mg/day and 1200 mg/day are recommended for pulmonary and meningeal MDR-TB treatment, respectively. Gatifloxacin has a susceptible dose-dependent zone at MICs 0.5–2 mg/L.
How Can Autonomy Be Maintained and Informal Care Improved for People With Dementia Living in Residential Care Facilities: A Systematic Literature Review
Authors: Boumans Jogé , van Boekel Leonieke C , Baan Caroline A , Luijkx Katrien G
Published: July 2018

Background and Objectives

For people with dementia living in residential care facilities, maintaining autonomy and receiving informal care are important. The objective of this review is to understand how caregiving approaches and physical environment, including technologies contribute to the maintenance of autonomy and informal care provision for this population.

Research Design and Methods

A literature review of peer-reviewed articles published between January 1995 and July 2017 was performed. Realist logic of analysis was used, involving context, mechanism and outcome configurations.

Results

Forty-nine articles were included. The improvement of the relationship between residents and formal/informal caregivers is important. This increases the knowledge (sharing) about the resident and contributes to their autonomy. A social, flexible, and welcoming attitude of the formal caregiver improves the provision of informal care. Specially designed spaces, for instance, therapeutic gardens, create activities for residents that remind them of themselves and contribute to their autonomy. Use of technologies reduces caregiver’s time for primary tasks and therefore enables secondary tasks such as interaction with the residents.

Discussion and Implications

The results revealed how residential care facilities could maintain autonomy of their residents and improve informal care delivery using caregiving approaches and the physical environment including technologies. The results are supporting toward each other in maintaining autonomy and also helped in enhancing informal care provision. For residential care facilities that want to maintain the autonomy of their residents and improve informal care delivery, it is important to pay attention to all aspects of living in a residential care facility.
Nighres: processing tools for high-resolution neuroimaging
Authors: Huntenburg Julia M , Steele Christopher J , Bazin Pierre-Louis
Published: July 2018

With recent improvements in human magnetic resonance imaging (MRI) at ultra-high fields, the amount of data collected per subject in a given MRI experiment has increased considerably. Standard image processing packages are often challenged by the size of these data. Dedicated methods are needed to leverage their extraordinary spatial resolution. Here, we introduce a flexible Python toolbox that implements a set of advanced techniques for high-resolution neuroimaging. With these tools, segmentation and laminar analysis of cortical MRI data can be performed at resolutions up to 500 μm in reasonable times. Comprehensive online documentation makes the toolbox easy to use and install. An extensive developer's guide encourages contributions from other researchers that will help to accelerate progress in the promising field of high-resolution neuroimaging.
The AGN luminosity fraction in merging galaxies
Authors: Dietrich Jamie , Weiner Aaron S , Ashby Matthew L N , Hayward Christopher C , Martínez-Galarza Juan Rafael , Ramos Padilla Andrés F , Rosenthal Lee , Smith Howard A , Willner S P , Zezas Andreas
Published: July 2018

Galaxy mergers are key events in galaxy evolution, often causing massive starbursts and fueling active galactic nuclei (AGNs). In these highly dynamic systems, it is not yet precisely known how much starbursts and AGNs, respectively, contribute to the total luminosity, at what interaction stages they occur, and how long they persist. Here we estimate the fraction of the bolometric infrared (IR) luminosity that can be attributed to AGNs by measuring and modeling the full ultraviolet to far-IR spectral energy distributions (SEDs) in up to 33 broad bands for 24 merging galaxies with the Code for Investigating Galaxy Emission. In addition to a sample of 12 confirmed AGNs in late-stage mergers, found in the Infrared Astronomical Satellite Revised Faint Source Catalog, our sample includes a comparison sample of 12 galaxy mergers from the Spitzer Interacting Galaxies Survey, mostly early stage. We also perform SED modeling of merger simulations to validate our methods, and we supplement the SEDs with mid-IR spectra of diagnostic lines obtained with Spitzer’s InfraRed Spectrograph. The estimated AGN contributions to the IR luminosities vary from system to system from 0 per cent up to ∼91 per cent but are significantly greater in the later-stage, more luminous mergers, consistent with what is known about galaxy evolution and AGN triggering.
Precision of VerifyNow P2Y12 Assessment of Clopidogrel Response in Patients Undergoing Cerebral Aneurysm Flow Diversion
Authors: Bender Matthew T , Zarrin David A , Campos Jessica K , Jiang Bowen , Chandra Arun , Vo Chau D , Caplan Justin M , Huang Judy , Tamargo Rafael J , Lin Li-Mei , Colby Geoffrey P , Coon Alexander L
Published: July 2018

Background

Dual antiplatelet therapy (DAT), most commonly with aspirin and Clopidogrel, is the standard of care for intracranial stenting, including flow diversion. Clopidogrel response varies by individual.

Objective

To investigate the real-world precision of VerifyNow P2Y12 assessment (Accumetrics, San Diego, California) of Clopidogrel response.

Methods

Using a prospectively-collected, IRB-approved cerebral aneurysm database 643 patients were identified who were treated with the Pipeline embolization device from 2011 to 2017. Patients with multiple P2Y12 assays drawn within a 24-h window were identified. A single patient could contribute multiple, independent sets. Levels drawn before a 5-d course of DAT and patients who received alternative antiplatelet agents were excluded. Therapeutic range was defined as platelet reaction units (PRU) 60–200.

Results

A total of 1586 P2Y12 measurements were recorded; 293 (46%) patients had more than one assay. One hundred forty (22%) patients had multiple P2Y12 measurements within 24 h. These patients accounted for 230 independent 24-h sets. The average P2Y12 fluctuation across all sets was 35 points; the 25th, 50th, and 75th percentiles were 12, 26, and 48 points, respectively. Of the 230 24-h sets of P2Y12 assays, 76% remained within their original therapeutic category: 100 (43%) all therapeutic, 54 (23%) all hypo-responsive, and 21 (9%) all hyper-responsive. Twenty-four percent of patients fluctuated between therapeutic categories when multiple P2Y12 assessments were drawn within a 24-h period: 29 (13%) between hypo-response and therapeutic, 23 (10%) between hyper-response and therapeutic, and 3 (1%) between hypo-response and hyper-response.

CONCLUSION

Our experience suggests P2Y12 is an often-imprecise measure, and this should be considered when utilizing P2Y12 levels for clinical decisions.
Comparison of Health-related Quality of Life Between Double-door Laminoplasty and Selective Laminoplasty for Degenerative Cervical Myelopathy, With a Minimum Follow-up of 5 Years
Authors: Hirota Ryosuke , Miyakoshi Naohisa , Yoshimoto Mitsunori , Hongo Michio , Hamada Shuto , Kasukawa Yuji , Oshigiri Tsutomu , Ishikawa Yoshinori , Iesato Noriyuki , Kudo Daisuke , Tanimoto Katsumasa , Terashima Yoshinori , Takebayashi Tsuneo , Shimada Yoichi , Yamashita Toshihiko
Published: July 2018

Study Design.

A retrospective analysis of prospectively collected multicenter observational data.

Objective.

The aim of this study was to compare the health-related quality of life (HR-QOL) of double-door laminoplasty (DDL) and selective laminoplasty (SL) in patients with degenerative cervical myelopathy (DCM) in two institutions, with a minimum follow-up of 5 years.

Summary of Background Data.

No study has compared DDL and SL regarding postoperative HR-QOL with a follow-up of more than 5 years.

Methods.

One-hundred ninety patients who underwent DDL (n = 77) or SL (n = 113) participated in this study. Short-form 36 (SF-36), Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), Neck Disability Index (NDI), and visual analog scale (VAS) values were compared between the groups.

Results.

Thirty-seven DDL and 52 SL patients were evaluated. The mean follow-up period was 8 years and the follow-up rate was 46.8%. No significant differences were found regarding age and JOA score at baseline. At the follow-up, there were no significant differences in SF-36, JOACMEQ, and VAS score, while the NDI score for headache and sleeping were higher in the SL group. After dividing the SL group into short and long SL subgroups, the long SL subgroup showed a significantly lower score in bodily pain in SF-36, lower and bladder function in JOACMEQ, and pain intensity, personal care, headaches, and sleeping in NDI compared with the other groups.

Conclusion.

No significant differences were found in SF-36, JOA score, and NDI, except for the NDI subscale of headache and sleeping. The subgroup analysis showed that the long SL group showed a decreased QOL compared with the short SL and DDL groups.

Level of Evidence: 3
Development and Validation of a Novel Survival Prediction Model in Patients With Spinal Metastasis From Non-small Cell Lung Cancer
Authors: Yang Minglei , Xu Wei , Liu Tielong , Yang Xinghai , Wang Peng , Wu Sujia , Wei Haifeng , Zhao Jian , Yang Cheng , Xiao Jianru
Published: July 2018

Study Design.

Retrospective study.

Objective.

The aim of this study was to develop a model for predicting survival of patients with non-small cell lung cancer (NSCLC) spinal metastasis and compare its accuracy with the existing scoring systems.

Summary of Background Data.

Spinal metastasis is commonly seen in advanced NSCLC and usually associated with poor survival prognosis.

Methods.

A total of 376 patients with NSCLC spinal metastases admitted to our institution from January 2010 to October 2016 were enrolled. They were randomly assigned at a 3:1 ratio to a training cohort (n = 282) and a validation cohort (n = 94). A nomogram for survival prediction was established by identifying and integrating significant prognostic factors, and then subjected to bootstrap validation in both training and validation cohorts. The discrimination was measured by concordance index (C-index). Predictive accuracy was compared with three existing models by the receiver-operating characteristic curve (ROC) and area under ROC in both training and validation cohorts.

Results.

Six independent prognostic factors including sex (P = 0.008), the presence of visceral metastasis (P = 0.008), the number of metastases in the vertebral body (P = 0.011), Frankel score (P < 0.001), d-dimer (P = 0.002), and sensitive epidermal growth factor receptor mutation (p < 0.001) were identified and entered into the nomogram. The calibration curves for probability of 3-, 6-, 12- and, 24-month overall survival showed good agreement between the predictive risk and the actual risk. The C-index of the nomogram was 0.708 (95% confidence interval [CI], 0.674–0.742) in the training cohort and 0.683 (95% CI, 0.619–0.747) in the validation cohort. Model comparison showed that this nomogram had better predictive accuracy than the Tomita et al, Tokuhashi et al, and Schwab et al scoring systems (P < 0.05 in the training cohort).

Conclusion.

We established and validated a novel nomogram that could be used to predict the survival outcome of patients with NSCLC spinal metastasis, thus helping clinicians in decision making and individualized care planning of such patients.

Level of Evidence: 4
Options for Failed Rotator Cuff Repair
Authors: Mannava Sandeep , Samborski Steven A. , Kenney Raymond J. , Maloney Michael D. , Voloshin Ilya
Published: July 2018

Failed rotator cuff repairs can pose a clinical challenge to the treating orthopedic surgeon. There are many nonsurgical and surgical options available to address the failed rotator cuff repair. Surgical options include revising the primary repair, partial or nonanatomic repair, tendon transfer, biological augmentation or use of tissue-engineered grafts for reconstruction, or total joint arthroplasty (typically with a modern reverse total shoulder arthroplasty system). The treating surgeon must assess the patient’s functional status, health status, and expectations in order to customize the appropriate treatment plan for addressing the failed rotator cuff repair. With the abundance of treatment options available, there is typically an adequate solution to help the patient regain function and experience less pain.
Incidence and Predictors of 30-Day Readmission Among Patients Hospitalized for Chronic Pancreatitis
Authors: Garg Sushil K. , Sarvepalli Shashank , Campbell James P. , Anugwom Chimaobi , Singh Dupinder , Wadhwa Vaibhav , Singh Rajeshwar , Sanaka Madhusudhan R.
Published: July 2018

Objectives

Chronic pancreatitis (CP) hospitalizations along with associated morbidity and costs are increasing. The goal of this study was to use the National Readmission Database to identify the incidence and risk factors for 30-day readmissions among patients with CP.

Methods

We performed a retrospective analysis of National Readmission Database from January 2013 to December 2013 to determine patient demographic and clinical characteristics predictive of 30-day hospital readmission for adult patients (aged >18 years) discharged with a principle diagnosis of CP. A survey logistic regression model was used to determine the predictive value of selected variables for 30-day readmission.

Results

In 2013, 12,545 admissions with primary diagnosis of CP were noted, and 30.4% were readmitted within 30 days. Cholecystectomy (odds ratio [OR], 0.53; P = 0.0024) or endoscopic retrograde cholangiopancreatography (OR, 0.70; P = 0.01) during index admission was associated with decreased all-cause readmissions. Pancreatectomy during index admission was associated with reduced (OR, 0.2; P = 0.0005) pancreatitis-related readmissions.

Conclusions

Hospital readmissions for CP are frequent and pose a significant healthcare burden. Performing cholecystectomy, endoscopic retrograde cholangiopancreatography, or pancreatectomy during index admission was associated with reduced odds of readmission.
Managing the Social Determinants of Health: Part II
Authors: Fink-Samnick Ellen
Published: July 2018

Behavioral Learning Objectives:

This article will:

Explore health care industry considerations for the social determinants of health (SDH).

Identify industry initiatives and reimbursement strategies.

Discuss SDH-focused assessment tools for professional case managers.

Present and apply the Comprehensive Case Management Path.

Primary Practice Settings(s):

Applicable to health and behavioral health settings where case management is practiced.

Findings/Conclusions:

When professional case managers use comprehensive assessments to inform their work with populations impacted by the SDH, barriers to care access can be more readily addressed (e.g., poverty, employment, housing insufficiency, health literacy, migration, and medication adherence). Initiatives, programming, and treatment plans can be advanced to provide target populations with individualized and appropriate intervention. Case management involvement can also be leveraged to coordinate and facilitate successful interprofessional team efforts (Casteneda, Holmes, Madrigal, DeTrinidad, Beyeler, & Quesada, 2015
;
Davis, 2016).

Implications for Case Management Practice:

Case managers must engage clients from a wholistic lens that reflects their standards of practice and accounts for all domains of assessment: medical, cognitive and behavioral, functional, and social. Comprehensive tools to guide a robust and exhaustive screening of issues and opportunities ensure more successful outcomes.
Elevated 68Ga-DOTATATE Activity in IgG4-Related Lymphadenopathy
Authors: Cheng Zhaoting , Song Shuang , Han Yunfeng , Zou Sijuan , Zhu Xiaohua
Published: July 2018

68Ga-DOTATATE PET/CT was performed in a 60-year-old man to detect culprit tumor responsible for tumor-induced osteomalacia (TIO). The images revealed multiple foci of abnormal activity in soft tissue lesion, which were not typical of tumor causing TIO in 68Ga-DOTATATE PET/CT. Considering other neoplastic processes, FDG PET/CT were subsequently performed, which showed all same lesions, although the lesions with highest activity were different between the scans. Pathological examination demonstrated that the patient experienced TIO caused by 1 lesion, but other lesions were due to IgG4-related lymphadenopathy.
Persistent Opioid Use Among Children, Adolescents, and Young Adults After Common Cleft Operations
Authors: Bennett Katelyn G. , Harbaugh Calista M. , Hu Hsou Mei , Vercler Christian J. , Buchman Steven R. , Brummett Chad M. , Waljee Jennifer F.
Published: July 2018

Background:

Surgical care represents an important source of opioid prescribing and chronic use, but rates of prolonged opioid use following pediatric procedures remain unclear. The authors describe the rates and risk factors for new persistent opioid use in patients after common cleft operations.

Methods:

The authors examined claims from the Truven Marketscan databases from January 1, 2010 to December 31, 2014. The authors included opioid-naive patients ages 8 to 25, who underwent 1 of 10 cleft-related procedures. Patients were considered opioid-naïve if they had no opioid prescription fills in the 11 months prior to the perioperative period. The authors obtained a random sample of age-matched, nonsurgical patients from the same dataset to be used as a control group. Included cleft patients had no procedural codes in the 6 months following surgery. All included patients filled an opioid prescription during the perioperative period, defined as 30 days before and 14 days after surgery. The primary outcome was new persistent opioid use, which is defined as continued opioid prescription fills between 90 and 180 days after the procedure.

Results:

This cohort included 2039 cleft patients and 2100 control patients. The incidence of new persistent opioid use following surgery was 4.4% and 0.1% in the control group. Higher odds of opioid use 3 months beyond surgery were associated with distractor placement (OR 5.34, CI 2.00–14.24, P = 0.001). Increasing age (OR 1.11, CI 1.04–1.17, P = 0.001) and presence of a gastrointestinal comorbidity (OR 7.37, CI 1.49–36.54, P = 0.014) were also associated with new persistent use.

Conclusions:

New persistent opioid use occurs after cleft-related procedures and could lead to chronic use in children, adolescents, and young adults.
The Double Thread Buried Nonincisional Blepharoplasty Technique
Authors: Jung Gyu Sik , Park Min Hyung
Published: July 2018

The nonincisional blepharoplasty technique is widely practiced because it is relatively simple, causes less scarring than the incisional technique, provides a quick recovery, and allows easy correction. Although various modified nonincisional techniques have been used to create a more natural appearance, complications such as loosening of the double fold and regression of the double fold line may still occur. So the authors introduce the double thread buried nonincisional blepharoplasty technique to reduce such complications. This study included 300 patients who underwent upper eyelid blepharoplasty between January 2016 and June 2017. Most patients displayed satisfactory aesthetic results, and no significant complications occurred, such as loosening of the double fold. There was no obvious regression of the double fold; however, of the patients who underwent surgery early, 1 patient required reoperation to correct loosening of the fold on one side during the follow-up period. One patient presented with a subcutaneous suture knot, and the knot was removed in the clinic. The double thread buried nonincisional blepharoplasty technique is a simple and less time-consuming method for a durable double fold and provides satisfactory aesthetic results.
Monocular Diplopia and Nondisplaced Inferior Rectus Muscle on Computed Tomography in a Pediatric Pure Orbital-Floor Fracture
Authors: Joganathan Varajini , Gupta Deepak , Beigi Bijan
Published: July 2018

Trapdoor fractures are common in children because of elastic nature of the pediatric bone. Clinical signs and radiological evidence in these cases may be minimal.

This study involves a 14-year-old girl who sustained blunt trauma to her left eye. Initial investigation, for pure orbital floor fracture included computerized tomography (CT scan) of the orbit, did not show any evidence of incarcerated rectus muscle. She had no limitation of extraocular movements nor enophthalmos. Following conservative treatment, she had a left persistent orbital pain and left monocular diplopia. This prompted a magnetic resonance imaging (MRI) of the orbit investigating soft tissue, which found fine partial muscle herniation through the self-sealed fracture needing surgical intervention.

Although an orbital CT imaging is preferrd, in this acute setting, magnetic resonance imaging should be considered to delineate the soft tissue anatomy in relation to a trapdoor fracture, especially when there are not cardinal associated physical symptoms with a trap door fracture such as restricted eye movement and enophthalmos. Mono-ocular diplopia can be noted as an associated symptom to prompt early surgical repair.
Citrated kaolin thrombelastography (TEG) thresholds for goal-directed therapy in injured patients receiving massive transfusion
Authors: Stettler Gregory R. , Sumislawski Joshua J. , Moore Ernest E. , Nunns Geoffrey R. , Kornblith Lucy Z. , Conroy Amanda S. , Callcut Rachael A. , Silliman Christopher C. , Banerjee Anirban , Cohen Mitchell J. , Sauaia Angela
Published: July 2018

INTRODUCTION

Goal-directed hemostatic resuscitation based on thrombelastography (TEG) has a survival benefit compared with conventional coagulation assays such as international normalized ratio, activated partial thromboplastin time, fibrinogen level, and platelet count. While TEG-based transfusion thresholds for patients at risk for massive transfusion (MT) have been defined using rapid TEG, cutoffs have not been defined for TEG using other activators such as kaolin. The purpose of this study was to develop thresholds for blood product transfusion using citrated kaolin TEG (CK-TEG) in patients at risk for MT.

METHODS

CK-TEG was assessed in trauma activation patients at two Level 1 trauma centers admitted between 2010 and 2017. Receiver operating characteristic (ROC) curve analyses were performed to test the predictive performance of CK-TEG measurements in patients requiring MT, defined as >10 units of red blood cells or death within the first 6 hours. The Youden Index defined optimal thresholds for CK-TEG-based resuscitation.

RESULTS

Of the 825 trauma activations, 671 (81.3%) were men, 419 (50.8%) suffered a blunt injury, and 62 (7.5%) received a MT. Patients who had a MT were more severely injured, had signs of more pronounced shock, and more abnormal coagulation assays. CK-TEG R-time was longer (4.9 vs. 4.4 min, p = 0.0084), angle was lower (66.2 vs. 70.3 degrees, p < 0.0001), maximum amplitude was lower in MT (57 vs. 65.5 mm, p < 0.0001), and LY30 was greater (1.8% vs. 1.2%, p = 0.0012) in patients with MT compared with non-MT. To predict MT, R-time yielded an area under the ROC curve (AUROC) = 0.6002 and a cut point of >4.45 min. Angle had an AUROC = 0.6931 and a cut point of <67 degrees. CMA had an AUROC = 0.7425, and a cut point of <60 mm. LY30 had an AUROC = 0.623 with a cut point of >4.55%.

CONCLUSION

We have identified CK-TEG thresholds that can guide MT in trauma. We propose plasma transfusion for R-time >4.45 min, fibrinogen products for an angle <67 degrees, platelet transfusion for MA <60 mm, and antifibrinolytics for LY30 >4.55%.

LEVEL OF EVIDENCE

Therapeutic study, level V.
Perceptual consciousness and cognitive access: an introduction
Authors: Fazekas Peter , Overgaard Morten
Published: July 2018

The problem of perceptual consciousness—the question of how our subjective experiences (colours as we see them; sounds as we hear them; tastes, etc., as we feel them) could be accounted for in terms of brain processes—is often regarded as the greatest unsolved mystery of our times. In recent literature, one of the most pressing questions in this regard is whether the neural basis of perceptual consciousness is independent of the neural basis of cognitive access mechanisms that make reporting and reflecting on conscious experiences possible. The Theme Issue focuses on this central problem of consciousness research and aims to contribute to the field by critically discussing state-of-the-art empirical findings, identifying methodological problems and proposing novel approaches.

This article is part of the theme issue ‘Perceptual consciousness and cognitive access’.
If perception is probabilistic, why does it not seem probabilistic?
Authors: Block Ned
Published: July 2018

The success of the Bayesian perspective in explaining perceptual phenomena has motivated the view that perceptual representation is probabilistic. But if perceptual representation is probabilistic, why does normal conscious perception not reflect the full probability functions that the probabilistic point of view endorses? For example, neurons in cortical area MT that respond to the direction of motion are broadly tuned: a patch of cortex that is tuned to vertical motion also responds to horizontal motion, but when we see vertical motion, foveally, in good conditions, it does not look at all horizontal. The standard solution in terms of sampling runs into the problem that sampling is an account of perceptual decision rather than perception. This paper argues that the best Bayesian approach to this problem does not require probabilistic representation.

This article is part of the theme issue ‘Perceptual consciousness and cognitive access'.
The relationship between attention and consciousness: an expanded taxonomy and implications for ‘no-report’ paradigms
Authors: Pitts Michael A. , Lutsyshyna Lydia A. , Hillyard Steven A.
Published: July 2018

Tensions between global neuronal workspace theory and recurrent processing theory have sparked much debate in the field of consciousness research. Here, we focus on one of the key distinctions between these theories: the proposed relationship between attention and consciousness. By reviewing recent empirical evidence, we argue that both theories contain key insights and that certain aspects of each theory can be reconciled into a novel framework that may help guide future research. Alternative theories are also considered, including attended intermediate-level representations theory, integrated information theory and higher order thought theory. With the aim of offering a fresh and nuanced perspective to current theoretical debates, an updated taxonomy of conscious and non-conscious states is proposed. This framework maps a wider spectrum of conscious states by incorporating contemporary views from cognitive neuroscience regarding the variety of attentional mechanisms that are known to interact with sensory processing. Whether certain types of attention are necessary for phenomenal and access consciousness is considered and incorporated into this extended taxonomy. To navigate this expanded space, we review recent ‘no-report’ paradigms and address several methodological misunderstandings in order to pave a clear path forward for identifying the neural basis of perceptual awareness.

This article is part of the theme issue ‘Perceptual consciousness and cognitive access'.
Dream experiences and the neural correlates of perceptual consciousness and cognitive access
Authors: Fazekas Peter , Nemeth Georgina
Published: July 2018

This paper approaches the debate whether perceptual consciousness requires cognitive access from the perspective of dream studies, and investigates what kind of findings could support the opposing views of this debate. Two kinds of arguments are discussed, one that claims that the hypoactivity of the dorsolateral prefrontal cortex in rapid eye movement sleep is directly relevant, and another that proposes that locating the neural correlates of dream experiences can indirectly inform the debate. It is argued that under closer reflection, neither the classical claim about dorsolateral prefrontal cortex hypoactivity nor the more recent emphasis on general posterior hot zone activity during dreaming stand up to scrutiny. White dreaming is identified as the phenomenon that, nevertheless, holds the most promise to have an impact on the debate. Going beyond the topic if studying dreams can contribute to this debate, it is argued that cognitive access is not a monolithic phenomenon, and its neural correlates are not well understood. There seems to be a relevant form of cognitive access that can operate in the absence of activity in the dorsolateral prefrontal cortex, and maybe also in the whole frontal region. If so, then exclusive posterior activation during conscious experiences might very well be compatible with the hypothesis that perceptual consciousness requires cognitive access.

This article is part of the theme issue ‘Perceptual consciousness and cognitive access'.
Why and how access consciousness can account for phenomenal consciousness
Authors: Naccache Lionel
Published: July 2018

According to a popular distinction proposed by the philosopher Ned Block in 1995, our conscious experience would overflow the very limited set of what we can consciously report to ourselves and to others. He proposed to coin this limited consciousness ‘Access Consciousness' (A-Cs) and to define ‘Phenomenal Consciousness’ as a much richer subjective experience that is not accessed but that would still delineate the extent of consciousness. In this article, I review and develop five major problems raised by this theory, and show how a strict A-Cs theory can account for our conscious experience. I illustrate such an A-Cs account within the global workspace (GW) theoretical framework, and revisit some seminal empirical findings and neuropsychological syndromes. In this strict A-Cs perspective, subjective reports are not conceived as the mere passive broadcasting of information to the GW, but as resulting from a dynamic and active chain of internal processes that notably include interpretative and belief attribution stages. Finally, I list a set of testable predictions, of unsolved questions and of some counterintuitive hypotheses.

This article is part of the theme issue ‘Perceptual consciousness and cognitive access’.
COMPASS: An Open-Source, General-Purpose Software Toolkit for Computational Psychiatry
Authors: Yousefi Ali , Paulk Angelique C. , Basu Ishita , Dougherty Darin D. , Eskandar Emad N. , Eden Uri T. , Widge Alik S.
Published: July 2018

Mathematical modeling of behavior during psychophysical tasks, referred to as “computational psychiatry”, could greatly improve our understanding of mental disorders. One barrier to broader adoption of computational methods is that they often require advanced programming skills. We developed the Computational Psychiatry Adaptive State-Space (COMPASS) toolbox, an open-source MATLAB-based software package. After specifying a few parameters in a small set of user-friendly functions, COMPASS allows the user to efficiently fit of a wide range of computational behavioral models. The model output can be analyzed as an experimental outcome or used as a regressor for neural data, and can be tested using goodness-of-fit methods. Here, we demonstrate that COMPASS can replicate two computational behavior analyses from different groups. COMPASS replicates and, in one case, slightly improves on the original modeling results. This flexible, general-purpose toolkit should accelerate the use of computational modeling in psychiatric neuroscience.
The role of rare copy number variants in depression
Authors: Kendall Kimberley M , Rees Elliott , Bracher-Smith Matthew , Riglin Lucy , Zammit Stanley , O’Donovan Michael C , Owen Michael J , Jones Ian , Kirov George , Walters James T R
Published: July 2018

The role of large, rare copy number variants (CNVs) in neurodevelopmental disorders is well-established,1–5 but their contribution to common psychiatric disorders, such as depression, remains unclear. We have previously shown that a substantial proportion of CNV enrichment in schizophrenia is explained by CNVs associated with neurodevelopmental disorders.6, 7 Depression shares genetic risk with schizophrenia8, 9 and is frequently comorbid with neurodevelopmental disorders10, 11, suggesting to us the hypothesis that if CNVs play a role in depression, neurodevelopmental CNVs are those most likely to be associated. We confirmed this in UK Biobank by showing that neurodevelopmental CNVs were associated with depression (24,575 cases, 5.87%; OR=1.36, 95% CI 1.22-1.51, p=1.61×10-8), whilst finding no evidence implicating other CNVs. Four individual neurodevelopmental CNVs increased risk of depression (1q21.1 duplication, PWS duplication, 16p13.11 deletion, 16p11.2 duplication). The association between neurodevelopmental CNVs and depression was partially explained by social deprivation but not by education attainment or physical illness.
Mechanical Behavior of Axonal Microtubules; the Effect of Fluid on the Rupture of Axonal Microtubules
Authors: Manuchehrfar Farid , Shamloo Amir
Published: July 2018

Axonal microtubules are dynamically instable bundles in the interior part of the axon. The dynamics of these bundles are of vital importance in the behavior of axon such as their degeneration. Each axon typically contains 10~100 microtubule bundles with average length of 4μm. These bundles are coated with cytoplasm and are cross linked with random number of tau proteins. In some circumstances such as acceleration or deceleration of head in space or during the strike, they are placed in tension which may cause rupture of these bundles or disconnection of tau protein cross links. Mechanical behavior and rupture modality of microtubule bundles are becoming more and more important recently. In our model, viscoelastic microtubule bundles constituted from several discrete masses connected to the neighboring mass with a standard linear solid (SLS), a spring damper model. In addition we take into account the effect of cytoplasm by Dissipative Particle Dynamic (DPD) to investigate the rupture nature and mechanical behavior of these bundles and the effect of cytoplasm on their mechanical behavior. We obtain these results for various amounts of suddenly applied end forces to the group of axonal microtubule bundles.