bluuebunny/crossref_metadata_2025 huggingface dataset:
StructureMapper: a high-throughput algorithm for analyzing protein sequence locations in structural data
Authors: Nurminen Anssi , Hytönen Vesa P
Published: February 2018

Motivation

StructureMapper is a high-throughput algorithm for automated mapping of protein primary amino sequence locations to existing three-dimensional protein structures. The algorithm is intended for facilitating easy and efficient utilization of structural information in protein characterization and proteomics. StructureMapper provides an analysis of the identified structural locations that includes surface accessibility, flexibility, protein–protein interfacing, intrinsic disorder prediction, secondary structure assignment, biological assembly information and sequence identity percentages, among other metrics.

Results

We have showcased the use of the algorithm by estimating the coverage of structural information of the human proteome, identifying critical interface residues in DNA polymerase γ, profiling structurally protease cleavage sites and post-translational modification sites, and by identifying putative, novel phosphoswitches.

Availability and implementation

The StructureMapper algorithm is available as an online service and standalone implementation at http://structuremapper.uta.fi.

Supplementary information

Supplementary data are available at Bioinformatics online.
Novel aspects of the assembly and activation of inflammasomes with focus on the NLRC4 inflammasome
Authors: Fusco William G , Duncan Joseph A
Published: February 2018

Inflammasomes are multiprotein structures that activate caspase-1, support secretion of pro-inflammatory cytokines, IL-1β and IL-18, and also induce inflammatory programmed cell death, termed pyoptosis. Inflammasomes are activated in response to the detection of endogenous and microbially derived danger signals and are mediated by several classes of inflammasome-forming sensors. These include several nucleotide-binding proteins of the NOD-like receptor (NLR) family, including NLRP1, NLRP3 and NLRC4, as well as the proteins Absent in Melanoma 2 (AIM2) and Pyrin. Mutations in genes encoding some of these sensors have been found to be associated with gain-of-function monogenetic inflammatory disorders in humans. Genetic, biochemical and structural studies have begun to demonstrate how these proteins sense danger signals and to shed light on the step-by-step processes that are necessary for the assembly of inflammasomes, in both physiologic responses to pathogens and potentially in autoinflammatory conditions. Recent biochemical studies of pro-caspase-1 and an adapter protein known as ASC suggest that inflammasomes act to initiate self-generating effector filaments responsible for activating caspase-1 and initiating downstream signaling. These studies have suggested a model of molecular events from sensor activation to inflammasome formation that may describe processes that are universal to inflammasome formation.
Mechanisms controlling nucleic acid-sensing Toll-like receptors
Authors: Miyake Kensuke , Shibata Takuma , Ohto Umeharu , Shimizu Toshiyuki , Saitoh Shin-Ichiroh , Fukui Ryutaro , Murakami Yusuke
Published: February 2018

Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and TLR8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization. Trafficking of ligand-activated TLRs in endosomal and lysosomal compartments is requisite for production of type I interferons. Activation of NA-sensing TLRs is required for the control of viruses such as herpes simplex virus and endogenous retroviruses. On the other hand, excessive activation of NA-sensing TLRs drives disease progression in a variety of inflammatory diseases including systemic lupus erythematosus, heart failure, arthritis and non-alcoholic steatohepatitis. NA-sensing TLRs are targets for therapeutic intervention in these diseases. We here focus on our recent progresses in our understanding of NA-sensing TLRs.
Origin of Syrinx Fluid in Syringomyelia: A Physiological Study
Authors: Heiss John D , Jarvis Katie , Smith René K , Eskioglu Eric , Gierthmuehlen Mortimer , Patronas Nicholas J , Butman John A , Argersinger Davis P , Lonser Russell R , Oldfield Edward H
Published: February 2018

BACKGROUND

The origin of syrinx fluid is controversial.

OBJECTIVE

To elucidate the mechanisms of syringomyelia associated with cerebrospinal fluid pathway obstruction and with intramedullary tumors, contrast transport from the spinal subarachnoid space (SAS) to syrinx was evaluated in syringomyelia patients.

METHODS

We prospectively studied patients with syringomyelia: 22 with Chiari I malformation and 16 with SAS obstruction-related syringomyelia before and 1 wk after surgery, and 9 with tumor-related syringomyelia before surgery only. Computed tomography-myelography quantified dye transport into the syrinx before and 0.5, 2, 4, 6, 8, 10, and 22 h after contrast injection by measuring contrast density in Hounsfield units (HU).

RESULTS

Before surgery, more contrast passed into the syrinx in Chiari I malformation-related syringomyelia and spinal obstruction-related syringomyelia than in tumor-related syringomyelia, as measured by (1) maximum syrinx HU, (2) area under the syrinx concentration-time curve (HU AUC), (3) ratio of syrinx HU to subarachnoid cerebrospinal fluid (CSF; SAS) HU, and (4) AUC syrinx/AUC SAS. More contrast (AUC) accumulated in the syrinx and subarachnoid space before than after surgery.

CONCLUSION

Transparenchymal bulk flow of CSF from the subarachnoid space to syrinx occurs in Chiari I malformation-related syringomyelia and spinal obstruction-related syringomyelia. Before surgery, more subarachnoid contrast entered syringes associated with CSF pathway obstruction than with tumor, consistent with syrinx fluid originating from the subarachnoid space in Chiari I malformation and spinal obstruction-related syringomyelia and not from the subarachnoid space in tumor-related syringomyelia. Decompressive surgery opened subarachnoid CSF pathways and reduced contrast entry into syringes associated with CSF pathway obstruction.
100 Years of Bedsores: How Much Have We Learned?
Authors: Levine Jeffrey M.
Published: February 2018

Just over 100 years ago, an article was published describing a plan to treat decubitus ulcers that can shed light upon medical progress and current practices. Key prevention and treatment elements included a dedicated ward, staff continuity, frequent position changes and special surfaces, cleanliness, disinfectants, and dressing changes. The necessity of resource allocation and interdisciplinary collaboration was acknowledged. This article sheds light on not only how much we have learned, but also how far we have to go.
The Characterization of Plantar Skin Across Environmental Condition and Time
Authors: Wendland Deborah M. , Sprigle Stephen H.
Published: February 2018

OBJECTIVE:

In the presence of pathologic conditions such as diabetes or neuropathy and activity-related forces, the plantar surface of the foot is a common place for skin breakdown. With this risk, foundational knowledge of typical plantar skin behavior is needed. The purpose of this study was to characterize the plantar skin properties (tangential stiffness, normal compliance, and thickness) across environmental condition and time.

DESIGN AND SETTING:

Nonexperimental laboratory design.

PATIENTS:

Sixteen individuals participated (age range, 19–78 years; mean age, 48.5 ± 19.23 years; mean body mass index, 31.5 ± 7.61 kg/m2).

MAIN OUTCOME MEASURES:

Tangential stiffness, normal compliance, and thickness were assessed with the Tissue Interrogation Device (TID), Myotonometer, and ultrasound, respectively. Measurements were taken at 5 anatomic locations over 4 visits across a day (morning and afternoon), week, and month. Measurements were taken in standard (20° C to 24° C, 35%–50% relative humidity) and shoe conditions (32° C, 66% relative humidity).

MAIN RESULTS:

Tangential stiffness (P = .000), normal compliance (P = .000), and thickness (epidermis, P = .000; dermis, P = .044) all varied by location. No main effect differences were noted across visits or environment across devices. Reliability varied across visits.

CONCLUSIONS:

All 3 skin properties were found to vary across location and people. Given skin property consistency over time and device reliability, it is reasonable to take and compare measurements within a week. Environmental conditions should be reported and controlled in research assessing plantar skin.
The role of race in clinical decision making
Authors: Moscou Susan , Baker Serena
Published: February 2018

Is race/ethnicity useful in clinical decision making? This article uses a case example to discuss the role of race/ethnicity in clinical decision making, how racial/ethnic categories were developed, potential problems of using racial/ethnic categories, and the difference between risk factors and risk markers. The authors make the argument that using a patient's race/ethnicity in clinical decision making often results in a missed or incorrect diagnosis.
Effects of Varenicline Alone and in Combination With Low-dose Naltrexone on Alcohol-primed Smoking in Heavy-drinking Tobacco Users: A Preliminary Laboratory Study
Authors: Roberts Walter , Shi Julia M. , Tetrault Jeanette M. , McKee Sherry A.
Published: February 2018

Objectives:

Heavy-drinking tobacco users are less likely to successfully quit smoking than their moderate-drinking counterparts, even when they are prescribed smoking cessation medication. One strategy for improving treatment outcomes in this subgroup of tobacco users may be to combine medication therapies to target both alcohol and tobacco use simultaneously. Adding naltrexone to frontline smoking cessation treatments may improve treatment outcomes in this group.

Method:

This double-blind, placebo-controlled human laboratory study examined the effects of varenicline (2 mg/d) and varenicline (2 mg/d), combined with a low dose of naltrexone (25 mg/d) on alcohol-primed smoking behavior in a laboratory model of smoking relapse in heavy-drinking tobacco users (n = 30). Participants attended a laboratory session and received an alcohol challenge (target breath alcohol concentration = 0.030 g/dL). They completed a smoking delay task that assessed their ability to resist smoking followed by an ad libitum smoking phase (primary outcomes). They also provided ratings of subjective drug effects and craving, and carbon monoxide levels were measured after smoking (secondary outcomes).

Results:

Participants receiving varenicline monotherapy delayed smoking longer and smoked fewer cigarettes than those on placebo. Participants receiving varenicline + low-dose naltrexone did not delay smoking longer than those receiving varenicline alone. Participants in both active medication arms smoked fewer cigarettes ad libitum than those receiving placebo.

Conclusions:

Varenicline can improve smoking outcomes even after an alcohol prime, supporting its use in heavy drinkers who wish to quit smoking. Findings did not support increased efficacy of combined varenicline + low-dose naltrexone relative to varenicline monotherapy.
New Techniques for Diagnosis and Treatment of Musculoskeletal Tumors: Methods of Intraoperative Margin Detection
Authors: Catanzano Anthony A. , Ryan Sean P. , Lazarides Alexander L. , Brigman Brian E. , Eward William C.
Published: February 2018

Although frozen section analysis remains the standard for intraoperative margin detection for some cancers, there are critical limitations with using this method in the treatment of musculoskeletal tumors. Extensive work has been done to develop more accurate methods of intraoperative assessment of resection margins. Successful limb-salvage surgery requires adequate resection of tumor without excessive resection of normal tissue. Traditional imaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography scans have been adapted for use with computer navigation to provide more accurate intraoperative assessment and resection. However, these modalities are not without their own disadvantages, such as cost and availability. Newer technologies are being investigated to evaluate tumors intraoperatively at the microscopic and molecular level using spectroscopy and fluorescence imaging. Despite the promise of these intraoperative modalities, there are limited long-term outcome studies to validate their efficacy. In this symposium, we discuss the current advances in modalities for intraoperative margin assessment and their application in treating musculoskeletal tumors. In addition, we outline the existing evidence, albeit limited, of their short, and long-term successes.
New Nitric Oxide Donor NCX 1443: Therapeutic Effects on Pulmonary Hypertension in the SAD Mouse Model of Sickle Cell Disease
Authors: Abid Shariq , Kebe Kanny , Houssaïni Amal , Tomberli Françoise , Marcos Elisabeth , Bizard Emilie , Breau Marielle , Parpaleix Aurelien , Tissot Claire-Marie , Maitre Bernard , Lipskaia Larissa , Derumeaux Genevieve , Bastia Elena , Mekontso-Dessap Armand , Adnot Serge
Published: February 2018

Nitric oxide (NO) donors may be useful for treating pulmonary hypertension (PH) complicating sickle cell disease (SCD), as endogenous NO is inactivated by hemoglobin released by intravascular hemolysis. Here, we investigated the effects of the new NO donor NCX1443 on PH in transgenic SAD mice, which exhibit mild SCD without severe hemolytic anemia. In SAD and wild-type (WT) mice, the pulmonary pressure response to acute hypoxia was similar and was abolished by 100 mg/kg NCX1443. The level of PH was also similar in SAD and WT mice exposed to chronic hypoxia (9% O2) alone or with SU5416 and was similarly reduced by daily NCX1443 gavage. Compared with WT mice, SAD mice exhibited higher levels of HO-1, endothelial NO synthase, and PDE5 but similar levels of lung cyclic guanosine monophosphate. Cultured pulmonary artery smooth muscle cells from SAD mice grew faster than those from WT mice and had higher PDE5 protein levels. Combining NCX1443 and a PDE5 inhibitor suppressed the growth rate difference between SAD and WT cells and induced a larger reduction in hypoxic PH severity in SAD than in WT mice. By amplifying endogenous protective mechanisms, NCX1443 in combination with PDE5 inhibition may prove useful for treating PH complicating SCD.
Traits associated with central pain augmentation in the Knee Pain In the Community (KPIC) cohort
Authors: Akin-Akinyosoye Kehinde , Frowd Nadia , Marshall Laura , Stocks Joanne , Fernandes Gwen S. , Valdes Ana , McWilliams Daniel F. , Zhang Weiya , Doherty Michael , Ferguson Eamonn , Walsh David A.
Published: February 2018

This study aimed to identify self-report correlates of central pain augmentation in individuals with knee pain. A subset of participants (n = 420) in the Knee Pain and related health In the Community (KPIC) baseline survey undertook pressure pain detection threshold (PPT) assessments. Items measuring specific traits related to central pain mechanisms were selected from the survey based on expert consensus, face validity, item association with underlying constructs measured by originating host questionnaires, adequate targeting, and PPT correlations. Pain distribution was reported on a body manikin. A “central pain mechanisms” factor was sought by factor analysis. Associations of items, the derived factor, and originating questionnaires with PPTs were compared. Eight self-report items measuring traits of anxiety, depression, catastrophizing, neuropathic-like pain, fatigue, sleep disturbance, pain distribution, and cognitive impact were identified as likely indices of central pain mechanisms. Pressure pain detection thresholds were associated with items representing each trait and with their originating scales. Pain distribution classified as “pain below the waist additional to knee pain” was more strongly associated with low PPT than were alternative classifications of pain distribution. A single factor, interpreted as “central pain mechanisms,” was identified across the 8 selected items and explained variation in PPT (R
2 = 0.17) better than did any originating scale (R
2 = 0.10-0.13). In conclusion, including representative items within a composite self-report tool might help identify people with centrally augmented knee pain.
Better compliance with triage criteria in trauma would reduce costs with maintained patient safety
Authors: Linder Fredrik , Holmberg Lina , Eklöf Hampus , Björck Martin , Juhlin Claes , Mani Kevin
Published: February 2018

Objective

To evaluate trauma triage criteria in terms of compliance, undertriage, and overtriage and identify risk factors for mistriage.

Methods

In a retrospective cohort study, all consecutive trauma patients at a University Hospital in Sweden in 2012 were included. Patients were stratified into three groups on the basis of trauma team activation (full trauma team, limited trauma team, and no trauma team). Case records were reviewed for mechanism of injury, vital signs, and injuries. Compliance with alert criteria was evaluated and injury severity score combined with the Matrix method was used for assessment of overtriage and undertriage.

Results

A total of 1424 trauma patients were included in the study. Seventy-three (5.1%) patients activated a full trauma team, 732 (51.4%) a limited trauma team, and 619 (43.5%) did not activate any trauma team. Undertriage was 2.7% [95% confidence interval (CI): 1.9–3.8%] and overtriage was 34.2% (95% CI: 23.5–46.3%) in the complete cohort. Compliance with ‘trauma triage criteria’ was assessed by comparing actual alerts with what was estimated to be the correct alert levels on the basis of prehospital case records. Compliance with full trauma team criteria was 80% (68–88%), limited trauma team was 54% (51–58%), and no trauma team was 79% (76–82%). Assuming full compliance with trauma criteria, the Matrix method resulted in an undertriage of 2.3% (95% CI: 1.6–3.3%) and an overtriage of 42.6% (95% CI: 32.4–53.2%).

Conclusion

The overtriage and undertriage in this study is in line with the recommendations of the American College of Surgeons Committee on Trauma. However, better compliance with trauma alert criteria would result in fewer trauma team activations without affecting patient safety.
Accuracy of ultrasound exam performed by emergency medicine versus radiology residents in the diagnosis of acute appendicitis
Authors: Shahbazipar Marzieh , Seyedhosseini Javad , Vahidi Elnaz , Motahar Vahedi Hojat Sheikh , Jahanshir Amirhossein
Published: February 2018

Background

Although the traditional approach to the diagnosis of acute appendicitis (AA) is using clinical methods, experience has shown that strict reliance on clinical data can lead to mismanagement or unnecessary surgery.

Objective

The objective of this study was to determine the total agreement of ultrasound (US) results in AA performed by emergency medicine (EM) versus radiology residents in emergency department.

Patients and methods

In this cross-sectional study, 121 patients with AA suspicion underwent an US exam by both trained EM and radiology residents in emergency department. The training course for EM residents consisted of attending an 8-h-workshop and then practicing an US exam on real patients within a 2-month period. The gold standards were either histopathologic or follow-up results. Total agreement of the results in both specialties was compared.

Results

There were 67 men and 54 women, with a mean age of 33.6 ± 16.1 years (18.2–88.7 years). Fifty-four (44.6%) patients underwent surgery with the initial diagnosis of AA and the rest were evaluated by follow-ups. On the basis of our gold standards, the diagnosis was finally confirmed in 46 (38%) cases. There was a high total agreement in AA diagnosis [96% agreement, κ = 0.90; 95% confidence interval (CI) = 0.81–0.99] between the two groups. The specificity and sensitivity of EM and radiology groups were 99% (95% CI = 93–100), 63% (95% CI = 48–77), 97% (95% CI = 91–100), and 72% (95% CI = 57–84), respectively.

Conclusion

US has a high diagnostic specificity in patients suspected of having AA and EM residents can perform this modality as accurately as radiologists after training in the emergency setting.
Intravenous Lidocaine for Intractable Renal Colic Unresponsive to Standard Therapy
Authors: Sin Billy , Cao John , Yang David , Ambert Karen , Punnapuzha Sheena
Published: February 2018

Clinical Features:

Renal colic is defined as a flank pain radiating to the groin caused by kidney stones in the ureter (urolithiasis). Renal colic is a frequent cause of Emergency Department visits. Most renal colic cases present as acute distress and severe back and/or abdominal pain that require prompt treatment with analgesics.

Therapeutic Challenge:

Nonsteroidal anti-inflammatory drugs and opioids are traditionally used for renal colic in the Emergency Department. This trend of practice is based on clinical experience and expert opinion. Consensus guidelines that provide evidence-based approach for the management of renal colic are limited. One consensus guideline from Europe provides a systematic approach for the management of pain with the use of nonsteroidal anti-inflammatory drugss and opioids. However, no guidance is provided on how to manage patients who do not respond to these agents.

Solution:

Intravenous lidocaine 120 mg in 100 mL normal saline was infused over 10 minutes for pain management for intractable renal colic unresponsive to standard therapy. Three minutes after initiation of lidocaine infusion, the patient reported numeric pain rating scale 1/10. At 5 minutes, the reported numeric pain rating scale was 0/10 and remained for 60 minutes after initiation of lidocaine infusion. No adverse events were reported during or after the infusion, and no subsequent analgesia was required.
Defining and Assessing Geriatric Risk Factors and Associated Health Care Utilization Among Older Adults Using Claims and Electronic Health Records
Authors: Kan Hong J. , Kharrazi Hadi , Leff Bruce , Boyd Cynthia , Davison Ashwini , Chang Hsien-Yen , Kimura Joe , Wu Shannon , Anzaldi Laura , Richards Tom , Lasser Elyse C. , Weiner Jonathan P.
Published: February 2018

Background:

Using electronic health records (EHRs), in addition to claims, to systematically identify patients with factors associated with adverse outcomes (geriatric risk) among older adults can prove beneficial for population health management and clinical service delivery.

Objective:

To define and compare geriatric risk factors derivable from claims, structured EHRs, and unstructured EHRs, and estimate the relationship between geriatric risk factors and health care utilization.

Research Design:

We performed a retrospective cohort study of patients enrolled in a Medicare Advantage plan from 2011 to 2013 using both administrative claims and EHRs. We defined 10 individual geriatric risk factors and a summary geriatric risk index based on diagnosed conditions and pattern matching techniques applied to EHR free text. The prevalence of geriatric risk factors was estimated using claims, structured EHRs, and structured and unstructured EHRs combined. The association of geriatric risk index with any occurrence of hospitalizations, emergency department visits, and nursing home visits were estimated using logistic regression adjusted for demographic and comorbidity covariates.

Results:

The prevalence of geriatric risk factors increased after adding unstructured EHR data to structured EHRs, compared with those derived from structured EHRs alone and claims alone. On the basis of claims, structured EHRs, and structured and unstructured EHRs combined, 12.9%, 15.0%, and 24.6% of the patients had 1 geriatric risk factor, respectively; 3.9%, 4.2%, and 15.8% had ≥2 geriatric risk factors, respectively. Statistically significant association between geriatric risk index and health care utilization was found independent of demographic and comorbidity covariates. For example, based on claims, estimated odds ratios for having 1 and ≥2 geriatric risk factors in year 1 were 1.49 (P<0.001) and 2.62 (P<0.001) in predicting any occurrence of hospitalizations in year 1, and 1.32 (P<0.001) and 1.34 (P=0.003) in predicting any occurrence of hospitalizations in year 2.

Conclusions:

The results demonstrate the feasibility and potential of using EHRs and claims for collecting new types of geriatric risk information that could augment the more commonly collected disease information to identify and move upstream the management of high-risk cases among older patients.
Changes in Health Insurance Coverage Associated With the Affordable Care Act Among Adults With and Without a Cancer History
Authors: Davidoff Amy J. , Guy Gery P. , Hu Xin , Gonzales Felisa , Han Xuesong , Zheng Zhiyuan , Parsons Helen , Ekwueme Donatus U. , Jemal Ahmedin
Published: February 2018

Background:

The Affordable Care Act (ACA) improved health care coverage accessibility by expanding Medicaid eligibility, creating insurance Marketplaces, and subsidizing premiums. We examine coverage changes associated with ACA implementation, comparing adults with and without a cancer history.

Methods:

We included nonelderly adults from the 2012 to 2015 National Health Interview Survey. Using information on state Medicaid policies (2013), expansion decisions (2015), family structure, income, insurance offers, and current coverage, we assigned adults in all 4 years to mutually exclusive eligibility categories including: Medicaid-eligible pre-ACA; expansion eligible for Medicaid; and Marketplace premium subsidy eligible. Linear probability regressions estimated pre-post (2012–2013 vs. 2014–2015) coverage changes by eligibility category, stratified by cancer history.

Results:

The uninsured rate for cancer survivors decreased from 12.4% to 7.7% (P<0.001) pre-post ACA implementation. Relative to income >400% of the federal poverty guideline, the uninsured rate for cancer survivors decreased by an adjusted 8.4 percentage points [95% confidence interval (CI), 1.3–15.6] among pre-ACA Medicaid eligible; 16.7 percentage points (95% CI, 9.0–24.5) among expansion eligible, and 11.3 percentage points (95% CI, −0.8 to 23.5, with a trend P=0.069) for premium subsidy eligible. Decreases in uninsured among expansion-eligible adults without a cancer history [9.7 percentage points (95% CI, 7.4–12.0), were smaller than for cancer survivors (with a trend, P=0.086)]. Despite coverage gains, ∼528,000 cancer survivors and 19.1 million without a cancer history remained uninsured post-ACA, yet over half were eligible for Medicaid or subsidized Marketplace coverage.

Conclusions:

ACA implementation was associated with large coverage gains in targeted expansion groups, including cancer survivors, but additional progress is needed.
Gastric Carcinomas With Lymphoid Stroma
Authors: Hissong Erika , Ramrattan Girish , Zhang Pan , Zhou Xi Kathy , Young Gloria , Klimstra David S. , Shia Jinru , Fernandes Helen , Yantiss Rhonda K.
Published: February 2018

Gastric carcinoma with lymphoid stroma is an uncommon variant enriched for mutually exclusive Epstein-Barr virus (EBV) positivity and mismatch repair (MMR) deficiency. We performed this study to evaluate molecular alterations in this morphologically homogeneous subtype and compare them with 295 conventional gastric cancers analyzed in The Cancer Genome Atlas study. We identified 31 study cases and subjected them to in situ hybridization for EBV-encoded RNAs and assessment for MMR status. Immunostains for PD-L1, β-catenin, and HER2 were performed; extracted DNA was sequenced with a Comprehensive Cancer Panel. Most study patients were older adult men with stage I or II disease (76%). Tumors were classified as EBV+/MMR-proficient (MMR-P) (n=7), EBV−/MMR deficient (n=12), and EBV−/MMR-P (n=12). EBV−/MMR-P tumors were usually located in the proximal stomach (83%) and showed heterogenous growth patterns with glandular differentiation (83%). Tumors in all groups showed numerous tumor infiltrating lymphocytes and PD-L1 expression, infrequent nuclear β-catenin accumulation (10%), and lacked both membranous HER2 staining and HER2 amplification. EBV−/MMR-deficient tumors showed significantly higher tumor mutation burden (P=0.001) and KRAS alterations (56%) compared with EBV−/MMR-P tumors (9%, P=0.05). TP53 variants were more common among EBV−/MMR-P tumors (82%) compared with EBV+/MMR proficient (0%, P=0.01) and EBV−/MMR-deficient (11%, P<0.01) tumors. Alterations in KRAS, ARID1A, PIK3CA, and TP53 followed similar patterns of distribution compared with The Cancer Genome Atlas dataset. We conclude that gastric carcinomas with lymphoid stroma show a spectrum of molecular changes and frequent PD-L1 expression, raising the possibility that this subgroup of tumors may be susceptible to checkpoint inhibitors and/or agents that target receptor tyrosine kinase-mediated signaling.
Presumed Systemic Inflammatory Response Syndrome in the Pediatric Emergency Department
Authors: Foo Cheryl P.Z. , Seabrook Jamie A. , Sangha Gurinder , Foster Jennifer Ruth
Published: February 2018

Objective

The aim of this study was to examine the incidence and outcomes of patients presenting with systemic inflammatory response syndrome (SIRS) in the pediatric emergency department (PED).

Methods

This was a descriptive, retrospective cohort study of all patients from birth to 18 years presenting to the PED of a single center on 16 days distributed over 1 year. The presence of presumed SIRS (pSIRS, defined as noncore temperature measurement and cell count when clinically indicated) and sepsis was determined for all study patients. Patients were followed up for 1 week.

Results

The incidence of pSIRS was 15.3% (216/1416). Suspected or proven infection was present in 37.1% (n = 525) of the study population and 76.4% (n = 165) with pSIRS, with no cases of severe sepsis or septic shock. Sensitivity and specificity of pSIRS for predicting infection were 31.4% (95% confidence interval [CI], 27.5%–35.6%) and 94.3% (95% CI, 92.5%–95.7%), respectively. Although patients with pSIRS had a relative risk of 2.4 (95% CI, 1.6–3.5; P < 0.0001) for admission, 74% were discharged home with no subsequent PED visits. Of defined sepsis cases, 75% were discharged home without return.

Conclusions

Presumed SIRS and sepsis are relatively common in the PED. Use of pSIRS to screen for sepsis risks missing infection, whereas using pSIRS in the current sepsis definition results in overinclusion of nonsevere illness.
Sonographic Evaluation and Monitoring of Pneumoperitoneum After Air Enema Reduction for Intussusception
Authors: Zhou Amy Z. , Toporowski Amy , Tsung James W.
Published: February 2018

Abdominal radiography and computed tomography scans are standard tests to diagnose pneumoperitoneum. With the growing availability of point-of-care ultrasound, pneumoperitoneum may be diagnosed in settings without easy access to radiography or computed tomography, such as in overcrowded emergency departments or resource-poor environments. The use of point-of-care ultrasound to diagnose or monitor pneumoperitoneum has been described in adult but not pediatric patients. We present a case of point-of-care ultrasound detection of pneumoperitoneum and monitoring for tension pneumoperitoneum, after failed air enema reduction for intussusception in an infant.
Power-Assisted Particulate Bone Grafting Effectively Prevents Osseous Defects After Cranial Vault Reconstruction
Authors: Gandolfi Brad M. , Hirji Sameer A. , Sobol Danielle L. , Allori Alexander C. , Marcus Jeffrey R.
Published: February 2018

Background:

Cranial vault reconstruction (CVR) is the gold standard in the operative treatment of craniosynostosis. Full thickness osseous defects (FTOD) of the calvaria have been observed in 5% to 15% patients after CVR, with higher rates cited in the fronto-orbital advancement (FOA) subset. Particulate bone graft (PBG) harvested manually has been shown to decrease FTOD after FOA from 24% to 5.5%. The authors used a modified technique using a powered craniotome, with the hypothesis that the technique would also improve outcomes.

Methods:

A retrospective review was performed of patients who underwent CVR for craniosynostosis between 2004 and 2014. Patient demographics, diagnosis, age, operative details, and postoperative care were reviewed in detail. Categorical, nonparametric variables were compared by Fisher exact tests.

Results:

A total of 135 patients met inclusion criteria. The most common diagnoses were metopic (n = 41), sagittal (n = 33), and unilateral coronal craniosynostosis (n = 31); 65% (n = 88) underwent FOA, 29% (n = 39) underwent single-stage total vault reconstruction, and 6% (n = 8) had a posterior vault reconstruction. CVR was performed without PBG in 95 patients and with PBG in 40 patients. Without PBG, FTOD were discovered on clinical examination in 18% of patients (n=17): 11 presented with subcentimeter defects, while 6 had larger defects requiring revision cranioplasty (6% operative revision rate). Among those receiving PBG, 1 patient presented a subcentimeter FTOD (2.5% FTOD incidence and 0% operative revision rate).

Conclusion:

Particulate bone graft harvested with a powered device decreases the rate of FTOD and reoperation rate after CVR for craniosynostosis.
Evaluation of Postoperative Stability After Open Reduction and Internal Fixation of Zygomaticomaxillary Complex Fractures Using Cone Beam Computed Tomography Analysis
Authors: Kim Hyo-Jung , Bang Kyung-Hwan , Park Eun-Ji , Cho Yeong-Cheol , Sung Iel-Yong , Son Jang-Ho
Published: February 2018

The aim of this study was to evaluate whether the amount of fracture displacement affects postoperative stability of isolated zygomaticomaxillary complex fractures and to determine whether the 1-point fixation method is as stable as 2- or 3-point fixation methods. The authors investigated 14 patients with 1-point fixation in the zygomaticomaxillary area (group A), 14 patients with 2-point fixation in the zygomaticomaxillary and frontozygomatic area (group B), and 13 patients with 3-point fixation in the zygomaticomaxillary, frontozygomatic, and infraorbital rim area (group C). Stability of the reduced zygomaticomaxillary complex was assessed by comparing immediate postoperative cone beam computed tomography images with those obtained at least 3 months later. Preoperatively, the total mean displacement was 3.79 ± 1.36 mm in group A, 3.43 ± 0.89 mm in group B, and 3.86 ± 1.57 mm in group C. The total postoperative orbital and screw changes were 0.91 ± 0.18 and 0.72 ± 0.08 mm, respectively, in group A; 0.92 ± 0.19 and 0.68 ± 0.09 mm, respectively, in group B; and 0.91 ± 0.11 and 0.66 ± 0.10 mm, respectively, in group C. There were no significant relationships between postoperative stability and amount of fracture displacement in any of the 3 groups, or between the 3 groups (P > 0.05). There was little difference in postoperative stability between the 3 groups. Hence, the amount of displacement is not a very important consideration when deciding the fixation method, including the number and location of miniplates applied for fixation.
Knockdown of TFPI-Anchored Endothelial Cells Exacerbates Lipopolysaccharide-Induced Acute Lung Injury Via NF-κB Signaling Pathway
Authors: Wang Bao Q. , Shi Meng , Zhang Jian P. , Wu Xie , Chang Mei J. , Chen Zhi H. , Shen Hua H. , Song Yuan L. , Zhou Jian , Bai Chun X.
Published: February 2018

As activation of the coagulation system is both a consequence and contributor to acute lung injury (ALI), pulmonary coagulopathy has become a potential target for therapeutic intervention in ALI patients. We investigated the effects and possible mechanisms of endothelial cell (EC)-anchored tissue factor pathway inhibitor (TFPI) on lipopolysaccharide (LPS)-induced ALI in mice. To assess the effect of EC-anchored TFPI deletion on ALI indices, TFPI knockout (cKO) mice were generated. Mice were instilled by direct intratracheal injection LPS for the preparation of an ALI model. Evans blue dye (EBD) was injected intravenously 2 h prior to animal sacrifice (48 h post-LPS). Lungs were fixed for histopathology and the prepared tissue was homogenized or used to extract bronchoalveolar lavage fluid (BALF) or detect EBD concentration. TFPI knockdown mice with ALI were compared to wild-type (WT) mice with ALI to assess the effect of TFPI on endothelial barrier function and inflammation. TFPI deletion markedly exacerbated LPS histopathological changes in lung, and the LPS changes in protein, EBD extravasation, proinflammatory cytokines TNF-α, IL-1β, and IL-6 in BALF in lung. The number and infiltration of white blood cells (WBCs) from BALF and lung tissue of TFPI cKO mice with LPS-challenged ALI was increased compared to WT mice with LPS-challenged ALI. We also found further increased toll-like receptor 4 and nuclear factor kappa-light-chain-enhancer of activated B cells activation and additional expression of vascular cell adhesion molecule 1 and reduction of angiotensin converting enzyme 2 expression in TFPI cKO+LPS mice compared with WT+LPS mice. Endothelial-specific TFPI deficiency promoted LPS-induced pulmonary inflammation and endothelial barrier permeability possibly via toll-like receptor 4-mediated nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway activation.
Toxins in pain
Authors: Cardoso Fernanda C. , Hasan Mahadhi , Zhao Tianjiao , Lewis Richard J.
Published: February 2018

Purpose of review

Pain is a distressing protective sensory experience warning of actual or potential tissue damage. Natural toxins have evolved to exploit pain and related neuronal pathways to facilitate prey capture and for defence, often producing either numbness, paralysis or intense pain by selectively modulating ion channels and receptors in pain pathways. Understanding how toxins modulate pain pathways can enhance our understanding of the physiological and pathological basis of pain.

Recent findings

Toxins continue to provide a rich source of unique pharmacological tools and novel drug leads to treat severe neurological disorders, including chronic pain. Recently discovered toxins that selectively modulate Nav1.7 and Nav1.1 have helped unravel their involvement in pain signalling.

Toxins have evolved to induce or inhibit pain by targeting a broad range of ion channels and receptors, including NaV, CaV,KV, TRP, ASIC, P2X, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,N-methyl-D-aspartate, NET and GPCRs. These toxins bind to specific sites to stimulate or inhibit the activity of these membrane proteins. Toxins continue to yield some of the most exciting leads for developing novel nonopioid analgesics.
Central and peripheral processes in headache
Authors: Varma Adithya , Jain Saurabh , Majid Arshad , De Felice Milena
Published: February 2018

Purpose of review

Migraine is an extremely incapacitating collection of neurological symptoms that usually includes a severe, throbbing, recurring pain on one side of the head. The World Health Organization ranks migraine as the third most prevalent disease and the seventh commonest primary pain condition in the world. Trigeminovascular-mediated central sensitization has been implicated in the development of migraine symptoms including pain following light touch. This review explores the activation and sensitization of the brain systems that have emerged from recent studies and that contribute to migraine.

Recent findings

A number of pathophysiological mechanisms have been implicated in the development of migraine and other primary headache disorders. Neuroimaging techniques used to identify both structural and functional features of the brain in migraineurs have helped identify brain regions that are active during or in between migraine attacks, with particular emphasis on those areas relevant to pain pathways, including the hypothalamus and periaqueductal grey.

Several key studies have helped address the long-standing debate over whether migraine originates from vascular or neuronal dysfunction and now support that migraine is a neurological disorder. However, a complete understanding of the central nervous system dysfunction underlying this condition has yet to be elucidated.
Validity and Acceptance of Color Vision Testing on Smartphones
Authors: Ozgur Omar K. , Emborgo Trisha S. , Vieyra Mark B. , Huselid Rebecca F. , Banik Rudrani
Published: February 2018

Background:

Ishihara color plates (ICP) are the most commonly used color vision test (CVT) worldwide. With the advent of new technologies, attempts have been made to streamline the process of CVT. As hardware and software evolve, smartphone-based testing modalities may aid ophthalmologists in performing more efficient ophthalmic examinations. We assess the validity of smartphone color vision testing (CVT) by comparing results using the Eye Handbook (EHB) CVT application with standard Ishihara color plates (ICP).

Methods:

Prospective case–control study of subjects 18 years and older with visual acuity of 20/100 or better at 14 inches. The study group included patients with any ocular pathology. The color vision deficient (CVD) group was patients who failed more than 2 plates. The control group had no known ocular pathology. CVT was performed with both ICP and EHB under standardized background illuminance. Eleven plates were tested with each modality. Validity of EHB CVT and acceptance of EHB CVT were analyzed. Statistical analyses were performed using Bland–Altman plot with limits of agreement (LOA) at the 95th percentile of differences in score, independent samples t tests with 95% confidence interval (CI), and Pearson χ
2 tests.

Results:

The Bland–Altman plot showed agreement between correct number of plates in EHB and ICP for the study subjects (bias, −0.25; LOA, −1.92 to 1.42). Agreement was also observed between the correct number of plates in EHB and ICP for the controls (bias, −0.01; LOA, −0.61 to 0.59) and CVD (bias, −0.50; LOA, −4.64 to 3.64) subjects. The sensitivity of EHB was 0.92 (95% CI 0.76–1.07) and the specificity of EHB was 1.00 (95% CI 1.00–1.00). Fifty-nine percent preferred EHB, 12% preferred ICP, and 29% had no preference.

Conclusions:

In healthy controls and patients with ocular pathology, there was an agreement of CVT results comparing EHB with ICP. Overall, the majority preferred EHB to ICP. These findings demonstrate that further testing is required to understand and improve the validity of smartphone CVT in subjects with ocular pathology.
EEG Factors After Pediatric Cardiac Arrest
Authors: Abend Nicholas S. , Wiebe Douglas J. , Xiao Rui , Massey Shavonne L. , Fitzgerald Mark , Fung France , Topjian Alexis A.
Published: February 2018

Purpose:

We aimed to determine whether conventional standardized EEG features could be consolidated into a more limited number of factors and whether the derived factor scores changed during the acute period after pediatric cardiac arrest.

Methods:

Children resuscitated after cardiac arrest underwent conventional continuous EEG monitoring. The EEG was scored in 12-hour epochs for up to 72-hours after return of circulation by an electroencephalographer using standardized critical care EEG terminology. We performed a polychoric factor analysis to determine whether numerous observed EEG features could be represented by a smaller number of derived factors. Linear mixed-effects regression models and heat maps evaluated whether the factor scores remained stable across epochs.

Results:

We performed EEG monitoring in 89 consecutive children, which yielded 453 EEG segments. We identified two factors, which were not correlated. The background features were factor loaded with the features continuity, voltage, and frequency. The intermittent features were factor loaded with the features of seizures, periodic patterns, and interictal discharges. Factor scores were calculated for each EEG segment. Linear, mixed-effect, regression results indicated that the factor scores did not change over time for the background features factor (coefficient, 0.18; 95% confidence interval, 0.04–0.07; P = 0.52) or the intermittent features factor (coefficient, −0.003; 95% confidence interval, −0.02 to 0.01; P = 0.70). However, heat maps showed that some individual subjects did experience factor score changes over time, particularly if they had medium initial factor scores.

Conclusions:

Subsequent studies assessing whether EEG is informative for neurobehavioral outcomes after pediatric cardiac arrest could combine numerous EEG features into two factors, each reflecting multiple background and intermittent features. Furthermore, the factor scores would be expected to remain stable during the acute period for most subjects.
Cultural transmission in an ever-changing world: trial-and-error copying may be more robust than precise imitation
Authors: Truskanov Noa , Prat Yosef
Published: February 2018

Cultural transmission facilitates the spread of behaviours within social groups and may lead to the establishment of stable traditions in both human and non-human animals. The fidelity of transmission is frequently emphasized as a core component of cultural evolution and as a prerequisite for cumulative culture. Fidelity is often considered a synonym of precise copying of observed behaviours. However, while precise copying guarantees reliable transmission in an ideal static world, it may be vulnerable to realistic variability in the actual environment. Here, we argue that fidelity may be more naturally achieved when the social learning mechanisms incorporate trial-and-error; and that the robustness of social transmission is thereby increased. We employed a simple model to demonstrate how culture that is produced through exact copying is fragile in an (even slightly) noisy world. When incorporating a certain degree of trial-and-error, however, cultures are more readily formed in a stochastic environment and are less vulnerable to rare ecological changes. We suggest that considering trial-and-error learning as a stabilizing component of social transmission may provide insights into cultural evolution in a realistic, variable, world.

This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Enquire within: cultural evolution and cognitive science
Authors: Heyes Cecilia
Published: February 2018

Cultural evolution and cognitive science need each other. Cultural evolution needs cognitive science to find out whether the conditions necessary for Darwinian evolution are met in the cultural domain. Cognitive science needs cultural evolution to explain the origins of distinctively human cognitive processes. Focusing on the first question, I argue that cultural evolutionists can get empirical traction on
third-way cultural selection
by rooting the distinction between replication and reconstruction, two modes of cultural inheritance, in the distinction between System 1 and System 2 cognitive processes. This move suggests that cultural epidemiologists are right in thinking that replication has higher fidelity than reconstruction, and replication processes are not genetic adaptations for culture, but wrong to assume that replication is rare. If replication is not rare, an important requirement for third-way cultural selection,
one-shot fidelity
, is likely to be met. However, there are other requirements, overlooked by dual-inheritance theorists when they conflate strong (Darwinian) and weak (choice) senses of ‘cultural selection’, including
dumb choices
and
recurrent fidelity
. In a second excursion into cognitive science, I argue that these requirements can be met by
metacognitive social learning strategies
, and trace the origins of these distinctively human cognitive processes to cultural evolution. Like other forms of cultural learning, they are not cognitive instincts but cognitive gadgets.

This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.