bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment-based Classification System for Patients With Low Back Pain: The Movement Control Approach
Authors: Alrwaily Muhammad , Timko Michael , Schneider Michael , Kawchuk Greg , Bise Christopher , Hariharan Karthik , Stevans Joel , Delitto Anthony
Published: August 2017

We present the movement control approach as part of the treatment-based classification system. This approach proposes a movement control schema that clarifies that movement control is a product of the interplay among multiple biopsychosocial components. The schema illustrates that for movement to occur in a dynamically controlled fashion, the lumbar spine requires both local mobility and global stability. Local mobility means that the lumbar spine and its adjacent regions possess adequate nerve and joint(s) mobility and soft tissue compliance (ie, the malleability of tissue to undergo elastic deformation). Global stability means that the muscles of the lumbar spine and its adjacent regions can generate activation that is coordinated with various joint movements and incorporated into activities of daily living. Local mobility and global stability are housed within the bio-behavioral and socio-occupational factors that should be addressed during movement rehabilitation. This schema is converted into a practical physical examination to help the rehabilitation provider to construct a clinical rationale as to why the movement impairment(s) exist. The examination findings are used to guide treatment. We suggest a treatment prioritization that aims to consecutively address neural sensitivity, joint(s) and soft tissue mobility, motor control, and endurance. This prioritization enables rehabilitation providers to better plan the intervention according to each patient's needs. We emphasize that treatment for patients with low back pain is not a static process. Rather, the treatment is a fluid process that changes as the clinical status of the patient changes. This movement control approach is based on clinical experience and indirect evidence; further research is needed to support its clinical utility.
Histochemical Analyses Reveal That Stronger Intrinsic Defenses in Gossypium barbadense Than in G. hirsutum Are Associated With Resistance to Verticillium dahliae
Authors: Zhang Yan , Wang Xingfen , Rong Wei , Yang Jun , Li Zhikun , Wu Liqiang , Zhang Guiyin , Ma Zhiying
Published: August 2017

Verticillium wilt, caused by Verticillium dahliae Kleb., is a serious threat to cotton (Gossypium spp.) crop production. To enhance our understanding of the plant’s complex defensive mechanism, we examined colonization patterns and interactions between V. dahliae and two cotton species, the resistant G. barbadense and the susceptible G. hirsutum. Microscopic examinations and grafting experiments showed that the progression of infection was restricted within G. barbadense. At all pre- and postinoculation sampling times, levels of salicylic acid (SA) were also higher in that species than in G. hirsutum. Comparative RNA-Seq analyses indicated that infection induced dramatic changes in the expression of thousands of genes in G. hirsutum, whereas those changes were fewer and weaker in G. barbadense. Investigations of the morphological and biochemical nature of cell-wall barriers demonstrated that depositions of lignin, phenolic compounds, and callose were significantly higher in G. barbadense. To determine the contribution of a known resistance gene to these processes, we silenced GbEDS1 and found that the transformed plants had decreased SA production, which led to the upregulation of PLASMODESMATA-LOCATED PROTEIN (PDLP) 1 and PDLP6. This was followed by a decline in callose deposition in the plasmodesmata, which then led to increased pathogen susceptibility. This comparison between resistant and susceptible species indicated that both physical and chemical mechanisms play important roles in the defenses of cotton against V. dahliae.
Performance on Balance Evaluation Systems Test (BESTest) Impacts Health-Related Quality of Life in Adult Spinal Deformity Patients
Authors: Moke Lieven , Severijns Pieter , Schelfaut Sebastiaan , Van de loock Kristel , Hermans Lore , Molenaers Guy , Jonkers Ilse , Scheys Lennart
Published: August 2017

Study Design.

Prospective single-center study.

Objective.

Study investigates how dynamic balance performance complements 2D static radiographic measurements and demographics in terms of understanding health-related quality of life in adult spinal deformity (ASD) patients.

Summary of Background Data.

Recent insights suggest that demographic variables have a stronger impact on health-related quality of life than 2D radiographic spinopelvic parameters in ASD patients.

Methods.

Nine healthy volunteers and 36 ASD patients following inclusion criteria were recruited. Demographics, Scoliosis Research Society Score-22r (SRS-22r), Oswestry Disability Index (ODI), Core Outcome Measures Index (COMI), 2D radiographic spinopelvic measurements, and performance on Balance Evaluation Systems Test (BESTest), and Trunk Control Measurement Scale (TCMS) were determined for each subject. Nonparametric tests, Spearman correlations, univariate, and stepwise-like linear multivariate regression analysis were performed.

Results.

BESTest and TCMS had significant lower values in the ASD group versus the control group (P = 0.000). In the ASD group, Cumulative Illness Rating Scale (CIRS) correlated fair to ODI, COMI (0.441 ≥ r ≥ 0.383, P < 0.021) and to SRS-22-r (r = −0.335, P = 0.046), Mini Mental State Examination correlated fair to COMI (r = −0.352, P = 0.035), “Pelvic Incidence minus Lumbar Lordosis” correlated fair to ODI (r = 0.361, P = 0.031), BESTest correlated moderate to ODI and COMI (r ≤ −0.505; P ≤ 0.002), TCMS correlated fair to ODI (r = −0.356; P = 0.033). CIRS and BESTest were significant predictive variables for COMI based on univariate analysis in ASD patients. Multivariate regression analysis including demographics, 2D static radiographic parameters, and dynamic balance scales identified BESTest as single independent variable (P = 0.000) to predict COMI (adjusted R
2 = 0.285) in ASD patients.

Conclusion.

BESTest has a higher potential than demographic and 2D radiographic spinopelvic parameters to predict quality of life in ASD patients. Further research is necessary to identify the impact of ASD on quality of life.

Level of Evidence: 3
Relapsed/refractory acute myeloid leukemia: any progress?
Authors: Schlenk Richard F. , Müller-Tidow Carsten , Benner Axel , Kieser Meinhard
Published: August 2017

Purpose of review

Aim of this review was to focus on prognostic and predictive factors, standard and new treatment approaches, and on statistical considerations for future clinical trials in patients with relapsed/refractory acute myeloid leukemia (r/r-AML).

Recent findings

New prognostic molecular markers were identified in r/r-AML, FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations. Intensive combination chemotherapy including gemtuzumab ozogamicin emerged as an effective salvage therapy in refractory AML. Timing of allo-HCT in r/r-AML may be oriented at the probability to achieve a response to intensive salvage therapy. Several new treatment approaches ranging from new and modified cytotoxic drugs to targeted approaches are in clinical development with first efficacy assessment in single-arm phase II studies. Their external validity may be considerably increased by using a novel design based on a matching approach.

FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations are identified as prognostic molecular markers in r/r-AML. Timing of allo-HCT should be based on the probability to achieve a response to intensive salvage therapy. Several new approaches are currently evaluated and matching for controls may help to increase external validity.
Clinical potential of oxytocin in autism spectrum disorder: current issues and future perspectives
Authors: Benner Seico , Yamasue Hidenori
Published: August 2017

The effects of oxytocin on social cognition and behavior have recently attracted considerable attention. In particular, oxytocin has been proposed as a novel therapeutic for psychiatric disorders with social deficits such as autism spectrum disorders. This review provides a brief overview of behavioral and neural responses to oxytocin manipulations in humans and animal models. Although the differences in findings between human and animal studies should be interpreted carefully, shared behavioral phenotypes have been recognized, such as social bonding, social responses, and recognition and usage of social cues. Previous literature suggests that the neural effects of oxytocin in humans and animals overlap in the prefrontal, limbic, and paralimbic cortices. Oxytocin-induced alterations in these regions may indicate a fundamental basis for how oxytocin modulates social behaviors and facilitate the discovery of new pharmaceutical targets for treating social deficits.
In-utero cigarette smoke exposure and the risk of earlier menopause
Authors: Honorato Talita C. , Haadsma Maaike L. , Land Jolande A. , Boezen Marike H. , Hoek Annemieke , Groen Henk
Published: August 2017

Objective:

Cigarette smoking is a risk factor for earlier menopause. Animal studies show that in-utero smoke exposure is toxic to developing ovaries. Our aim was to evaluate whether in-utero smoke exposed women reach menopause earlier compared with nonexposed women.

Methods:

This is a cohort study within the Avon Longitudinal Study of Parents and Children. Participants included in this study were followed from 1991/1992 until 2010. Participant characteristics for the current analysis were obtained from obstetric records and from annual follow-up questionnaires. When not available, age at natural menopause was estimated by age at filling in the questionnaire minus 1 year. Cox proportional hazards modeling was used to estimate hazard ratios of menopause for in-utero exposed and nonexposed women.

Results:

There were 695/2,852 postmenopausal women, of whom 466 had natural menopause, 117 had hormonal therapy, and 112 had surgical menopause. Age at natural menopause was 50.6 ± 3.7 years. Of all participants, 20.2% (577/2,852) were exposed to smoke in-utero. Participants who were in-utero exposed but were not smokers did not have higher hazards of menopause (adjusted hazard ratio [HR] 0.92, 95% CI 0.72-1.18), whereas participants who were ever smokers (current or previous) and were in-utero exposed (adjusted HR 1.41, 95% CI 1.01-1.95) or were ever smokers but not exposed (adjusted HR 1.24, 95% CI 1.00-1.53) did have higher hazards of earlier menopause.

Conclusions:

In-utero smoke exposure was not associated with earlier menopause, but the effect of in-utero smoke exposure was modified by the smoking habits of the participants themselves increasing the risk for smokers who were in-utero exposed.
Double-Pedicled Free Deep Inferior Epigastric Perforator Flap for the Coverage of Thigh Soft-Tissue Defect
Authors: Bota Olimpiu , Spindler Nick , Sauber Jeannine , Aydogan Emrah , Langer Stefan
Published: August 2017

Soft-tissue defects caused by radiation injury are a challenging task for the reconstructive surgeon, due to the extent of the soft-tissue damage and the associated injuries of the local blood vessels and bone tissue. We present the application of the versatile deep inferior epigastric perforator (DIEP) flap for the coverage of an extended lateral thigh soft-tissue defect after the surgical resection of an undifferentiated pleomorphic high-grade sarcoma, neoadjuvant chemotherapy, and adjuvant chemo- and radiotherapy. A double-pedicled free DIEP flap (756 cm2) was harvested and anastomosed to the transverse branch of the lateral femoral circumflex artery and a lateral branch of the popliteal artery (P1). The flap survived completely without serious complications, and the patient was able to walk with crutches 3 months postoperatively. This is the first case report of a free bipedicled DIEP flap for the coverage of a thigh defect in a male patient.
Expert Evaluation of Visual Field Decay in Glaucoma Correlates With the Fast Component of Visual Field Loss
Authors: Cirineo Nila , Morales Esteban , Lee Jun Mo , Ramanathan Meera , Hirunpatravong Pradtana , Lin Mark , Capistrano Vicente , Abdelmonen Afifi , Yu Fei , Nouri-Mahdavi Kouros , Coleman Anne L. , Caprioli Joseph
Published: August 2017

Purpose:

To compare the assessment of serial visual fields (VFs) based on subjective expert evaluation with the fast and slow VF component rates determined with pointwise exponential regression (PER) and pointwise linear regression (PLR).

Materials and Methods:

A total of 5272 VF examinations from 376 eyes diagnosed with open-angle glaucoma were included. Three glaucoma specialists assessed each VF qualitatively to evaluate progression status and the qualitative rate of progression. The rates of VF decay were determined with PER and PLR at each VF location, which were ranked according to the regression coefficient and partitioned into 2 groups (fast and slow). A mean rate for the fast and slow partitions was obtained based on the average of the regression coefficients in each partition. κ-values were used to measure the agreement among the experts and the PER and PLR algorithms.

Results:

The average baseline VF mean deviation for the study sample was −6.6 (±5.9) dB. The agreement of the likelihood of progression among the dichotomized experts’ score and PER was moderate (κ=0.41, P<0.01) and fair (κ=0.39, P<0.01) for PLR. The agreement of the likelihood of progression among the 3 dichotomized experts’ scores was fair (κ=0.22, P<0.01). The agreement of the area of worsening among the dichotomized experts’ score and PER and PLR were both moderate (κ=0.48, P<0.01; κ=0.46, P<0.01). The eyes flagged by experts as having “fast” progression rates had a higher average rates of decay for PER and PLR at −2.7 (±4.1) %/year and −0.8 (±1.2) dB/year; eyes flagged as “slow” had lower rates of decay at −0.3 (±1.5) %/year and −0.1 (±0.5) dB/year.

Conclusions:

Expert qualitative evaluation of field series for change and rate of change correlate more closely with the fast component than with the slow component of VF decay.
Attenuation Coefficients From SD-OCT Data: Structural Information Beyond Morphology on RNFL Integrity in Glaucoma
Authors: Thepass Gijs , Lemij Hans G. , Vermeer Koenraad A.
Published: August 2017

Purpose:

The purpose of this study is to explore the attenuation coefficient (AC) of the retinal nerve fiber layer (RNFL) in spectral domain optical coherence tomography (OCT) images, in healthy eyes and eyes affected by glaucoma. To assess the relation between RNLF AC, disease severity, RNFL thickness, visual field sensitivity threshold, spatial location and age.

Patients and Methods:

We analyzed peripapillary circle scans of a clinical OCT device (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) in 102 glaucoma patients and 90 healthy controls. The images were fully automatically converted into depth-resolved AC images. Next, the median AC within the RNFL was calculated based on the Spectralis segmentation. We compared the RNFL AC between healthy, mild, moderate and advanced glaucomatous eyes and assessed the correlation with patient characteristics such as age and visual field sensitivity threshold (HFA, Carl Zeiss Meditec, Dublin, CA) in a generalized estimating equations (GEE) model. Finally, we explored the ability to discriminate between glaucomatous and healthy eyes by RNFL AC.

Results:

Median RNFL AC decreased with increasing disease severity up to moderate glaucoma (P<0.001) in all 4 sectors around the optic nerve head. The largest relative decrease occurred in the nasal sector. The RNFL AC (AUC, 0.834±0.028) effectively discriminated healthy from glaucomatous eyes, although RNFL thickness (AUC, 0.975±0.013) performed even better (P<0.001). Prediction of visual field sensitivity improved significantly when RNFL thickness was augmented with RNFL AC as covariates (P<0.001).

Conclusions:

This study demonstrated that RNFL AC provides complementary information on the RNFL’s health compared with RNFL thickness measurements alone.
No Detection of Entamoeba Histolytica by Multiplex Polymerase Chain Reaction in Children With Acute Non-bloody Diarrhea in Guatemala
Authors: Kamidani Satoshi , Melgar Mario , Robinson Christine , Asturias Edwin , Berman Stephen , Gaensbauer James
Published: August 2017

Entamoeba histolytica is believed to be a ubiquitous cause of pediatric non-bloody diarrhea. Using a multiplex polymerase chain reaction assay, we identified stool pathogens in 298 Guatemalan children presenting with acute, non-bloody diarrhea. Despite a high overall pathogen burden, we identified no cases of E. histolytica. Knowledge of local epidemiology is important to inform E. histolytica therapeutic strategies in low-income settings.
Reporting From the Front Lines
Authors: Cottrell Erika K. , Hall Jennifer D. , Kautz Glenn , Angier Heather , Likumahuwa-Ackman Sonja , Sisulak Laura , Keller Sara , Cameron David C. , DeVoe Jennifer E. , Cohen Deborah J.
Published: August 2017

Alternative payment models have been proposed as a way to facilitate patient-centered medical home model implementation, yet little is known about how payment reform translates into changes in care delivery. We conducted site visits, observed operations, and conducted interviews within 3 Federally Qualified Health Center organizations that were part of Oregon's Alternative Payment Methodology demonstration project. Data were analyzed using an immersion-crystallization approach. We identified several care delivery changes during the early stages of implementation, as well as challenges associated with this new model of payment. Future research is needed to further understand the implications of these changes.
Competing Visions for Consumer Engagement in the Dawn of the Trump Administration
Authors: Hwang Ann , Garrett Danielle , Miller Michael
Published: August 2017

Two different models of consumer engagement use largely the same language but represent 2 distinct paradigms: the first focuses on patients as partners in health care decision making and the second focuses on financial incentives/penalties for patients. While the 2 paradigms coexist to some degree, they have different implications particularly for populations with complex health and social needs. For these populations, financial barriers can undermine the ability to recognize and promote patients as partners in a system of integrated, coordinated care. We describe these 2 competing visions and their adoption to date and offer our assessment of future directions for consumer engagement.
Commentary on “Competing Visions for Consumer Engagement in the Dawn of the Trump Administration”
Authors: Rother John , McNeely Larry
Published: August 2017

In this commentary on Hwang, Garrett and Miller's piece, we explain how value-based insurance design can help bring together both supporters and skeptics of the consumer-directed health care. Our commentary also notes the hazards that disruptive repeal-and-replace legislation might pose for consumer engagement efforts generally.
Comparison of Machine Learning Algorithms for the Prediction of Preventable Hospital Readmissions
Authors: Garcia-Arce Andres , Rico Florentino , Zayas-Castro José L.
Published: August 2017

A diverse universe of statistical models in the literature aim to help hospitals understand the risk factors of their preventable readmissions. However, these models are usually not necessarily applicable in other contexts, fail to achieve good discriminatory power, or cannot be compared with other models. We built and compared predictive models based on machine learning algorithms for 30-day preventable hospital readmissions of Medicare patients. This work used the same inclusion/exclusion criteria for diseases used by the Centers for Medicare and Medicaid Services. In addition, risk stratification techniques were implemented to study covariate behavior on each risk strata. The new models resulted in improved performance measured by the area under the receiver operating characteristic curve. Finally, factors such as higher length of stay, disease severity index, being discharged to a hospital, and primary language other than English were associated with increased risk to be readmitted within 30 days. In the future, better predictive models for 30-day preventable hospital readmissions can point to the development of systems that identify patients at high risk and lead to the implementation of interventions (e.g., discharge planning and follow-up) to those patients, providing consistent improvement in the quality and efficiency of the healthcare system.
Outcomes of patients hospitalized with peptic ulcer disease diagnosed in acute upper endoscopy
Authors: Malmi Hanna , Kautiainen Hannu , Virta Lauri J. , Färkkilä Martti A.
Published: August 2017

Objectives

The incidence and complications of peptic ulcer disease (PUD) have declined, but mortality from bleeding ulcers has remained unchanged. The aims of the current study were to evaluate the significance of PUD among patients admitted for acute upper endoscopy and to evaluate the survival of PUD patients.

Patients and methods

In this prospective, observational cohort study, data on 1580 acute upper endoscopy cases during 2012–2014 were collected. A total of 649 patients were included with written informed consent. Data on patients’ characteristics, living habits, comorbidities, drug use, endoscopy and short-term and long-term survival were collected.

Results

Of all patients admitted for endoscopy, 147/649 (23%) had PUD with the main symptom of melena. Of these PUD patients, 35% had major stigmata of bleeding (Forrest Ia–IIb) in endoscopy. Patients with major stigmata had significantly more often renal insufficiency, lower level of blood pressure with tachycardia and lower level of haemoglobin, platelets and ratio of thromboplastin time. No differences in drug use, Charlson comorbidity class, BMI, smoking or alcohol use were found. Of the PUD patients, 31% were Helicobacter pylori positive. The 30-day mortality was 0.7% (95% confidence interval: 0.01–4.7), 1-year mortality was 12.9% (8.4–19.5) and the 2-year mortality was 19.4% (13.8–26.8), with no difference according to major or minor stigmata of bleeding. Comorbidity (Charlson>1) was associated with decreased survival (P=0.029) and obesity (BMI≥30) was associated with better survival (P=0.023).

Conclusion

PUD is still the most common cause for acute upper endoscopy with very low short-term mortality. Comorbidity, but not the stigmata of bleeding, was associated with decreased long-term survival.
Human Immunodeficiency Virus, Chlamydia, and Gonorrhea Testing in New York Medicaid–Enrolled Adolescents
Authors: Wang Li Yan , Chang Man-Huei , Burstein Gale , Hocevar Adkins Susan
Published: August 2017

Background

Although growing public health efforts have been expended on increasing adolescents' access to human immunodeficiency virus (HIV) and sexually transmitted infection (STI) testing, little is known about the current utilization of those services in clinical settings.

Methods

Using 2010 to 2012 New York State Center for Medicare and Medicaid Services Medicaid Analytic eXtract data, we estimated the annual percentage of 13- to 19-year-olds who were tested for HIV, chlamydia (CT), and gonorrhea (GC). A regression analysis was performed to identify factors independently associated with testing utilization. We further examined testing utilization in all adolescent females with 1 or more health care encounter, pregnant females, and adolescents at increased risk for HIV/STI.

Results

From 2010 to 2012, HIV, CT, and GC testing rates increased in the overall study population and in most demographic subgroups. Female adolescents, black and Hispanic adolescents, at-risk adolescents, and adolescents with 6 months or longer of enrollment were significantly more likely to be tested. Among adolescent females with 1 or more health care encounter, 19.2% were tested for CT and 16.9% tested for GC in 2012. Among pregnant females, 35.2%, 53.9%, and 46.1% were tested for HIV, CT, and GC, respectively. Among at-risk adolescents, 39.9%, 63.7%, and 54.4% were tested for HIV, CT, and GC, respectively.

Conclusions

Although progress had been made by New York State providers to adhere to recommended testing for adolescents, there was a clear gap between the recommended level of testing and the actual level of utilization among sexually active females, pregnant females, and at-risk adolescents. Opportunities exist for community provider and public health collaboration to increase adolescent HIV and STI testing.
2015 Charles F. Prentice Medal Award Lecture: Neural Organization of Binocular Vision
Authors: Freeman Ralph D.
Published: August 2017

During a Research Career Development Award from the National Eye Institute, I spent a year at the University of Cambridge doing research with John Robson. The goal was to use a visual stimulation approach that had not been previously attempted, with the intention of exploring fundamental organization principles of the neural basis of binocular vision. The idea was to use sinusoidal gratings that drifted before both eyes such that the relative phase for one eye was fixed while that of the other was varied. This provided binocular stimuli of variable relative phase, i.e. retinal disparity, to enable testing of binocular response characteristics. We were able to obtain different types of disparity tuning functions for neurons in the primary visual cortex. This work, followed by extended investigations in Berkeley, provided basic information regarding response characteristics of simple and complex cells. We have also shown for monocular deprivation, an approximate model for human amblyopia, that many neurons remain connected to the deprived eye, as demonstrated with dichoptic activation. A selected portion of this work is described here.
Motion-Corrected Real-Time Cine Magnetic Resonance Imaging of the Heart
Authors: Rahsepar Amir Ali , Saybasili Haris , Ghasemiesfe Ahmadreza , Dolan Ryan S. , Shehata Monda L. , Botelho Marcos P. , Markl Michael , Spottiswoode Bruce , Collins Jeremy D. , Carr James C.
Published: August 2017

Objectives

Free-breathing real-time (RT) imaging can be used in patients with difficulty in breath-holding; however, RT cine imaging typically experiences poor image quality compared with segmented cine imaging because of low resolution. Here, we validate a novel unsupervised motion-corrected (MOCO) reconstruction technique for free-breathing RT cardiac images, called MOCO-RT. Motion-corrected RT uses elastic image registration to generate a single heartbeat of high-quality data from a free-breathing RT acquisition.

Materials and Methods

Segmented balanced steady-state free precession (bSSFP) cine images and free-breathing RT images (Cartesian, TGRAPPA factor 4) were acquired with the same spatial/temporal resolution in 40 patients using clinical 1.5 T magnetic resonance scanners. The respiratory cycle was estimated using the reconstructed RT images, and nonrigid unsupervised motion correction was applied to eliminate breathing motion. Conventional segmented RT and MOCO-RT single-heartbeat cine images were analyzed to evaluate left ventricular (LV) function and volume measurements. Two radiologists scored images for overall image quality, artifact, noise, and wall motion abnormalities. Intraclass correlation coefficient was used to assess the reliability of MOCO-RT measurement.

Results

Intraclass correlation coefficient showed excellent reliability (intraclass correlation coefficient ≥ 0.95) of MOCO-RT with segmented cine in measuring LV function, mass, and volume. Comparison of the qualitative ratings indicated comparable image quality for MOCO-RT (4.80 ± 0.35) with segmented cine (4.45 ± 0.88, P = 0.215) and significantly higher than conventional RT techniques (3.51 ± 0.41, P < 0.001). Artifact and noise ratings for MOCO-RT (1.11 ± 0.26 and 1.08 ± 0.19) and segmented cine (1.51 ± 0.90, P = 0.088 and 1.23 ± 0.45, P = 0.182) were not different. Wall motion abnormality ratings were comparable among different techniques (P = 0.96).

Conclusions

The MOCO-RT technique can be used to process conventional free-breathing RT cine images and provides comparable quantitative assessment of LV function and volume measurements to conventional segmented cine imaging while providing improved image quality and less artifact and noise. The free-breathing MOCO-RT reconstruction method may have considerable clinical utility in cardiac magnetic resonance imaging for patients with difficulty breath-holding.
Albuminuria in Pediatric Patients With Adenotonsillar Hypertrophy
Authors: Unsal Ozlem , Bozkurt Gulpembe , Esen Akpinar Meltem , Salepci Egehan , Aktas Oguz Gokce , Uslu Coskun Berna
Published: August 2017

The relationship between intermittent nocturnal hypoxia and albuminuria in pediatric patients with adenotonsillar hypertrophy was evaluated in this prospective study. Fifty children with grade 3 to 4 adenotonsillar hypertrophy scheduled for adenoidectomy and/or adenotonsillectomy were selected for study group. Fifteen patients with adenotonsillar grade 1 to 2 or adenotonsillectomized subjects in a similar range of sex, age, and body mass index scheduled for other surgeries were selected for control group. All children were monitored using finger pulse oximeter during the night before surgery. At the day of surgery, first morning urine samples were sent to the laboratory for analysis of albuminuria.

Albuminuria was determined in 8 (16%) patients in study group and 1 (6.7%) patient in control group. This difference between groups was determined not to be statistically significant (P > 0.05). None of the pulse oximetry parameters was also found to be associated with albuminuria statistically (P > 0.05). However, the adenoid grade was observed to be associated with albuminuria (P = 0.011).

This study revealed no relationship between albuminuria and intermittent hypoxia in children, although previous studies have reported that intermittent hypoxia causes albuminuria in adults. On the contrary, the adenoid grade was found to be in association with albuminuria. The reason seems to be unclear because of the lack of studies investigating albuminuria in children with adenotonsillar hypertrophy. However, inflammatory mediators arising from adenoid tissue may cause increase in renal capillary permeability and urine albumin excretion.
Can Clinical Findings Predict Orbital Fractures and Treatment Decisions in Patients With Orbital Trauma? Derivation of a Simple Clinical Model
Authors: Scolozzi Paolo , Jacquier Paul , Courvoisier Delphine S.
Published: August 2017

The aim of this study was to determine the predictive value of 4 clinical signs (periorbital ecchymosis, periorbital emphysema, diplopia, and inferior orbital nerve hypoesthesia) for the diagnosis of orbital fractures (OFs) and the need for surgical treatment in patients with orbital trauma. The investigators designed and implemented a retrospective cohort study composed of patients with orbital trauma. The primary and secondary outcomes were respectively the diagnosis of OFs and the need for surgical treatment. Multivariable logistic regressions including the clinical signs, age, and causes of injury were used to determine the independent contribution of each clinical sign to the prediction of the outcomes and to obtain weights to compute OF and surgery scores. The outcomes were assessed by receiver-operating characteristic (ROC) curves, sensitivity, specificity, and positive and negative predictive values. A total of 912 patients were included. All clinical signs except periorbital ecchymosis were significantly associated with OFs and the need for surgical treatment (P < 0.001). The predictive power of each clinical sign taken separately was moderate for the 2 outcomes (area under ROC curve [AUC] <0.7). A better predictive value was found when all clinical signs were used together (AUC >0.7). Patients with an OF score >3 were likely to have an OF and patients with a surgery score ≤2 were unlikely to have surgery.

The present study demonstrated that our OF and surgery scores resulted in an effective model that allowed the stratification of patients with orbital trauma based on their risk of having OFs and risk of needing a surgical treatment.
The role of ubiquitin-dependent segregase p97 (VCP or Cdc48) in chromatin dynamics after DNA double strand breaks
Authors: Torrecilla Ignacio , Oehler Judith , Ramadan Kristijan
Published: August 2017

DNA double strand breaks (DSBs) are the most cytotoxic DNA lesions and, if not repaired, lead to chromosomal rearrangement, genomic instability and cell death. Cells have evolved a complex network of DNA repair and signalling molecules which promptly detect and repair DSBs, commonly known as the DNA damage response (DDR). The DDR is orchestrated by various post-translational modifications such as phosphorylation, methylation, ubiquitination or SUMOylation. As DSBs are located in complex chromatin structures, the repair of DSBs is engineered at two levels: (i) at sites of broken DNA and (ii) at chromatin structures that surround DNA lesions. Thus, DNA repair and chromatin remodelling machineries must work together to efficiently repair DSBs. Here, we summarize the current knowledge of the ubiquitin-dependent molecular unfoldase/segregase p97 (VCP in vertebrates and Cdc48 in worms and lower eukaryotes) in DSB repair. We identify p97 as an essential factor that regulates DSB repair. p97-dependent extraction of ubiquitinated substrates mediates spatio-temporal protein turnover at and around the sites of DSBs, thus orchestrating chromatin remodelling and DSB repair. As p97 is a druggable target, p97 inhibition in the context of DDR has great potential for cancer therapy, as shown for other DDR components such as PARP, ATR and CHK1.

This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.
Time-resolved Interaction Proteomics of the Putative Scaffold Protein GIGANTEA inArabidopsis thaliana
Authors: Krahmer Johanna , Goralogia Greg , Kubota Akane , Johnson Richard S. , Song Young Hun , MacCoss Michael J. , LeBihan Thierry , Halliday Karen J , Imaizumi Takato , Millar Andrew J.
Published: August 2017

The large, plant-specific protein GIGANTEA (GI) is involved in many physiological processes, mediating rhythmic, post-translational regulation in part through circadian and light regulation ofGIRNA expression. GI binds several proteins implicated in the circadian clock, the control of photoperiodic flowering, and abiotic stress responses, and has co-chaperone activity. By extension, further interaction partners might mediate the less well-understood roles of GI but the number and rhythmicity of these interactors is unknown. Here, we seek potential interactors in a time-specific manner, using quantitative proteomics from a time series study of transgenicArabidopsis thalianaplants constitutively expressing an epitope-tagged GI protein. Previously-identified, direct and indirect interactors of GI were detected but no further F-box proteins related to known GI partners ZTL/FKF1/LKP2. The predominantly non-rhythmic, interacting proteins were implicated in protein folding or degradation, metabolism and chromatin modification, including a small set of partners shared with other clock-related proteins. A transcription factor homologue that we nameCYCLING DOF FACTOR 6(CDF6) was shown to interact both with GI and the ZTL/FKF1/LKP2 proteins and to control photoperiodic flowering. Our results indicate the biochemical pathways, beyond circadian and flowering regulation, that might be affected by GIGANTEA’s rhythmic, post-translational control.

Significance Statement

Significance statement of up to two sentences of no more than 75 words total;

The GIGANTEA protein of Arabidopsis was known for circadian and flowering functions, mediated by the FKF1/LKP2/ZTL family of GI-interacting, F-box proteins, then for a co-chaperone activity of unknown scope. We performed time-resolved, interaction proteomics, identifying CDF6 (At1g26790) as a morning-specific GI interactor that controls flowering time. Unlike FKF1 and CDF proteins, most of the 240 candidate partners were not rhythmically enriched. They link GI to proteostasis and metabolic functions that might mediate GI’s physiological functions.
Inter-homologue repair in fertilized human eggs?
Authors: Egli Dieter , Zuccaro Michael V. , Kosicki Michal , Church George M. , Bradley Allan , Jasin Maria
Published: August 2017

Many human diseases have an underlying genetic component. The development and application of methods to prevent the inheritance of damaging mutations through the human germline could have significant health benefits, and currently include preimplantation genetic diagnosis and carrier screening. Ma et al. take this a step further by attempting to remove a disease mutation from the human germline through gene editing1. They assert the following advances: (i) the correction of a pathogenic gene mutation responsible for hypertrophic cardiomyopathy in human embryos using CRISPR-Cas9 and (ii) the avoidance of mosaicism in edited embryos. In the case of correction, the authors conclude that repair using the homologous chromosome was as or more frequent than mutagenic nonhomologous end-joining (NHEJ). Their conclusion is significant, if validated, because such a “self-repair” mechanism would allow gene correction without the introduction of a repair template. While the authors’ analyses relied on the failure to detect mutant alleles, here we suggest approaches to provide direct evidence for inter-homologue recombination and discuss other events consistent with the data. We also review the biological constraints on inter-homologue recombination in the early embryo.
CRISPR-based herd immunity limits phage epidemics in bacterial populations
Authors: Payne Pavel , Geyrhofer Lukas , Barton Nicholas H. , Bollback Jonathan P.
Published: August 2017

Pathogens are a driving force in evolution, giving rise to a diversity of host immune defenses. In order for a pathogen to spread in a population a sufficient number of its members must be susceptible to infection, as resistant individuals can prevent the spread of a pathogen among susceptible hosts in a process known as herd immunity. While herd immunity has been extensively studied in vertebrate populations, little is known about its role, if any, in the dynamics between bacteria and their phage pathogens. Here we explore the dynamics of T7 phage epidemics in structured and unstructuredEscherichia colipopulations consisting of differing mixtures of susceptible and resistant individuals harboring CRISPR immunity to the phage. Using both experiments and mathematical modelling we describe the conditions under which herd immunity arises in bacterial populations. Notably, the effects of herd immunity depend strongly on the presence of spatial structure in the population, the bacterial growth rate, and phage replication rate. The results of our model can apply to other host-pathogen systems to determine the herd immunity threshold from the relative speed of an epidemic wave in partially resistant populations. In addition, our findings suggest that herd immunity plays an important role in bacterial communities, as seen in other host-pathogen systems, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity.
Fast and Simple Tool for the Quantification of Biofilm-Embedded Cells Sub-Populations from Fluorescent Microscopic Images
Authors: Bogachev Mikhail I , Volkov Vladimir Yu , Markelov Oleg A , Trizna Elena Yu , Baydamshina Diana R , Melnikov Vladislav , Murtazina Regina R , Zelenikhin Pavel V , Sharafutdinov Irshad S , Kayumov Airat R
Published: August 2017

Fluorescent staining is a common tool for both quantitative and qualitative assessment of pro- and eukaryotic cells sub-population fractions by using microscopy and flow cytometry. However, direct cell counting by flow cytometry is often limited, for example when working with cells rigidly adhered either to each other or to external surfaces like bacterial biofilms or adherent cell lines and tissue samples. An alternative approach is provided by using fluorescent microscopy and confocal laser scanning microscopy (CLSM), which enables the evaluation of fractions of cells subpopulations in a given sample. For the quantitative assessment of cell fractions in microphotographs, we suggest a simple two-step algorithm that combines single cells selection and the statistical analysis. To facilitate the first step, we suggest a simple procedure that supports finding the balance between the detection threshold and the typical size of single cells based on objective cell size distribution analysis. Based on a series of experimental measurements performed on bacterial and eukaryotic cells under various conditions, we show explicitly that the suggested approach effectively accounts for the fractions of different cell sub-populations (like the live/dead staining in our samples) in all studied cases that are in good agreement with manual cell counting on microphotographs and flow cytometry data. This algorithm is implemented as a simple software tool that includes an intuitive and user-friendly graphical interface for the initial adjustment of algorithm parameters to the microphotographs analysis as well as for the sequential analysis of homogeneous series of similar microscopic images without further user intervention. The software tool entitled BioFilmAnalyzer is freely available online at https://bitbucket.org/rogex/biofilmanalyzer/downloads/.
Optical Coherence Tomography Reveals Self-Organizing Di-Fork Architecture of Mice Cutaneous Scars
Authors: Ghosh Biswajoy , Mandal Mousumi , Mitra Pabitra , Chatterjee Jyotirmoy
Published: August 2017

Scientific studies report crucial impacts of biomechanical effectors to modulate wound healing either by scarring or regeneration. Further, the biological decision to predominantly favor the former is still cryptic. Real-time visualization of biomechanical manifestationsin situin scarring is hence necessary. Endorsed by nanostructural testing, synthetic phantom analysis, and computational simulations, we found strong mechanobiological correlates for Swept Source Optical Coherence Tomography (SS-OCT) speckles in mice cutaneous repair (full-thickness) up to 10 months. The theoretical basis of the optomechanics to provide insights into scar form-factor and evolution is proposed. Optomechanical changes have been considered as the resultant of intrinsic (e.g. fiber elastic modulus) and gross tissue mechanics (extracellular matrix (ECM)) in maturing scars. Non-invasive optomechanics supported with microscopic findings reveal scar’s cross-sectional self-organizing di-fork architecture. Dual-compartment heterogeneity of di-fork exhibits stress-evading features with a dichotomy in inhabitant cellular stress-fiber distributions. This differential interactivity of scar with adjoining tissues reflects its architectural intelligence to compensate tissue loss (hypodermis/muscle) by assembling into a di-fork. Gradual establishment of baseline shifted lasting mechanobiological steady-state, later in scarring, expose scar as an alternate stable state within the skin.

Significance Statement

Wound repair in mammals, predominantly culminates into function compromising scar that is occasionally fatal in vital organs. How the biological system often adopts scarring over a restorative regeneration is yet a conundrum. Wound and ambient mechanics play a pivotal role in deciding the healing fate. SS-OCT is hence demonstrated here as a non-invasive window to such mechanical manifestations during skin wound healing. This exposed gradual emergence of temporally maintained and stress-resilient di-fork architecture of the scar with differential neighborhood interfaces. Accommodation of such an alternate self-organizing steady-state of scar sheds light on its sustenance and paradoxical selection.
A Rho-GTPase based model explains spontaneous collective migration of neural crest cell clusters
Authors: Merchant Brian , Edelstein-Keshet Leah , Feng James J.
Published: August 2017

We propose a model to explain the spontaneous collective migration of neural crest cells in the absence of an external gradient of chemoattractants. The model is based on the dynamical interaction between Rac1 and RhoA that is known to regulate the polarization, contact inhibition and co-attraction of neural crest cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and RhoA on the cell membrane with a mechanical model for the overdamped motion of membrane vertices, we show that co-attraction and contact inhibition cooperate to produce persistence of polarity in a cluster of neural crest cells by suppressing the random onset of Rac1 hotspots that may mature into new protrusion fronts. This produces persistent directional migration of cell clusters in corridors. Our model confirms a prior hypothesis that co-attraction and contact inhibition are key to spontaneous collective migration, and provides an explanation of their cooperative working mechanism in terms of Rho GTPase signaling. The model shows that the spontaneous migration is more robust for larger clusters, and is most efficient in a corridor of optimal confinement.
Structural insights into the interaction of the conserved mammalian proteins GAPR-1 and Beclin 1, a key autophagy protein
Authors: Li Yue , Zhao Yuting , Su Minfei , Glover Karen , Chakravarthy Srinivas , Colbert Christopher L. , Levine Beth , Sinha Sangita C.
Published: August 2017

Mammalian Golgi-associated plant pathogenesis-related protein 1 (GAPR-1) is a negative autophagy regulator that binds Beclin 1, a key component of the autophagosome nucleation complex. Beclin 1 residues 267–284 are required for binding GAPR-1. Here, sequence analyses, structural modeling, mutagenesis combined with pull-down assays, X-ray crystal structure determination and small-angle X-ray scattering were used to investigate the Beclin 1–GAPR-1 interaction. Five conserved residues line an equatorial GAPR-1 surface groove that is large enough to bind a peptide. A model of a peptide comprising Beclin 1 residues 267–284 docked onto GAPR-1, built using theCABS-dockserver, indicates that this peptide binds to this GAPR-1 groove. Mutation of the five conserved residues lining this groove, H54A/E86A/G102K/H103A/N138G, abrogates Beclin 1 binding. The 1.27 Å resolution X-ray crystal structure of this pentad mutant GAPR-1 was determined. Comparison with the wild-type (WT) GAPR-1 structure shows that the equatorial groove of the pentad mutant is shallower and more positively charged, and therefore may not efficiently bind Beclin 1 residues 267–284, which include many hydrophobic residues. Both WT and pentad mutant GAPR-1 crystallize as dimers, and in each case the equatorial groove of one subunit is partially occluded by the other subunit, indicating that dimeric GAPR-1 is unlikely to bind Beclin 1. SAXS analysis of WT and pentad mutant GAPR-1 indicates that in solution the WT forms monomers, while the pentad mutant is primarily dimeric. Thus, changes in the structure of the equatorial groove combined with the improved dimerization of pentad mutant GAPR-1 are likely to abrogate binding to Beclin 1.