bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiostereometric Analysis of Stability and Inducible Micromotion After Locked Lateral Plating of Distal Femur Fractures
Authors: Galea Vincent P. , Botros Mina A. , McTague Michael F. , Weaver Michael J. , Vrahas Mark S. , Malchau Henrik , Heng Marilyn , Bragdon Charles
Published: December 2019

Objectives:

To evaluate interfragmentary motion over 1 year after distal femoral fracture fixation using radiostereometric analysis (RSA). The secondary aim was to assess whether RSA data are consistent with diagnoses of nonunion.

Design:

Prospective cohort study.

Setting:

Level I urban trauma center.

Patients:

Sixteen patients between 22 and 89 years of age with distal femoral fracture (OTA/AO type 33).

Intervention:

All fractures were treated with a lateral locking plate, and tantalum markers were inserted into the main proximal and distal fracture fragments. RSA was performed at 2, 6, 12, 18, and 52 weeks postoperatively. Both unloaded and loaded RSA measurements were performed.

Main Outcome Measurements:

Unloaded fracture migration over time and inducible micromotion at the fracture site in the coronal plane were determined at each follow-up interval.

Results:

RSA precision in the coronal plane of interfragmentary motion over time and inducible micromotion were 1.2 and 0.9 mm in the coronal plane, respectively. Two cases required revision surgery for nonunion 1 year postoperatively. For cases of union, unloaded fracture migration stopped being detectable between 12 and 18 weeks, and inducible micromotion was no longer detectable by the 12-week visit. For cases of nonunion, both unloaded migration and inducible micromotion were detected throughout the study period.

Conclusions:

RSA may be used to reliably assess distal femoral fracture healing. RSA revealed differences in cases of union and nonunion by 3 months and more consistently than traditional x-rays.

Level of Evidence:

Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Influences of two significant variants located in the ST6GAL1 3′-untranslated region on lung carcinoma susceptibility in the Chinese Han population
Authors: Liu Xi , Chen Lei , Ren Zhipeng , Tian Xiaodong
Published: December 2019

The aim of this study was to identify the associations of the ST6GAL1 gene 3′-untranslated region polymorphisms with lung carcinoma risk in a Chinese Han population. Three single-nucleotide polymorphisms (SNPs; rs1042757, rs2284749, and rs2239611) in ST6GAL1 were genotyped in 322 lung carcinoma patients and 384 healthy controls. The relationships between these variants and lung cancer risk were examined by logistic regression analysis. Stratified analysis was conducted to detect the influence of these SNPs on lung carcinoma susceptibility among individuals aged younger or older than 50 years. In addition, bioinformatics analysis predicted the potential microRNAs that target the region containing the selected SNPs. We determined rs2284749 in the ST6GAL1 gene that was associated with a decreased risk of lung cancer in the Chinese Han population, based on the recessive model (odds ratio: 0.66; 95% confidence interval: 0.44–0.99, P = 0.045). Among individuals older than 50 years, we observed a protective effect of rs2284749 in the recessive model (P = 0.020) and log-additive model (P = 0.045), and rs2239611 associated with the decreased lung cancer risk under codominant (P = 0.037), dominant (P = 0.010), overdominant (P = 0.026) and log-additive (P = 0.015) models. Furthermore, bioinformatics analyses revealed distinct roles for rs2284749 and rs2239611 in the microRNA targeting sites. These findings suggested that rs2284749 and rs2239611 in the ST6GAL1 gene are associated with lung carcinoma risk in the Chinese Han population. Our results yield new insights into ST6GAL1 in lung cancer development.
Understanding Relationships Between Chlamydial Infection, Symptoms, and Testing Behavior
Authors: Lewis Joanna , White Peter J.
Published: December 2019

Background:

Genital chlamydia is the most commonly diagnosed sexually transmitted infection worldwide and can have serious long-term sequelae. Numerous countries invest substantially in testing but evidence for programs’ effectiveness is inconclusive. It is important to understand the effects of testing programs in different groups of people.

Methods:

We analyzed data on sexual behavior and chlamydia tests from 16-to 24-year olds in Britain’s third National Survey of Sexual Attitudes and Lifestyles, considering test setting, reason, and result. We conducted descriptive analysis accounting for survey design and nonresponse, and Bayesian analysis using a mathematical model.

Results:

Most men testing due to symptoms tested in sexual health settings (63%; 95% confidence interval 43%–84%) but most women testing due to symptoms were tested by general practitioners (59%; 43%–76%). Within behavioral groups, positivity of chlamydia screens (tests not prompted by symptoms or partner notification) was similar to population prevalence. Screening rates were higher in women and in those reporting more partners: median (95% credible interval) rates per year in men were 0.30 (0.25–0.36) (0 new partners), 0.45 (0.37–0.54) (1 new partner), and 0.60 (0.50–0.73) (≥2 new partners). In women, they were 0.61 (0.53–0.69) (0 new partners), 0.89 (0.75–1.04) (1 new partner), and 1.2 (1.0–1.4) (≥2 new partners).

Conclusions:

Proportion of testing occurring in sexual health is not a proxy for proportion prompted by symptoms. Test positivity depends on a combination of force of infection and screening rate and does not simply reflect prevalence or behavioral risk. The analysis highlights the value of recording testing reason and behavioral characteristics to inform cost-effective control.
Daily luteal serum and urinary hormone profiles in the menopause transition: Study of Women's Health Across the Nation
Authors: Santoro Nanette , El Khoudary Samar R. , Nasr Alexis , Gold Ellen B. , Greendale Gail , McConnell Dan , Neal-Perry Genevieve , Pavlovic Jelena , Derby Carol , Crawford Sybil
Published: December 2019

Objective:

To further characterize the endocrinology of the menopause transition, we sought to determine: whether relationships between urine and serum hormones are maintained as women enter their sixth decade; whether a single luteal phase serum progesterone (P) is reflective of integrated-luteal urinary pregnanediol glucuronide (uPdg); and whether serum P, like luteal uPdg, declines as women approach their final menses (FMP).

Methods:

The Study of Women's Health Across the Nation (SWAN) Daily Hormone Study's (DHS) is a community-based observational study. A subset of participants underwent a timed, luteal blood draw planned for cycle days 16 to 24 during the same month of DHS collection. Serum-luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and P, and urine LH, FSH, estrone conjugates (E1c), and daily and integrated luteal uPdg were measured in 268 samples from 170 women. Serum/urine hormone associations were determined using Pearson's correlation and linear regression, adjusted for concurrent age, body mass index, smoking status, and race/ethnicity.

Results:

Pearson's r ranged from 0.573 (for LH) to 0.843 (for FSH) for serum/urine correlations. Integrated luteal uPdg weakly correlated with serum P (Pearson's r = 0.26, P = 0.004) and explained 7% of the variability in serum P in adjusted linear regression (total R
2 0.09, P = 0.002). Serum P demonstrated a marginally significant decline with approaching FMP in adjusted analysis (P = 0.04).

Conclusions:

Urine and serum hormones maintain a close relationship in women into their sixth decade of life. Serum luteal P was weakly reflective of luteal Pdg excretion.
Impact of Changes in the Optical Density of Postlens Fluid on the Clinical Performance of Miniscleral Lenses
Authors: Akkaya Turhan Semra , Dizdar Yigit Didem , Toker Ebru
Published: December 2019

Purpose:

To determine the impact of optical density changes in postlens fluid on clinical performance and to quantify these changes over time during miniscleral lens wear.

Methods:

Twenty-three eyes of 13 patients with keratoconus were fitted with a miniscleral lens (scleral Misa lenses; Microlens Contactlens Technology, Arnhem, Netherlands). The lens fit was evaluated using the fluorescein pattern and also through anterior segment optical coherence tomography imaging. The optical density changes were measured using Scheimpflug tomography at 30 min, 1, 2, 3, and 4 hr. High- and low-contrast visual acuity (VA), subjective performance with comfort and vision (5-point Likert scale), and overall satisfaction with the lens (100-mm visual analog scale) were measured before and after lens-wear.

Results:

The mean Snellen high-contrast VA (best spectacle-corrected VA: 0.4±0.2 vs. VA with the scleral lens: 0.8±0.1, P<0.0001) and low-contrast VA (best spectacle-corrected VA: 1.2±0.2 vs. VA with the scleral lens: 1.3±0.2, P=0.019) significantly improved with dispensed scleral lens. Patients reported high scores for comfort (3.8±0.8), vision (3.8±0.6), and overall satisfaction with the lens (68.7±19.1). Compared with preoperative values, optical density significantly increased over time (P<0.0001). High-contrast VA remained stable, whereas low-contrast VA significantly decreased at 2 hr (P=0.035).

Conclusion:

This study shows that the optical density of postlens fluid increases over time with miniscleral lens wear, and it has a negative impact on low-contrast VA.
Early Integumentary Practice Expectations Experienced by 2 Physical Therapist Graduate Cohorts
Authors: Gibbs Karen A. , Bachman Teresa , Patrick Rikki , Spivey Steve , Gibbs David
Published: December 2019

Purpose:

The primary purpose of this study was to determine integumentary knowledge and skill expectations experienced by 2 physical therapist graduate cohorts. Perceptions of comfort with integumentary examination, evaluation, and intervention were assessed. A secondary purpose was to inform entry-level integumentary curriculum revision.

Methods:

Seventy-six graduates from 2 cohorts were invited to participate in the online survey with 41 active participants. Frequency counts were determined from quantitative data and thematic coding was developed from qualitative data.

Results:

All but one participant indicated they met or partially met entry-level integumentary practice expectations. Participants reported negative-pressure wound therapy, paste compression wraps, and suture removal as techniques with which they felt uncomfortable. Wound examination and treatment for common etiologies, inflammation versus infection differentiation, patient education, and when to refer were topics with which participants felt the most comfortable. Curricular changes included increased practice for “uncomfortable” topics and increased exposure to patients with wounds during didactic training.

Conclusion:

Results offer a good example of entry-level integumentary practice expectations in Texas. Feedback regarding program weaknesses will be incorporated for the next cohort. While this study reflects early practice expectations in Texas, results could help other physical therapist programs undergoing integumentary curriculum review.
Early cardiac dysfunction in children and young adults with perinatally acquired HIV
Authors: McCrary Andrew W. , Nyandiko Winstone M. , Ellis Alicia M. , Chakraborty Hrishikesh , Muehlbauer Michael J. , Koech Myra M. , Daud Ibrahim , Birgen Elcy , Thielman Nathan M. , Kisslo Joseph A. , Barker Piers C.A. , Bloomfield Gerald S.
Published: December 2019

Objective:

To define the prevalence of early cardiac dysfunction in children and young adults with perinatally acquired HIV and predictors of cardiac function.

Design:

Cross-sectional design.

Methods:

Early cardiac dysfunction was defined as left ventricular (LV) global longitudinal strain z-score less than −2 or myocardial performance index at least 0.5 with normal LV ejection fraction. Regression models were fitted to assess the relationship between measures of cardiac function and HIV RNA levels, clinical variables, and markers of inflammation.

Results:

Six hundred and forty-three individuals (mean age 14.1 ± 5.2 years) were enrolled. The average time on combination antiretroviral treatment was 6.8 ± 3.6 years. Nearly 28% of individuals met criteria for early cardiac dysfunction. Individuals with early cardiac dysfunction were older (15.3 vs. 13.5 years, P < 0.001), had more frequently detectable HIV RNA (52.5 vs. 41.7%, P = 0.018), were more likely exposed to azidothymidine or zidovudine (ZDV) (55.6 vs. 41.2%, P = 0.002), and had higher median level of plasma IL-6 concentrations (1.00 vs. 0.88 pg/ml, P = 0.011). Multivariable models show LV ejection fraction negatively associated with HIV RNA levels [β −0.18; 95% confidence interval (CI) −0.33, −0.03] and ZDV exposure (β −1.75; 95% CI −2.62, −0.88) and positively associated with proportion of life on combination antiretroviral treatment (β 2.65; 95% CI 0.90, 4.41). Higher myocardial performance index was positively associated with serum inflammation marker (IL-6 β 0.01; 95% CI 0.0001, 0.001). Left ventricular global longitudinal strain was not significantly associated with clinical and laboratory variables of interest.

Conclusion:

Over one-quarter of children and young adults living with HIV demonstrated evidence of cardiac dysfunction, which may be associated with increasing levels of systemic inflammation.
Use of viral load to improve survey estimates of known HIV-positive status and antiretroviral treatment coverage
Authors: Young Peter W. , Zielinski-Gutierrez Emily , Wamicwe Joyce , Mukui Irene , Kim Andrea A. , Waruru Anthony , Zeh Clement , Kretzschmar Mirjam E. , De Cock Kevin M.
Published: December 2019

Objective:

To compare alternative methods of adjusting self-reported knowledge of HIV-positive status and antiretroviral (ARV) therapy use based on undetectable viral load (UVL) and ARV detection in blood.

Design:

Post hoc analysis of nationally representative household survey to compare alternative biomarker-based adjustments to population HIV indicators.

Methods:

We reclassified HIV-positive participants aged 15–64 years in the 2012 Kenya AIDS Indicator Survey (KAIS) who were unaware of their HIV-positive status by self-report as aware and on antiretroviral treatment if either ARVs were detected or viral load was undetectable (<550 copies/ml) on dried blood spots. We compared self-report to adjustments for ARV measurement, UVL, or both.

Results:

Treatment coverage among all HIV-positive respondents increased from 31.8% for self-report to 42.5% [95% confidence interval (CI) 37.4–47.8] based on ARV detection alone, to 42.8% (95% CI 37.9–47.8) when ARV-adjusted, 46.2% (95% CI 41.3–51.1) when UVL-adjusted and 48.8% (95% CI 43.9–53.8) when adjusted for either ARV or UVL. Awareness of positive status increased from 46.9% for self-report to 56.2% (95% CI 50.7–61.6) when ARV-adjusted, 57.5% (95% CI 51.9–63.0) when UVL-adjusted, and 59.8% (95% CI 54.2–65.1) when adjusted for either ARV or UVL.

Conclusion:

Undetectable viral load, which is routinely measured in surveys, may be a useful adjunct or alternative to ARV detection for adjusting survey estimates of knowledge of HIV status and antiretroviral treatment coverage.
Anatomical and Clinical Implications in Neocondyle Stability After a Condylectomy
Authors: Nelke Kamil H. , Morawska-Kochman Monika , Nienartowicz Jan , Grzelak Joanna , Staszak Katarzyna , Frączek Marcin , Łuczak Klaudiusz , Guziński Maciej
Published: December 2019

A condylectomy of the mandibular condyle is considered to be the treatment of choice in most cases of condylar head hyperactivity. The aim of the procedure is to remove the growth center of the mandible which is responsible for the mandibular enlargement and asymmetry. This surgical procedure has an impact on the condyle shape and position, but the restoration of mandibular movement and a stable joint position (namely, the proper alignment of the newly shaped condylar head within the condyle fossa) should also be considered important surgical outcomes. In this article, the authors present their own experience in performing condylectomies with an arthroplasty procedure and a special forced suturing technique (FST) in terms of achieving early, accurate mandibular movement and maintaining a stable condyle position in early and late outcomes.

Materials and Methods:

A modified high condylectomy with arthroplasty and FST results had been studied in anatomical, radiological, and clinical model.

Results:

Early findings after FST are promising. A slight improvement in lateral jaw movement was noted after condylectomy with arthroplasty (P < 0.05) both in early and late follow-up. Incisal opening, mandibular protrusion, and lateral movement were sustained. A stable condyle position within the fossa was achieved in each case of condylectomy with arthroplasty (P < 0.05).

Conclusions:

The FST condylectomy and reattachment of the lateral pterygoid muscle in a new, wider position provided an improvement in lateral jaw movement as well as in incisal opening and mandibular protrusion in early follow-up examination compared to the presurgical values. It seems that the FST enabled a better new condylar head position in the glenoid fossa and improved early functional mandibular movement.
Periorbital Injection of Hyaluronic Acid Gel in Patients With Deep Superior Sulcus
Authors: Sung Youngje , Goldberg Robert Alan , Lew Helen
Published: December 2019

Purpose:

Hyaluronic acid gel (HAG) fillers provide a versatile and safe correction method for a sunken superior sulcus (SS) resulting from soft tissue volume loss occurring with aging, previous surgery, or enophthalmos related to trauma or phthisis bulbi. The purpose of this study was to report the long-term clinical outcomes of filler injection for soft-tissue augmentation in patients with a deep SS.

Design:

Retrospective, interventional case series

Methods:

The medical records of 27 patients (32 eyes) with deep superior sulci were reviewed. Twenty injections of hyaluronic acid fillers (Restylane; Q-med AB, Uppsala, Sweden) were performed in the retrobulbar (RB) area, and 15 injections were performed in the SS. Pre- and post-treatment photographs were taken.

Main Outcomes Measures:

Visual acuity for seeing eyes, intraocular pressure, exophthalmos measurement, marginal reflex distance 1, interpalpebral fissure, tarsal platform show, and SS hollowing depth grade

Results:

Enophthalmos corrections were 1.3 ± 0.8 mm (P < 0.001) and the SS hollowing grade decrease was 1.2 ± 0.9 (P < 0.01) after 1 month of RB injection. Enophthalmos corrections were 0.1 ± 0.4 mm (P = 0.317) and the SS sunkeness grade decrease was 1.7 ± 0.8 (P < 0.001) after 1 month of SS injection. The amount of filler to correct enophthalmos of 1 mm was 0.83 ± 0.53 mL using the RB injection. Using Kaplan-Meier survival analysis, the mean period of maintenance for deep SS correction was 9.1 months for RB injections and 8.5 months for SS injections.

Conclusion:

Retrobulbar (RB) hyaluronic acid gel (HAG) injections corrected enophthalmos and a deep SS, while SS injections corrected only a deep SS. These 2 techniques of RB and direct sulcus injection are safe and effective methods for the correction of a deep SS.
Pediatric Mandible Reconstruction for Osteomyelitis During Largest Reported Mycobacterium Abscessus Outbreak
Authors: Mueller Melissa A. , Kanack Melissa D. , Singh Jasjit , Jaffurs Daniel , Vyas Raj M.
Published: December 2019

In 2016, water lines at a children's dental clinic in Orange County, California were contaminated with Mycobacterium abscessus (MA), a non-tuberculosis rapidly-growing mycobacterium, leading to the largest MA outbreak ever reported. Mandatory reporting and active case finding directed by the Public Health Department was conducted in collaboration with community Pediatric Infectious Disease physicians for patients who underwent dental pulpotomies at the contaminated Dental Clinic from January 1 to September 6, 2016. Seventy-one cases (22 confirmed and 49 probable) were identified. One case that required extensive debridement and reconstruction of the mandible is presented in detail. CT maxillofacial demonstrated osteomyelitis extending from the right mandibular angle to the left ramus with multifocal periapical lucencies. CT chest and neck revealed numerous pulmonary nodules and bilateral cervical lymphadenopathy. Extraction of several involved teeth, bilateral selective neck dissection, and extensive mandibular debridement was performed, followed by mandibular stabilization with a custom pre-bent 2.0-mm locking plate. CT images 1-year post-operative showed clearance of infection and sufficient bony stability. Subsequent removal of hardware and bone grafting was performed and the patient is doing well. In the event of a future odontogenic mycobacterium outbreak, the experience at our institution can inform multidisciplinary treatment approaches. Prophylactic extraction of primary teeth that received pulpotomies with contaminated water should be performed. Early and thorough debridement of affected bone, including enucleation of secondary teeth, should be performed if necessary for early source control.
Atlantoaxial Rotatory Subluxation: A Rare Complication of Craniofacial Surgery
Authors: Patel Viren , Yang Robin , Shakir Sameer , Groves Mari , Bartlett Scott P.
Published: December 2019

Introduction:

Neck pain is common in the post-operative period after craniofacial procedures. If patients present with neck pain and torticollis, it could be a manifestation of atlantoaxial rotatory subluxlation (AARS), which describes a rare condition in which there is lateral displacement of C1 relative to C2. When this occurs in the post-operative patient, it is termed Grisel syndrome. In this case series, we report on 3 patients diagnosed with Grisel syndrome after a craniofacial procedure.

Methods:

A retrospective chart review of a single craniofacial surgeon at a pediatric hospital was conducted over the last 3 decades. Demographics, procedures performed, and management strategies of AARS were included for review.

Results:

Three patients were identified who were diagnosed with Grisel syndrome after a craniofacial procedure and required inpatient cervical traction. All patients presented with torticollis within 1 week of their operation. Conservative management was ineffective, and all 3 patients were admitted for inpatient cervical traction, for an average of 13 days followed by an average of 47 days of outpatient therapy. No patients showed any signs of recurrence after removal of outpatient traction device.

Conclusion:

Grisel syndrome is a rare, but serious complication of craniofacial procedures. Physicians caring for these patients must have a high degree of suspicion if a patient with a recent craniofacial procedure presents with torticollis. Delaying the initiation of therapy has been shown to lead to higher rates of recurrence and increases the likelihood that patients will require surgical intervention.
Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space
Authors: Babola Travis A. , Kersbergen Calvin J. , Wang Han Chin , Bergles Dwight E.
Published: December 2019

Neurons in developing sensory pathways exhibit spontaneous bursts of electrical activity that are critical for survival, maturation and circuit refinement. In the auditory system, intrinsically generated activity arises within the cochlea, but the molecular mechanisms that initiate this activity remain poorly understood. We show that burst firing of mouse inner hair cells prior to hearing onset requires P2RY1 autoreceptors expressed by inner supporting cells. P2RY1 activation triggers K+ efflux and depolarization of hair cells, as well as osmotic shrinkage of supporting cells that dramatically increased the extracellular space and speed of K+ redistribution. Pharmacological inhibition or genetic disruption of P2RY1 suppressed neuronal burst firing by reducing K+ release, but unexpectedly enhanced their tonic firing, as water resorption by supporting cells reduced the extracellular space, slowing K+ clearance. These studies indicate that purinergic signaling in supporting cells regulates hair cell excitability by controlling the volume of the extracellular space.
Causal modulation of right fronto-parietal phase synchrony with Transcranial Magnetic Stimulation during a conscious visual detection task
Authors: Stengel Chloé , Vernet Marine , Amengual Julià L. , Valero-Cabré Antoni
Published: December 2019

Correlational evidence in non-human primates has reported evidence of increased frontoparietal high-beta band (22-30 Hz) synchrony during the endogenous allocation of visuospatial attention. But may the engagement of inter-regional synchrony at this specific frequency band provide the causal mechanism by which top-down processes are engaged and they facilitate visual perception in humans? Here we further analyzed electroencephalographic (EEG) signals from a group of healthy human participants who performed a conscious visual detection task, under the influence of briefrhythmic(30 Hz) orrandombursts of Transcranial Magnetic Stimulation (TMS), with an identical number of pulses and duration, delivered to the right Frontal Eye Field (FEF) prior to the onset of a lateralized near-threshold target. We report increases of inter-regional synchronization in the high-beta band (25-35 Hz) between the electrode closest to the stimulated region (right FEF) and parietal leads, and increases of local inter-trial coherence in the same frequency band over parietal contacts, both driven byrhythmicbut notrandomTMS patterns. Importantly, such increases were accompained by increases of visual sensitivity for left visual targets (contralateral to the stimulation) in therhythmicbut not therandomTMS condition at the group level. These outcomes suggest that human high-beta synchrony between right frontal and parietal regions can be modulated non-invasively and that high-beta oscillatory activity across the right dorsal fronto-parietal network may contribute to the facilitation of conscious visual detection. Our study also supports future applications of non-invasive brain stimulation technologies for the manipulation of inter-regional synchrony, which could be administered to improve visual behaviors in healthy humans or neurological patients.
Piriform cortex provides a dominant gamma LFP oscillation in the anterior limbic system
Authors: Carmichael James E. , Yuen Matthew M. , van der Meer Matthijs A. A.
Published: December 2019

Oscillations in the local field potential (LFP) are widespread throughout the rodent limbic system, including in structures such as the orbitofrontal cortex and nucleus accumbens. Synchrony between LFPs across these structures, as seen during specific behavioral events, is often interpreted as evidence of a functional interaction. However, the source of these oscillations is often tacitly assumed to be local, leading to a potential misattribution of function. Using in vivo simultaneous multisite recordings in freely moving male rats (n = 7) we demonstrate that gamma-band LFP oscillations (45-90 Hz) in multiple anterior limbic structures are highly synchronous not only with each other, but also with those in piriform cortex. Phase reversals across the piriform cortex cell layer and susceptibility to nasal occlusion indicate that piriform cortex is the source of these common gamma oscillations. Thus, gamma-band LFP oscillations seen in brain regions adjacent to the piriform cortex are likely not generated locally, but are instead volume conducted from the piriform cortex. This emerging view of gamma oscillations in anterior limbic circuits highlights the importance of the common piriform cortex input as a major influence and introduces caveats in the interpretation of locally recorded LFPs.
A new method of Bayesian causal inference in non-stationary environments
Authors: Shinohara Shuji , Manome Nobuhito , Suzuki Kouta , Chung Ung-il , Takahashi Tatsuji , Okamoto Hiroshi , Gunji Pegio-Yukio , Nakajima Yoshihiro , Mitsuyoshi Shunji
Published: December 2019

Bayesian inference is the process of narrowing down the hypotheses (causes) to the one that best explains the observational data (effects). To accurately estimate a cause, a considerable amount of data is required to be observed for as long as possible. However, the object of inference is not always constant. In this case, a method such as exponential moving average (EMA) with a discounting rate is used to improve the ability to respond to a sudden change; it is also necessary to increase the discounting rate. That is, a trade-off is established in which the followability is improved by increasing the discounting rate, but the accuracy is reduced. Here, we propose an extended Bayesian inference (EBI), wherein human-like causal inference is incorporated. We show that both the learning and forgetting effects are introduced into Bayesian inference by incorporating the causal inference. We evaluate the estimation performance of the EBI through the learning task of a dynamically changing Gaussian mixture model. In the evaluation, the EBI performance is compared with those of the EMA and a sequential discounting expectation-maximization algorithm. The EBI was shown to modify the trade-off observed in the EMA.
Phase separation of Ede1 promotes the initiation of endocytic events
Authors: Kozak Mateusz , Kaksonen Marko
Published: December 2019

Clathrin-mediated endocytosis is a major pathway that eukaryotic cells use to produce transport vesicles from the plasma membrane. The assembly of the endocytic coat is initiated by a dynamic network of weakly interacting proteins, but the exact mechanism of initiation is unknown. Ede1, the yeast homologue of mammalian Eps15, is one of the early-arriving endocytic proteins and a key initiation factor. In the absence of Ede1, most other early endocytic proteins lose their punctate localization and the frequency of endocytic initiation is decreased. We show here that in mutants with increased amounts of cytoplasmic Ede1, the excess protein forms large condensates which exhibit properties of phase separated liquid protein droplets. These Ede1 condensates recruit many other early-arriving endocytic proteins. Their formation depends on the core region of Ede1 that contains a coiled coil and a low-complexity domain. We demonstrate that Ede1 core region is essential for the endocytic function of Ede1. The core region can also promote clustering of a heterologous lipid-binding domain into discrete sites on the plasma membrane that initiate endocytic events. We propose that the clustering of the early endocytic proteins and cargo depend on phase separation mediated by Ede1.
Shuffle-Seq: En masse combinatorial encoding for n-way genetic interaction screens
Authors: Dixit Atray , Kuksenko Olena , Feldman David , Regev Aviv
Published: December 2019

Genetic interactions, defined as the non-additive phenotypic impact of combinations of genes, are a hallmark of the mapping from genotype to phenotype. However, genetic interactions remain challenging to systematically test given the massive number of possible combinations. In particular, while large-scale screening efforts in yeast have quantified pairwise interactions that affect cell viability, or synthetic lethality, between all pairs of genes as well as for a limited number of three-way interactions, it has previously been intractable to perform the large screens needed to comprehensively assess interactions in a mammalian genome. Here, we develop Shuffle-Seq, a scalable method to assay genetic interactions. Shuffle-Seq leverages the co-inheritance of genetically encoded barcodes in dividing cells and can scale in proportion to sequencing throughput. We demonstrate the technical validity of Shuffle-Seq and apply it to screening for mechanisms underlying drug resistance in a melanoma model. Shuffle-Seq should allow screens of hundreds of millions of combinatorial perturbations and facilitate the understanding of genetic dependencies and drug sensitivities.
Cluster Analysis Based on Fasting and Postprandial Plasma Glucose and Insulin Concentrations
Authors: Altuve Miguel , Severeyn Erika
Published: December 2019

Plasma glucose and insulin concentrations are clinical markers used in the diagnosis of metabolic diseases, particularly prediabetes and diabetes. In this paper, we carried out a cluster analysis using plasma glucose and insulin data in fasting and two-hour postprandial. Different clustering experiments were performed by changing the attributes, from one (fasting glucose) to four (fasting and postprandial glucose and insulin) attribute input to a k-means clustering algorithm. Based on the elbow and silhouette methods, three clusters were chosen to carry out the clustering experiments. The Pearson correlation coefficient was used to assess the dependence between the glucose and insulin levels for each cluster created. Results show that one cluster contained prediabetics, another cluster contained diabetics, and subjects without prediabetes and diabetes were assigned to another cluster. Although age was not used as an attribute, we have found that subjects in the three clusters have a different age range. Finally, significant correlations were found between insulin levels in fasting and postprandial and between glucose levels in fasting and postprandial. These associations were stronger in the cluster containing diabetics, where insulin production or action is compromised.
Modeling Resistance and Recurrence Patterns of Combined Targeted-Chemoradiotherapy Predicts Benefit of Shorter Induction Period
Authors: McClatchy David M. , Willers Henning , Hata Aaron N. , Piotrowska Zofia , Sequist Lecia V , Paganetti Harald , Grassberger Clemens
Published: December 2019

The optimal integration of molecularly targeted therapies with concurrent chemotherapy and radiation (CRT) to improve cures in genotype-defined cancers is unknown. Here, we develop a bio-mathematical framework to simulate patterns of local versus distant recurrences in a heterogeneous lung cancer population receiving combined targeted therapy and CRT. Our validated model predicts that targeted induction before CRT, an approach currently being tested in clinical trials, may render adjuvant targeted therapy less effective due to proliferation of drug-resistant cancer cells when using very long induction periods. Furthermore, our simulations not only demonstrate the competing effects of drug-resistant cell expansion versus overall tumor regression as a function of induction length, but can also directly estimate the probability of observing an improvement in progression-free survival at a given cohort size. We thus demonstrate that such stochastic biological simulations have the potential to quantitatively inform the design of multimodality clinical trials in genotype-defined cancers.
Decoupling of Dopamine Release and Neural Activity in Major Depressive Disorder during Reward Processing Assessed by Simultaneous fPET-fMRI
Authors: Zhang Xue , Wang Fuyixue , Hamilton J. Paul , Sacchet Matthew D. , Chen Jingyuan , Khalighi Mehdi , Gotlib Ian H. , Glover Gary H.
Published: December 2019

The interaction of the midbrain dopaminergic system and the striatum is implicated in reward processing; it is still unknown, however, how this interaction is altered in Major Depressive Disorder (MDD). In the current study, we related the dopamine release/binding inferred by [11C] Raclopride functional Positron Emission Tomography (fPET) to neural activity monitored by blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in adults diagnosed with MDD and healthy controls (CTL). Participants completed a monetary incentive delay (MID) task during simultaneous [11C] Raclopride fPET and fMRI. Instead of the usual kinetic modeling method for analyzing dynamic PET time activity curves (TACs), we used a simpler general linear model (GLM) approach, which includes introducing a fPET dopamine activation response function to model changes in the TAC associated with the MID task. In addition, using simulations, we show that the GLM approach has several advantages over kinetic modeling. This is achieved without invoking erroneous steady-state assumptions or selecting a suitable reference region. Our results include the observation of both decreased fMRI activation and dopamine release/binding in the striatum in the MDD cohort, implying a reduced reward processing capacity in MDD. Furthermore, in the MDD group, individuals with lower fMRI activations in the right middle putamen and ventral medial prefrontal cortex (vmPFC) had higher reflection rumination scores, and individuals with lower dopamine release/binding in the left putamen and the right nucleus accumbens (NAcc) also had higher reflection rumination scores. Significant cross-modal inter-subject and intra-subject correlations of dopamine release/binding and fMRI activation were observed in the CTL group, but not in the MDD group. The intra-subject correlation of the two modalities was negatively associated with reflection rumination scores in the CTL group, indicating that decoupling of the dopaminergic system and striatum may be important in the pathophysiology of MDD.
Construction and Integration of Three De Novo Japanese Human Genome Assemblies toward a Population-Specific Reference
Authors: Takayama Jun , Tadaka Shu , Yano Kenji , Katsuoka Fumiki , Gocho Chinatsu , Funayama Takamitsu , Makino Satoshi , Okamura Yasunobu , Kikuchi Atsuo , Kawashima Junko , Otsuki Akihito , Yasuda Jun , Kure Shigeo , Kinoshita Kengo , Yamamoto Masayuki , Tamiya Gen
Published: December 2019

The complete sequence of the human genome is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the international human reference genome (e.g., GRCh37), especially Asian populations, due to a strong bias toward European and African ancestries in a single mosaic haploid genome consisting chiefly of a single donor. Here, we performed de novo assembly of the genomes from three Japanese male individuals using >100× PacBio long reads and Bionano optical maps per sample. We integrated the genomes using the major allele for consensus, and anchored the scaffolds using sequence-tagged site markers from conventional genetic and radiation hybrid maps to reconstruct each chromosome sequence. The resulting genome sequence, designated JG1, is highly contiguous, accurate, and carries the major allele in the majority of single nucleotide variant sites for a Japanese population. We adopted JG1 as the reference for confirmatory exome re-analyses of seven Japanese families with rare diseases and found that re-analysis using JG1 reduced false-positive variant calls versus GRCh37 while retaining disease-causing variants. These results suggest that integrating multiple genome assemblies from a single ethnic population can aid next-generation sequencing analyses of individuals originated from the population.
Spatial suppression in visual motion perception is driven by inhibition: evidence from MEG gamma oscillations
Authors: Orekhova E.V. , Rostovtseva E.N. , Manyukhina V.O. , Prokofiev A.O. , Obukhova T.S. , Nikolaeva A.Yu. , Schneiderman J.F. , Stroganova T.A.
Published: December 2019

Spatial suppression (SS) is a visual perceptual phenomenon that is manifest in a reduction of directional sensitivity for drifting high-contrast gratings whose size exceeds the center of the visual field. Gratings moving at faster velocities induce stronger SS. The neural processes that give rise to such size- and velocity-dependent reductions in directional sensitivity are currently unknown, and the role of surround inhibition is unclear. In magnetoencephalogram (MEG), large high-contrast drifting gratings induce a strong gamma response (GR), which also attenuates with an increase in the gratings’ velocity. It has been suggested that the slope of this GR attenuation is mediated by inhibitory interactions in the primary visual cortex. Herein, we investigate whether SS is related to this inhibitory-based MEG measure. We evaluated SS and GR in two independent samples of participants: school-age boys and adult women. The slope of GR attenuation predicted inter-individual differences in SS in both samples. Test-retest reliability of the neuro-behavioral correlation was assessed in the adults, and was high between two sessions separated by several days or weeks. Neither frequencies nor absolute amplitudes of the GRs correlated with SS, which highlights the functional relevance of velocity-related changes in GR magnitude caused by augmentation of incoming input. Our findings provide evidence that links the psychophysical phenomenon of SS to inhibitory-based neural responses in the human primary visual cortex. This supports the role of inhibitory interactions as an important underlying mechanism for spatial suppression.

Highlights

The role of surround inhibition in perceptual spatial suppression (SS) is debated

GR attenuation with increasing grating’s velocity may reflect surround inhibition

People with greater GR attenuation exhibit stronger SS

The neuro-behavioral correlation is replicated in school-age boys and adult women

The surround inhibition in the V1 is an important mechanism underlying SS
Impute.me: an open source, non-profit tool for using data from DTC genetic testing to calculate and interpret polygenic risk scores
Authors: Folkersen Lasse , Pain Oliver , Ingasson Andres , Werge Thomas , Lewis Cathryn M. , Austin Jehannine
Published: December 2019

To date, interpretation of genomic information has focused on single variants conferring disease risk, but most disorders of major public concern have a polygenic architecture. Polygenic risk scores (PRS) give a single measure of disease liability by summarising disease risk across hundreds of thousands of genetic variants. They can be calculated in any genome-wide genotype data-source, using a prediction model based on genome-wide summary statistics from external studies.

As genome-wide association studies increase in power, the predictive ability for disease risk will also increase. While PRS are unlikely ever to be fully diagnostic, they may give valuable medical information for risk stratification, prognosis, or treatment response prediction.

Public engagement is therefore becoming important on the potential use and acceptability of PRS. However, the current public perception of genetics is that it provides ‘Yes/No’ answers about the presence/absence of a condition, or the potential for developing a condition, which in not the case for common, complex disorders with of polygenic architecture.

Meanwhile, unregulated third-party applications are being developed to satisfy consumer demand for information on the impact of lower risk variants on common diseases that are highly polygenic. Often applications report results from single SNPs and disregard effect size, which is highly inappropriate for common, complex disorders where everybody carries risk variants.

Tools are therefore needed to communicate our understanding of genetic predisposition as a continuous trait, where a genetic liability confers risk for disease. Impute.me is one such a tool, whose focus is on education and information on common, complex disorders with polygenetic architecture. Its research-focused open-source website allows users to upload consumer genetics data to obtain PRS, with results reported on a population-level normal distribution. Diseases can only be browsed by ICD10-chapter-location or alphabetically, thus prompting the user to consider genetic risk scores in a medical context of relevance to the individual.

Here we present an overview of the implementation of the impute.me site, along with analysis of typical usage-patterns, which may advance public perception of genomic risk and precision medicine.
Swimming performance traits of twenty-one Australian fish species: a fish passage management tool for use in modified freshwater systems
Authors: Watson Jabin R. , Goodrich Harriet R. , Cramp Rebecca L. , Gordos Matthew A. , Yan Yulian , Ward Patrick J. , Franklin Craig E.
Published: December 2019

Freshwater ecosystems have been severely fragmented by artificial in-stream structures designed to manage water for human use. Significant efforts have been made to reconnect freshwater systems for fish movement, through the design and installation of dedicated fish passage structures (fishways) and by incorporating fish-sensitive design features into conventional infrastructure (e.g. culverts). Key to the success of these structures is making sure that the water velocities within them do not exceed the swimming capacities of the local fish species. Swimming performance data is scarce for Australian fish, which have a reduced swimming capacity when compared to many North American and European species. To help close this knowledge gap and assist fisheries management and civil engineering, we report the swimming performance capacities of twenty-one small-bodied fish and juveniles (< 10 cm) of large bodied species native to Australia as measured by critical swimming speed (Ucrit) and burst swimming speed (Usprint) in a recirculating flume. This data is complemented by endurance swim trials in a 12-meter hydraulic flume channel, and by measures of flume traverse success. Building on the utility of this dataset, we used a panel of morphological, behavioural and ecological traits to first assess their relative contributions to the observed swimming performance data, and second, to determine if they could be used to predict swimming performance capacity – a useful tool to assist in the management of species of conservation concern where access to swimming performance data may be limited. We found that body length combined with depth station (benthic, pelagic or surface) explained most of the interspecific variation in observed swimming performance data, followed by body shape and tail shape. These three traits were the most effective at predicting swimming performance in a model/unknown fish. This data will assist civil engineers and fisheries managers in Australia to mitigate the impact of in-stream structures on local fish populations.
Role of centromere sites in activation of ParB proteins for partition complex assembly
Authors: Audibert Sylvain , Tanguy-Le Gac Nicolas , Rech Jérôme , Turlan Catherine , Bouet Jean-Yves , Bystricky Kerstin , Lane David
Published: December 2019

The ParB-parSpartition complexes that bacterial replicons use to ensure their faithful inheritance also find employment in visualization of DNA loci, as less intrusive alternatives to fluorescent repressor-operator systems. The ability of ParB molecules to interact via their N-terminal domains and to bind to non-specific DNA enables expansion of the initial complex to a size both functional in partition and, via fusion to fluorescent peptides, visible by light microscopy. We have investigated whether it is possible to dispense with the need to insertparSin the genomic locus of interest, by determining whether ParB fused to proteins that bind specifically to natural DNA sequences can still assemble visible complexes. In yeast cells, coproduction of fusions of ParB to a fluorescent peptide and to a TALE protein targeting an endogenous sequence did not yield visible foci; nor did any of several variants of these components. InE.coli, coproduction of fusions of SopB (F plasmid ParB) to fluorescent peptide, and to dCas9 together with specific guide RNAs, likewise yielded no foci. The result of coproducing analogous fusions of SopB proteins with distinct binding specificities was also negative. We conclude that in order to assemble higher order partition complexes, ParB proteins need specific activation through binding to their cognateparSsites.