bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related Quality of Life of Adolescents With Severe Untreated Congenital Kyphosis and Kyphoscoliosis in a Developing Country
Authors: Soliman Hany Abdel Gawwad
Published: February 2018

Study Design.

A cross-sectional study

Objective.

The aim of this study was to study the health-related quality of life (HRQOL) of adolescents with severe untreated congenital kyphosis (CK) and congenital kyphoscoliosis (CKS) in a developing country.

Summary of Background Data.

Surgical intervention is generally indicated early in patients with progressive CK or CKS to prevent the progression of deformity and to improve the quality of life of the patients. HRQOL of adolescents with untreated CK and CKS in developing countries has never been investigated.

Methods.

Arabic version of the Scoliosis Research Society 22 revision (SRS-22r) questionnaire used to study HRQOL of adolescents with severe untreated CK or CKS in a dev eloping country.

Results.

A total of 134 adolescent (mean age 17.1 years) completed SRS-22r questionnaire: 38 patients with CK from 80° to 110° (group 1), 24 patients with CK > 110° (group 2), 27 patients with CKS (group 3), and 45 healthy controls (group 4). Group 1 had significant lower scores than group 4 in all SRS 22r domains (P < 0.001). Scores of all domains except pain showed significant (P < 0.001) decrease with increase of the severity of CK. Group 3 had significant lower scores than group 2 in all SRS-22r domains except mental health. Satisfaction domain had significant lower scores than all other SRS-22r domains for group 1, 2, and 3. All patients of groups 2 and 3 gave the minimum answers for satisfaction domain questions. A total of 69%, 84% and 94% of group 1, 2, and 3, respectively, gave the minimum answer when asked whether their back condition affects their personal relationships. Female patients of group 1, 2, and 3 had significant lower scores for self-image domain.

Conclusion.

HRQOL is severely affected in adolescents with untreated severe CK and CKS in a developing country.

Level of Evidence: 3
Iliac Crest Bone Graft for Minimally Invasive Transforaminal Lumbar Interbody Fusion
Authors: Haws Brittany E. , Khechen Benjamin , Narain Ankur S. , Hijji Fady Y. , Cardinal Kaitlyn L. , Guntin Jordan A. , Singh Kern
Published: February 2018

Study Design.

Retrospective Analysis

Objective.

The aim of this study was to determine whether an association between increased acute pain, postoperative time, and direct hospital costs exists between the use of iliac crest bone grafting (ICBG) and bone morphogenic protein (BMP)-2 following a primary, single-level minimally invasive transforaminal lumbar interbody fusion (MIS TLIF).

Summary of Background Data.

ICBG has been associated with enhanced fusion rates. Concerns have been raised in regards to increased operative time and postoperative pain. The advantages of ICBG compared to other spinal fusion adjuncts have been debated.

Methods.

Prospective, consecutive analysis of patients undergoing primary, single-level MIS TLIF with ICBG was compared to a historical cohort of consecutive patients that received BMP-2. Operative characteristics were compared between groups using χ
2 analysis or independent t test for categorical and continuous variables, respectively. Postoperative inpatient pain was measured using the Visual Analog Scale, and inpatient narcotics consumption was quantified as oral morphine equivalents. Outcomes were compared between groups using multivariate regression controlling for preoperative characteristics.

Results.

A total of 98 patients were included in this analysis, 49 in each cohort. No significant differences were noted between cohorts with exception to sex (Females: ICBG, 53.06% vs. BMP-2, 32.65%, P = 0.041). There was a significant increase in operative time (14.53 minutes, P = 0.006) and estimated blood loss (16.64 mL, P = 0.014) in the ICBG cohort. Narcotics consumption was similar between groups on postoperative days 0 and 1. ICBG was associated with decreased total direct costs ($19,315 vs. $21,645, P < 0.001) as compared to BMP-2.

Conclusion.

Patients undergoing MIS TLIF with ICBG experienced increases in operative time and estimated blood loss that were not clinically significant. Furthermore, iliac crest harvesting did not result in an increase in acute pain or narcotics consumption. Further follow-up is necessary to determine the associated arthrodesis rates and long-term outcomes between each cohort.

Level of Evidence: 3
Anterior to Dorsal Root Entry Zone Myelotomy (ADREZotomy)
Authors: Ren Jian , He Chuan , Hong Tao , Li Xiaoyu , Ma Yongjie , Yu Jiaxing , Ling Feng , Zhang Hongqi
Published: February 2018

Study Design.

A retrospective review of prospectively collected data.

Objective.

To confirm the feasibility of using anterior to dorsal root entry zone myelotomy (ADREZotomy), a new surgical approach, for the treatment of ventrolateral deep intramedullary spinal cord cavernous malformation (ISCCMs).

Summary of Background Data.

Surgical removal of ventrolateral deep ISCCMs is highly risky and remains problematic.

Methods.

The authors performed a retrospective study exploring the surgical removal of ventrolateral intrinsic ISCCMs using ADREZotomy in 10 patients. The Frankel grading system was used to evaluate the patients’ neurological function at the preoperative, postoperative and follow-up stages. American Spinal Injury Association Scale scores at the preoperative and postoperative were also obtained. The patient characteristics and surgical outcomes were analyzed. The indication, operative steps, complications, and anatomical basis of the myelotomies were described and discussed.

Results.

In total, nine (90%) patients presented with mild symptoms before surgery. Gross total resections were performed in all 10 patients. Immediately after surgery, the neurological function of eight (80.0%) patients remained the same. One patient improved and one (10%) patient worsened. There were no other immediate or delayed complications related to the surgical procedure. No decrease of total American Spinal Injury Association sensory scores was observed. The follow-up neurological function evaluation showed that two (20%) patients improved from a Frankel grade of D to E and eight (80.0%) patients were stable. No recurrences or other additional neurological deterioration was observed.

Conclusion.

Surgical removal of ventrolateral deep ISCCMs can be feasible using proper surgical techniques. ADREZotomy is a minimally invasive technique for the removal of cervical and thoracic ventrolateral deep ISCCMs, without disrupting the important spinal cord tracts or the need to broadly expose bone.

Level of Evidence: 4
High Incidence of Tuberculosis Infection in HIV-exposed Children Exiting an Isoniazid Preventive Therapy Trial
Authors: Cranmer Lisa M. , Draper Heather R. , Mandalakas Anna M. , Kim Soyeon , McSherry George , Krezinski Emma , Coetzee Joan , Mitchell Charles , Nachman Sharon , van der Linde Mercia , Cotton Mark F. , Hesseling Anneke C.
Published: February 2018

Young HIV-exposed children are at high risk for TB infection. We performed QuantiFERON-TB Gold among HIV-exposed children in South Africa at enrolment and 1-year follow-up. The incidence of TB infection was high for HIV+ (11 cases per 100 child-years) and HIV-exposed uninfected children (15 cases per 100 child-years). QuantiFERON-TB Gold may identify HIV-exposed children at risk for TB disease progression.
Group A Streptococcal Brain Abscess in the Pediatric Population
Authors: Capua Tali , Klivitsky Amir , Bilavsky Efraim , Ashkenazi- Hoffnung Liat , Roth Jonathan , Constantini Shlomi , Grisaru-Soen Galia
Published: February 2018

Background:

Group A Streptococcus (GAS) is a rare cause of central nervous system infections.

Methods:

We describe 3 new cases of GAS brain abscess in previously healthy children treated by us between 2015 and 2016 and review the 5 cases reported in the literature since 1988.

Results:

All 8 children received early empiric antibiotic therapy and surgical intervention, and 5 made a full recovery.

Conclusions:

GAS brain abscess is a rare infection; however its incidence may be rising. We suggest that if patients show symptoms such as fever, vomiting and lethargy, with contiguous infection such as otitis media, mastoiditis, sinusitis or meningitis, GAS brain abscess should be suspected. Prognosis is expected to be good with early implementation of appropriate treatment.
Tracheal Microbiota in Patients With a Tracheostomy Before, During and After an Acute Respiratory Infection
Authors: Pérez-Losada Marcos , Graham Robert J. , Coquillette Madeline , Jafarey Amenah , Castro-Nallar Eduardo , Aira Manuel , Hoptay Claire , Freishtat Robert J. , Mansbach Jonathan M.
Published: February 2018

Examining tracheal microbiota before, during and after acute respiratory infection in patients with a tracheostomy demonstrated large baseline intrapatient microbiota variability and a significant bloom of Haemophilus and Moraxella on day 1 of acute respiratory infection symptoms. The tracheal microbiota community composition changed significantly from baseline to 1 month after acute respiratory infection.
Hospital, Maternal and Birth Factors Associated With Hepatitis B Vaccination at Birth
Authors: Massey Joel , Nair Anil , Dietz Stephanie , Snaman Deborah , Bixler Danae
Published: February 2018

Background:

Hepatitis B virus is a bloodborne pathogen typically transmitted through sexual contact, injection drug use or perinatally. A hepatitis B vaccine (HepB) is available; the first dose is recommended at birth. We sought to identify hospital policy, maternal characteristics and birth factors associated with HepB receipt at birth in West Virginia.

Methods:

We conducted a retrospective cohort study of West Virginia live births in 2015 using vital records matched to immunization registry records to determine frequency of HepB birth dose receipt (<3 days postdelivery). We surveyed all West Virginia birthing facilities in 2015 (N = 26) about perinatal hepatitis B virus prevention policies. We examined associations of hospital policy, maternal characteristics and birth factors with HepB receipt at birth by using a mixed-effects regression model to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs).

Results:

Of 17,458 births, 14,006 (80.2%) infants received a HepB birth dose. Hospital use of preprinted newborn routine admission vaccination orders was associated with HepB birth dose receipt (aPR: 10.60; 95% CI: 2.12–52.72). Not using illicit drugs during pregnancy, maternal age <35 years and weekday births were associated with HepB birth dose receipt (aPR: 1.81; 95% CI: 1.54–2.13; aPR: 1.34, 95% CI: 1.17–1.54 and aPR: 1.15; 95% CI: 1.03–1.28, respectively).

Conclusions:

Hospitals using preprinted admission orders had higher frequencies of HepB birth dose receipt. Additional study is needed to identify HepB birth dose receipt barriers among infants with maternal illicit drug use, maternal age ≥35 years or deliveries during a weekend.
Prevalence of Occult Bacteremia in Infants With Very High Fever Without a Source
Authors: Gangoiti Iker , Rodriguez Elva , Zubizarreta Ane , Benito Javier , Mintegi Santiago
Published: February 2018

We carried out a prospective registry-based cohort study at the emergency department of 363 previously healthy well-appearing infants 3–24 months of age with fever without a source ≥40.5°C based on local protocol. Four were diagnosed with occult bacteremia (1.1%; 95% confidence interval: 0–2.2). Recommendations for nontesting for occult bacteremia screening in these children may have to be reconsidered when fever ≥40.5°C. Larger studies are needed to confirm these results.
Advocating the Development of Next-Generation High-Relaxivity Gadolinium Chelates for Clinical Magnetic Resonance
Authors: Runge Val M. , Heverhagen Johannes T.
Published: February 2018

The question of improved relaxivity, and potential efficacy therein, for a next-generation of magnetic resonance gadolinium chelates with extracellular distribution and renal excretion, which could also be viewed from the perspective of dose, is addressed on the basis of historical development, animal experimentation, and human trials. There was no systematic evaluation that preceded the choice of 0.1 mmol/kg as the standard dose for human imaging with the gadolinium chelates. In part, this dose was chosen owing to bloodwork abnormalities seen in phase I and phase II studies. Animal investigations and early clinical trials demonstrated improved lesion detectability at higher doses in the brain, liver, and heart. By designing an agent with substantially improved relaxivity, higher enhancement equivalent to that provided with the conventional gadolinium agents at high dose could be achieved, translating to improved diagnosis and, thus, clinical care. Implicit in the development of such high-relaxivity agents would be stability equivalent to or exceeding that of the currently approved macrocyclic agents, given current concern regarding dechelation and gadolinium deposition in the brain, skin, and bone with the linear agents that were initially approved. Development of such next-generation agents with a substantial improvement in relaxivity, in comparison with the current group of approved agents, with a 2-fold increase likely achievable, could lead to improved lesion enhancement, characterization, diagnosis, and, thus, clinical efficacy.
Gender Differences in Utilization of Duty-hour Regulations, Aspects of Burnout, and Psychological Well-being Among General Surgery Residents in the United States
Authors: Dahlke Allison R. , Johnson Julie K. , Greenberg Caprice C. , Love Remi , Kreutzer Lindsey , Hewitt Daniel B. , Quinn Christopher M. , Engelhardt Kathryn E. , Bilimoria Karl Y.
Published: February 2018

Objective:

The aim of the study was to (1) assess differences in how male and female general surgery residents utilize duty-hour regulations and experience aspects of burnout and psychological well-being, and (2) to explore reasons why these differing experiences exist.

Background:

There may be differences in how women and men enter, experience, and leave residency programs.

Methods:

A total of 7395 residents completed a survey (response rate = 99%). Logistic regression models were developed to examine the association between gender and resident outcomes. Semistructured interviews were conducted with 42 faculty and 56 residents. Transcripts were analyzed thematically using a constant comparative approach.

Results:

Female residents reported more frequently staying in the hospital >28 hours or working >80 hours in a week (≥3 times in a month, P < 0.001) and more frequently feeling fatigued and burned out from their work (P < 0.001), but less frequently “treating patients as impersonal objects” or “not caring what happens” to them (P < 0.001). Women reported more often having experienced many aspects of poor psychological well-being such as feeling unhappy and depressed or thinking of themselves as worthless (P < 0.01). In adjusted analyses, associations remained significant. Themes identified in the qualitative analysis as possible contributory factors to gender differences include a lack of female mentorship/leadership, dual-role responsibilities, gender blindness, and differing pressures and approaches to patient care.

Conclusions:

Female residents report working more, experiencing certain aspects of burnout more frequently, and having poorer psychological well-being. Qualitative themes provide insights into possible cultural and programmatic shifts to address the concerns for female residents.
Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer
Authors: Jang Jin-Young , Han Youngmin , Lee Hongeun , Kim Sun-Whe , Kwon Wooil , Lee Kyung-Hun , Oh Do-Youn , Chie Eui Kyu , Lee Jeong Min , Heo Jin Seok , Park Joon Oh , Lim Do Hoon , Kim Seong Hyun , Park Sang Jae , Lee Woo Jin , Koh Young Hwan , Park Joon Seong , Yoon Dong Sup , Lee Ik Jae , Choi Seong Ho
Published: February 2018

Objective:

This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC.

Summary Background Data:

Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to support the role of such treatment.

Methods:

This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment.

Results:

After excluding the patients who withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall 2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat analysis, the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs 26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66–3.36),P= 0.028]. R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%,P= 0.004). The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy.

Conclusion:

This is the first prospective randomized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront surgery, neoadjuvant chemoradiation provides oncological benefits in patients with BRPC.
A Combination of Robotic Approach and ERAS Pathway Optimizes Outcomes and Cost for Pancreatoduodenectomy
Authors: Kowalsky Stacy J. , Zenati Mazen S. , Steve Jennifer , Esper Stephen A. , Lee Kenneth K. , Hogg Melissa E. , Zeh Herbert J. , Zureikat Amer H.
Published: February 2018

Objective:

To determine the impact of enhanced recovery after surgery (ERAS) pathway implementation on outcomes, and cost of robotic and open pancreatoduodenectomy.

Background:

ERAS pathways have shown benefit in open pancreatoduodenectomy (OPD). The impact of ERAS on robotic pancreatoduodenectomy (RPD) is unknown.

Methods:

Retrospective review of consecutive RPD and OPDs in the pre-ERAS (July, 2014–July, 2015) and ERAS (July, 2015–July, 2016) period. Univariate and multivariate logistic regression was used to determine impact of ERAS and operative approach alone, or in combination (pre-ERAS + OPD, pre-ERAS + RPD, ERAS + OPD, ERAS + RPD) on length of hospital stay (LOS) and overall cost.

Results:

In all, 254 consecutive pancreatoduodenectomies (RPD 62%, OPD 38%) were analyzed (median age 67, 47% female). ERAS patients had shorter LOS (6 vs 8 days; P = 0.004) and decreased overall cost (USD 20,362 vs 24,277; P = 0.001) compared with non-ERAS patients, whereas RPD was associated with decreased LOS (7 vs 8 days; P = 0.0001) and similar cost compared with OPD. On multivariable analysis (MVA), RPD was predictive of shorter LOS [odds ratio (OR) 0.33, confidence interval (CI) 0.16–0.67, P = 0.002), whereas ERAS was protective against high cost (OR 0.57, CI 0.33–0.97, P = 0.037). On MVA, when combining operative approach with ERAS pathway use, a combined ERAS + RPD approach was associated with reduced LOS and optimal cost compared with other combinations (pre-ERAS + OPD, pre-ERAS + RPD, ERAS + OPD).

Conclusion:

ERAS implementation is independently associated with cost savings for pancreatoduodenectomy. A combination of ERAS and robotic approach synergistically decreases hospital stay and overall cost compared with other strategies.
Risk Factors for Recurrence After Treatment of N1b Papillary Thyroid Carcinoma
Authors: Lee Sang Hun , Roh Jong-Lyel , Gong Gyungyup , Cho Kyung-Ja , Choi Seung-Ho , Nam Soon Yuhl , Kim Sang Yoon
Published: February 2018

Objectives:

To examine risk factors for posttreatment recurrence in papillary thyroid carcinoma (PTC) patients with initial presentation of lateral neck metastasis (N1b).

Summary of Background Data:

N1b PTC recurs after definitive treatment.

Methods:

Study subjects were 437 consecutive PTC patients who underwent total thyroidectomy and therapeutic neck dissection of central and lateral compartments and postoperative radioactive iodine ablation therapy. The patients’ demographics and pathological factors, including factors related to tumors and lymph nodes (LNs), and postoperative thyroglobulin levels were reviewed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify factors associated with recurrence-free survival (RFS).

Results:

During a median follow-up of 83 months (range, 32–135 months), recurrence occurred in 81 (18.1%) patients. Univariate analyses showed that male sex, tumor size, macroscopic extrathyroidal extension, perineural invasion, extranodal extension, LN involvement, LN ratio, MACIS score, and postoperative serum levels of thyroglobulin were significantly associated with RFS (P < 0.05). Multivariate analyses revealed that LN ratio (> 0.25) in the lateral compartment (adjusted hazard ratio = 2.099, 95% confidence interval = 1.278–3.448; P = 0.003), and postoperative serum levels of stimulated (>5.0 ng/mL; 3.172, 1.661–6.056, P < 0.001) and unstimulated (>0.1 ng/mL; 3.200, 1.569–6.526, P = 0.001) thyroglobulin were independent predictors of any-site RFS. Clinical and tumor factors were not independent predictors of RFS outcomes (P > 0.1).

Conclusions:

Posttreatment recurrence is predicted by the LN ratio in the lateral compartment and postoperative serum levels of thyroglobulin in patients with metastatic PTC in the lateral neck.
Opioid Overdose—the Surgeon's Role
Authors: Vu Joceline V. , Lin Lewei A.
Published: February 2018

With increased focus on the potential harms of surgical opioid prescribing, surgeons should be cognizant of the risk of opioid-related adverse events in their patients, including overdose. Risk factors for overdose may be more prevalent than surgeons think, and include high current opioid use, previous or existing substance use disorder, history of overdose, or certain medical comorbidities. The first step to protecting surgical patients from opioid overdose is adequate screening for risk factors; appropriate patient counseling and prudent prescribing practices can then help protect at-risk patients.
Alpha-band oscillations track the retrieval of precise spatial representations from long-term memory
Authors: Sutterer David W. , Foster Joshua J. , Serences John T. , Vogel Edward K. , Awh Edward
Published: February 2018

A hallmark of episodic memory is the phenomenon of mentally re-experiencing the details of past events, and a well-established concept is that the neuronal activity that mediates encoding is reinstated at retrieval. Evidence for reinstatement has come from multiple modalities, including functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG). These EEG studies have shed light on the time-course of reinstatement, but have been limited to distinguishing between a few categories and/or limited measures of memory strength. The goal of this work was to investigate whether recently developed experimental and technical approaches, namely an inverted encoding model applied to alpha oscillatory power in conjunction with sensitive tests of memory retrieval in a continuous space, can track and reconstruct memory retrieval of specific spatial locations. In Experiment 1, we establish that an inverted encoding model applied to multivariate alpha topography can track retrieval of precise spatial memories. In Experiment 2, we demonstrate that the pattern of multivariate alpha activity at study is similar to the pattern observed during retrieval. Finally, we observe that these encoding models predict memory retrieval behavior, including the accuracy and latency of recall. These findings highlight the broad potential for using encoding models to characterize long-term memory retrieval.
Temporal and spatial factors that influence magnetotaxis in C. elegans
Authors: Vidal-Gadea A.G. , Caldart C.S. , Bainbridge C. , Clites B.L. , Palacios B. , Bakhtiari L.A. , Gordon V.D. , Golombek D.A. , Pierce J.T.
Published: February 2018

Many animals can orient using the earth’s magnetic field. In a recent study, we performed three distinct behavioral assays providing evidence that the nematode Caenorhabditis elegans orients to earth-strength magnetic fields (Vidal-Gadea et al., 2015). In addition to these behavioral assays, we found that magnetic orientation in C. elegans depends on the AFD sensory neurons and conducted subsequent physiological experiments showing that AFD neurons respond to earth-strength magnetic fields. A new behavioral study by Landler et al. (2017) suggested that C. elegans does not orient to magnetic fields and raises issues that cast doubt on our study. Here we reanalyze Lander et al.’s data to show how they appear to have missed observing positive results, and we highlight differences in experimental methods and interpretations that may explain our different results and conclusions. Moreover, we present new data from our labs together with replication by an independent lab to show how temporal and spatial factors influence the unique spatiotemporal trajectory that worms make during magnetotaxis. Together, these findings provide guidance on how to achieve robust magnetotaxis and reinforce our original finding that C. elegans is a suitable model system to study magnetoreception.
Estimating the cortex-wide overlap between wordless narrative scene comprehension, reading comprehension, and topological visual, auditory, and somatomotor maps
Authors: Sood Mariam R. , Sereno Martin I.
Published: February 2018

Previous imaging research in scene comprehension has mostly focussed on isolated scenes and objects. Here we use narrative picture stimuli and a novel controlled presentation technique to identify the full extent of activation during naturalistic narrative scene comprehension. We then situate it with respect to topologically-mapped sensory and motor regions as well as cortical regions activated during naturalistic narrative reading comprehension. The data for all experiments was obtained from the same set of subjects, and analyzed using cortical surface based methods from start to finish. The results suggest that scene and reading activations are spread across occipital, parietal, temporal, and frontal cortex, and largely aligned with each other. Within these regions, there were also sites uniquely activated when subjects were engaged in either narrative scene comprehension or in reading comprehension. Finally, the cortical activations for both scene and reading comprehension contrasts substantially overlap topological cortical maps, specifically retinotopic and tonotopic maps in occipital, parietal, temporal, and frontal cortex.
Structured illumination microscopy combined with machine learning enables the high throughput analysis and classification of virus structure
Authors: Laine Romain F. , Goodfellow Gemma , Young Laurence J. , Travers Jon , Carroll Danielle , Dibben Oliver , Bright Helen , Kaminski Clemens F.
Published: February 2018

Optical super-resolution microscopy techniques enable high molecular specificity with high spatial resolution and constitute a set of powerful tools in the investigation of the structure of supramolecular assemblies such as viruses. Here, we report on a new methodology which combines Structured Illumination Microscopy (SIM) with machine learning algorithms to image and classify the structure of large populations of biopharmaceutical viruses with high resolution. The method offers information on virus morphology that can ultimately be linked with functional performance. We demonstrate the approach on viruses produced for oncolytic viriotherapy (Newcastle Disease Virus) and vaccine development (Influenza). This unique tool enables the rapid assessment of the quality of viral production with high throughput obviating the need for traditional batch testing methods which are complex and time consuming. We show that our method also works on non-purified samples from pooled harvest fluids directly from the production line.
Aging alters envelope representations of speech-like sounds in the inferior colliculus
Authors: Parthasarathy Aravindakshan , Herrmann Björn , Bartlett Edward L.
Published: February 2018

Hearing impairment in aging is thought to arise from impaired temporal processing in auditory circuits. We used a systems-level (scalp recordings) and a microcircuit-level (extracellular recordings) approach to investigate how aging affects the sensitivity to temporal envelopes of speech-like sounds in rats. Scalp-recorded potentials suggest an age-related increase in sensitivity to temporal regularity along the ascending auditory pathway. The underlying cellular changes in the midbrain were examined using extracellular recordings from inferior colliculus neurons. We observed an age-related increase in sensitivity to the sound’s onset and temporal regularity (i.e., periodicity envelope) in the spiking output of inferior colliculus neurons, relative to their synaptic inputs (local field potentials). This relative enhancement for aged animals was most prominent for multi-unit (relative to single-unit) spiking activity. Spontaneous multi-unit, but not single-unit, activity was also enhanced in aged compared to young animals. Our results suggest that aging is associated with altered sensitivity to a sound’s temporal regularities, and that these effects may be due to increased gain of neural network activity in the midbrain.
Inverted Face with Upright Body: Evidence for Face Inversion Effect in Japanese Macaques (Macaca fuscata) under the Preferential Looking Procedure
Authors: Tomonaga Masaki
Published: February 2018

Young Japanese macaques (Macaca fuscata) looked at the photographs that contained faces of the two species of macaques (M. fuscata and M. mulatta) for longer time when they were presented at upright orientation than inverted orientation, and that species discrimination was deteriorated when the photographs were presented at inverted orientation [16]. The present experiment further explored the factor affecting the inversion effect observed in the previous experiments. Five young laboratory-born Japanese macaques looked at the photographs by pressing the lever under the conjugate schedule of sensory reinforcement, that is, successive preferential looking procedure. Photographs of macaques were scrambled and made up two types of the bizarre photographs: upright face with upright body (orientation consistent) and inverted face with upright body (orientation inconsistent). These two types of photographs were presented at upright and inverted orientations. The monkeys looked longer when the face was upright than inverted. Orientation of body and background had no effect on looking time duration. The present results strongly suggest that inversion effect found in macaques is face-specific.
Automatic and feature-specific (anticipatory) prediction-related neural activity in the human auditory system
Authors: Demarchi Gianpaolo , Sanchez Gaëtan , Weisz Nathan
Published: February 2018

Prior experience shapes sensory perception by enabling the formation of expectations with regards to the occurrence of upcoming sensory events. Especially in the visual modality, an increasing number of studies show that prediction-related neural signals carry feature-specific information about the stimulus. This is less established in the auditory modality, in particular without bottom-up signals driving neural activity. We studied whether auditory predictions are sharply tuned to even carry tonotopic specific information. For this purpose, we conducted a Magnetoencephalography (MEG) experiment in which participants passively listened to sound sequences that varied in their regularity (i.e. entropy). Sound presentations were temporally predictable (3 Hz rate), but were occasionally omitted. Training classifiers on the random (high entropy) sound sequence and applying them to all conditions in a time-generalized manner, allowed us to assess whether and how carrier frequency specific information in the MEG signal is modulated according to the entropy level. We show that especially in an ordered (most predictable) sensory context neural activity during the anticipatory and omission periods contains carrier-frequency specific information. Overall our results illustrate in the human auditory system that prediction-related neural activity can be tuned in a tonotopically specific manner.
De novoassembly of two Swedish genomes reveals missing segments from the human GRCh38 reference and improves variant calling of population-scale sequencing data
Authors: Ameur Adam , Che Huiwen , Martin Marcel , Bunikis Ignas , Dahlberg Johan , Höijer Ida , Häggqvist Susana , Vezzi Francesco , Nordlund Jessica , Olason Pall , Feuk Lars , Gyllensten Ulf
Published: February 2018

We have performedde novoassembly of two Swedish genomes using long-read sequencing and optical mapping, resulting in total assembly sizes of nearly 3 Gb and hybrid scaffold N50 values of over 45 Mb. A further analysis revealed over 10 Mb of sequences absent from the human GRCh38 reference in each individual. Around 6 Mb of these novel sequences (NS) are shared with a Chinese personal genome. The NS are highly repetitive, have elevated GC-content and are primarily located in centromeric or telomeric regions. A BLAST search showed that 31% of the NS are different from any sequences deposited in nucleotide databases. The remaining NS correspond to human (62%) or primate (6%) nucleotide entries, while 1% of hits show the highest similarity to other species, including mouse and a few different classes of parasitic worms. Up to 1 Mb of NS can be assigned to chromosome Y, and large segments are missing from GRCh38 also at chromosomes 14, 17 and 21. Inclusion of these novel sequences into the GRCh38 reference radically improves the alignment and variant calling of whole-genome sequencing data at several genomic loci. Through a re-analysis of 200 samples from a Swedish population-scale sequencing project, we obtained over 75,000 putative novel SNVs per individual when using a custom version of GRCh38 extended with 17.3 Mb of NS. In addition, about 10,000 false positive SNV calls per individual were removed from the GRCh38 autosomes and sex chromosomes in the re-analysis, with some of them located in protein coding regions.
PhysiBoSS: a multi-scale agent based modelling framework integrating physical dimension and cell signalling
Authors: Letort Gaelle , Montagud Arnau , Stoll Gautier , Heiland Randy , Barillot Emmanuel , Macklin Paul , Zinovyev Andrei , Calzone Laurence
Published: February 2018

Due to the complexity of biological systems, their heterogeneity, and the internal regulation of each cell and its surrounding, mathematical models that take into account cell signalling, cell population behaviour and the extracellular environment are particularly helpful to understand such complex systems. However, very few of these tools, freely available and computationally efficient, are currently available. To fill this gap, we present here our open-source software, PhysiBoSS, which is built on two available software packages that focus on different scales: intracellular signalling using continuous-time markovian Boolean modelling (MaBoSS) and multicellular behaviour using agent-based modelling (PhysiCell).

The multi-scale feature of PhysiBoSS - its agent-based structure and the possibility to integrate any Boolean network to it - provide a flexible and computationally efficient framework to study heterogeneous cell population growth in diverse experimental set-ups. This tool allows one to explore the effect of environmental and genetic alterations of individual cells at the population level, bridging the critical gap from genotype to phenotype. PhysiBoSS thus becomes very useful when studying population response to treatment, mutations effects, cell modes of invasion or isomorphic morphogenesis events.

To illustrate potential use of PhysiBoSS, we studied heterogeneous cell fate decisions in response to TNF treatment in a 2-D cell population and in a tumour cell 3-D spheroid. We explored the effect of different treatment regimes and the behaviour and selection of several resistant mutants. We highlighted the importance of spatial information on the population dynamics by considering the effect of competition for resources like oxygen. PhysiBoSS is freely available on GitHub (https://github.com/gletort/PhysiBoSS), and is distributed open source under the BSD 3-clause license. It is compatible with most Unix systems, and a Docker package (https://hub.docker.com/r/gletort/physiboss/) is provided to ease its deployment in other systems.
Mechanistic model of temperature influence on flowering through whole-plant accumulation of FT
Authors: Kinmonth-Schultz Hannah A. , MacEwen Melissa J. , Seaton Daniel D. , Millar Andrew J. , Imaizumi Takato , Kim Soo-Hyung
Published: February 2018

We assessed temperature influence on flowering by incorporating temperature-responsive flowering mechanisms across developmental age into an existing model. Temperature influences both the leaf production rate and expression of FLOWERING LOCUS T (FT), a photoperiodic flowering regulator, in leaves. The Arabidopsis Framework Model incorporated temperature influence on leaf growth but ignored the consequences of leaf growth on and direct temperature influence of FT expression. We measured FT production in differently aged leaves and modified the model, adding the mechanistic temperature influence on FT transcription, and linking FT to leaf growth. Our simulations suggest that in long days, the developmental timing (leaf number) at which the reproductive transition occurs is influenced by day length and temperature through FT, while temperature influences the rate of leaf production and the time (in days) the transition occurs. Further, we demonstrated that FT is mainly produced in the first 10 leaves in the Columbia ecotype, and that FT accumulation alone cannot explain flowering in conditions in which flowering is delayed. Our simulations supported our hypotheses that: 1) temperature regulation of FT, accumulated with leaf growth, is a component of thermal time, and 2) incorporating mechanistic temperature regulation of FT can improve model predictions in fluctuating temperatures.
DNAscan: a fast, computationally and memory efficient bioinformatics pipeline for the analysis of DNA next-generation-sequencing data
Authors: Iacoangeli A , Al Khleifat A , Sproviero W , Shatunov A , Jones AR , Dobson R , Newhouse SJ , Al-Chalabi A
Published: February 2018

The generation of DNA Next Generation Sequencing (NGS) data is a commonly applied approach for studying the genetic basis of biological processes, including diseases, and underpins the aspirations of precision medicine. However, there are significant challenges when dealing with NGS data. A huge number of bioinformatics tools exist and it is therefore challenging to design an analysis pipeline; NGS analysis is computationally intensive, requiring expensive infrastructure which can be problematic given that many medical and research centres do not have adequate high performance computing facilities and the use of cloud computing facilities is not always possible due to privacy and ownership issues. We have therefore developed a fast and efficient bioinformatics pipeline that allows for the analysis of DNA sequencing data, while requiring little computational effort and memory usage. We achieved this by exploiting state-of-the-art bioinformatics tools. DNAscan can analyse raw, 40x whole genome NGS data in 8 hours, using as little as 8 threads and 16 Gbs of RAM, while guaranteeing a high performance. DNAscan can look for SNVs, small indels, SVs, repeat expansions and viral genetic material (or any other organism). Its results are annotated using a customisable variety of databases including ClinVar, Exac and dbSNP, and a local deployment of the gene.iobio platform is available for an on-the-fly result visualisation.
Collective motion conceals fitness differences in crowded cellular populations
Authors: Kayser Jona , Schreck Carl , Gralka Matti , Fusco Diana , Hallatschek Oskar
Published: February 2018

Many cellular populations are tightly-packed, for example microbial colonies and biofilms [39, 10, 41], or tissues and tumors in multi-cellular organisms [11, 29]. Movement of one cell inside such crowded assemblages requires movement of others, so that cell displacements are correlated over many cell diameters [28, 6, 31]. Whenever movement is important for survival or growth [15, 34, 38, 9], such correlated rearrangements could couple the evolutionary fate of different lineages. Yet, little is known about the interplay between mechanical stresses and evolution in dense cellular populations. Here, by tracking deleterious mutations at the expanding edge of yeast colonies, we show that crowding-induced collective motion prevents costly mutations from being weeded out rapidly. Joint pushing by neighboring cells generates correlated movements that suppress the differential displacements required for selection to act. Such mechanical screening of fitness differences allows the mutants to leave more descendants than expected under non-mechanical models, thereby increasing their chance for evolutionary rescue [2, 5]. Our work suggests that mechanical interactions generally influence evolutionary outcomes in crowded cellular populations, which has to be considered when modeling drug resistance or cancer evolution [1, 22, 34, 30, 36, 42].
Investigation of Electrical Stimulation Effect on Intracellular Calcium Dynamics Using Locally Uniform Mesh Refinement
Authors: Oftadeh Mohammad Omid
Published: February 2018

Modeling-based methods are conventionally exploited to simulate and predict the dynamics of a system in various fields of engineering. However, due to the intricacy of biological systems, these methods were rarely utilized in bioengineering until recently. By developing advanced computers with the ability to cope with enormous calculations and extending our knowledge about biological systems, modeling-based approaches have been adopted to manipulate biological systems. While utilizing the models to investigate the behavior of a system has some advantages including lower cost and time consumption, such methods were used for tissue engineering scarcely. Exploiting modeling-based methods to tissue engineering field requires developing and utilizing efficient computational methods to model gene regulation and signaling networks, which determine cell response to environmental changes and cellular fate.

In the present work, a novel spatio-temporal method was proposed, predicated on locally uniform mesh refinement. A benchmark comparison was performed with the previously used method and the results indicated the better performance of the incipiently adopted method. Besides, the model was utilized to investigate the effect of a popular differentiating stimulator, namely electrical stimulation, on mesenchymal stem cells as a type of stem cells widely used in tissue engineering. The results of the simulations demonstrated the puissance of such computational models in analyzing and predicting the effect of biochemical and biophysical perturbations on the cells and hence, their potential utility in tissue engineering.
Generation of functional human adipose tissue in mice from primed progenitor cells
Authors: Rojas-Rodriguez Raziel , Lujan-Hernandez Jorge , Min So Yun , DeSouza Tiffany , Teebagy Patrick , Desai Anand , Tessier Heather , Slamin Robert , Siegel-Reamer Leah , Berg Cara , Baez Angel , Lalikos Janice , Corvera Silvia
Published: February 2018

Abstarct

Adipose tissue is used extensively in reconstructive and regenerative therapies, but transplanted fat often undergoes inflammation and cell death, requiring further revision surgery. We report that functional human adipose tissue can be generated from mesenchymal progenitor cells in-vivo, providing an alternative approach to its therapeutic use. We leveraged previous findings that progenitor cells within the vasculature of human adipose tissue robustly proliferate in 3-dimensional culture under proangiogenic conditions. Implantation of these progenitor cells into immunocompromised mice results in differentiation towards non-adipocyte fates, incapable of generating a distinct tissue structure. However, priming of these progenitor cells in-vitro towards adipogenic differentiation results in formation of functional adipose tissue in-vivo. Mechanistically, priming induces the expression of genes encoding specific extracellular matrix and remodeling proteins, and induces extensive vascularization by host blood vessels. In comparison, grafts from adipose tissue obtained by liposuction undergo poor vascularization, adipocyte death, cyst formation, calcification and inefficient adiponectin secretion. Thus, primed mesenchymal adipose tissue progenitors reveal mechanisms of human adipose tissue development, and have potential to improve outcomes in reconstructive and regenerative medicine.
Microbial Engraftment and Efficacy of Fecal Microbiota Transplant for Clostridium difficile Patients With and Without IBD
Authors: Hirten Robert P , Grinspan Ari , Fu Shih-Chen , Luo Yuying , Suarez-Farinas Mayte , Rowland John , Contijoch Eduardo J. , Mogno Ilaria , Yang Nancy , Luong Tramy , Labrias Philippe R. , Peter Inga , Cho Judy H. , Sands Bruce E. , Colombel Jean Frederic , Faith Jeremiah J. , Clemente Jose C.
Published: February 2018

Background & Aims

Recurrent and refractory Clostridium difficile infections (CDI) are effectively treated with fecal microbiota transplant (FMT). Uncertainty exists regarding the effectiveness of FMT for CDI with underlying inflammatory bowel disease (IBD), its effects on disease activity and its effectiveness transferring the donor microbiome to patients with and without IBD. This study aims to determine FMTs effectiveness in subjects with and without IBD, its impact on IBD activity, the level of microbiome engraftment, and predictors of CDI recurrence.

Methods

Subjects with and without IBD who underwent FMT for recurrent or refractory CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) Frequency of IBD flare after FMT; (3) Microbiome engraftment after FMT; (4) Predictors of CDI recurrence.

Results

Overall, 134 patients, 46 with IBD, were treated with FMT. There was no difference in recurrence in patients with and without IBD at 2 months (22.5% vs 17.9%; p=0.63) and 6 months (38.7% vs 36.5%; p>0.99). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. The pre-FMT microbiome was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment. There was no difference in engraftment based on IBD endoscopic severity at FMT.

Conclusions

IBD did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiome was not predictive of recurrence, and microbial engraftment was dependent on IBD treatment escalation but not on underlying disease severity.