bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pediatric Forearm Fractures Are Effectively Immobilized With a Sugar-Tong Splint Following Closed Reduction
Authors: Dittmer Alison J. , Molina Domingo , Jacobs Cale A. , Walker Janet , Muchow Ryan D. 
Published: November 2018

Introduction:
Following closed reduction and initial casting of pediatric forearm fractures, loss of reduction (LOR) occurs in ∼5% to 75% of fractures. Sugar-tong splinting has been shown to maintain acceptable reduction in pediatric distal radius fractures while potentially avoiding issues associated with circumferential casting. We hypothesized that the sugar-tong splint would be an acceptable method for initial immobilization to prevent LOR in distal, mid-shaft, and proximal pediatric forearm fractures.

Methods:
This is an IRB-approved, retrospective study. Inclusion criteria included pediatric patients age 4 to 16 years old, open growth plates, with a displaced forearm fracture (radius, ulna, or both bone) that underwent closed reduction. The clinical protocol involved closed reduction and application of a sugar-tong splint by an orthopaedic resident under conscious sedation in the emergency room. Clinical follow-up occurred at 1, 2, 4, and 6-week intervals with a long-arm cast overwrap applied at the initial clinic visit. Primary outcome was radiographic LOR which was defined as a change of >10 degrees of angulation on anterior posterior/lateral projections from initial postreduction radiograph or previous follow-up radiograph. The secondary outcome was the need for further intervention.

Results:
Sixty-four (38%) patients demonstrated radiographic LOR with 90% of LORs occurring in the first 2 weeks. LOR was significantly more common in distal radius fractures [48/110 (44%)] than with either proximal [2/14 (14%), P=0.04] or mid-shaft radius fractures [7/41 (17%), P=0.004]. There was no difference in LOR by location for ulna fractures [proximal=2/13 (15%), middle=4/38 (11%), distal=20/77 (26%), P>0.08]. There was no difference in radial LOR in patients with isolated radius fractures compared with both bone forearm fracture (17/40 vs. 40/125, P=0.22), or ulnar LOR between isolated ulna and both bone forearm fracture (0/3 vs. 26/125, P>0.99).

Conclusion:
The sugar-tong splint is effective at maintaining reduction of pediatric forearm fractures similar to published rates for casting. While effective at all levels of the forearm, the sugar-tong splint performed best in proximal and mid-shaft forearm fractures.

Level of Evidence:
Level IV.
Assessment of Mass Effect Sign at High-Resolution Computed Tomography in Prediction of Cholesteatoma
Authors: Gamaleldin Omneya A. , Elsebaie Nermine A. , Khalifa Mohamed Hossameldin , Abdel Razek Ahmed Abdel Khalek , Mehanna Ahmed Mohamed , Shehata Gihan Mohamed 
Published: November 2018

Objective
The aim of this study was to assess the accuracy of mass effect sign in the diagnosis of cholesteatoma at high-resolution computed tomography (HRCT).

Methods
This prospective study included 32 ears in 24 patients with chronic otitis media who underwent HRCT of the temporal bone. Otoscopic and operative notes were recorded. Image analysis was done both qualitatively and quantitatively. In the qualitative analysis, mass effect was evaluated visually by comparing both ears together in 4 certain anatomical sites. Ossicular erosions, erosion of tegmen tympani, erosion of tympanic segment of facial nerve canal, and the presence of lobulated nondependent opacity were also evaluated. In the quantitative analysis, we calculated the difference between the distances of the described anatomical sites in both ears.

Results
Qualitative analysis of mass effect sign showed 97.1% accuracy in detecting cholesteatoma. Ossicular erosions showed 69.2% accuracy in the diagnosis of cholesteatoma. In the quantitative analysis, we found that the cutoff point of 0.45 mm in the difference of aditus measure between both ears showed 85.3% accuracy in differentiating cholesteatoma from otitis media. The cutoff point of 0.75 mm in the differences in supratubal measure showed 86.1% accuracy. The cutoff point of 0.45 mm in the medial to incus measure showed 100% accuracy.

Conclusion
High-resolution computed tomography is highly valuable for the detection of mass effect sign, which has great importance in diagnosing cholesteatoma.
Transmural Myocardial Scar Assessed by Cardiac Computed Tomography: Predictor of Echocardiographic Versus Clinical Response to Cardiac Resynchronization Therapy?
Authors: Fyenbo Daniel Benjamin , Sommer Anders , Kühl J. Tobias , Kofoed Klaus F. , Nørgaard Bjarne L. , Kronborg Mads B. , Bouchelouche Kirsten , Nielsen Jens C. 
Published: November 2018

Objectives
Before cardiac resynchronization therapy (CRT) implantation, cardiac computed tomography (CT) can provide assessment of cardiac venous anatomy and visualize left ventricular (LV) myocardial scar. We hypothesized that localization and burden of transmural myocardial scar verified by cardiac CT are associated with echocardiographic and clinical response to CRT.

Methods
We prospectively included 140 CRT recipients undergoing preimplant cardiac CT. We assessed transmural scar, defined as hypoperfusion involving more than one-half of the myocardial wall in each LV segment using a 17-segment model. Echocardiographic nonresponse was defined as less than 5% absolute improvement in LV ejection fraction at 6 months' follow-up. Clinical nonresponse was defined as 1 or more of the following at 6 months' follow-up: death, heart failure hospitalization, or no improvement in New York Heart Association class and less than 10% increase in 6-minute walk-test distance.

Results
Higher burden of myocardial scar was associated with echocardiographic nonresponse (adjusted odds ratio, 3.02; 95% confidence interval, 1.03–8.91; P = 0.045). Scar concordant or adjacent to LV pacing site was associated with echocardiographic nonresponse (adjusted odds ratio, 8.2; 95% confidence interval, 1.51–44.27; P = 0.015). No association between scar and clinical nonresponse was demonstrated.

Conclusions
Higher scar burden and scar in proximity to the LV pacing site assessed by cardiac CT are associated with echocardiographic nonresponse to CRT. Burden and location of scar were not associated with clinical nonresponse. Further large-scale studies are needed to assess the potential association between myocardial scar detected by cardiac CT and clinical CRT outcome.
Cardiac Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine
Authors: Datzmann Thomas , Wepler Martin , Wachter Ulrich , Vogt Josef A. , McCook Oscar , Merz Tamara , Calzia Enrico , Gröger Michael , Hartmann Clair , Asfar Pierre , Radermacher Peter , Nussbaum Benedikt Lukas 
Published: November 2018

ABSTRACT
Hyperoxia (ventilation with FIO2 = 1.0) has vasoconstrictor properties, in particular in the coronary vascular bed, and, hence, may promote cardiac dysfunction. However, we previously showed that hyperoxia attenuated myocardial injury during resuscitation from hemorrhage in swine with coronary artery disease. Therefore, we tested the hypothesis whether hyperoxia would also mitigate myocardial injury and improve heart function in the absence of chronic cardiovascular comorbidity.
After 3 h of hemorrhage (removal of 30% of the calculated blood volume and subsequent titration of mean arterial pressure to 40 mm Hg) 19 anesthetized, mechanically ventilated, and instrumented pigs received FIO2 = 0.3(control) or hyperoxia(FIO2 = 1.0) during the first 24 h. Before, at the end of and every 12 h after shock, hemodynamics, blood gases, metabolism, cytokines, and cardiac function (pulmonary artery thermodilution, left ventricular pressure-conductance catheterization) were recorded. At 48 h, cardiac tissue was harvested for western blotting, immunohistochemistry, and mitochondrial respiration.
Except for higher left ventricular end-diastolic pressures at 24 h (hyperoxia 21 (17;24), control 17 (15;18) mm Hg; P = 0.046), hyperoxia affected neither left ventricular function cardiac injury (max. Troponin I at 12 h: hyperoxia:9 (6;23), control:17 (11;24) ng mL−1; P = 0.395), nor plasma cytokines (except for interleukin-1β: hyperoxia 10 (10;10) and 10 (10;10)/control 14 (10;22), 12 (10;15) pg mL−1, P = 0.023 and 0.021 at 12 and 24 h, respectively), oxidation and nitrosative stress, and mitochondrial respiration. However, hyperoxia decreased cardiac tissue three-nitrotyrosine formation (P < 0.001) and inducible nitric oxide synthase expression (P = 0.016). Ultimately, survival did not differ significantly either.
In conclusion, in contrast to our previous study in swine with coronary artery disease, hyperoxia did not beneficially affect cardiac function or tissue injury in healthy swine, but was devoid of deleterious side effects.
Effect of Coagulation Factor Concentrates on Markers of Endothelial Cell Damage in Experimental Hemorrhagic Shock
Authors: Hofmann Nikolaus , Zipperle Johannes , Brettner Florian , Jafarmadar Mohammad , Ashmwe Mostafa , Keibl Claudia , Ponschab Martin , Kipman Ulrike , Bahrami Arian , Redl Heinz , Bahrami Soheyl , Fuhrmann Valentin , Schöchl Herbert 
Published: November 2018

ABSTRACT

Background:
Plasma-based resuscitation showed protective effects on the endothelial glycocalyx compared with crystalloid resuscitation. There is paucity of data regarding the effect of coagulation factor concentrates (CFC) on the glycocalyx in hemorrhagic shock (HS). We hypothesized that colloid-based resuscitation supplemented with CFCs offers a therapeutic value to treat endothelial damage following HS.

Methods:
Eighty-four rats were subjected to pressure-controlled (mean arterial pressure (MAP) 30–35 mm Hg) and lab-guided (targeted cutoff: lactate >2.2. mmol/L and base deficit > 5.5 mmol/L) HS. Animals were resuscitated with fresh frozen plasma (FFP), human albumin (HA) or Ringer's lactate (RL) and RL or HA supplemented with fibrinogen concentrate (FC) or prothrombin complex concentrate (PCC). Serum epinephrine and the following markers of endothelial damage were assessed at baseline and at the end-of-observation (120 min after shock was terminated): syndecan-1, heparan sulfate, and soluble vascular endothelial growth factor receptor 1 (sVEGFR 1).

Results:
Resuscitation with FFP had no effect on sVEGFR1 compared with crystalloid-based resuscitation (FFP: 19.3 ng/mL vs. RL: 15.9 ng/mL; RL+FC: 19.7 ng/mL; RL+PCC: 18.9 ng/mL; n.s.). At the end-of-observation, syndecan-1 was similar among all groups. Interestingly, HA+FC treated animals displayed the highest syndecan-1 concentration (12.07 ng/mL). Resuscitation with FFP restored heparan sulfate back to baseline (baseline: 36 ng/mL vs. end-of-observation: 36 ng/mL).

Conclusion:
The current study revealed that plasma-based resuscitation normalized circulating heparan sulfate but not syndecan-1. Co-administration of CFC had no further effect on glycocalyx shedding suggesting a lack of its therapeutic potential.

Level of evidence:
V
Experimental in vivo study.
The research progress of p53 tumour suppressor activity controlled by Numb in triple-negative breast cancer
Authors: Xian Jie , Cheng Yu , Qin Xue , Luo Yequn , Cao Yijia , Cao Youde 
Published: November 2018

AbstractNumb is known as a cell fate determinant as it determines the direction of cell differentiation by asymmetrically partitioning at mitosis. It has been shown to be a tumor suppressor, and there is frequent loss of Numb expression in breast cancer. Numb enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. The aim of this study was to investigate the expression and migration of Numb, HDM2 and p53 proteins in the membrane, cytoplasmic and nuclear fractions of MCF-10A cells and MDA-MB-231 cells. We extracted the cell fractions to detect changes of these three protein levels after re-expression of NUMB in the basal-like triple-negative cell line MDA-MB-231 and knocking down NUMB in the normal mammary epithelial cell line MCF-10A. Our results show that Numb protein can migrate from cytoplasm to nucleus of the MDA-MB-231 cells. Numb protein regulates p53 levels in nucleus of MCF-10A cells and MDA-MB-231 cells, and the Numb levels is positively correlated with p53 levels. We have a finding on HDM2 protein that after knocking down NUMB in MCF-10A cells, it was remarkably reduced in the membrane fraction of NUMB knockdown cells, but its mRNA levels was significantly increased. We also examined the Numb expression in 125 patients with triple-negative breast cancer, 61(48.8%) displayed deficient or reduced expression of Numb. The percent of Ki67>14% in retained Numb group was significantly lower than that in the reduced and deficient Numb group (86.00% vs. 98.40%, P=0.0171).
Plum is a novel regulator of synaptic function and muscle size inD. melanogaster
Authors: Augustin Hrvoje , Spiers Jereme G. , Woodling Nathaniel S. , Steinert Joern R. , Partridge Linda 
Published: November 2018

ABSTRACTAlterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-β superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), theDrosophilahomolog of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction (NMJ), and a negative regulator of body weight and muscle size and function in flies. Here, we identified Plum, a cell surface immunoglobulin homologous to mammalian developmental regulators Protogenin and Nope, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum specifically in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function, likely by de-sequestrating the remaining MYO. In addition, downregulation of Plum on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions.
Characterization of glutamatergic VTA neural population responses to aversive and rewarding conditioning in freely-moving mice
Authors: Montardy Quentin , Zhou Zheng , Lei Zhuogui , Liu Xuemei , Zeng Pengyu , Chen Chen , Liu Yuanming , Sanz-Leon Paula , Huang Kang , Wang Liping 
Published: November 2018

AbstractThe Ventral Tegmental Area (VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, a function involving VTA Dopaminergic and GABAergic neurons. VTA also contains a less known population: glutamatergic (VGluT2) neurons. Direct activation of VGluT2 soma evokes rewarding behaviors, while stimulation of their axonal projections to the Nucleus Accumbens (NAc) and the Lateral Habenula (LHb) evokes aversive behaviors. Here, a systematic investigation of the VTAVGluT2+ population response to aversive or rewarding conditioning facilitated our understanding these conflicting properties. We recorded calcium signals from VTA glutamatergic population neurons using fiber photometry in VGluT2-cre mice to investigate how the VTA glutamatergic neuronal population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTAVGluT2+ neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAVGluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. The inputs and outputs of VTAVGluT2+ neurons were then investigated using Cholera Toxin B (CTB) and rabies virus, and we propose based on all results that VTAVGluT2+ neurons specialized function may be partially due to their connectivity.
Olfactory sensory neurons mediate ultra-rapid antiviral immune responses in teleosts in a TrkA-dependent manner
Authors: Sepahi Ali , Kraus Aurora , Johnston Christopher A , Galindo-Villegas Jorge , Kelly Cecelia , García-Moreno Diana , Muñoz Pilar , Mulero Victoriano , Huertas Mar , Salinas Irene 
Published: November 2018

SummaryThe nervous system is known to regulate host immune responses. However, the ability of neurons to detect danger and initiate immune responses at barrier tissues is unclear. Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with the external environment and therefore directly exposed to pathogens. Here, we report that nasal delivery of rhadboviruses induced apoptosis in crypt OSNs in rainbow trout olfactory organ (OO) via the interaction of the OSN TrkA receptor with viral glycoprotein. This signal resulted in pro-inflammatory responses in the OO and dampened inflammation in the olfactory bulb (OB). CD8α+cells infiltrated the OO within minutes of nasal viral delivery and this response was abrogated when TrkA was blocked. Infiltrating CD8α+cells originated from the microvasculature surrounding the OB and not the periphery. Ablation of crypt neurons in zebrafish resulted in increased susceptibility to rhabdoviral challenge. Our results, therefore, indicate a novel function for OSNs as a first layer of pathogen detection in vertebrates.
NCLX prevents cell death during adrenergic activation of the brown adipose tissue
Authors: Assali Essam A. , Jones Anthony E. , Veliova Michaela , Taha Mahmoud , Miller Nathanael , Shum Michaël , Oliveira Marcus F. , Las Guy , Liesa Marc , Sekler Israel , Shirihai Orian S. 
Published: November 2018

AbstractA sharp increase in mitochondrial Ca2+marks the activation of the brown adipose tissue (BAT) thermogenesis, yet the mechanisms preventing Ca2+deleterious effects are poorly understood. Here, we show that adrenergic stimulation of BAT activates a PKA-dependent mitochondrial Ca2+extrusion via the mitochondrial Na+/Ca2+exchanger, NCLX. Adrenergic stimulation of NCLX-ablated brown adipocytes (BA) induces a profound mitochondrial Ca2+overload and impaired uncoupled respiration. Core body temperature, PET imaging and VO2 measurements confirm a BAT specific thermogenic defect in NCLX-null mice.We show that mitochondrial Ca2+overload induced by adrenergic stimulation of NCLX-null BAT, triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to remarkable mitochondrial swelling, Cytochromecrelease and cell death in BAT. However, treatment with mPTP inhibitors rescue mitochondrial respiratory function and thermogenesis in NCLX-null BA,in vitroandin vivo.Our findings identify a novel pathway enabling non-lethal mitochondrial Ca2+elevation during adrenergic stimulation of uncoupled respiration. Deletion of NCLX transforms the adrenergic pathway responsible for the stimulation of thermogenesis into a death pathway.
Unlocking HDR-mediated Nucleotide Editing by identifying high-efficiency target sites using machine learning
Authors: O’Brien Aidan R. , Wilson Laurence O.W. , Burgio Gaetan , Bauer Denis C. 
Published: November 2018

AbstractEditing individual nucleotides is a crucial component for validating genomic disease association. It currently is hampered by CRISPR-Cas-mediated “base editing” being limited to certain nucleotide changes, and only achievable within a small window around CRISPR-Cas target sites. The more versatile alternative, HDR (homology directed repair), has a 4-fold lower efficiency with known optimization factors being largely immutable in experiments. Here, we investigated the variable efficiency-governing factors on a novel mouse dataset using machine learning. We found the sequence composition of the repair template (ssODN) to be a governing factor, where different regions of the ssODN have variable influence, which reflects the underlying biophysical mechanism. Our model improves HDR efficiency by 83% compared to traditionally chosen targets. Using our findings, we develop CUNE (Computational Universal Nucleotide Editor), which enables users to identify and design the optimal targeting strategy using traditional base editing or – for-the-first-time – HDR-mediated nucleotide changes.CUNE can be run via the web at:https://gt-scan.net/cune
Inferring B cell specificity for vaccines using a mixture model
Authors: Fowler Anna , Galson Jacob D. , Trück Johannes , Kelly Dominic F. , Lunter Gerton 
Published: November 2018

AbstractVaccines have greatly reduced the burden of infectious disease, ranking in their impact on global health second only after clean water. Most vaccines confer protection by the production of antibodies with binding affinity for the antigen, which is the main effector function of B cells. This results in short term changes in the B Cell receptor (BCR) repertoire when an immune response is launched, and long term changes when immunity is conferred. Analysis of antibodies in the serum is usually used to evaluate vaccine response, however this is limited and therefore the investigation of the BCR repertoire provides far more detail for the analysis of vaccine response. Here, we introduce a novel Bayesian model to describe the observed distribution of BCR sequences and the pattern of sharing across time and between individuals, with the goal to identify vaccine-specific BCR sequences. We use data from two studies to assess the model and estimate that we can identify vaccine-specific sequences with 69% sensitivity.
Probiotic Associated Therapeutic Curli Hybrids (PATCH)
Authors: Praveschotinunt Pichet , Duraj-Thatte Anna M. , Gelfat Ilia , Bahl Franziska , Chou David B. , Joshi Neel S. 
Published: November 2018

AbstractThere is an unmet need for new treatment methods for inflammatory bowel disease (IBD) that can reliably maintain remission without leading to detrimental side effects. Beneficial bacteria have been utilized as an alternative treatment for IBD albeit with low efficacy. We genetically engineered Escherichia coli Nissle 1917 (EcN) to create an anti-inflammatory fibrous matrix in situ. This matrix consists of EcN-produced curli nanofibers displaying trefoil factors (TFFs), known to promote intestinal barrier function and epithelial restitution. We confirmed that engineered EcN was able to secrete the curli-fused TFFs in vitro and in vivo, and was non-pathogenic. We observed an enhanced protective effect of engineered EcN against dextran sodium sulfate induced colitis in mice, associated with barrier function reinforcement and immunomodulation. This work sets the foundation for the development of a novel therapeutic platform in which the in situ production of a therapeutic protein matrix from beneficial bacteria can be exploited.