bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Healthcare Cost of Mandibular Nonunions
Authors: Lee Kevin C. , Chuang Sung-Kiang , Koch Alia 
Published: July 2019

Abstract
The aim of this retrospective cohort study was to compare the costs and characteristics between isolated mandible fractures and mandibular nonunions. From October 2015 to December 2016, the National Inpatient Sample (NIS) was searched for patients admitted with a primary diagnosis of a mandible fracture. The sample was divided between those admitted for an initial evaluation of an isolated fracture and a fracture nonunion. Demographic descriptors, injury characteristics, and inpatient factors were recorded. A total of 1432 patients were included in the final sample, of whom 51 (3.6%) were admitted for a nonunion. Nonunion patients were significantly older (P < 0.01), and nonunions were more often localized to the body (24 vs 11%; P = 0.02). Compared to that of isolated fractures, a greater proportion of nonunions required open reduction and internal fixation (86 vs 59%; P < 0.01) and bone grafting (37 vs 1.4%; P < 0.01), and nonunions imparted +32.6% greater hospitals costs (median: $10,680 vs 14,162; P < 0.01). In conclusion, compared to isolated mandible fractures, mandibular nonunions occurred in older patients, had a higher frequency in body of the mandible, and utilized significantly more hospital resources per admission.
Application of a Layered Muscle Flap Technique for the Reconstruction of the Cupid's Bow and Vermilion in the Repair of Secondary Cleft Lip Deformities
Authors: Ma Hengyuan , Zhang Nong , Yin Ningbei , Guo Bin 
Published: July 2019

Abstract
In the repair of unilateral cleft lip, the Cupid's bow, and vermilion on the affected side are sometimes lowered excessively. Methods involving skin and mucosa flaps have been used to correct this issue, but they pose some risk of scarring. The authors here describe a layered muscle flap technique that was based on the anatomical research of nasal-labial muscles, especially the levator labii superioris alaeque nasi muscle. This technique can be used to suspend the Cupid's bow and vermilion in secondary unilateral cleft lip repair. Forty-five patients with secondary unilateral cleft lip with excessively lowered Cupid's bows and vermilion on the affected side were included in this study, which lasted 3 years. These patients were treated using the layered muscle flap surgical technique. The heights of specific bilateral landmarks were measured on patient photos and used to define the symmetry of bilateral Cupid's bow and vermilion. The comparison between post-operative and pre-operative symmetries was used to evaluate the post-operative results, and most of them were satisfactory. The results were also mostly well retained in follow-up investigations. This layered muscle flap technique could be effective in selected cases.
Transition from abdominal aortic and junctional tourniquet to zone 3 resuscitative endovascular balloon occlusion of the aorta is feasible with hemodynamic support after porcine class IV hemorrhage
Authors: Brännström Andreas , Dahlquist Albin , Gustavsson Jenny , Arborelius Ulf P. , Günther Mattias 
Published: July 2019

BACKGROUND
Traumatic hemorrhage remains a major cause of death in rural civilian and combat environments. Potential interventions to control hemorrhage from the pelvis and lower junctional regions include the abdominal aortic and junctional tourniquet (AAJT) and resuscitative endovascular balloon occlusion of the aorta (REBOA). The AAJT requires low technical skills and may thus be used by nonmedical professionals, but is associated with time-dependent ischemic complications. In combination with delayed patient evacuation, it may therefore be deleterious. Transition to zone 3 REBOA in higher levels of care may be a possibility to maintain hemostasis, mitigate adverse effects and enable surgery in patients resuscitated with the AAJT. It is possible that a transition between the interventions could lead to hemodynamic penalties. Therefore, we investigated the feasibility of replacing the AAJT with zone 3 REBOA in a porcine model of uncontrolled femoral hemorrhage.

METHODS
Domestic pigs (n = 12) averaging 57 kg were exposed to a class IV uncontrolled hemorrhage from the common femoral artery. The animals were randomized to 60-minute AAJT (n = 6) or 30-minute AAJT with transition to 30-minute zone 3 REBOA. Hemodynamic and metabolic parameters and ultrasonographic measurements of the common femoral artery were collected.

RESULTS
Transition from AAJT to zone 3 REBOA caused a significant decrease in mean arterial pressure (25 mm Hg). Hemostasis was maintained. The common femoral artery diameter decreased by 1.8 mm (38%) after hemorrhage and further 0.7 mm (23%) after aortic occlusion.

CONCLUSION
Transition from AAJT to zone 3 REBOA after a class IV bleeding is feasible with hemodynamic support. Vascular access to the femoral artery for REBOA insertion poses a technical challenge after hemorrhage and AAJT application.

LEVEL OF EVIDENCE
Laboratory animal study, level IV.
Hypoxia/reoxygenation decreases endothelial glycocalyx via reactive oxygen species and calcium signaling in a cellular model for shock
Authors: Jackson-Weaver Olan , Friedman Jessica K. , Rodriguez Laura A. , Hoof Marcus A. , Drury Robert H. , Packer Jacob T. , Smith Alison , Guidry Chrissy , Duchesne Juan C. 
Published: July 2019

BACKGROUND
Ischemia/reperfusion injury (IRI) has been shown to cause endothelial glycocalyx (EG) damage.
Whether the hypoxic/ischemic insult or the oxidative and inflammatory stress of reperfusion plays a greater part in glycocalyx damage is not known. Furthermore, the mechanisms by which IRI causes EG damage have not been fully elucidated. The aims of this study were to determine if hypoxia alone or hypoxia/reoxygenation (H/R) caused greater damage to the glycocalyx, and if this damage was mediated by reactive oxygen species (ROS) and Ca2+ signaling.

METHODS
Human umbilical vein endothelial cells were cultured to confluence and exposed to either normoxia (30 minutes), hypoxia (2% O2 for 30 minutes), or H/R (30 minutes hypoxia followed by 30 minutes normoxia). Some cells were pretreated with ROS scavengers TEMPOL, MitoTEMPOL, Febuxostat, or Apocynin, or with the Ca2+ chelator BAPTA or Ca2+ channel blockers 2-aminoethoxydiphenyl borate, A967079, Pyr3, or ML204. Intracellular ROS was quantified for all groups. Endothelial glycocalyx was measured using fluorescently tagged wheat germ agglutinin and imaged with fluorescence microscopy.

RESULTS
Glycocalyx thickness was decreased in both hypoxia and H/R groups, with the decrease being greater in the H/R group. TEMPOL, MitoTEMPOL, BAPTA, and 2-aminoethoxydiphenyl borate prevented loss of glycocalyx in H/R. The ROS levels were likewise elevated compared with normoxia in both groups, but were increased in the H/R group compared with hypoxia alone. BAPTA did not prevent ROS production in either group.

CONCLUSION
In our cellular model for shock, we demonstrate that although hypoxia alone is sufficient to produce glycocalyx loss, H/R causes a greater decrease in glycocalyx thickness. Under both conditions damage is dependent on ROS and Ca2+ signaling. Notably, we found that ROS are generated upstream of Ca2+, but that ROS-mediated damage to the glycocalyx is dependent on Ca2+.
Short-term versus long-term trauma mortality: A systematic review
Authors: Frydrych Lynn M. , Keeney-Bonthrone Toby P. , Gwinn Elizabeth , Wakam Glenn K. , Anderson Maia S. , Delano Matthew J. 
Published: July 2019

BACKGROUND
Trauma is the leading cause of death in the United States for persons under 44 years and the fourth leading cause of death in the elderly. Advancements in clinical care and standardization of treatment protocols have reduced 30-day trauma mortality to less than 4%. However, these improvements do not seem to correlate with long-term outcomes. Some reports have shown a greater than 20% mortality rate when looking at long-term outcomes. The aim of this study was to systematically review the incongruence between short- and long-term mortality for trauma patients.

METHODS
For this systematic review, we searched the Cochrane Library, EMBASE, Ovid Medline, Google Scholar, and Web of Science database to obtain relevant English, German, French, and Portuguese articles from 1965 to 2018.

RESULTS
Trauma patients have decreased long-term survival when compared to the general population and when compared with age-matched cohorts. Postdischarge trauma mortality is significantly higher (mean, 4.6% at 3–6 months, 15.8% at 2–3 years, 26.3% at 5–25 years) compared with controls (mean, 1.3%, 2.2%, and 15.6%, respectively). Patient comorbidities likely contribute to long-term trauma deaths. Trauma patients discharged to a skilled nursing facility have worse mortality compared with those discharged either to home or a rehabilitation center. In contrast to data available which illustrate that short-term mortality has improved, quality of evidence was not sufficient to determine if any improvements in long-term trauma mortality outcomes have also occurred.

CONCLUSIONS
The decreased short-term mortality observed in trauma patients does not appear correlated with decreased long-term mortality. The extent to which increased long-term trauma mortality is related to the initial traumatic insult—versus rising population age and comorbidity burden as well as suboptimal discharge location—requires further study.

LEVEL OF EVIDENCE
Systematic Review, level IV.
The macrophage checkpoint CD47 : SIRPα for recognition of ‘self’ cells: from clinical trials of blocking antibodies to mechanobiological fundamentals
Authors: Andrechak Jason C. , Dooling Lawrence J. , Discher Dennis E. 
Published: July 2019

Immunotherapies against some solid tumour types have recently shown unprecedented, durable cures in the clinic, and the most successful thus far involves blocking inhibitory receptor ‘checkpoints’ on T cells. A similar approach with macrophages is emerging by blocking the ubiquitously expressed ‘marker of self’ CD47 from binding the inhibitory receptor SIRPα on macrophages. Here, we first summarize available information on the safety and efficacy of CD47 blockade, which raises some safety concerns with the clearance of ‘self’ cells but also suggests some success against haematological (liquid) and solid cancers. Checkpoint blockade generally benefits from parallel activation of the immune cell, which can occur for macrophages in multiple ways, such as by combination with a second, tumour-opsonizing antibody and perhaps also via rigidity sensing. Cytoskeletal forces in phagocytosis and inhibitory ‘self’-signalling are thus reviewed together with macrophage mechanosensing, which extends to regulating levels of SIRPα and the nuclear protein lamin A, which affects phenotype and cell trafficking. Considerations of such physical factors in cancer and the immune system can inform the design of new immunotherapies and help to refine existing therapies to improve safety and efficacy.This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.
Is cell migration a selectable trait in the natural evolution of cancer development?
Authors: Disanza Andrea , Bisi Sara , Frittoli Emanuela , Malinverno Chiara , Marchesi Stefano , Palamidessi Andrea , Rizvi Abrar , Scita Giorgio 
Published: July 2019

Selective evolutionary pressure shapes the processes and genes that enable cancer survival and expansion in a tumour-suppressive environment. A distinguishing lethal feature of malignant cancer is its dissemination and seeding of metastatic foci. A key requirement for this process is the acquisition of a migratory/invasive ability. However, how the migratory phenotype is selected for during the natural evolution of cancer and what advantage, if any, it might provide to the growing malignant cells remain open issues. In this opinion piece, we discuss three possible answers to these issues. We will examine lines of evidence from mathematical modelling of cancer evolution that indicate that migration is an intrinsic selectable property of malignant cells that directly impacts on growth dynamics and cancer geometry. Second, we will argue that migratory phenotypes can emerge as an adaptive response to unfavourable growth conditions and endow cells not only with the ability to move/invade, but also with specific metastatic traits, including drug resistance, self-renewal and survival. Finally, we will discuss the possibility that migratory phenotypes are coincidental events that emerge by happenstance in the natural evolution of cancer.This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.
Cell migration through three-dimensional confining pores: speed accelerations by deformation and recoil of the nucleus
Authors: Krause Marina , Yang Feng Wei , te Lindert Mariska , Isermann Philipp , Schepens Jan , Maas Ralph J. A. , Venkataraman Chandrasekhar , Lammerding Jan , Madzvamuse Anotida , Hendriks Wiljan , te Riet Joost , Wolf Katarina 
Published: July 2019

Directional cell migration in dense three-dimensional (3D) environments critically depends upon shape adaptation and is impeded depending on the size and rigidity of the nucleus. Accordingly, the nucleus is primarily understood as a physical obstacle; however, its pro-migratory functions by stepwise deformation and reshaping remain unclear. Using atomic force spectroscopy, time-lapse fluorescence microscopy and shape change analysis tools, we determined the nuclear size, deformability, morphology and shape change of HT1080 fibrosarcoma cells expressing the Fucci cell cycle indicator or being pre-treated with chromatin-decondensating agent TSA. We show oscillating peak accelerations during migration through 3D collagen matrices and microdevices that occur during shape reversion of deformed nuclei (recoil), and increase with confinement. During G1 cell-cycle phase, nucleus stiffness was increased and yielded further increased speed fluctuations together with sustained cell migration rates in confinement when compared to interphase populations or to periods of intrinsic nuclear softening in the S/G2 cell-cycle phase. Likewise, nuclear softening by pharmacological chromatin decondensation or after lamin A/C depletion reduced peak oscillations in confinement. In conclusion, deformation and recoil of the stiff nucleus contributes to saltatory locomotion in dense tissues.This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.
Forces and constraints controlling podosome assembly and disassembly
Authors: Rafiq Nisha Bte Mohd , Grenci Gianluca , Lim Cheng Kai , Kozlov Michael M. , Jones Gareth E. , Viasnoff Virgile , Bershadsky Alexander D. 
Published: July 2019

Podosomes are a singular category of integrin-mediated adhesions important in the processes of cell migration, matrix degradation and cancer cell invasion. Despite a wealth of biochemical studies, the effects of mechanical forces on podosome integrity and dynamics are poorly understood. Here, we show that podosomes are highly sensitive to two groups of physical factors. First, we describe the process of podosome disassembly induced by activation of myosin-IIA filament assembly. Next, we find that podosome integrity and dynamics depends upon membrane tension and can be experimentally perturbed by osmotic swelling and deoxycholate treatment. We have also found that podosomes can be disrupted in a reversible manner by single or cyclic radial stretching of the substratum. We show that disruption of podosomes induced by osmotic swelling is independent of myosin-II filaments. The inhibition of the membrane sculpting protein, dynamin-II, but not clathrin, resulted in activation of myosin-IIA filament formation and disruption of podosomes. The effect of dynamin-II inhibition on podosomes was, however, independent of myosin-II filaments. Moreover, formation of organized arrays of podosomes in response to microtopographic cues (the ridges with triangular profile) was not accompanied by reorganization of myosin-II filaments. Thus, mechanical elements such as myosin-II filaments and factors affecting membrane tension/sculpting independently modulate podosome formation and dynamics, underlying a versatile response of these adhesion structures to intracellular and extracellular cues.
This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.
Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells
Authors: Chavali Venkata R. M. , Haider Naqi , Rathi Sonika , Vrathasha Vrathasha , Alapati Teja , He Jie , Gill Kamaljot , Nikonov Roman , Duong Thu T. , McDougald Devin S. , Nikonov Sergei , O’ Brien Joan , Mills Jason A. 
Published: July 2019

AbstractGlaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the optic nerve and visual field loss caused by death of retinal ganglion cells (RGCs). The loss of RGCs manifests as characteristic cupping or optic nerve degeneration, resulting in visual field loss in patients with Glaucoma. Published studies on in vitro RGC differentiation from stem cells utilized classical RGC signaling pathways mimicking retinal development in vivo. Although many strategies allowed for the generation of RGCs, increased variability between experiments and lower yield hampered the cross comparison between individual lines and between experiments. To address this critical need, we developed a reproducible chemically defined in vitro methodology for generating retinal progenitor cell (RPC) populations from iPSCs, that are efficiently directed towards RGC lineage. Using this method, we reproducibly differentiated iPSCs into RGCs with greater than 80% purity, without any genetic modifications. We used small molecules and peptide modulators to inhibit BMP, TGF-β (SMAD), and canonical Wnt pathways that reduced variability between iPSC lines and yielded functional and mature iPSC-RGCs. Using CD90.2 antibody and Magnetic Activated Cell Sorter (MACS) technique, we successfully purified Thy-1 positive RGCs with nearly 95% purity.
Intensity of infection with intracellularEimeriaspp. and pinworms is reduced in hybrid mice compared to parental subspecies
Authors: Balard Alice , Jarquín-Díaz Víctor Hugo , Jost Jenny , Martincová Iva , Ďureje Ľudovít , Piálek Jaroslav , Macholán Miloš , Goüy de Bellocq Joëlle , Baird Stuart J. E. , Heitlinger Emanuel 
Published: July 2019

AbstractThe longstanding impression that hybrid mice are more highly parasitized and therefore less fit than parentals persists despite the findings of recent studies. Working across a novel transect of the European House Mouse hybrid zone we assessed intracellular infections byEimeria, a parasite of high pathogenicity, and infections by pinworms, assumed to be less pathogenic. ForEimeriawe found lower intensities in hybrid hosts than in parental mice but no evidence of lowered probability of infection in the centre of the hybrid zone. This means ecological and epidemiological factors are very unlikely to be responsible for the reduced load of infected hybrids. Focussing on parasite intensity (load in infected hosts) we also corroborated reduced pinworm loads reported for hybrid mice in previous studies. In addition we questioned whether differences in body condition during infection would indicate different impacts on hybrid vs. parental hosts’ health. We couldn’t show such an effect. We conclude that intensity of diverse parasites, including the previously unstudiedEimeria, is reduced in hybrid mice compared to parental subspecies. We suggest caution in extrapolating this to differences in hybrid host fitness in the absence of, for example, evidence for a link between parasitemia and health.
Developing critical thinking in STEM education through inquiry-based writing in the laboratory classroom
Authors: Jeon Ah-Jung , Kellogg David , Khan Mohammed Asif , Tucker-Kellogg Greg 
Published: July 2019

AbstractLaboratory pedagogy is moving away from step-by-step instructions and toward inquiry-based learning (IBL), but only now developing methods for integrating inquiry-based writing (IBW) practices into the laboratory course. Based on an earlier proposal (Science 332:919 (2011)), we designed and implemented an IBW sequence in a university bioinformatics course.We automatically generated unique, double-blinded, biologically plausible DNA sequences for each student. After guided instruction, students investigated sequences independently and responded through IBW writing assignments. IBW assignments were structured as condensed versions of a scientific research paper, and because the sequences were double blinded, they were also assessed as authentic science and evaluated on clarity and persuasiveness.We piloted the approach in a seven-day workshop (35 students) at Perdana University Graduate School of Medicine in Kuala Lumpur. We observed dramatically improved student engagement and indirect evidence of improved learning outcomes over a similar workshop without IBW. Based on student feedback, initial discomfort with the writing component abated in favor of an overall positive response and increasing comfort with the high demands of student writing. Similarly encouraging results were found in a semester length undergraduate module at the National University of Singapore (155 students).
Mechanical effects of MitraClip on leaflet stress and myocardial strain in functional mitral regurgitation – A finite element modeling study
Authors: Zhang Yue , Wang Vicky Y , Morgan Ashley E , Kim Jiwon , Handschumacher Mark D , Moskowitz Chaya S , Levine Robert A , Ge Liang , Guccione Julius M , Weinsaft Jonathan W , Ratcliffe Mark B 
Published: July 2019

AbstractPurposeMitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD).MethodsSimulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated.ResultsMitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increasedErrin the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p=0.0268) and in PL by 22.5±23.7 kPa (p=0.0101).ConclusionsMitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement.