bluuebunny/crossref_metadata_2025_split huggingface dataset:
isiKnock: in silico knockouts in signaling pathways
Authors: Hannig Jennifer , Giese Heiko , Schweizer Börje , Amstein Leonie , Ackermann Jörg , Koch Ina 
Published: August 2018

Abstract

Summary
isiKnock is a new software that automatically conducts in silico knockouts for mathematical models of signaling pathways. The software allows for the prediction of the behavior of biological systems after single or multiple knockout. The implemented algorithm applies transition invariants and the novel concept of Manatee invariants. A knockout matrix visualizes the results. The tool enables the analysis of dependencies, for example, in signal flows from the receptor activation to the cell response at steady state.

Availability and implementation
isiKnock is an open-source tool, freely available at http://www.bioinformatik.uni-frankfurt.de/tools/isiKnock/. It requires at least Java 8 and runs under Microsoft Windows, Linux, and Mac OS.
The effect of monoamines reuptake inhibitors on aerobic exercise performance in bank voles from a selection experiment
Authors: Jaromin Ewa , Sadowska Edyta T , Koteja Paweł 
Published: August 2018

Abstract
Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivation). We tested the hypothesis that evolution of increased aerobic exercise performance can be facilitated by evolution of neuropsychological mechanisms responsible for motivation to undertake physical activity. We used a unique model system: lines of bank voles Myodes glareolus selected for high swim-induced aerobic metabolism (“aerobic” A lines). In generation 21, voles from the 4 A lines achieved a 57% higher “voluntary maximum” swim-induced aerobic metabolism (VO2swim) than voles from 4 unselected, “control” C lines. In C lines, VO2swim was 9% lower than the maximum forced-exercise aerobic metabolism (VO2run; P = 0.007), while in A lines it was even higher than VO2run, although not significantly (4%, P = 0.15). Thus, we hypothesized that selection changed both the aerobic capacity and the neuronal mechanisms behind motivation to undertake activity. We investigated the influence of reuptake inhibitors of dopamine (DARI), serotonin (SSRI), and norepinephrine (NERI) on VO2swim. The drugs decreased VO2swim both in C and A lines (% decrease compared with saline: DARI 8%, P < 0.001; SSRI 6%, P < 0.001; NERI 8%, P < 0.001), but the proportional response differed between selection directions only for NERI (stronger effect in C lines: P = 0.008) and the difference was marginally non-significant for SSRI (P = 0.07) and DARI (P = 0.06). Thus, the results suggest that all the 3 monoamines are involved in signaling pathways controlling the motivation to be active and that norepinephrine could have played a role in the evolution of increased aerobic exercise performance in our animal model.
Implementation of the Stopping Elderly Accidents, Deaths, and Injuries Initiative in Primary Care: An Outcome Evaluation
Authors: Johnston Yvonne A , Bergen Gwen , Bauer Michael , Parker Erin M , Wentworth Leah , McFadden Mary , Reome Chelsea , Garnett Matthew 
Published: August 2018

Abstract

Background and Objectives
Older adult falls pose a growing burden on the U.S. health care system. The Centers for Disease Control and Prevention’s Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative was developed as a multifactorial approach to fall prevention that includes screening for fall risk, assessing for modifiable risk factors, and prescribing evidence-based interventions to reduce fall risk. The purpose of this study was to determine the impact of a STEADI initiative on medically treated falls within a large health care system in Upstate New York.

Research Design and Methods
This cohort study classified older adults who were screened for fall risk into 3 groups: (a) At-risk and no Fall Plan of Care (FPOC), (b) At-risk with a FPOC, and (c) Not-at-risk. Poisson regression examined the group’s effect on medically treated falls when controlling for other variables. The sample consisted of 12,346 adults age 65 or older who had a primary care visit at one of 14 outpatient clinics between September 11, 2012, and October 30, 2015. A medically treated fall was defined as a fall-related treat-and-release emergency department visit or hospitalization.

Results
Older adults at risk for fall with a FPOC were 0.6 times less likely to have a fall-related hospitalization than those without a FPOC (p = .041), and their postintervention odds were similar to those who were not at risk.

Discussion and Implications
This study demonstrated that implementation of STEADI fall risk screening and prevention strategies among older adults in the primary care setting can reduce fall-related hospitalizations and may lower associated health care expenditures.
A Framework of Minority Stress: From Physiological Manifestations to Cognitive Outcomes
Authors: Forrester Sarah N , Gallo Joseph J , Whitfield Keith E , Thorpe Roland J 
Published: August 2018

Abstract
Cognitive impairment and dementia continue to threaten the aging population. Although no one is immune, certain groups, namely black older persons, are more likely to have a diagnosis of certain dementias. Because researchers have not found a purely biological reason for this disparity, they have turned to a biopsychosocial model. Specifically, black persons in the United States are more likely to live with social conditions that affect their stress levels which in turn affect physiological regulation leading to conditions that result in higher levels of cognitive impairment or dementia. Here we discuss some of these social conditions such as discrimination, education, and socioeconomic status, and how physiological dysregulation, namely allostatic load that can lead to cognitive impairment and dementia in black persons especially.
Impacts of a multi-trap line on benthic habitat containing emergent epifauna within the Mid-Atlantic Bight
Authors: Schweitzer Cara C , Lipcius Romuald N , Stevens Bradley G 
Published: August 2018

Abstract
Alteration and degradation of benthic structure by fishing gear can impede efforts to manage fish stock sustainably. Although the impacts of mobile gear are well known, effects of passive gear (e.g. fish traps) upon structure have been little studied. We modified commercial traps for American lobster Homarus americanus and black sea bass Centropristis striata by attaching GoPro® cameras to ascertain the degree and nature of impacts to seafloor habitats. Customized traps were included within a line of 20 traps, deployed and retrieved according to standard commercial fishing practice. Less than 5% of traps landed directly on bedforms when deployed. However, during retrieval traps dragged along the ocean floor, increasing trap–habitat contact rate to 50%, and causing traps to collide with corals, bryozoans, and other epifauna. Drag time of traps depended on the position in the trap line. Experimentally extending the trap line reduced drag time during retrieval for traps near the distal end of the line. Our results show that impacts of commercial trap fishing can be substantial during trap retrieval, and that the impact depends on their location on a trap line. Fishing practices should be developed that minimize effects of trap retrieval on structural benthic habitat.
Exponential Sums Over Finite Fields and the Large Sieve
Authors: Perret-Gentil Corentin 
Published: August 2018

Abstract
By using a variant of the large sieve for Frobenius in compatible systems developed in [24] and [27], we obtain zero-density estimates for arguments of $\ell $-adic trace functions over finite fields with values in some algebraic subsets of the cyclotomic integers, when the monodromy groups are known. This applies in particular to hyper-Kloosterman sums and general exponential sums considered by Katz.
Towards Evidence-Based Guidelines in Neurological Surgery
Authors: Shank Christopher D , Lepard Jacob R , Walters Beverly C , Hadley Mark N 
Published: August 2018

Abstract
Neurological surgery practice is based on the science of balancing probabilities. A variety of clinical guidance documents have influenced how we collectively practice our art since the early 20th century. The quality of the science within these guidelines varies widely, as does their utility in positively shaping our practice.
The guidelines development process in neurological surgery has evolved significantly over the last 30 yr. Historically based in expert opinion, as a specialty we have increasingly relied on objective medical evidence to guide our clinical practice. We assessed the changing practice guidelines development process and the impact of scientifically robust guidelines on patient care.
The evolution of the guidelines development process in neurological surgery was chronicled. Several subspecialty guidelines were extracted and reviewed in detail. Their impact on practice patterns was evaluated. The importance of evidence-based research and practice guidelines development was discussed.
Evidence-based practice guidelines serve to chronicle multiple acceptable treatment options and help us move towards more standardized care for specific disease processes. They help refute false “standards of care.” Guidelines-based care supported by solid medical evidence has the potential to streamline patient care and improve patient outcomes. The guidelines development process identifies areas, issues, and strategies for which little medical evidence exists, as well as topics that need focused scientific investigation and future study.
The production of evidence-based practice recommendations is a vital part of furthering our specialty. Guidelines development advances our science, augments the resident education process, and protects our practice from undue external influence.
Quitting Failure and Success With and Without Using Medication: Latent Classes of Abstinence and Adherence to Nicotine Monotherapy, Combination Therapy, and Varenicline
Authors: McCarthy Danielle E , Versella Mark V 
Published: August 2018

AbstractIntroductionNonadherence to pharmacotherapies complicates studies of comparative pharmacotherapy effectiveness. Modeling adherence and abstinence simultaneously may facilitate analysis of both treatment acceptability and effectiveness.MethodsSecondary analyses of a three-arm randomized comparative trial of nicotine patch, varenicline, and combination nicotine patch and lozenge among adult daily smokers (N = 1086) were conducted. Adherence rates collected via interactive voice response systems during the first 27 days of quitting were compared across treatment conditions. Repeated measures latent class analyses of adherence and abstinence in 3-day parcels through 27 days of a quit attempt were conducted with treatment, demographic, and smoking history covariates.ResultsAdherence varied across treatments and was lowest for nicotine lozenge use in combination nicotine replacement therapy (NRT). Five latent classes that differed significantly in 6-month abstinence rates were retained, including three subgroups of adherent participants varying in treatment response and two nonadherent groups varying in abstinence probabilities. Nonadherence was more likely among those receiving varenicline and combination NRT, relative to patch monotherapy. Varenicline and combination NRT did not promote abstinence among adherent latent classes but did promote abstinence among those partially adherent, relative to patch alone. Combination therapy attenuated increased risk of treatment disengagement with more years smoking. Minority smokers, those high in dependence, and those with shorter past abstinence were at increased risk for low-adherence and low-abstinence latent classes.ConclusionsVarenicline and combination nicotine patch and lozenge are less likely to be used as directed and may not increase first-month abstinence better than patch alone when taken adherently.ImplicationsThis secondary analysis of adherence and abstinence in a comparative effectiveness trial shows that adherence is highest for the nicotine patch, next highest for varenicline, and lowest for combination nicotine patch and lozenge therapy due to low lozenge use. Distinct latent classes were found that varied in both first-month abstinence and adherence. Varenicline and combination NRT may not enhance abstinence over patch alone among smokers who take medication adherently. Adherent use of medication especially benefits those who are low in dependence and have positive quitting histories; it is less beneficial to at-risk smokers and members of racial minorities.
Multiple Aneurysms Clipping Through the Eyebrow Approach: 2-Dimensional Operative Video
Authors: Aldea Sorin , Gaillard Stephan 
Published: August 2018

Abstract
The eyebrow approach is a versatile technique that may apply to various vascular and tumoral pathologies of the anterior skull base. We present a case of multiple aneurysms clipping through the eyebrow approach and we discuss the nuances of this technique. A 44-yr-old patient presented with incidentally found aneurysms. Angiography showed 2 4.5-mm aneurysms on the left middle cerebral artery (MCA) and internal carotid artery (ICA) bifurcations. At surgery, the patient is positioned supine with the head elevated, slightly rotated, and extended in order to obtain good access and gravity retraction of the brain. A 3-cm incision is placed in the eyebrow and a small supraorbital bone flap is raised. The floor of the orbit and the edges of the craniotomy are thoroughly drilled in order to maximize the working space. After dural opening, the sylvian fissure was widely dissected and the MCA aneurysm was identified. A large opening of the sylvian and carotid cistern allows retractor free surgery. The ICA bifurcation aneurysm is then dissected and clipped. The MCA aneurysm is treated last in order to avoid a conflict between instruments especially during clipping. Aneurysms occlusion and vessel permeability is verified by Doppler ultrasonography and indocyanine green (ICG) angiography. After achieving hemostasis, the dura is closed and a subcuticular continuous suture is used at the skin. The postoperative course was uneventful. The eyebrow approach allows simultaneous treatment of multiple aneurysms of the anterior circle of Willis in selected cases. Proper positioning, drilling of the orbital floor and extensive arachnoid dissection are the key steps of this procedure.
Expanding the toolbox for Synechocystis sp. PCC 6803: validation of replicative vectors and characterization of a novel set of promoters
Authors: Ferreira Eunice A , Pacheco Catarina C , Pinto Filipe , Pereira José , Lamosa Pedro , Oliveira Paulo , Kirov Boris , Jaramillo Alfonso , Tamagnini Paula 
Published: August 2018

AbstractCyanobacteria are promising ‘low-cost’ cell factories since they have minimal nutritional requirements, high metabolic plasticity and can use sunlight and CO2 as energy and carbon sources. The unicellular Synechocystis sp. PCC 6803, already considered the ‘green’ Escherichia coli, is the best studied cyanobacterium but to be used as an efficient and robust photoautotrophic chassis it requires a customized and well-characterized toolbox. In this context, we evaluated the possibility of using three self-replicative vectors from the Standard European Vector Architecture (SEVA) repository to transform Synechocystis. Our results demonstrated that the presence of the plasmid does not lead to an evident phenotype or hindered Synechocystis growth, being the vast majority of the cells able to retain the replicative plasmid even in the absence of selective pressure. In addition, a set of heterologous and redesigned promoters were characterized exhibiting a wide range of activities compared to the reference PrnpB, three of which could be efficiently repressed. As a proof-of-concept, from the expanded toolbox, one promoter was selected and assembled with the ggpS gene [encoding one of the proteins involved in the synthesis of the native compatible solute glucosylglycerol (GG)] and the synthetic device was introduced into Synechocystis using one of the SEVA plasmids. The presence of this device restored the production of the GG in a ggpS deficient mutant validating the functionality of the tools/device developed in this study.
Differentiation of diabetic foot ulcer–derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes
Authors: Kashpur Olga , Smith Avi , Gerami-Naini Behzad , Maione Anna G. , Calabrese Rossella , Tellechea Ana , Theocharidis Georgios , Liang Liang , Pastar Irena , Tomic-Canic Marjana , Mooney David , Veves Aristidis , Garlick Jonathan A. 
Published: August 2018

ABSTRACTDiabetic foot ulcers (DFUs) are a major complication of diabetes, and there is a critical need to develop novel cell‐ and tissue‐based therapies to treat these chronic wounds. Induced pluripotent stem cells (iPSCs) offer a replenishing source of allogeneic and autologous cell types that may be beneficial to improve DFU wound‐healing outcomes. However, the biologic potential of iPSC‐derived cells to treat DFUs has not, to our knowledge, been investigated. Toward that goal, we have performed detailed characterization of iPSC‐derived fibroblasts from both diabetic and nondiabetic patients. Significantly, gene array and functional analyses reveal that iPSC‐derived fibroblasts from both patients with and those without diabetes are more similar to each other than were the primary cells from which they were derived. iPSC‐derived fibroblasts showed improved migratory properties in 2‐dimensional culture. iPSC‐derived fibroblasts from DFUs displayed a unique biochemical composition and morphology when grown as 3‐dimensional (3D), self‐assembled extracellular matrix tissues, which were distinct from tissues fabricated using the parental DFU fibroblasts from which they were reprogrammed. In vivo transplantation of 3D tissues with iPSC‐derived fibroblasts showed they persisted in the wound and facilitated diabetic wound closure compared with primary DFU fibroblasts. Taken together, our findings support the potential application of these iPSC‐derived fibroblasts and 3D tissues to improve wound healing.—Kashpur, O., Smith, A., Gerami‐Naini, B., Maione, A. G., Calabrese, R., Tellechea, A., Theocharidis, G., Liang, L., Pastar, I., Tomic‐Canic, M., Mooney, D., Veves, A., Garlick, J. A. Differentiation of diabetic foot ulcer–derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes. FASEB J. 33, 1262–1277 (2019). www.fasebj.org
The Incidence, Clinical Features, and a Comparison Between Early and Delayed Onset of Postoperative Spinal Epidural Hematoma
Authors: Anno Masato , Yamazaki Takashi , Hara Nobuhiro , Ito Yusuke 
Published: August 2018

Study Design.
A retrospective observational study.

Objective.
To investigate the incidence and clinical features of symptomatic postoperative spinal epidural hematoma (PSEH) with regard to spinal level and to compare early and delayed onset cases.

Summary of Background Data.
PSEH is a serious complication of spinal surgeries. The difference in clinical manifestations between early and delayed PSEH remains unclear.

Methods.
Patients who underwent spinal surgeries between 1999 and 2013 at our institution, were reviewed through their medical records. For patients with PSEH, the incidence, duration to onset, duration from onset to evacuation, symptoms, recovery rate (American Spinal Injury Association grade), neurological outcomes, comorbidities, and preoperative use of anticoagulant drugs were examined. We next compared patients with early onset PSEH (onset until day 3) versus delayed onset (onset day 4 or later) regarding these clinical factors.

Results.
Fourteen patients (0.42%, 14/3371) developed symptomatic PSEH. Initial symptoms were observed between 0 and 7 days (mean 2.6 ± 2.4 d) and almost half (43%, 6/14) occurred during the delayed phase (mean 5.0 ± 1.1 d postsurgery). Paralysis was the predominant symptom in patients with cervical and thoracic surgeries (100%, 6/6), whereas severe pain was most frequent in patients with lumbar procedures (63%, 5/8) (P = 0.019). No significant differences were identified between early and delayed groups. Neurological outcome was good in 10 cases, partial in two cases, and poor in two cases.

Conclusion.
The frequency was consistent in every spinal region, and the symptoms due to PSEH were correlated with spinal level. Almost half the cases were diagnosed after a delay (day 4 or later), which supports the necessity to follow up patients with spinal surgeries more carefully for a week or so and to educate patients and comedical staff about the possibility of delayed hematoma disorders in order not to defer timely intervention.

Level of Evidence: 4
Incidence and Prevalence of Pressure Injuries in Adult Intensive Care Patients: A Systematic Review and Meta-Analysis
Authors: Chaboyer Wendy P. , Thalib Lukman , Harbeck Emma L. , Coyer Fiona M. , Blot Stijn , Bull Claudia F. , Nogueira Paula C. , Lin Frances F. 
Published: August 2018

Objectives:To systematically assess the incidence and prevalence of pressure injuries in adult ICU patients and the most frequently occurring pressure injury sites.Data Sources:MEDLINE, Embase, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature.Study Selection:Observational studies reporting incidence rates, cumulative incidence, and prevalence of pressure injuries.Data Extraction:Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Meta-analyses of pooled weighted estimates were calculated using random effect models with 95% CIs reported due to high heterogeneity. Sensitivity analyses included studies that used skin inspection to identify a pressure injury, studies at low risk of bias, studies that excluded stage 1 and each stage of pressure injury.Data Synthesis:Twenty-two studies, 10 reporting cumulative incidence of pressure injury irrespective of stage, one reporting incidence rate (198/1,000 hospital-days), and 12 reporting prevalence were included. The 95% CI of cumulative incidence and prevalence were 10.0–25.9% and 16.9–23.8%. In studies that used skin inspection to identify pressure injuries, the 95% CI of cumulative incidence was 9.4–27.5%; all prevalence studies used skin inspection therefore the results were unchanged. In studies assessed as low risk of bias, the 95% CI of cumulative incidence and prevalence were 6.6–36.8% and 12.2–24.5%. Excluding stage 1, the 95% CI of cumulative incidence and prevalence were 0.0–23.8% and 12.4–15.5%. Five studies totalling 406 patients reported usable data on location; 95% CI of frequencies of PIs were as follows: sacrum 26.9–48.0%, buttocks 4.1–46.4%, heel 18.5–38.9%, hips 10.9–15.7%, ears 4.3–19.7%, and shoulders 0.0–40.2%.Conclusions:Although well-designed studies are needed to ensure the scope of the problem of pressure injuries is better understood, it is clear prevention strategies are also required.