bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends Over Time in Drug Administration During Adult In-Hospital Cardiac Arrest*
Authors: Moskowitz Ari , Ross Catherine E. , Andersen Lars W. , Grossestreuer Anne V. , Berg Katherine M. , Donnino Michael W. 
Published: November 2018

Objectives:
Clinical providers have access to a number of pharmacologic agents during in-hospital cardiac arrest. Few studies have explored medication administration patterns during in-hospital cardiac arrest. Herein, we examine trends in use of pharmacologic interventions during in-hospital cardiac arrest both over time and with respect to the American Heart Association Advanced Cardiac Life Support guideline updates.

Design:
Observational cohort study.

Setting:
Hospitals contributing data to the American Heart Association Get With The Guidelines–Resuscitation database between 2001 and 2016.

Patients:
Adult in-hospital cardiac arrest patients.

Interventions:
The percentage of patients receiving epinephrine, vasopressin, amiodarone, lidocaine, atropine, bicarbonate, calcium, magnesium, and dextrose each year were calculated in patients with shockable and nonshockable initial rhythms. Hierarchical multivariable logistic regression was used to determine the annual adjusted odds of medication administration. An interrupted time series analysis was performed to assess change in atropine use after the 2010 American Heart Association guideline update.

Measurements and Main Results:
A total of 268,031 index in-hospital cardiac arrests were included. As compared to 2001, the adjusted odds ratio of receiving each medication in 2016 were epinephrine (adjusted odds ratio, 1.5; 95% CI, 1.3–1.8), vasopressin (adjusted odds ratio, 1.5; 95% CI, 1.1–2.1), amiodarone (adjusted odds ratio, 3.4; 95% CI, 2.9–4.0), lidocaine (adjusted odds ratio, 0.2; 95% CI, 0.2–0.2), atropine (adjusted odds ratio, 0.07; 95% CI, 0.06–0.08), bicarbonate (adjusted odds ratio, 2.0; 95% CI, 1.8–2.3), calcium (adjusted odds ratio, 2.0; 95% CI, 1.7–2.3), magnesium (adjusted odds ratio, 2.2; 95% CI, 1.9–2.7; p < 0.0001), and dextrose (adjusted odds ratio, 2.8; 95% CI, 2.3–3.4). Following the 2010 American Heart Association guideline update, there was a downward step change in the intercept and slope change in atropine use (p < 0.0001).

Conclusions:
Prescribing patterns during in-hospital cardiac arrest have changed significantly over time. Changes to American Heart Association Advanced Cardiac Life Support guidelines have had a rapid and substantial effect on the use of a number of commonly used in-hospital cardiac arrest medications.
The benefits of agreeing on what matters most: Team cooperative norms mediate the effect of co-leaders’ shared goals on safety climate in neonatal intensive care units
Authors: Kuntz Ludwig , Scholten Nadine , Wilhelm Hendrik , Wittland Michael , Hillen Hendrik Ansgar 
Published: November 2018

Background:
Safety climate research suggests that a corresponding climate in work units is crucial for patient safety. Intensive care units are usually co-led by a nurse and a physician, who are responsible for aligning an interprofessional workforce and warrant a high level of safety. Yet, little is known about whether and how these interprofessional co-leaders jointly affect their unit’s safety climate.

Purpose:
This empirical study aims to explain differences in the units’ safety climate as an outcome of the nurse and physician leaders’ degree of shared goals. Specifically, we examine whether the degree to which co-leaders share goals in general fosters a safety climate by pronouncing norms of interprofessional cooperation as a behavioral standard for the team members’ interactions.

Methodology/Approach:
A cross-sectional design was used to gather data from 70 neonatal intensive care units (NICUs) in Germany. Survey data for our variables were collected from the unit’s leading nurse and the leading physician, as well as from the unit’s nursing and physician team members. Hypotheses testing at unit level was conducted using multivariate linear regression.

Results:
Our analyses show that the extent to which nurse–physician co-leaders share goals covaries with safety climate in NICUs. This relationship is partially mediated by norms of interprofessional cooperation among NICU team members. Our final model accounts for 54% of the variability in safety climate of NICUs.

Conclusion:
Increasing the extent to which co-leaders share goals is an effective lever to strengthen interprofessional cooperation and foster a safety climate among nursing and physician team members of hospital units.
Surgical Factors Affecting Changes in Ocular Surface Dynamics in the Early Postoperative Period After 25-Gauge Vitrectomy
Authors: Sato Tatsuhiko , Koh Shizuka , Yasukura Yu-ichi , Kanai Masanori , Noguchi Yumi , Jhanji Vishal , Nishida Kohji 
Published: November 2018

Objectives:
Because vitrectomy-associated postoperative ocular surface changes are not well known, we evaluated such changes before and after vitrectomy in eyes with posterior segment diseases and investigated their associations with patients' characteristics and surgical procedures.

Methods:
Thirty-five eyes of 32 consecutive patients (16 women; average age 66.6±11.1 years) were included in this prospective, noncomparative case series from tertiary care university hospital. Contact lens wearers and patients with history of ocular surgery or regular use of topical eyedrops were excluded. Patients had undergone primary 25-gauge vitrectomy at Osaka University Hospital in Japan between July and December 2016. Tear break-up time (TBUT), corneal and conjunctival fluorescein staining score (FSS), and tear meniscus height (TMH) were evaluated before, 1 week after, and 1 month after vitrectomy.

Results:
Conjunctival FSS and TMH were significantly higher at 1 week after vitrectomy than preoperatively. However, they decreased significantly 1 month after. Changes in TBUT and corneal FSS showed a similar course at 1 week, but this was not statistically significant. Multiple linear regression analysis showed no significant correlation between significantly increased ocular parameters and patients' characteristics. By contrast, surgical time and combined cataract surgery significantly contributed to increased and decreased conjunctival FSS, respectively (P=0.011 and 0.033, respectively). Sclerotomy site suturing significantly contributed to increased TMH (P=0.025).

Conclusions:
We showed associations between ocular surface changes and specific surgical procedures. Caution should be exercised to minimize the effect of surgical procedures on the ocular surface during vitrectomy.
Pupillometry Trends in the Setting of Increased Intracranial Pressure
Authors: McNett Molly , Moran Cristina , Grimm Dawnetta , Gianakis Anastasia 
Published: November 2018

ABSTRACT
Serial pupil examinations remain a mainstay of neurological assessments performed by neuroscience nurses. Integration of pupillometer technology has increased in recent years, because of its ability to address limitations of manual examinations and to evaluate trended data over time. Preliminary research has linked pupillometer values to intracranial pressure (ICP) values, but data on pupillary changes in the setting of increased ICP remain sparse. The purpose of this study was to determine trends in pupillometer values in the setting of increased ICP among critically ill patients with neurological injury. This is a secondary analysis of data where serial pupillometer and ICP readings were recorded hourly on adult patients with neurological injury necessitating critical care management. More than 2100 paired serial pupillometer and ICP readings were obtained from 76 subjects, with a total of 2107 paired readings for the left eye and 2175 for the right eye. There were statistically significant differences in pupillometry values in the setting of increased ICP. Time series analysis indicates that spikes in ICP values resulted in corresponding variations in pupillometer values. Use of automated pupillometry remains a value adjunct to traditional invasive therapies. Evaluation of trended data may provide insight into ICP elevations in the absence of invasive monitoring and warrants additional research.
Prevalence of Celiac Disease in a Long‐term Study of a Spanish At‐genetic‐risk Cohort From the General Population
Authors: Fernández‐Fernández Sonia , Borrell Belén , Cilleruelo María L. , Tabares Ana , Jiménez‐Jiménez Juana , Rayo Ana I. , Perucho Teresa , García‐García Maria L. 
Published: November 2018

ABSTRACTObjectives:To perform long‐term celiac disease (CD) screening in an HLA‐DQ2 (+) cohort from the general population and to assess the influence of risk genotypes on its development.Methods:In 2004, an HLA‐DQ2 (+) cohort was selected. After the first CD screening at age 2 to 3 years, we performed a follow‐up screening 8 to 10 years later. Antitransglutaminase 2 antibodies were determined using a rapid test kit. Results were confirmed by serum IgA antitransglutaminase 2 and IgA endomysial antibody determination. CD diagnosis was carried out by intestinal biopsies. Four HLA‐DQ2 genotypic groups were used: G1: DQ2.5/DQ2.5 (G1A) or DQ2.5/ DQ2.2 (G1B); G2: DQ2.2/DQ7.5 (DQ2.5 trans); G3: DQ2.5/ X; G4: DQ2.2/X.Results:CD prevalence after 10 years of follow‐up was 5.8% (95% confidence interval 3.8–8.7). One of every 3 HLA‐DQ2(+) children carried at least 1 haplotype DQ2.2 or DQ7. The homozygous genotype DQ2.5/DQ2.5 and the HLA‐DQ2.5 trans genotype increased CD risk 4‐ and 3‐fold, respectively. The homozygous genotype DQ2.5/ DQ2.2 did not increase the CD risk. Children carrying G1 or G2 genotypes were diagnosed with CD earlier and more frequently during the follow‐up compare with those carrying G3 or G4 genotypes. Approximately 81% of children with spontaneous antibody negativization after the first screening maintained negative antibodies.Conclusions:A repeated screening of at‐risk children during their follow‐up allowed us to diagnose new CD cases. In our cohort, HLA‐ DQ2.5 trans genotype conferred a higher risk in the development of CD than HLA‐ DQ2.5/DQ2.2. The majority of children with potential CD and CD autoimmunity at 10 years of age remained healthy.
Recanalization of Chronic Extrahepatic Portal Vein Obstruction in Pediatric Patients Using a Minilaparotomy Approach
Authors: Muratore Sydne , Flanagan Siobhan , Hunter David , Acton Robert 
Published: November 2018

ABSTRACTPurpose:Extrahepatic portal vein obstruction (EHPVO) is the most frequent cause of portal hypertension in children. Some patients are not amenable to meso‐Rex bypass and alternative surgeries do not restore physiologic flow. We aim to demonstrate the feasibility and safety of minilaparotomy for recanalization of chronic EHPVO.Methods:This 2013–2015 single‐center, retrospective review included pediatric patients with chronic EHPVO who underwent minilaparotomy, mesenteric vein access, and attempted recanalization of the occluded portal vein. Outcomes included portal patency, resolution of variceal bleeding, size and number of varices, spleen size, and platelet count.Results:There were 6 EHPVO patients. The median age was 9.9 years and median duration of EHPVO was 7 years (3–16 years). EHPVO etiologies were liver transplantation (50%), idiopathic (33%), and umbilical vein catheterization (17%). Four patients (67%) had successful portal vein recanalization and stenting. At last follow‐up [median 3.1 years (2.2–4.3 years)] all successfully recanalized patients had patent portal vein stents and resolution of varices and variceal bleeding. The median reduction in spleen size was 26%, with improvement in platelet counts (50–310/μL). The 2 patients with an idiopathic etiology may have never had a main extrahepatic portal vein based on imaging, and both were unable to be recanalized.Conclusions:Recanalization and stenting of a prolonged occlusion of the portal vein via a minilaparotomy approach is feasible, safe, and may provide an alternative to shunt surgery or endoscopic therapy in selected patients.
Simple Electroencephalographic Treatment-Emergent Marker Can Predict Repetitive Transcranial Magnetic Stimulation Antidepressant Response—A Feasibility Study
Authors: Isserles Moshe , Daskalakis Zafiris J. , George Mark S. , Blumberger Daniel M. , Sackeim Harold A. , Shahaf Goded 
Published: November 2018

Objectives
Prefrontal repetitive transcranial magnetic stimulation (rTMS) repeated daily for 4 to 6 weeks is used to treat major depressive disorder, but more than 50% of patients do not achieve significant response. Here we test the validity of a simple electroencephalographic (EEG) marker that predicts nonresponse to rTMS. Such a marker could potentially increase rTMS effectiveness by directing nonresponders to alternative treatments or by guiding early modification of stimulation parameters.

Methods
We retrospectively analyzed 2-channel EEG data captured in the OPT-TMS National Institute of Mental Health–sponsored, multicenter study. Cumulative Brain Engagement Index (cBEI), a measure derived from template matching that allows scoring EEG dynamics along treatment, was computed.

Results
Six hundred sixty-five EEG recordings were analyzed. In the rTMS group, the median cBEI was found to increase in the responder group but remained unchanged in the nonresponder group. The difference between the cBEI of the groups became statistically significant by the third valid EEG sample. Within 5 samples, 91% of the responders presented with a cBEI above a preset threshold. Within 9 samples, 17% of the nonresponders had a cBEI above the threshold.

Conclusions
This study demonstrates the feasibility of a simple-to-capture EEG marker as a treatment-emergent marker of response to rTMS treatment of depression. In the OPT-TMS study, discontinuing treatment when the cBEI dropped below the threshold between the fifth to ninth treatment potentially could have avoided administration of 485 (63%) of 765 treatments. Because the marker can be generated online, it would be of interest to evaluate, in future studies, whether it could be used to tune treatment parameters and improve remission rates.
Does women’s interpersonal anxiety track changes in steroid hormone levels?
Authors: Hahn Amanda C , DeBruine Lisa M , Pesce Lola A , Diaz Andrew , Aberson Christopher L , Jones Benedict C 
Published: November 2018

AbstractFindings for progesterone and anxiety in non-human animals led to the hypothesis that women’s interpersonal anxiety will track changes in progesterone during the menstrual cycle. There have been few direct tests of this hypothesis, however. Consequently, we used a longitudinal design to investigate whether interpersonal anxiety (assessed using the anxious jealousy subscale of the relationship jealousy questionnaire) tracked changes in salivary steroid hormones during the menstrual cycle in a large sample of young adult women (N=383). We found no evidence for within-subject effects of progesterone, estradiol, their interaction or ratio, testosterone, or cortisol on anxious jealousy. There was some evidence that other components of jealousy (e.g., reactive jealousy) tracked changes in women’s cortisol, however. Collectively, these results provide no evidence for the hypothesis that interpersonal anxiety tracks changes in progesterone during the menstrual cycle.
Overcoming non-small cell lung cancer radiation resistance by modulating the tumor-immune ecosystem
Authors: Nizzero S. , Alfonso J.C.L. , Álvarez-Arenas A. , Mirzaev I. , Zervantonakis I.K. , Lewin T. , Rishi A. , Piretto E. , Joshi T.V. , Santiago D.N. , Karolak A. , Walker R. , Karreth F.A. , Torres-Roca J. , Enderling H. 
Published: November 2018

AbstractNon-small-cell lung cancer is the leading cause of cancer death worldwide. Although radiotherapy is an effective treatment choice for early-stage cases, the 5-year survival rate of patients diagnosed in late-stages remains poor. Increasing evidence suggests that the local and systemic effects of radiotherapy dependent on the induced anti-tumor immune responses. We believe that an educated adaptation of radiotherapy plans based not only on the induced immune responses, but also on the tumor-immune ecosystem composition at the beginning of treatment might increase local tumor control. We propose two different mathematical models to evaluate the potential of the tumor-immune context to inform adaptation of treatment plans with the aim of improving outcomes.
Human Nerve-on-a-Chip. Engineering 3D functional human peripheral nerve in vitro
Authors: Sharma Anup D. , McCoy Laurie , Jacobs Elizabeth , Willey Hannah , Behn Jordan Q. , Ngyuen Hieu , Bolon Brad , Curley J. Lowry , Moore Michael J. 
Published: November 2018

AbstractDevelopment of “organ-on-a-chip” systems in the space of the nervous system is lagging because of lack of availability of human neuronal & glial cells and the structural complexity of the nervous system. Furthermore, a sizeable challenge in the drug development pipeline and an often-cited reason for failure in a vast number of clinical trials conducted for neuropathological ailments is the lack of translation from animal models. A preclinical in vitro model capable of mimicking the function and structure of the human nervous system is well desired. We present an in vitro biomimetic model of all-human peripheral nerve tissue capable of showing a robust neurite outgrowth (~5mm), myelination of human induced pluripotent stem cells (iPSCs)-derived neurons by primary human Schwann cells and evaluation of nerve conduction velocity (NCV), previously unrealized for any human cell-based in vitro system. This Human Nerve-on-a-chip (HNoaC) system is the first microphysiological system of human peripheral nerve which can be used for evaluating electrophysiological and histological metrics, which are gold-standard assessment techniques previously only possible with in vivo studies.
GSAP modulates γ-secretase specificity by inducing conformational change in PS1
Authors: Wong Eitan , Liao George P. , Chang Jerry , Xu Peng , Li Yue-Ming , Greengard Paul 
Published: November 2018

AbstractThe mechanism by which GSAP (γ-secretase activating protein) regulates γ-secretase activity has not yet been elucidated. Here, we show that knockout of GSAP in cultured cells directly reduces γ-secretase activity for Aβ production, but not for Notch1 cleavage, suggesting that GSAP may induce a conformational change contributing to the specificity of γ-secretase. Furthermore, using an active site directed photoprobe with double cross-linking moieties, we demonstrate that GSAP modifies the orientation and/or distance of PS1-NTF and PS1-CTF, a region containing the active site of γ-secretase. This work offers insight into how GSAP regulates γ-secretase specificity.
Rate variation in the evolution of non-coding DNA associated with social evolution in bees
Authors: Rubin Benjamin E.R. , Jones Beryl M. , Hunt Brendan G. , Kocher Sarah D. 
Published: November 2018

AbstractThe evolutionary origins of eusociality represent increases in complexity from individual to caste-based, group reproduction. These behavioral transitions have been hypothesized to go hand-in-hand with an increased ability to regulate when and where genes are expressed. Bees have convergently evolved eusociality up to five times, providing a framework to test this hypothesis. To examine potential links between putative gene regulatory elements and social evolution, we compare alignable, non-coding sequences in eleven diverse bee species, encompassing three independent origins of reproductive division of labor and two elaborations of eusocial complexity. We find that rates of evolution in a number of non-coding sequences correlate with key social transitions in bees. Interestingly, while we find little evidence for convergent rate changes associated with independent origins of social behavior, a number of molecular pathways exhibit convergent rate changes in conjunction with subsequent elaborations of social organization. We also present evidence that many novel non-coding regions may have been recruited alongside the origin of sociality in corbiculate bees; these loci could represent gene regulatory elements associated with division of labor within this group. Thus, our findings are consistent with the hypothesis that gene regulatory innovations are associated with the evolution of eusociality and illustrate how a thorough examination of both coding and non-coding sequence can provide a more complete understanding of the molecular mechanisms underlying behavioral evolution.
Candida albicanswhite and opaque cells exhibit distinct spectra of organ colonization in mouse models of infection
Authors: Takagi Julie , Singh-Babak Sheena D. , Lohse Matthew B. , Dalal Chiraj K. , Johnson Alexander D. 
Published: November 2018

AbstractCandida albicans, a species of fungi, can thrive in diverse niches of its mammalian hosts; it is a normal resident of the GI tract and mucosal surfaces but it can also enter the bloodstream and colonize internal organs causing serious disease. The ability ofC. albicansto thrive in these different host environments has been attributed, at least in part, to its ability to assume different morphological forms. In this work, we examine one such morphological change known as white-opaque switching. White cells are the default state ofC. albicans, and most animal studies have been carried out exclusively with white cells. Here, we compared the proliferation of white and opaque cells in two murine models of infection and also monitored, using specially constructed strains, switching between the two states in the host. We found that white cells outcompeted opaque cells in many niches; however, we show for the first time that in some organs (specifically, the heart and spleen), opaque cells competed favorably with white cells and, when injected on their own, could colonize these organs. In environments where the introduced white cells outcompeted the introduced opaque cells, we observed high rates of opaque-to-white switching. We did not observe white-to-opaque switching in any of the niches we examined.
Brain neurosteroids are natural anxiolytics targeting α2 subunit γ-aminobutyric acid type-A receptors
Authors: Durkin Elizabeth J , Muessig Laurenz , Herlt Tanja , Lumb Michael J , Patel Ryan , Thomas Philip , Bright Damian P. , Jurd Rachel , Moss Stephen J , Dickenson Anthony H. , Cacucci Francesca , Smart Trevor G 
Published: November 2018

AbstractNeurosteroids are naturally-occurring molecules in the brain that modulate neurotransmission. They are physiologically important since disrupting their biosynthesis precipitates neurological disorders, such as anxiety and depression. The endogenous neurosteroids, allopregnanolone and tetrahydro-deoxycorticosterone are derived from sex and stress hormones respectively, and exhibit therapeutically-useful anxiolytic, analgesic, sedative, anticonvulsant and antidepressant properties. Their main target is the γ-aminobutyric acid type-A inhibitory neurotransmitter receptor (GABAAR), whose activation they potentiate. However, whether specific GABAAR isoforms and neural circuits differentially mediate endogenous neurosteroid effects is unknown. By creating a knock-in mouse that removes neurosteroid potentiation from α2-GABAAR subunits, we reveal that this isoform is a key target for neurosteroid modulation of phasic and tonic inhibition, and is essential for the anxiolytic role of endogenous neurosteroids, but not for their anti-depressant or analgesic properties. Overall, α2-GABAAR targeting neurosteroids may act as selective anxiolytics for the treatment of anxiety disorders, providing new therapeutic opportunities for drug development.