bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cochlear Dysfunction is not Common in Human Meningioma of the Internal Auditory Canal
Authors: Landegger Lukas D. , Lee Jong D. , Linthicum Fred H. , Stankovic Konstantina M. 
Published: October 2017

Hypothesis:
Cochlear dysfunction is not common in human meningioma of the internal auditory canal.

Background:
Meningiomas arising from the cerebellopontine angle and internal auditory canal typically cause hearing loss. Cochlear dysfunction is known to contribute to sensorineural hearing loss induced by vestibular schwannoma, the most common tumor of the internal auditory canal. Detailed cochlear histopathology in meningioma has not been reported.

Methods:
Retrospective analysis of cochlear histopathology in five unoperated and five operated meningiomas of the internal auditory canal identified after screening human temporal bone collections from three academic medical centers.

Results:
While some dysfunction of all analyzed cochlear cell types was identified, a predominant or exclusive loss of hair cells was not observed in any meningioma. Only 14.3% of temporal bones showed significantly more hair cell damage on the side of the tumor when compared with the contralateral ear; cochlear neuronal damage was more prevalent in meningiomas. The incidence of hydrops, perilymphatic precipitate, or endolymphatic precipitate was low.

Conclusions:
Substantial cochlear damage in human meningioma of the internal auditory canal is not common. This may explain the anecdotal hearing improvement observed after surgical resection of meningioma. Our findings underline the importance of developing therapeutic strategies to prevent cochlear neuronal degeneration due to tumors of the internal auditory canal.
Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring
Authors: Wiciński Michał , Węclewicz Mateusz M. 
Published: October 2017

Purpose of review
Clozapine-induced agranulocytosis/granulocytopenia (CIAG) is an uncommon condition, but potentially fatal in consequences. The pathogenesis, despite multiple experiments, is not fully elucidated. The current theory suggests reactive oxygen species – nitrenium ion as the most important factor of CIAG. In this review, mechanism and monitoring of CIAG will be discussed.

Recent findings
The mechanism of CIAG seems to have an autoimmune background, rather than toxic. Clozapine has a high potential to undergo biochemical activation to nitrenium ion. The role of the primary metabolite of clozapine – N-desmethylclozapine – is in decline. Nitrenium ion is mainly synthesized by CYP3A4, CYP2D6, and myeloperoxidase system in leukocytes. An important component of CIAG pathogenesis is genetic aberration in human leukocyte antigen genes, and also genes associated with apoptosis and ubiquitination. Clozapine monitoring regimes differ between countries. US-derived clozapine Risk Evaluation and Mitigation Strategy is the most tolerant in the aspect of blood parameter thresholds. Therefore, it provides the opportunities for physician to continue the treatment and also to rechallenge the drug after the episode of CIAG.

Summary
Each patient with the episode of CIAG should be assessed individually, with special attention to risk factors and drug–drug interactions. Upon that, the decision about clozapine rechallenge or withdrawal should be made.
Clinical Nurse Specialist-Driven Practice Change
Authors: Derby Kelly M. , Hartung Natalie A. , Wolf Sherry L. , Zak Heather L. , Evenson Laura K. 
Published: October 2017

Purpose
The purpose of this project was to standardize vital sign (VS) monitoring throughout a patient’s stay in the hospital, including at admission, following transitions to different levels of care, reassessment of abnormal VS results, daily monitoring, and before dismissal. The population of focus was adult general and progressive care patients.

Description of the Project
Standards for VS monitoring, documentation, and provider notification were established. Unit routines, nursing procedural guidelines, and order sets were updated with the new standards. Nursing staff received Web-based education. Compliance with the new standards was monitored monthly, and data were shared with nursing leadership. Leadership reviewed the data with nursing staff to identify opportunities and recognize achievements.

Outcomes
Overall, improvement in VS documentation was achieved. Continued opportunities exist for monitoring and reassessment of a full set of VSs after an abnormal result.

Conclusion
Establishing a minimum standard of VS frequency and documentation allows for all healthcare providers to trend and monitor a patient’s clinical status. Variability in patient care can be diminished by establishing minimum standards of VS monitoring.
Transitioning Into Practice
Authors: Bath Jennifer , Lucas Amy , Ward Cynthia W. 
Published: October 2017

Purpose/Objectives:
The purposes of this article are to explore the shared experiences and feelings of clinical nurse specialists (CNSs) who were new to the role and to identify strategies that were helpful in making the transition.

Description of Project/Program:
Transitioning to a CNS role may be challenging and emotional, causing fear or anxiety. The authors reflected on their experiences of transitioning into CNS practice.

Outcome:
Reflection on the literature led to advice and helpful strategies for new CNSs as they transition into practice.

Conclusion:
The strategies identified can be used to develop a structured orientation that may ease the transition into the CNS role.
Gonococcal and Chlamydial Cases of Pelvic Inflammatory Disease at 2 Canadian Sexually Transmitted Infection Clinics, 2004 to 2014: A Retrospective Cross-sectional Review
Authors: Chen Justin Z. , Gratrix Jennifer , Smyczek Petra , Parker Penny , Read Ron , Singh Ameeta E. 
Published: October 2017

Abstract
One hundred thirteen patients with gonococcal and chlamydial pelvic inflammatory disease were reviewed at 2 Canadian sexually transmitted infection clinics. Most patients (81%) with pelvic inflammatory disease were diagnosed as having chlamydia alone. Three treatment failures were seen in patients treated with ofloxacin.
Building Professionalism Through Management Training: New England Public Health Training Center's Low-Cost, High-Impact Model
Authors: MacVarish Kathleen , Kenefick Hope , Fidler Anne , Cohen Bradley , Orellana Yuri , Todd Karla 
Published: October 2017

Context:
Evolving practices, accreditation, and priorities established in Public Health 3.0 are adding to the long-identified need for management training among public health practitioners.

Program:
The New England Public Health Training Center is addressing this need with a flexible, open-source, 16-topic training program. The program is designed to build competencies for current and future managers, preparing them for their day-to-day tasks and for the kinds of adaptation suggested by Public Health 3.0 advocates.

Implementation:
The training program uses live expert instructors for 10 webinars and 2 in-person trainings. Experts have also created the content for multiple self-paced E-Learnings that trainees undertake in addition to the instructor-led sessions. A webinar platform with breakout rooms and an advanced learning management system allows for online discussion and mentor interaction. The course has now been offered, evaluated, and modified 3 times, and the materials are available for noncommercial use by the public health community.

Evaluation:
Using the Kirkpatrick training evaluation model, the recent cohort was satisfied (87.5%) with the training, reported identifying actions to apply information learned to their work (85.8%), and experienced statistically significant knowledge gains. Earlier trainees reported work-related behavior change.

Discussion:
Management training offers the hope of increasing professionalism; creating better, more effective workplaces and programs; and preparing practitioners for an evolving public health landscape. Early results indicate that NEPHTC's program, Managing Effectively in Today's Public Health Environment, is a useful tool in realizing that hope.
Simulation-Based Education Enhances Patient Safety Behaviors During Central Venous Catheter Placement
Authors: Jagneaux Tonya , Caffery Terrell S. , Musso Mandi Wilkes , Long Ann C. , Zatarain Lauren , Stopa Erik , Freeman Nathan , Quin Cara Cantelli , Jones Glenn N. 
Published: October 2017

Objective
We describe the effect of simulation-based education on residents’ adherence to protocols for and performance of central venous access.

Methods
Internal medicine and emergency medicine residents underwent a central venous access course that included a lecture, video presentation, readings, and simulation demonstrations presented by faculty. Baseline data were collected before the course was initiated. After a skills session where they rehearsed their ultrasound-guided central venous access skills, residents were evaluated using a procedural checklist and written knowledge exam. Residents also completed questionnaires regarding confidence in performing ultrasound-guided central venous access and opinions about the training course.

Results
Residents demonstrated significant improvement on the written knowledge exam (P < 0.0001) and Standard Protocol Checklist (P < 0.0001) after the training course. Training improved a number of patient safety elements, including adherence to sterile technique, transparent dressing, discarding sharps, and ordering postprocedure x-rays. However, a number of residents failed to wash their hands, prepare with chlorhexidine, drape the patient using a sterile technique, anesthetize the site, and perform a preprocedure time-out. Significant improvement in procedural skills was also noted for reduction in skin-to-vein time (P < 0.003) as well as a reduction in number of residents who punctured the carotid artery (P < 0.02).

Conclusions
Simulation-based education significantly improved residents’ knowledge and procedural skills along with their confidence. Adherence to the protocol also improved. This study illustrates that simulation-based education can improve patient safety through training and protocols.
Regulation of Electroconvulsive Therapy
Authors: Livingston Robin , Wu Chester , Mu Kathy , Coffey M. Justin 
Published: October 2017

Objectives
The goal of this study was to systematically review current US state laws on electroconvulsive therapy (ECT) in order to provide a comprehensive resource to educate practitioners, potential patients, and lawmakers.

Methods
Individual state legislative Web sites were searched by 2 independent authors using the following search terms: “electroconvulsive therapy,” “convulsive therapy,” “electroconvulsant therapy,” “electroshock therapy,” and “shock therapy” from March 2017 to May 2017. All sections of state law pertaining to ECT were reviewed, and pertinent data regarding consent, age restrictions, treatment limitations, required reporting, defined qualified professionals, fees, and other information were extracted.

Results
State regulation on ECT widely varied from none to stringent requirements. There were 6 states without any laws pertaining to ECT. California, Illinois, Massachusetts, Missouri, New York, South Dakota, Tennessee, and Texas were noted to be the most regulatory on ECT.

Conclusions
There are no US national laws on ECT leaving individual state governments to regulate treatment. Whereas some states have detailed restrictions on use, other states have no regulation at all. This variation applies to multiple areas of ECT practice, including who can receive ECT, who can provide informed consent, who can prescribe or perform ECT, and what administrative requirements (eg, fees, reporting) must be met by ECT practitioners. Knowledge of these state laws will help providers not only to be aware of their own state's regulations, but also to have a general awareness of what other states mandate for better patient care and utilization of ECT.
Genetic study links components of the autonomous nervous system to heart-rate profile during exercise
Authors: Verweij Niek , de Vegte Yordi van , der Harst Pim van 
Published: October 2017

ABSTRACTHeart rate (HR) response to exercise, as defined by HR-increase upon exercise and HR-recovery after exercise, is an important predictor of mortality and believed to be modulated by the autonomic nervous system. However, the mechanistic basis underlying inter-individual differences remains to be elucidated. To investigate this, we performed a large-scale genome wide analysis of HR-increase and HR-recovery in 58,818 individuals. A total of 25 significant independent SNPs in 23 loci (P<8.3×10−9) were associated with HR-increase or HR-recovery, and 36 candidate causal genes were prioritized that were enriched for pathways related to neuron biology. There was no evidence of a causal relationship with mortality or cardiovascular diseases, however, a nominal association with parental lifespan was observed (5.5×10−4) that requires further study. In conclusion, our findings provide new biological and clinical insight into the mechanistic under-pinning of HR response to exercise, underscoring the role of the autonomous nervous system in HR-recovery.ABBREVIATIONSBMIBody mass indexECGElectrocardiographyHRHeart rateHRRHeart rate recoveryGWASGenome-wide association studyLDLinkage disequilibriumMAFMinor allele frequencySEStandard errorCIConfidence interval
A circadian clock in the blood-brain barrier regulates xenobiotic efflux from the brain
Authors: Zhang Shirley L. , Yue Zhifeng , Arnold Denice M. , Sehgal Amita 
Published: October 2017

HighlightsTheDrosophilaBBB displays a circadian rhythm of permeabilityCyclic efflux driven by a clock in the BBB underlies the permeability rhythmCircadian control is non-cell-autonomous via gap junction regulation of [Mg2+]iAn anti-seizure drug is more effective when administered at nightSummaryEndogenous circadian rhythms are thought to modulate responses to external factors, but mechanisms that confer time-of-day differences in organismal responses to environmental insults / therapeutic treatments are poorly understood. Using a xenobiotic, we find that permeability of theDrosophila“blood”-brain barrier (BBB) is higher at night. The permeability rhythm is driven by circadian regulation of efflux and depends upon a molecular clock in the perineurial glia of the BBB, although efflux transporters are restricted to subperineurial glia (SPG). We show that transmission of circadian signals across the layers requires gap junctions, which are expressed cyclically. Specifically, during nighttime gap junctions reduce intracellular magnesium ([Mg2+]i), a positive regulator of efflux, in SPG. Consistent with lower nighttime efflux, nighttime administration of the anti-epileptic phenytoin is more effective at treating aDrosophilaseizure model. These findings identify a novel mechanism of circadian regulation and have therapeutic implications for drugs targeted to the central nervous system.
Clogging-free continuous operation with whole blood in a radial pillar device (RAPID)
Authors: Mehendale Ninad , Sharma Oshin , Pandey Shilpi , Paul Debjani 
Published: October 2017

AbstractPillar-based passive microfluidic devices combine the advantages of simple designs, low device footprint, and high selectivity for size-based separation of blood cells. Most of these device designs have been validated with dilute blood samples. Handling whole blood in pillar-based devices is extremely challenging due to clogging. The high proportion of cells (particularly red blood cells) in blood, the varying sizes and stiffness of the different blood cells, and the tendency of the cells to aggregate lead to clogging of the pillars within a short period. We recently reported aradialpillardevice (RAPID) design for contin-uous and high throughput separation of multi-sized rigid polystyrene particles in a single experiment. In this manuscript, we have given detailed guidelines to modify the design of RAPID for any application with deformable objects (e.g. cells). We have adapted RAPID to work with blood samples directly without any pre-processing steps. We were successful in operating the device with whole blood for almost 6 hours, which is difficult to achieve with most pillar-based devices. Finally, we demonstrated up to ~ 60-fold enrichment of platelets as an illustration of the improved device design. Whole blood pillar-based platelet clog-free RAPID
A set informative multiple autosomal markers for human identification: forensic research and population genetics analysis in a Chinese Xinjiang Hui group
Authors: Xie Tong , Guo Yuxin , Chen Ling , Fang Yating , Tai Yunchun , Zhou Yongsong , Qiu Pingming , Zhu Bofeng 
Published: October 2017

AbstractIn recent years, insertion/deletion (InDel) markers became a promising and useful supporting tool in forensic identification cases and biogeographic research field. In this study, 30 InDel loci were explored to reveal the genetic diversities and genetic relationships between Chinese Xinjiang Hui group and the 24 previously studied populations using varies methods such as forensic statistical parameter analysis, phylogenetic reconstruction, STRUCTURE analysis, multi-dimensional scaling, and principal component analysis. The observed heterozygosity and expected heterozygosity ranged from 0.1971 (HLD118) to 0.5092 (HLD 92), 0.2222 (HLD 114) to 0.5000 (HLD 6), respectively. Besides, after Bonferroni correction, no deviations from Hardy-Weinberg equilibrium tests were found at all 30 loci in Xinjiang Hui group. The cumulative probability of exclusion and combined discrimination power were 0.988849 and 0.99999999999378, respectively, which indicated that the 30 loci could be used as complementary genetic markers for paternity test and be qualified for personal identification in forensic cases. In this study, we found that Xinjiang Hui group had close relationships with most Chinese groups, especially Han populations, and all the results based on different genetic methods we used had a strong support for this finding. The 30 InDel loci has important significance in forensic identification research, in spite of this, for a better understanding of genetic background of the Chinese Xinjiang Hui group, molecular genetic genotyping at various genetic markers is necessary in future studies.Summary StatementWe report here, a promising Individual identification and population differentiation maker which could be used in forensic cases.
ZMPSTE24Missense Mutations that Cause Progeroid Diseases Decrease Prelamin A Cleavage Activity and/or Protein Stability
Authors: Spear Eric D. , Hsu Ehr-Ting , Nie Laiyin , Carpenter Elisabeth P. , Hrycyna Christine A. , Michaelis Susan 
Published: October 2017

ABSTRACTThe human zinc metalloprotease ZMPSTE24 is an integral membrane protein critical for the final step in the biogenesis of the nuclear scaffold protein lamin A, encoded byLMNA. After farnesylation and carboxyl methylation of its C-terminal CAAX motif, the lamin A precursor, prelamin A, undergoes proteolytic removal of its modified C-terminal 15 amino acids by ZMPSTE24. Mutations inLMNAorZMPSTE24that impede this prelamin A cleavage step cause the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) and the related progeroid disorders mandibuloacral dysplasia-type B (MAD-B) and restrictive dermopathy (RD). Here we report a “humanized yeast” system to assay ZMPSTE24-dependent cleavage of prelamin A and examine the eight known disease-associatedZMPSTE24missense mutations. All show diminished prelamin A processing and fall into three classes, with defects in activity, protein stability, or both. Notably, some ZMPSTE24 mutants can be rescued by deleting the E3 ubiquitin ligase Doa10, involved in ER-associated degradation of misfolded membrane proteins, or by treatment with the proteasome inhibitor bortezomib, which may have important therapeutic implications for some patients. We also show that ZMPSTE24-mediated prelamin A cleavage can be uncoupled from the recently discovered role of ZMPSTE24 in clearance of ER membrane translocon-clogged substrates. Together with the crystal structure of ZMPSTE24, this “humanized yeast system” can guide structure-function studies to uncover mechanisms of prelamin A cleavage, translocon unclogging, and membrane protein folding and stability.
Identification of a Small Molecule Inhibitor of the Aminoglycoside 6’-N-Acetyltransferase Type Ib [AAC(6’)-Ib] Using Mixture-Based Combinatorial Libraries
Authors: Tran Tung , Chiem Kevin , Jani Saumya , Arivett Brock A. , Lin David , Lad Rupali , Jimenez Verónica , Farone Mary B. , Debevec Ginamarie , Santos Radleigh , Giulianotti Marc , Pinilla Clemencia , Tolmasky Marcelo E. 
Published: October 2017

AbstractThe aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6’)-Ib] is the most widely distributed enzyme among AAC(6’)-I-producing Gram-negative pathogens and confers resistance to clinically relevant aminoglycosides including amikacin. This enzyme is therefore ideal to target with enzymatic inhibitors that could overcome resistance to aminoglycosides. The search for inhibitors was carried out using mixture-based combinatorial libraries, the scaffold ranking approach, and the positional scanning strategy. A library with high inhibitory activity had pyrrolidine pentamine scaffold and was selected for further analysis. This library contained 738,192 compounds with functionalities derived from 26 different amino acids (R1, R2 and R3) and 42 different carboxylic acids (R4) in four R group functionalities. The most active compounds all contained S-phenyl (R1 and R3) and S-hydromethyl (R2) functionalities at three locations and differed at the R4 position. The compound containing 3-phenylbutyl at R4 (compound206) was a robust enzymatic inhibitor in vitro, in combination with amikacin potentiated the inhibition of growth of three resistant bacteria in culture, and improved survival when used as treatment ofGalleria mellonellainfected withaac(6’)-Ib-harboringKlebsiella pneumoniaeandAcinetobacter baumanniistrains.
On a ‘failed’ attempt to manipulate conscious perception with transcranial magnetic stimulation to prefrontal cortex
Authors: Ruby Eugene , Maniscalco Brian , Lau Hakwan , Peters Megan A.K. 
Published: October 2017

AbstractIt has been reported that continuous theta burst transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (DLPFC) impairs metacognitive awareness in visual perception (Rounis et al., 2010). Bor et al. (2017) recently attempted to replicate this result. However, the authors modified the experimental design of the original study considerably, meaning that this was not strictly a replication. In some cases, the changes area prioriexpected to lower the chance of obtaining positive findings. Despite these changes, the researchers in fact still found an effect similar to Rounis et al.’s, but they claimed that it was necessary to adopt certain criteria to discard ∽30% of their subjects, after which a null result was reported. Using computer simulations, we evaluated whether the subject exclusion criteria Bor et al. adopted was appropriate or beneficial. We found that, contrary to their intended purpose, excluding subjects by their criteria does not actually reduce false positive rates. Taking into account both their positive result (without subject exclusion) and negative result (after exclusion) in a Bayesian framework, we further found that their results suggest a 75% or greater likelihood that TMS to DLPFC does in fact impair metacognition, directly contradicting their claim of replication failure. That lesion and chemical inactivation studies are known to demonstrate positive effects in similar paradigms further suggests that Bor et al.’s alleged negative finding cannot be taken as evidence against the role of the prefrontal cortex in conscious perception in general.