bluuebunny/crossref_metadata_2025 huggingface dataset:
ascend: R package for analysis of single-cell RNA-seq data
Authors: Senabouth Anne , Lukowski Samuel W , Hernandez Jose Alquicira , Andersen Stacey B , Mei Xin , Nguyen Quan H , Powell Joseph E
Published: August 2019

Background

Recent developments in single-cell RNA sequencing (scRNA-seq) platforms have vastly increased the number of cells typically assayed in an experiment. Analysis of scRNA-seq data is multidisciplinary in nature, requiring careful consideration of the application of statistical methods with respect to the underlying biology. Few analysis packages exist that are at once robust, are computationally fast, and allow flexible integration with other bioinformatics tools and methods.

Findings

ascend is an R package comprising tools designed to simplify and streamline the preliminary analysis of scRNA-seq data, while addressing the statistical challenges of scRNA-seq analysis and enabling flexible integration with genomics packages and native R functions, including fast parallel computation and efficient memory management. The package incorporates both novel and established methods to provide a framework to perform cell and gene filtering, quality control, normalization, dimension reduction, clustering, differential expression, and a wide range of visualization functions.

Conclusions

ascend is designed to work with scRNA-seq data generated by any high-throughput platform and includes functions to convert data objects between software packages. The ascend workflow is simple and interactive, as well as suitable for implementation by a broad range of users, including those with little programming experience.
Computing Euler Obstruction Functions Using Maximum Likelihood Degrees
Authors: Rodriguez Jose Israel , Wang Botong
Published: August 2019

We give a numerical algorithm computing Euler obstruction functions using maximum likelihood degrees. The maximum likelihood degree is a well-studied property of a variety in algebraic statistics and computational algebraic geometry. In this article we use this degree to give a new way to compute Euler obstruction functions. We define the maximum likelihood obstruction function and show how it coincides with the Euler obstruction function. With this insight, we are able to bring new tools of computational algebraic geometry to study Euler obstruction functions.
Characterization of cefotaxime-resistant urinary Escherichia coli from primary care in South-West England 2017–18
Authors: Findlay Jacqueline , Gould Virginia C , North Paul , Bowker Karen E , Williams Martin O , MacGowan Alasdair P , Avison Matthew B
Published: August 2019

Objectives

Third-generation cephalosporin-resistant Escherichia coli from community-acquired urinary tract infections are increasingly reported worldwide. We sought to determine and characterize the mechanisms of cefotaxime resistance employed by urinary E. coli obtained from primary care, over 12 months, in Bristol and surrounding counties in South-West England.

Methods

Cefalexin-resistant E. coli isolates were identified from GP-referred urine samples using disc susceptibility testing. Cefotaxime resistance was determined by subsequent plating onto MIC breakpoint plates. β-Lactamase genes were detected by PCR. WGS was performed on 225 isolates and analyses were performed using the Center for Genomic Epidemiology platform. Patient information provided by the referring general practices was reviewed.

Results

Cefalexin-resistant E. coli (n=900) isolates were obtained from urines from 146 general practices. Following deduplication by patient approximately 69% (576/836) of isolates were cefotaxime resistant. WGS of 225 isolates identified that the most common cefotaxime-resistance mechanism was blaCTX-M carriage (185/225), followed by plasmid-mediated AmpCs (pAmpCs) (17/225), AmpC hyperproduction (13/225), ESBL blaSHV variants (6/225) or a combination of both blaCTX-M and pAmpC (4/225). Forty-four STs were identified, with ST131 representing 101/225 isolates, within which clade C2 was dominant (54/101). Ciprofloxacin resistance was observed in 128/225 (56.9%) of sequenced isolates, predominantly associated with fluoroquinolone-resistant clones ST131 and ST1193.

Conclusions

Most cefalexin-resistant E. coli isolates were cefotaxime resistant, predominantly caused by blaCTX-M carriage. The correlation between cefotaxime resistance and ciprofloxacin resistance was largely attributable to the high-risk pandemic clones ST131 and ST1193. Localized epidemiological data provide greater resolution than regional data and can be valuable for informing treatment choices in the primary care setting.
A Retrospective Review of the Outcomes and Utility of Percutaneous Radiofrequency Rhizotomy for Trigeminal Neuralgia Using Anatomic Landmark Guidance in Asleep Patients
Authors: Stone Lauren E , Falowski Steven M
Published: August 2019

BACKGROUND

Radiofrequency rhizotomy is a percutaneous procedure for trigeminal neuralgia frequently performed with intermittent awakening, although the utility and accuracy of this procedure in continuously sedated patients have not yet been evaluated.

OBJECTIVE

To evaluate pain relief in patients with trigeminal neuralgia undergoing radiofrequency rhizotomy under continuous sedation.

METHODS

Patients from 2012 to 2017 who underwent radiofrequency rhizotomy for trigeminal neuralgia were evaluated retrospectively. Barrow Neurological Institute Pain Intensity scores were assigned to determine relapse at 1 mo, 1 yr, 3 yr, and 5 yr. Descriptive relapse rates for patients with multiple sclerosis and those undergoing repeat procedures are also reported.

RESULTS

A total of 90.8% of procedures reported Barrow Neurological Institute I-III score at 1 mo (P < .0001), 66.3% at 1 yr (P = .0012), and 71.1% at 3 yr (P = .0003). Duration to relapse was 3.0 and 6.0 at 1 and 3 yr, respectively. Procedures in patients with multiple sclerosis reported 100% relief at 1 mo and 87.5% relief at 1 yr (P = .0099). The presence of numbness and postoperative medication changes were not associated with pain relief (P = .0063, P = .1338).

CONCLUSION

The use of continuous sedation in radiofrequency rhizotomy for trigeminal neuralgia provides pain relief comparable to the recorded literature rate for procedures with intermittent awakening.
Dual Microwire Rail Technique to Advance a Microcatheter Past the Ostium of a Dissecting Carotid Artery Aneurysm for Flow Diverter Deployment: 2-Dimensional Operative Video
Authors: Vakharia Kunal , Munich Stephan A , Waqas Muhammad , McPheeters Matthew J , Levy Elad I
Published: August 2019

Flow diversion using a Pipeline embolization device (PED; Medtronic, Dublin, Ireland) is an effective therapy for treating cavernous aneurysms. Currently, flow diverters require a 0.027-inch microcatheter for deployment. To navigate across these aneurysms, a 0.014-inch microwire is used, which often does not offer a sturdy enough rail to advance a 0.027-inch microcatheter past dissecting artery aneurysm ostia. We present a patient with a right cavernous dissecting carotid artery aneurysm. A step off between the 0.027-inch VIA microcatheter (MicroVention Terumo, Tustin, California) and 0.014-inch Synchro 2 microwire (Stryker Neurovascular, Fremont, California) resulted in difficulty with navigation of the microcatheter across the dissected portion of the aneurysm. A dual microwire rail technique involving two 0.014-inch Synchro 2 microwires was used to advance the VIA microcatheter past the dissecting artery aneurysm ostia for PED deployment. The introduction of the second microwire eliminated the step off between the microwire and microcatheter, providing a stronger rail and easier navigation of the microcatheter, without aggressive pushing. Postembolization runs showed optimal wall apposition and contrast stasis within the aneurysm, with successful flow diversion of the aneurysm.

The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary.
Microsurgical Resection of Brain Stem Ependymoma: 2-Dimensional Operative Video
Authors: Pojskić Mirza , Nguyen Vincent , Lakičević Goran , Arnautović Kenan I
Published: August 2019

The brainstem is a less-common location for ependymomas than the spinal cord where they are the most common adult intramedullary tumor.
1-18
In this first video case report in the peer-reviewed literature, we demonstrate microsurgical resection of a medulla oblongata ependymoma.

 There are several case reports of medulla oblongata ependymomas
1
,
3
,
5
,
6
,
13
and a few series of spinal cord ependymomas that included cases of ependymomas of the cervicomedullary junction.
9
,
10
The goal of surgery was to stabilize the preoperative neurological function; favorable outcome is achieved in patients with good preoperative statuses and well-defined tumor boundaries.
9
Although gross total resection (GTR) provides the best overall outcome, it is most effective for classic grade II tumors, but not grade I (myxopapillary) and ependymomas, which have a lower GTR rate.
14
,
15

 A 55-yr-old patient developed 4-extremity weakness and dysphagia. Pre-/postcontrast magnetic resonance imaging (MRI) revealed centrally located brainstem lesion situated at the lower half of the medulla oblongata. Surgery, performed by the senior author, was performed in the prone position with a small suboccipital craniectomy and C1 posterior arch removal, followed by pia opening and posterior midline myelotomy. Tumor was debulked, dissected from the white matter, and resected. Histology revealed ependymoma (World Health Organization grade II). Postoperative pre-/postcontrast MRI revealed total resection. The patient's neurological deficit completely resolved postoperatively.

 Written consent was obtained from the patient.
Benefits of Medicaid Expansion on CV Mortality and Cancer Screening Rates
Authors: Brodhead Frank
Published: August 2019

Two studies explore outcomes for low-income, middle-aged adults.
Weight Loss After Gastric Bypass is Similar in Adolescents and Adults
Authors: Rosenberg Karen
Published: August 2019

According to this study:

Five years after gastric bypass, adolescents and adults had weight loss that was similar in magnitude.

Remission of diabetes and hypertension occurred more often in adolescents than adults.
Babies at the Border: Reflections on Nursing on Ellis Island
Authors: Keeling Arlene W.
Published: August 2019

Updated several times a week with posts by a wide variety of authors, AJN's blog Off the Charts allows us to provide more timely—and often more personal—perspectives on professional, policy, and clinical issues. Best of the Blog will be a regular column to draw the attention of AJN readers to posts we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.
Heparin vs. Normal Saline Locking for Prevention of Catheter Occlusion
Authors: Levett-Jones Tracy
Published: August 2019

Editor's note: This is a summary of a nursing care–related systematic review from the Cochrane Library. For more information, see http://nursingcare.cochrane.org.
Manufacturing and quality assessment of allergenic extracts for immunotherapy: state of the art
Authors: Bonertz Andreas , Mahler Vera , Vieths Stefan
Published: August 2019

Purpose of review

The recent developments in the manufacturing and quality assessment of allergenic extracts in Europe are summarized.

Recent findings

Quality assessment has always been a fundamental part of allergen product evaluation. New analytical methods have been reported that fill currently existing gaps in the characterization of commonly used allergen products. New types of products require innovative considerations and concepts for their assessment. Advanced standardization efforts aim at increasing reliability and comparability of analytical tools applied for allergen product characterization. In consequence, regulatory requirements are updated in line with such developments.

Current demands on the quality of allergen products ensure production of well characterized products of consistent quality. While experience with manufacturing processes and successful product characterization approaches increase, accompanying and continuous re-evaluation of underlying quality control and assessment concepts is being performed.
Back Pain
Authors: Tailor Yogita , Preston-Hsu Elisabeth
Published: August 2019

Every age group experiences back pain, a common reason for activity limitation. Management of back pain in a woman is challenging because of physiologic and hormonal changes through the woman’s life cycle. The treatment is dictated by etiology and a woman’s stage of life or reproductive events, such as pregnancy, breastfeeding, and menopause. Most episodes of low back pain are temporary with minimal long-term sequelae, but recurrent and long-lasting episodes require more thorough clinical evaluation. This monograph describes the anatomy of the spine; illustrates a focused, thorough evaluation, including obtaining a medical history and performing a physical examination; discusses warning signs and symptoms of more serious etiologies; provides recommendations for further testing or referral; and offers case vignettes of common causes of low back pain as a woman progresses from young adulthood to advanced age.
RBC Transfusion Strategies in the ICU: A Concise Review
Authors: Cable Casey A. , Razavi Seyed Amirhossein , Roback John D. , Murphy David J.
Published: August 2019

Objectives:

To critically assess available high-level clinical studies regarding RBC transfusion strategies, with a focus on hemoglobin transfusion thresholds in the ICU.

Data Sources:

Source data were obtained from a PubMed literature review.

Study Selection:

English language studies addressing RBC transfusions in the ICU with a focus on the most recent relevant studies.

Data Extraction:

Relevant studies were reviewed and the following aspects of each study were identified, abstracted, and analyzed: study design, methods, results, and implications for critical care practice.

Data Synthesis:

Approximately 30–50% of ICU patients receive a transfusion during their hospitalization with anemia being the indication for 75% of transfusions. A significant body of clinical research evidence supports using a restrictive transfusion strategy (e.g., hemoglobin threshold < 7 g/dL) compared with a more liberal approach (e.g., hemoglobin threshold < 10 g/dL). A restrictive strategy (hemoglobin < 7 g/dL) is recommended in patients with sepsis and gastrointestinal bleeds. A slightly higher restrictive threshold is recommended in cardiac surgery (hemoglobin < 7.5 g/dL) and stable cardiovascular disease (hemoglobin < 8 g/dL). Although restrictive strategies are generally supported in hematologic malignancies, acute neurologic injury, and burns, more definitive studies are needed, including acute coronary syndrome. Massive transfusion protocols are the mainstay of treatment for hemorrhagic shock; however, the exact RBC to fresh frozen plasma ratio is still unclear. There are also emerging complimentary practices including nontransfusion strategies to avoid and treat anemia and the reemergence of whole blood transfusion.

Conclusions:

The current literature supports the use of restrictive transfusion strategies in the majority of critically ill populations. Continued studies of optimal transfusion strategies in various patient populations, coupled with the integration of novel complementary ICU practices, will continue to enhance our ability to treat critically ill patients.
Emerging mechanistic underpinnings and therapeutic targets for chemotherapy-related cognitive impairment
Authors: Gibson Erin M. , Monje Michelle
Published: August 2019

Purpose of review

Modern innovations in cancer therapy have dramatically increased the number of cancer survivors. An unfortunately frequent side-effect of cancer treatment is enduring neurological impairment. Persistent deficits in attention, concentration, memory, and speed of information processing afflict a substantial fraction of cancer survivors following completion of these life-saving therapies. Here, we highlight chemotherapy-related cognitive impairment (CRCI) and discuss the current understanding of mechanisms underlying CRCI.

Recent findings

New studies emphasize the deleterious impact of chemotherapeutic agents on glial–glial and neuron–glial interactions that shape the form, function and plasticity of the central nervous system. An emerging theme in cancer therapy-related cognitive impairment is therapy-induced microglial activation and consequent dysfunction of both neural precursor cells and mature neural cell types. Recent work has highlighted the complexity of dysregulated intercellular interactions involving oligodendrocyte lineage cells, microglia, astrocytes, and neurons following exposure to traditional cancer therapies such as methotrexate. This new understanding of the mechanistic underpinnings of CRCI has elucidated potential therapeutic interventions, including colony-stimulating factor 1 receptor inhibition, TrkB agonism, and aerobic exercise.

Traditional cancer therapies induce lasting alterations to multiple neural cell types. Therapy-induced microglial activation is a critical component of the cause of CRCI, contributing to dysregulation of numerous processes of neural plasticity. Therapeutic targeting of microglial activation or the consequent dysregulation of neural plasticity mechanisms are emerging.
Acute Respiratory Distress Syndrome Definition, Causes, and Pathophysiology
Authors: Virani Ahmed , Ma Kiet , Leap Jennifer , Dumont Tiffany , Hertel Joshua , Singh Ashley , Cheema Tariq
Published: August 2019

First successfully described in 1967, acute respiratory distress syndrome has since garnered much interest and debate. Extensive studies and clinical trials have been carried out in efforts to address the associated high mortality; however, it remains a significant burden on health care. Despite the heterogeneous etiologies that lead to the development of acute respiratory distress syndrome, this rapidly progressing form of respiratory failure, characterized by severe hypoxemia and nonhydrostatic pulmonary edema, has a recognizable pattern of lung injury. In this chapter, we will review the clinical manifestations, definitions, causes, and a brief overview of the pathophysiology of this complex syndrome.
Acute Kidney Injury in the Context of Acute Respiratory Distress Syndrome
Authors: Velliyattikuzhi Sreejith M. , Ma Kiet , Bihler Eric J. , Sureshkumar Kalathil K. , Cheema Tariq
Published: August 2019

Acute kidney injury is a heterogeneous syndrome defined by rapid (hours to days) decline in the glomerular filtration rate leading to retention of metabolic waste products including creatinine and urea, resulting in declination of the body's ability to manage fluid status and acid-base regulation. Acute kidney injury is seen commonly in acute respiratory distress syndrome and this article will explore the relationship between the 2 entities.
Prone Positioning in ARDS
Authors: Gordon Ayla , Rabold Erica , Thirumala Raghukumar , Husain Ahmad Alhaj , Patel Samir , Cheema Tariq
Published: August 2019

Adult respiratory distress syndrome (ARDS) is a clinical entity characterized by hypoxemic respiratory failure in the setting of noncardiogenic pulmonary edema. It is associated with significant morbidity and mortality. Prone positioning is a beneficial strategy in patients with severe ARDS because it improves alveolar recruitment, ventilation/perfusion (V/Q) ratio, and decreases lung strain. The outcome is improved oxygenation, decreased severity of lung injury, and, subsequently, mortality benefit. In this article, we discuss the physiology of prone positioning on chest mechanics and V/Q ratio, the placement and maintenance of patients in the prone position with use of a prone bed and the current literature regarding benefits of prone positioning in patients with ARDS.
Mechanical Ventilation in ARDS
Authors: Young Meilin , DiSilvio Briana , Rao Sheldon , Velliyattikuzhi Sreejith , Balaan Marvin
Published: August 2019

Mechanical ventilation is the primary supportive, invasive measure utilized in patients with acute respiratory distress syndrome. Throughout the years, many large multicenter randomized controlled trials and observational studies were analyzed to determine what ventilator parameters to use that would produce a mortality benefit after initial diagnosis. This article discusses the concepts of ventilator-induced lung injury, permissive hypercapnia, high-versus-low peep strategies, oxygenation goals, and recruitment strategies from a physiologic perspective and the major studies that produced recommendations for each. Newer concepts, such as driving pressure, are also discussed.
A Tool Kit for Improving Communication in Your Healthcare Organization
Authors: Cunningham Lynne
Published: August 2019

Effective leadership starts with communication. The ability to communicate can help healthcare leaders gain the trust and confidence of their entire team, leading to better employee engagement and patient outcomes. As the scope of roles, adoption of technology, and needs of the workforce evolve, it is important for leaders to have a tool kit to help them communicate strategically consistent messages to key stakeholders. This article presents an array of evidence-based tools to strengthen leadership skills and drive better, sustainable results for healthcare organizations.
Building Professional Capacity to Strengthen Parent/Professional Relationships in Early Intervention: The FAN Approach
Authors: Cosgrove Kimberly , Gilkerson Linda , Leviton Audrey , Mueller Mary , Norris-Shortle Carole , Gouvêa Marcia
Published: August 2019

A strong relationship between parents and professionals is essential to successful early intervention. Yet, programs struggle to engage families in services. This article describes a successful pilot project to strengthen parent/professional relationships for families with children with disabilities living in a high-poverty urban area. Early intervention (EI) providers were trained to use the FAN (Facilitating Attuned Interactions) approach to increase their attunement to parent concerns and capacity to collaborate with parents during early intervention therapy sessions. Over the pilot project, the providers felt more empathic with parents, more collaborative, and more effective and satisfied in their roles. FAN is a promising approach and practical tool to strengthen relationships between parents and professionals in EI.
Neurotransmitter systems involved in placebo and nocebo effects in healthy participants and patients with chronic pain: a systematic review
Authors: Skyt Ina , Lunde Sigrid J. , Baastrup Cathrine , Svensson Peter , Jensen Troels S. , Vase Lene
Published: August 2019

The investigation of neurotransmitter systems in placebo and nocebo effects has improved our understanding of these phenomena. Yet, most studies involve healthy participants. Because the pain modulatory system may differ in healthy participants and patients with chronic pain, it is important to investigate the evidence for neurotransmitter involvement in placebo and nocebo effects in each of these populations. PubMed, Embase, and Scopus databases, and the Cochrane Library were searched for articles investigating the endogenous opioid, endocannabinoid, dopaminergic, oxytocinergic, vasopressinergic, and cholecystokininergic (CCKergic) systems in placebo and nocebo effects in pain. Twenty-eight placebo and 2 nocebo studies were included. Vote counting was used to balance the number of positive vs negative findings. In healthy participants, the endogenous opioid, endocannabinoid, and vasopressinergic systems were involved in placebo effects, whereas findings on the dopaminergic and oxytocinergic systems were mixed. In patients with chronic pain, only 4 studies investigated neurotransmitters showing no involvement of the endogenous opioid system and mixed findings regarding the dopaminergic system. As to nocebo effects, 2 studies suggest that the CCKergic system is involved in nocebo effects in healthy participants. Overall, research has come a long way in specifying the neurotransmitter systems involved in placebo effects in healthy participants. Yet, evidence for the involvement of neurotransmitter systems in placebo effects in patients with chronic pain and in nocebo effects in healthy participants and patients is scarce. Based on the existing evidence, this systematic review suggests that knowledge obtained in healthy participants may not necessarily be transferred to chronic pain.
Chronic Condition Measurement Requires Engagement, Not Measurement Alone
Authors: Austin Andrea M. , Carmichael Don , Berry Scott , Gozansky Wendolyn S. , Nelson Eugene C. , Skinner Jonathan S. , Barr Paul J.
Published: August 2019

Patient-reported outcome measures (PROMs) have great promise, but evidence of success is mixed. This study uses data from Dartmouth-Hitchcock Medical Center and Kaiser-Permanente Colorado to evaluate providing PROMs directly to the primary care physician. We compared changes over time in urinary incontinence, falls, and mental and physical health between clinics providing augmented PROMs (N = 202 patients) and control clinics (N = 102 patients). Both the control and treatment groups exhibited improvements, but there was no significant difference in outcomes over time. These results suggest that measuring and printing out PROMs for primary care physicians will not result in better patient outcomes without physician clinical engagement.
Accountable Care Program Implementation and Effects on Participating Health Care Systems in Washington State
Authors: Wood Suzanne J. , Albertson Elaine M. , Conrad Douglas A.
Published: August 2019

This study is based on key informant interviews with health care executives representing 5 large health systems that had entered into contracts with the Washington State Health Care Authority to provide accountable care network services under the State Innovation Model initiative. The purpose of this study was to explain effects of accountable care program (ACP) implementation on participating health care systems. Between January 2017 and May 2018, we conducted 2 rounds of semistructured interviews (n = 20). Results indicate the need to present a modified conceptual model aligned with ACP implementation in the current context.
Differences in Outcomes After Anesthesia-Related Adverse Events in Older and Younger Patients
Authors: Root Christopher W. , Beilin Yaakov , McCormick Patrick J. , Curatolo Christopher J. , Katz Daniel , Hyman Jaime B.
Published: August 2019

Because more older adults undergo surgical procedures, it is incumbent on us to learn how to provide them with the safest possible perioperative care. We conducted a retrospective cohort study at a large tertiary care center to determine whether outcomes after anesthesia-related adverse events differed between patients aged 65 years and older versus patients under age 65. One thousand four hundred twenty-four cases were referred to the Performance Improvement committee of the Department of Anesthesiology from the years 2007–2015. After exclusions of cases that were not anesthesia-related, could not be identified, or were duplicates, 747 cases with anesthesia-related adverse events were included in the study. Two hundred eighty-six were aged 65 years and older and 461 were under age 65. Anesthesia-related adverse events occurred more commonly in the postoperative period in older patients relative to younger patients (37.7% vs. 21.9%, p = .001), and older patients had a greater incidence of mortality compared with a propensity-matched group of younger patients (adjusted odds ratio 1.87 [1.14–3.12], p < .05). We concluded that older patients have a greater likelihood of mortality as a result of suffering an anesthesia-related adverse event and may benefit from increased vigilance in the postoperative period.
Virtual Surgical Planning Assisted Management for Cleft-Related Maxillary Hypoplasia
Authors: Wang Yu , Zhang Zhen , Liu Yao , Ye Bin , Luo En , Li Jihua
Published: August 2019

Maxillary hypoplasia is a common developmental deformity affecting patients with cleft lip and palate. Various surgical techniques including conventional orthognathic surgery, total maxillary distraction osteogenesis, and anterior maxillary segmental distraction have been applied to address the deformity. With the evolution of 3D computed tomography imaging, the visualization of skeletal complexities in different perspectives is greatly enhanced and comprehensive surgical planning is achieved. Intraoperative efficiency is also improved with the fabrication of 3D-printed templates. The study aims to present different surgical techniques with virtual surgical planning (VSP) and 3D-printed surgical templates and the solution of representative cases. From January 2014 to January 2019, VSP was transferred to actual surgery or distraction precisely in 80 adult patients with cleft-related maxillary hypoplasia. The accuracy was analyzed and the relapse was also estimated and observed in 18 patients after 1-year follow-up. Based on our experience, VSP provides a more reliable and effective option to conventional model surgery. It facilitates the preoperative planning and accurately transfers the virtual plan to correct the cleft-related maxillary hypoplasia.
Is Bilateral Sagittal Split Osteotomy of the Mandible With no Step Possible? A Modification in the Technique
Authors: Mont’Alverne Antonio Lopes Filho , Xavier Felipe Gomes , Meneses Anderson Maia , Santos Eliardo Silveira , Franco Jéferson Martins Pereira Lucena
Published: August 2019

The mandibular ramus sagittal osteotomy is a usual procedure used to correct deformities of the lower third of the face. Modifications of the procedure will be presented to avoid the presence of palpable gap at mandibular body, easily seen in greater movements.
Effects of Maxillary Skeletal Expansion on Upper Airway Airflow: A Computational Fluid Dynamics Analysis
Authors: Zhao Tingting , Zhang Xiaotie , Ngan Peter , Yuan Wenjun , Chen Xiong , Hua Fang , He Hong
Published: August 2019

The effect of maxillary skeletal expansion (MSE) on upper airway in adolescent patients is not clear. The purpose of this study was to determine the upper airway airflow with MSE treatment using computational fluid dynamics analysis. Three-dimensional upper airway finite element models fabricated from cone beam computed tomography images were obtained before and after treatment in an adolescent patient with maxillary constriction. Turbulent analyses were applied. The nasal cavity (NC) was divided into 6 planes along the y-axis and the pharynx was divided into 7 planes in the z-axis. Changes in cross-sectional area, airflow velocity, pressure, and total resistance at maximum expiration and maximum inspiration were determined at each plane after MSE treatment. The greatest increase in area occurred in the oropharynx which was around 40.65%. The average increase in area was 7.42% in the NC and 22.04% in the pharynx. The middle part of pharynx showed the greatest increase of 212.81 mm2 and 217.99 mm2 or 36.58% and 40.66%, respectively. During both inspiration and expiration, airflow pressure decreased in both the NC and pharynx, which ranged from −11.34% to −23.68%. In the NC, the average velocity decrease was -0.18 m/s at maximum expiration (ME) and −0.13 m/s at maximum inspiration (MI). In the pharynx, the average velocity decrease was -0.07 m/s for both ME and MI. These results suggest that treatment of maxillary constriction using MSE appliance may show positive effects in improvement of upper airway cross-sectional areas and reduction of upper airway resistance and velocity.
Closed and Open Reduction of Nasal Fractures
Authors: James Joanne Grace , Izam Azza Shafiqah , Nabil Syed , Rahman Normastura Abd , Ramli Roszalina
Published: August 2019

Aim:

The objective of this review was to determine the different types of surgical intervention in the management of nasal bone fractures, the outcomes, and complications associated with each intervention.

Methods:

A search was conducted using the PubMed and Cochrane Database of Systematic Review databases from January 1, 1997 until September 9, 2017. The search strategy was constructed using the Population Intervention Comparison Outcome framework with keywords related to nasal fracture and its treatment. Two sets of independent researchers performed the analysis. Qualitative analysis was performed using the Methodological Index for Non-Randomized Studies and National Institute for Clinical Excellence methodology for randomized controlled trial checklists.

Results:

The 4276 titles were obtained from PubMed database alone. Exclusion was made based on the title, abstract and full-text analysis. Finally, 23 papers were included and analyzed. Of the 23 papers, 13 (56.5%) were retrospective record review, 2 (8.7%) were randomized clinical trial or a randomized study and 8 case series (34.8%). 16 (69.6%) studies addressed closed reduction, 3 studies (13%) on open reduction and 4 studies (17.4%) addressed both open and closed reduction. The main focus in the outcome in all studies was accuracy of the anatomical reduction of the nasal bones. Three studies (13.0%) reported restoration of function such as breathing comfort or release in respiratory obstruction and another 3 (13.0%) addressed both cosmetic and breathing outcomes. Residual deformity was the most described complications in the studies (30.4%). In general, most of the studies were not of high quality as they lacked in some key elements in the Methodological Index for Non-Randomized Studies checklist.

Conclusion:

Both closed and open reduction provided good outcomes in cosmetic and breathing. Septoplasty is recommended to be performed simultaneously with fracture reduction.
Effect of a Mandibular Advancement Device on the Upper Airway in a Patient With Obstructive Sleep Apnea
Authors: Flores-Orozco Elan Ignacio , Tiznado-Orozco Gaby Esthela , Díaz-Peña Rogelio , Orozco Esteban Isaí Flores , Galletti Cosimo , Gazia Francesco , Galletti Francesco
Published: August 2019

The authors present a case of a 33-year-old male patient with obstructive sleep apnea syndrome who was treated with a mandibular advancement device with excellent results. The aim of this study is to underline the importance of new instruments that allow evaluating the upper airway with greater precision, such as cone beam tomography. Given the diagnosis and treatment, the upper airway was assessed using cone beam tomography; an increase in UA volume of 22% was observed (initial volume 22,962 mm3), along with a 28% increase in area (initial area 971 mm2). The evaluation of the UA using teleradiography also showed an increase in the points evaluated, with the midpoint of the soft palate presenting the greatest increase.
Clivus Intraosseous Meningioma Mimicking Chordoma
Authors: Abuzayed Bashar , Alawneh Khaled , Al Qawasmeh Majdi , Raffee Liqaa
Published: August 2019

A 78-year-old woman with progressive worsening vertigo and new onset of diplopia. Neurological examination revealed bilateral abducens nerve paralysis and gait disturbance with truncal ataxia. Neuroimaging revealed a mass lesion within the clivus with brain stem compression. The patient was operated with provisional diagnosis of clivus chordoma by neuro-navigation-guided extended endoscopic endonasal approach. Subtotal resection of the tumor was achieved with no intra- or postoperative complications. Histopathologic examination revealed intraosseous meningioma (WHO grade I). To the authors’ best knowledge this is the first case reporting clivus site of intraosseous meningioma.
A Virtual Crossmatch-based Strategy Facilitates Sharing of Deceased Donor Kidneys for Highly Sensitized Recipients
Authors: Roll Garrett R. , Webber Allison B. , Gae David H. , Laszik Zoltan , Tavakol Mehdi , Mayen Luis , Cunniffe Kelly , Syed Shareef , Hirose Ryutaro , Freise Chris , Feng Sandy , Roberts John P. , Ascher Nancy L. , Stock Peter G. , Rajalingam Raja
Published: August 2019

Background.

It is estimated that 19.2% of kidneys exported for candidates with >98% calculated panel reactive antibodies are transplanted into unintended recipients, most commonly due to positive physical crossmatch (PXM). We describe the application of a virtual crossmatch (VXM) that has resulted in a very low rate of transplantation into unintended recipients.

Methods.

We performed a retrospective review of kidneys imported to our center to assess the reasons driving late reallocation based on the type of pretransplant crossmatch used for the intended recipient.

Results.

From December 2014 to October 2017, 254 kidneys were imported based on our assessment of a VXM. Of these, 215 (84.6%) were transplanted without a pretransplant PXM. The remaining 39 (15.4%) recipients required a PXM on admission using a new sample because they did not have an HLA antibody test within the preceding 3 months or because they had a recent blood transfusion. A total of 93% of the imported kidneys were transplanted into intended recipients. There were 18 late reallocations: 9 (3.5%) due to identification of a new recipient medical problem upon admission, 5 (2%) due to suboptimal organ quality on arrival, and only 4 (1.6%) due to a positive PXM or HLA antibody concern. A total of 42% of the recipients of imported kidneys had a 100% calculated panel reactive antibodies. There were no hyperacute rejections and very infrequent acute rejection in the first year suggesting no evidence for immunologic memory response.

Conclusions.

Seamless sharing is within reach, even when kidneys are shipped long distances for highly sensitized recipients. Late reallocations can be almost entirely avoided with a strategy that relies heavily on VXM.
Further Evidence That the Soluble Urokinase Plasminogen Activator Receptor Does Not Directly Injure Mice or Human Podocytes
Authors: Harel Efrat , Shoji Jun , Abraham Vivek , Miller Loan , Laszik Zoltan G. , King Andrew , Dobi Dejan , Szabo Gyula , Hann Byron , Sarwal Minnie M. , Craik Charles S. , Vincenti Flavio
Published: August 2019

Background.

The role of the soluble urokinase plasminogen activator receptor (suPAR) in focal segmental glomerulosclerosis (FSGS) as the circulating factor or as a predictor of recurrence after transplantation remains controversial. Previously published studies in mice and isolated podocytes produced conflicting results on the effect of suPAR on podocyte injury, effacement of foot processes, and proteinuria. These discordant results were in part due to diverse experimental designs and different strains of mice. The aim of our study was to determine the reasons for the inconsistencies of the previous studies results with suPAR by using uniform methods and studies in different strains of mice.

Methods.

We utilized a primary culture of human podocytes and 2 mouse models, the wild type (WT) and the urokinase plasminogen activator receptor (uPAR) KO (uPAR−/−), in an attempt to resolve the reported conflicting results.

Results.

In both WT and uPAR−/− mouse models, injection of recombinant uPAR, even at a high dose (100 μg), did not induce proteinuria, effacement of podocytes, or disruption of the cytoskeleton. Injection of suPAR resulted in its deposition exclusively in the glomerular endothelial cells and not in the podocytes of WT mice and was not detected at the uPAR KO mice. Kidneys from patients with recurrent FSGS had negative immunostaining for uPAR. We also evaluated the effect of recombinant uPAR on primary culture of human podocytes. uPAR did not result in podocytes damage.

Conclusions.

suPAR by itself is not the cause for direct podocyte injury, in vitro or in vivo. These findings suggest a more complex and still poorly understood role of suPAR in FSGS.
PGRMC1 phosphorylation and cell plasticity 1: glycolysis, mitochondria, tumor growth
Authors: Thejer Bashar M. , Adhikary Partho P. , Kaur Amandeep , Teakel Sarah L. , Van Oosterum Ashleigh , Seth Ishith , Pajic Marina , Hannan Kate M. , Pavy Megan , Poh Perlita , Jazayeri Jalal A. , Zaw Thiri , Pascovici Dana , Ludescher Marina , Pawlak Michael , Cassano Juan C. , Turnbull Lynne , Jazayeri Mitra , James Alexander C. , Coorey Craig P. , Roberts Tara L. , Kinder Simon J. , Hannan Ross D. , Patrick Ellis , Molloy Mark P. , New Elizabeth J. , Fehm Tanja N. , Neubauer Hans , Goldys Ewa M. , Weston Leslie A. , Cahill Michael A.
Published: August 2019

Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Here, we demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated mouse xenograft tumor growth. An accompanying paper demonstrates altered metabolism, mutation incidence, and epigenetic status in these cells, indicating that PGRMC1 phosphorylation strongly influences cancer biology.
PGRMC1 phosphorylation and cell plasticity 2: genomic integrity and CpG methylation
Authors: Thejer Bashar M. , Adhikary Partho P. , Teakel Sarah L. , Fang Johnny , Weston Paul A. , Gurusinghe Saliya , Anwer Ayad G. , Gosnell Martin , Jazayeri Jalal A. , Ludescher Marina , Gray Lesley-Ann , Pawlak Michael , Wallace Robyn H. , Pant Sameer D. , Wong Marie , Fischer Tamas , New Elizabeth J. , Fehm Tanja N. , Neubauer Hans , Goldys Ewa M. , Quinn Jane C. , Weston Leslie A. , Cahill Michael A.
Published: August 2019

Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.
The Gut Microbiota composition of Feral and Tamworth Pigs determined using High-Throughput Culturomics and Metagenomics Reveals Compositional Variations When Compared to the Commercial Breeds
Authors: Fenske Gavin J. , Ghimire Sudeep , Antony Linto , Christopher-Hennings Jane , Scaria Joy
Published: August 2019

Bacterial communities in the hindguts of pigs have a profound impact on health and disease. Yet very limited studies have been performed outside intensive swine farms to determine pig gut microbiome composition in natural populations. Feral pigs represent a unique situation where the microbiome structure can be observed outside the realm of modern agriculture. Additionally, Tamworth pigs that freely forage were included to characterize the microbiome structure of this rare breed. In this study, gut microbiome of feral and Tamworth pigs were determined using metagenomics and culturomics. Tamworth pigs are highly dominated by Bacteroidetes primarily composed of the genus Prevotella whereas feral samples were more diverse with almost equal proportions of Firmicutes and Bacteroidetes. In total, 46 distinct species were successfully isolated from 1000 colonies selected. The combination of metagenomics and culture techniques facilitated a greater retrieval of annotated genes than either method alone. Furthermore, the naturally raised Tamworth pig microbiome contained more number of antibiotic resistance genes when compared to feral pig microbiome. The single medium based pig microbiota library we report is a resource to better understand pig gut microbial ecology and function by assembling simple to complex microbiota communities in bioreactors or germfree animal models.
Association between Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration
Authors: Seddon Johanna M. , Dossett James , Widjajahakim Rafael , Rosner Bernard
Published: August 2019

PURPOSE

To determine associations between macular drusen parameters derived from an automatic optical coherence tomography (OCT) algorithm, age-related macular degeneration (AMD) stage and genetic variants.

METHODS

Eyes classified as early or intermediate AMD with OCT imaging and genetic data were selected (n=239 eyes). Drusen area and volume measurements were estimated using the Zeiss Cirrus advanced retinal pigment epithelium (RPE) analysis algorithm in a 5mm diameter (perifoveal) zone centered on the fovea. Associations between drusen measurements and common genetic variants in the complement and high density lipoprotein (HDL) lipid pathways and theARMS2variant were calculated using generalized estimating equations and linear mixed models adjusting for age, sex, smoking, BMI, and education.

RESULTS

When compared to eyes with no measurable drusen, drusen area ≥ the median was independently associated with a higher number of risk alleles forCFHrisk score, risk variants inC3andARMS2/HTRA1. Similar results were obtained for drusen volume. When all genes were analyzed in the same model, onlyCFHscore andARMS2/HTRA1were associated with drusen measurements. HDL pathway genes were not significantly related to drusen parameters. Early and intermediate AMD stages were associated with OCT derived drusen area and volume.

CONCLUSION

Genetic variants inCFHandARMS2/HTRA1, commonly associated with advanced AMD, were independently associated with higher drusen burden determined by OCT in eyes with early and intermediate AMD. The automatic RPE algorithm using OCT provides a quantitative classification of non-advanced AMD. Drusen morphology and other OCT-derived sub-phenotypes are biomarkers that could provide early anatomic endpoints for clinical trials.