bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Sex–Obesity Intersectionality Play a Role in Labor Inactivity? Results From the Brazilian National Health Survey
Authors: Pilecco Flávia Bulegon , Ferreira Marcelo José Monteiro , Antigo Mariangela Furlan , Araújo Larissa Fortunato
Published: November 2020

Objective:

To investigate the association between sex–obesity intersection and labor inactivity and whether education modifies this relationship in a national health survey.

Methods:

Cross-sectional study using the database of 43,456 participants from the Brazilian National Health Survey. Logistic Regression analyses were performed.

Results:

To be women with or without obesity was associated with higher frequency of labor inactivity in comparison to non-obese men. Among men, only those with central obesity had a higher rate of inactivity than non-obese men, especially those with incomplete elementary school.

Conclusions:

The double burden of judgment (sexism and fatphobia) suffered by obese women can lead to socioeconomic inequalities which may strength poorness and/or exclusion. Thus, there are urgent measures for empowerment and equity in the labor market.
An evaluation of treatments and survival rates for pancreatic adenocarcinoma through survival analysis with inverse probability of treatment weighting: a population-based study
Authors: Wang Suzhen , Wang Chen , Shi Fuyan , Tao Enxue , Zhu Gaopei , Li Juan , Feng Jianing , Wang Xiaoxuan , Guo Jing , Zheng Qingfeng , Zhang Bo
Published: November 2020

Objective:

This study conducted inverse probability of treatment weighting (IPTW) survival analysis to examine survival in pancreatic adenocarcinoma patients.

Methods:

In this population-based study, data from the Surveillance, Epidemiology, and End Results program of the United States were analyzed to identify patients diagnosed with adenocarcinoma of the pancreas 2004 to 2014. Differences in survival rates were examined among patients who underwent pancreatectomy alone, radiotherapy alone, and those who had pancreatectomy plus adjuvant radiotherapy. Kaplan–Meier estimates and Cox proportional hazards models with the IPTW were performed to determine the effect of different treatments on overall and cancer-specific survival. This study was approved by the Ethics Review Board of Weifang Medical University.

Results:

A total of 8191 patients were included, with 3409 taking pancreatectomy only, 2865 taking radiotherapy only, and 1917 taking pancreatectomy plus adjuvant radiotherapy. Patients who received surgery plus adjuvant radiotherapy had statistically a higher survival rate than those who received the other 2 treatments. Survival analysis with the IPTW for the 3 different groups showed that the difference in median overall survival time among these patient groups was significant.

Conclusion:

Using IPTW survival analysis, the present study shows that surgery with adjuvant radiotherapy is significantly associated with improved overall and cancer-specific survival among patients with pancreatic adenocarcinoma.
Outcome of Cochlear Implantation in NLRP3-related Autoinflammatory Inner Ear Disorders
Authors: Kim Bong Jik , Kim Young Ho , Han Jin Hee , Lee Sang-Yeon , Carandang Marge , Lee Dong-Han , Lee Soyoung , Choi Byung Yoon
Published: November 2020

Objective:

Hearing loss is a highly penetrant phenotype in NLRP3 (Nod-Like-Receptor-Pyrin containing 3) gene-related autoinflammatory disorders. A recent study revealed potential medical treatment of hearing loss with anakinra (anti-interleukin 1 receptor antagonist) in selected cases. However, for severely aggravated hearing loss not responsive to anakinra, cochlear implantation (CI) would be the last resort for hearing rehabilitation. Outcome of CI is not clearly elucidated yet in this emerging type of hearing loss related to NLRP3-related autoinflammatory disorders, which has a systemic nature and ubiquitous distribution of resident macrophages involving the spiral ganglion neuron and the cochlear nerve. Here, we report the successful outcome of CI in NLRP3-related autoinflammatory disorder.

Patients:

Three subjects representing each type of NLRP3-related autoinflammatory disorder: chronic infantile, neurological, cutaneous, and articular syndrome; Muckle-Wells syndrome; and DFNA34, who underwent CI for auditory rehabilitation, were recruited.

Interventions:

Phenotypes as well as genotypes were reviewed in the subjects.

Main Outcome Measures:

Audiologic performances before/after CI over time were evaluated.

Results:

All three subjects showed excellent audiological outcomes with rapid improvement of speech perception test result reaching plateau at 3 months after CI, although distribution of the disease predicted poor outcome based on theoretical analysis.

Conclusions:

This is the first report to present outcome of CI among subjects with a confirmed NLRP3 genetic etiology and resultant systemic inflammation, and suggests that CI is a viable treatment option in this disease entity.
Risky Business: A Mediated Model of Antecedents and Consequences of Presenteeism in Nursing
Authors: Rainbow Jessica G. , Gilbreath Brad , Steege Linsey M.
Published: November 2020

Background

Nurses are a high-risk group for presenteeism: When one is present at work but not fully engaged. Presenteeism can occur because of multiple work, personal, and event factors and is linked to negative nurse, patient, and organizational outcomes. A model that accounts for the multiple antecedents that lead to presenteeism, as well as its consequences, is needed.

Objective

The aim of this study was to evaluate our proposed presenteeism in nursing model among registered nurses in the United States by examining the fit of the data with the model.

Methods

Four hundred forty-seven registered nurses who provide direct patient care completed a cross-sectional survey on presenteeism, its antecedents and consequences, and demographics. Structural equation modeling was used to test relationships in the proposed model and overall model fit.

Results

The presenteeism in nursing model holistically accounted for significant presenteeism antecedents and consequences. There were significant relationships between work environment, perceived stress and work–life balance, and presenteeism. There were also significant relationships between presenteeism and missed care, and burnout.

Discussion

These relationships align with prior research and identify antecedents and consequences of presenteeism. This model can be used by practitioners and researchers to develop interventions addressing presenteeism to improve health system, nurse, and patient outcomes.
Understanding and addressing global inequities in cancer survivorship care
Authors: Jacobsen Paul B. , Mollica Michelle A.
Published: November 2020

Cancer survivorship focuses on efforts to understand and address the health care needs of people diagnosed with cancer beyond the acute diagnosis and treatment phase. To date, work in this area has been concentrated in a limited number of high-income countries and has progressed to identifying and implementing effective models of survivorship care. The situation is likely quite different in low- and middle-income countries where awareness of and ability to address issues affecting cancer survivors may be limited. Four recommendations are offered for advancing cancer survivorship care more equitably across the globe: conduct research to better understand the current state of survivorship care in low-, middle-, and high-income countries; expand the number of national cancer control plans that address cancer survivorship; develop and disseminate resource-stratified guidelines for survivorship care; and form regional partnerships to improve survivorship care similar to those formed to improve palliative care.
Psychological reactions and interventions to help Cancer patients cope during the COVID-19 pandemic in China
Authors: Liu Xiaohong , Liu Feng , Tong Fei , Peng Wanglian , Wen Minni , Zou Ran , Zhang Lemeng , Jiang Ling , Yang Hui , Yi Lili , Huang Xufen
Published: November 2020

During COVID-19 pandemic, how can cancer patients adjust their psychological status? In this article, some questions and suggestions are given to share. I listed some of negative emotions could happen on cancer patients and showed their harm and gave suggestions accordingly, especially in how to keep cancer patients in a healthy attitude during the difficult time.
Computed Tomography Angiography of the Aorta—Optimization of Automatic Tube Voltage Selection Settings to Reduce Radiation Dose or Contrast Medium in a Prospective Randomized Trial
Authors: Euler André , Taslimi Tilo , Eberhard Matthias , Kobe Adrian , Reeve Kelly , Zimmermann Alexander , Krauss Andreas , Gutjahr Ralf , Schmidt Bernhard , Alkadhi Hatem
Published: November 2020

Objectives

The aim of this study was to compare the image quality of low-kV protocols with optimized automatic tube voltage selection (ATVS) settings to reduce either radiation dose or contrast medium (CM) with that of a reference protocol for computed tomography angiography (CTA) of the thoracoabdominal aorta.

Materials and Methods

In this institutional review board–approved, single-center, prospective randomized controlled trial, 126 patients receiving CTA of the aorta were allocated to one of three computed tomography protocols: (A) reference protocol at 120 kVp and standard weight-adapted CM dose; (B) protocol at 90 kVp, reduced radiation and standard CM dose; and (C) protocol at 90 kVp, standard radiation and reduced CM dose. All three protocols were performed on a third-generation dual-source computed tomography scanner using the semimode of the ATVS system. The image-task-dependent optimization settings of the ATVS (slider level) were adjusted to level 11 (high-contrast task) for protocols A and B and level 3 (low-contrast task) for protocol C. Radiation dose parameters were assessed. The contrast-to-noise ratios (CNRs) of protocols B and C were tested for noninferiority compared with A. Subjective image quality was assessed using a 5-point Likert scale.

Results

Size-specific dose estimate was 34.3% lower for protocol B compared with A (P < 0.0001). Contrast medium was 20.2% lower for protocol C compared with A (P < 0.0001). Mean CNR in B and C was noninferior to protocol A (CNR of 30.2 ± 7, 33.4 ± 6.7, and 30.5 ± 8.9 for protocols A, B, and C, respectively). There was no significant difference in overall subjective image quality among protocols (4.09 ± 0.21, 4.03 ± 0.19, and 4.08 ± 0.17 for protocols A, B, and C, respectively; P = 0.4).

Conclusions

The slider settings of an ATVS system can be adjusted to optimize either radiation dose or CM at noninferior image quality in low-kV CTA of the aorta. This optimization could be used to extend future ATVS algorithms to take clinical risk factors like kidney function of individual patients into account.
Incidental Detection of Urothelial Carcinoma on 18F-Fluciclovine PET/CT
Authors: Surasi Devaki Shilpa Sudha , Lu Yang , Corn Paul , Pettaway Curtis , Bathala Tharakeswara
Published: November 2020

18F-Fluciclovine PET/CT has become a common diagnostic imaging study used in the evaluation of biochemical recurrence in prostate cancer since its approval in 2016. We present a case report of an 82-year-old man with history of both prostate and bladder cancer who presented for a fluciclovine study due to rising PSA levels. There was incidental detection of focal penile activity, and a subsequent urethral biopsy performed showed urothelial carcinoma, which was also seen on a subsequent MRI study.
Internal Jugular Vein and Cerebral Venous Sinus Infective Thrombophlebitis Detected With 99mTc-HMPAO White Blood Cell Scintigraphy
Authors: Sistani Golmehr , Zukotynski Katherine A. , Akincioglu Cigdem , Romsa Jonathan G. , Warrington James C.
Published: November 2020

A 35-year-old man with a history of renal transplant, congenital cystinosis, and diabetes was admitted to the hospital with fever, bilateral parotid gland swelling, and acute renal failure. He had 99mTc-HMPAO-WBC (99mTc-hexamethylpropyleneamineoxime white blood cell) imaging for the evaluation of possible parotitis. There was intense radiopharmaceutical uptake along the right internal jugular vein extending to the right sigmoid and transverse and superior sagittal sinuses, suggestive of infective thrombophlebitis or Lemierre syndrome. This study illustrates the value of 99mTc-HMPAO-WBC imaging as a tool for evaluating thrombophlebitis, particularly in patients with renal failure in whom contrast-enhanced CT may not be possible.
Advantage of 68Ga-PSMA PET/CT on Postradiotherapy Response Assessment of Juvenile Nasal Angiofibroma
Authors: Sakthivel Pirabu , Thakar Alok , Thankarajan Arunraj Sreedharan , Bhalla Ashu Seith , Kumar Rakesh
Published: November 2020

Prostate-specific membrane antigen (PSMA) is universally expressed in the endothelial cells of tumor-associated neovasculature of juvenile nasopharyngeal angiofibroma. Functional 68Ga-PSMA PET/CT also enables easier differentiation of the residual tumor from postoperative changes. An 18-year-old man with the residual intracranial disease received radiotherapy after surgery. In PSMA PET/CT imaging, uptake was noted initially only in the residual disease, and the same was absent after successful response to radiotherapy, unlike contrast MRI, which showed persistent enhancement. Functional 68Ga-PSMA PET/CT may be a very useful tool clinically for identifying early responses to radiotherapy compared with conventional structural imaging.
Angiosarcoma of the Abdominal Aorta After Endovascular Aneurysm Repair
Authors: Walker Kadeem , Khan Neiladri , Scherer Philip
Published: November 2020

Primary angiosarcomas of the aorta are rare, highly aggressive malignant tumors for which there have been limited documented cases in the medical literature. Diagnosis is challenging due to nonspecific symptomatology and imitation of common aortic pathologies. A subset of these primary aortic angiosarcoma cases is seen in association with endovascular aneurysm repair, or EVAR; however, the connection between the 2 entities is not completely understood. Here, we present 18F-FDG PET/CT imaging findings of an angiosarcoma of the aorta in a 69-year-old man status post EVAR.
Optic Canal Analysis in Syndromic Craniosynostosis: Volumetric and Surface Area Validation Study Using Different Measurement Modalities
Authors: Hariri Firdaus , Zainudin Nur Afiqah Aina , Anuar Ahmad Muizz Shariful , Ibrahim Norliza , Abdullah Norli Anida , Aziz Izhar Abdul , Ramli Norlisah , Rahman Zainal Ariff Abdul
Published: November 2020

Background:

In syndromic craniosynostosis (SC), unlike persistent corneal irritation due to severe exophthalmos and increased intracranial pressure, optic canal (OC) stenosis has been scarcely reported to cause visual impairment. This study aimed to validate the OC volumetric and surface area measurement among SC patients.

Methods:

Sixteen computed tomography scan of SC patients (8 months–6 years old) were imported to Materialise Interactive Medical Image Control System (MIMICS) and Materialise 3-matics software. Three-dimensional (3D) OC models were fabricated, and linear measurements were obtained. Mathematical formulas were used for calculation of OC volume and surface area from the 3D model. The same measurements were obtained from the software and used as ground truth. Data normality was investigated before statistical analyses were performed. Wilcoxon test was used to validate differences of OC volume and surface area between 3D model and software.

Results:

The mean values for OC surface area for 3D model and MIMICS software were 103.19 mm2 and 31.27 mm2, respectively, whereas the mean for OC volume for 3D model and MIMICS software were 184.37 mm2 and 147.07 mm2, respectively. Significant difference was found between OC volume (P = 0.0681) and surface area (P = 0.0002) between 3D model and software.

Conclusion:

Optic canal in SC is not a perfect conical frustum thus making 3D model measurement and mathematical formula for surface area and volume estimation not ideal. Computer software remains the best modality to gauge dimensional parameter and is useful to elucidates the relationship of OC and eye function as well as aiding intervention in SC patients.
Vascularized Clavicular Bone With Supraclavicular Artery Island Flap for Oromandibular Reconstruction
Authors: Johnson Jeffrey , Naqvi Syed , Jain Kunal , Karni Ron J. , Ho Tang
Published: November 2020

Objective:

To explore the feasibility of an original surgical technique for head and neck oncologic reconstruction utilizing a pedicled osteocutaneous supraclavicular artery island flap (SCAIF) in a cadaver model.

Method:

Cadaver dissection, Review of literature

Description:

Two fresh frozen cadavers, 1 male and 1 female, were used for the dissection. Prior to dissection, measurements were taken on length of clavicle and distance between clavicular articulations and mandibular landmarks with the head in a neutral position. The SCAIF flap was raised in a subfascial plane and a 4.0 cm partial thickness clavicular bone graft was harvested attached to the flap. The pedicle was identified and the length of the supraclavicular artery was noted. The skin paddle was tunneled into the floor of mouth and the bone was placed into a pre-cut 4.0 cm mandibular body defect and fixated with a 1.7 mm Stryker mandibular reconstruction plate.

Results:

The male cadaver clavicle measured 16.4 cm in length. The distance from the sternoclavicular joint (SC) to the angle and symphysis of the mandible was 15.3 cm and 15.0 cm, respectively. In this cadaver, the bony graft and the vascular pedicle was not of sufficient length to reach the mandibular defect after tracing the vascular pedicle to the thyrocervical trunk (TCT), which was 13.3 cm from the mandibular angle (MA). The female cadaver had an average clavicular length of 15.0 cm, SC to angle 10.5 cm and SC to symphysis 8.1 cm. The bony graft and the vascular pedicled effortlessly reached without tension, with TCT only 7.8 cm from the MA and allowed sufficient bone graft mobility for plating.

Conclusion:

In this cadaveric model, a novel approach utilizing an osteocutaneous SCAIF was shown as a feasible reconstruction option for oromandibular defects in selected patients. This technique is limited by the anatomical relationship between the neck and vascular pedicle length. Viability could be determined by pre-operative measurements, where the clavicular length should be significantly greater than the distance from SC to MA.
Crouzon Syndrome and Acanthosis Nigricans With Fibrous Dysplasia of the Maxilla: An Unreported Suggested Triad
Authors: Olshinka Asaf , Tal David , Gillman Leon , Ad-El Dean , Kalish Eyal , Kropach Nesia , Yaacobi Dafna Shilo , Kornreich Liora , Staffenberg David A.
Published: November 2020

The aim of this report is to describe the combination of Crouzon syndrome and acanthosis nigricans with fibrous dysplasia of the maxilla. The diagnosis of fibrous dysplasia was confirmed clinically and pathologically during Le Fort III osteotomy and midface advancement with distraction osteogenesis. Crouzon syndrome with acanthosis nigricans is a known syndrome with an incidence of 1:1,000,000. This is the first report in the literature of Crouzon syndrome and acanthosis nigricans combined with fibrous dysplasia. As all 3 pathologies are related to fibroblasts, they may be different manifestations of malfunction of a single molecular pathway. The detection of fibrous dysplasia in a patient with Crouzon syndrome and acanthosis nigricans is important because it may complicate midface osteotomies and fixation of the hardware on the bones during craniofacial surgery.
Distinguishing Craniomorphometric Characteristics of Unilateral Lambdoid Craniosynostosis
Authors: Allam Omar , Park Kitae E. , Pourtaheri Navid , Mozaffari Mohammad Ali , Smetona John , Lu Xiaona , Ahmad Maham , Persing John A. , Alperovich Michael
Published: November 2020

Background:

Unilateral lambdoid synostosis (ULS) represents the rarest form of single suture nonsyndromic craniosynostosis. Differentiating between posterior deformational plagiocephaly (DP) and ULS has been difficult due to overlapping clinical findings. Past analyses have been limited by sample size. This study was undertaken to clarify anatomical features of ULS.

Methods:

A multiinstitution study was undertaken, analyzing CT imaging from patients with documented ULS to determine clinical and pathological characteristics. Similar analyses were performed on DP patients to differentiate the 2 conditions.

Results:

Twenty-seven ULS patient scans and 10 DP scans were included. For ULS patients mean age was 6.6 months, majority male (75%), and majority left-sided ULS (71%). The synostosed side ear was anteriorly displaced in 100% of ULS patients, mean difference of 9.6° (P < 0.001), and inferiorly in 96.3% of patients, mean difference of 4.4 mm, relative to the nonsynostosed side. The posterior fossa deflection (PFD) was deviated 5.9° toward the synostosed side relative to the anterior midline. In DP, there was no significant difference between sides in EAC measurements. The PFD and EAC displacements were significantly smaller in DP relative to ULS (P < 0.001 for each). An ipsilateral mastoid bulge was found in 100% of ULS and 0% of DP on CT imaging.

Conclusion:

Contrary to some previously published findings, the ear is more anteriorly displaced ipsilateral to the fused lambdoid suture in 100% of ULS patients. Ear position alone is not a reliable indicator to differentiate between DP and ULS. A mastoid bulge is a more reliable indicator of ULS.
Visual Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines
Authors: Zillgitt Andrew , Barkley Gregory L. , Bowyer Susan M.
Published: November 2020

Using visual evoked fields (VEFs) to differentiate healthy, normal brain function from dysfunctional cortex has been demonstrated to be both valid and reliable. Currently, VEFs are widely implemented to guide intracranial surgeries for epilepsy and brain tumors. There are several areas of possible future clinical use of VEFs, including early identification of disorders, such as multiple sclerosis, Parkinson's disease, stroke, and human immunodeficiency virus–associated neurocognitive disorders. These studies have suggested that VEFs could be used to study disease pathophysiology or as a biomarker for early identification of a disorder. The current clinical practice guidelines of the American Clinical Magnetoencephalography Society for VEFs are sufficient. At this time, VEFs should be used clinically to identify visual cortex and potentially tailor surgical resections.
Normal Variants in Magnetoencephalography
Authors: Rampp Stefan , Kakisaka Yosuke , Shibata Sumiya , Wu Xingtong , Rössler Karl , Buchfelder Michael , Burgess Richard C.
Published: November 2020

Normal variants, although not occurring frequently, may appear similar to epileptic activity. Misinterpretation may lead to false diagnoses. In the context of presurgical evaluation, normal variants may lead to mislocalizations with severe impact on the viability and success of surgical therapy. While the different variants are well known in EEG, little has been published in regard to their appearance in magnetoencephalography. Furthermore, there are some magnetoencephalography normal variants that have no counterparts in EEG. This article reviews benign epileptiform variants and provides examples in EEG and magnetoencephalography. In addition, the potential of oscillatory configurations in different frequency bands to appear as epileptic activity is discussed.
Towards Best Practices in Clinical Magnetoencephalography: Patient Preparation and Data Acquisition
Authors: Mosher John C. , Funke Michael E.
Published: November 2020

A magnetoencephalography (MEG) recording for clinical purposes requires a different level of attention and detail than that for research. As contrasted with a research subject, the MEG technologist must work with a patient who may not fully cooperate with instructions. The patient is on a clinical schedule, with generally no opportunity to return due to an erroneous or poor acquisition. The data will generally be processed by separate MEG analysts, who require a consistent and high-quality recording to complete their analysis and clinical report. To assure a quality recording, (1) MEG technologists must immediately recheck their scalp measurement data during the patient preparation, to catch disturbances and ensure registration accuracy of the patient fiducials, electrodes, and head position indicator coils. During the recording, (2) the technologist must ensure that the patient remains quiet and as far as possible into the helmet. After the recording, (3) the technologist must consistently prepare the data for subsequent clinical analysis. This article aims to comprehensively address these matters for practitioners of clinical MEG in a helpful and practical way. Based on the authors' experiences in recording over three thousand patients between them, presented here are a collection of techniques for implementation into daily routines that ensure good operation and high data quality. The techniques address a gap in the clinical literature addressing the multitude of potential sources of error during patient preparation and data acquisition, and how to prevent, recognize, or correct those.
Recognizing and Correcting MEG Artifacts
Authors: Burgess Richard C.
Published: November 2020

Noise sources in magnetoencephalography (MEG) include: (1) interference from outside the shielded room, (2) other people and devices inside the shielded room, (3) physiologic or nonphysiologic sources inside the patient, (4) activity from inside the head that is unrelated to the signal of interest, (5) intrinsic sensor and recording electronics noise, and (6) artifacts from other apparatus used during recording such as evoked response stimulators. There are other factors which corrupt MEG recording and interpretation and should also be considered “artifacts”: (7) inadequate positioning of the patient, (8) changes in the head position during the recording, (9) incorrect co-registration, (10) spurious signals introduced during postprocessing, and (11) errors in fitting. The major means whereby magnetic interference can be reduced or eliminated are by recording inside a magnetically shielded room, using gradiometers that measure differential magnetic fields, real-time active compensation using reference sensors, and postprocessing with advanced spatio-temporal filters. Many of the artifacts that plague MEG are also seen in EEG, so an experienced electroencephalographer will have the advantage of being able to transfer his knowledge about artifacts to MEG. However, many of the procedures and software used during acquisition and analysis maythemselvescontribute artifact or distortion that must be recognized or prevented. In summary, MEG artifacts are not worse than EEG artifacts, but many aredifferent, and—as with EEG—must be attended to.
MEG Reporting
Authors: Burgess Richard C.
Published: November 2020

The report generated by the magnetoencephalographer's interpretation of the patient's magnetoencephalography examination is the magnetoencephalography laboratory's most important product and is a representation of the quality of the laboratory and the clinical acumen of the personnel. A magnetoencephalography report is not meant to enumerate all the technical details that went into the test nor to fulfill some imagined requirements of the electronic health record. It is meant to clearly and concisely answer the clinical question posed by the referring doctor and to convey the key findings that may inform the next step in the patient's care. The graphical component of a magnetoencephalography report is ordinarily the most welcomed by the referring doctor. Much of the text of the report may be glossed over, so the illustrations must be sufficiently annotated to provide clear and unambiguous findings. The particular images chosen for the report will be a function of the analysis software but should be selected and edited for maximum clarity. There should be a composite pictorial summary slide at the beginning or at the end of the report, which accurately conveys the gist of the report. Along with representative source localizations, reports should contain examples of the simultaneously recorded EEG that enable the referring physician to determine whether epileptic discharges occurred and whether they are consistent with the patient's previously recorded spikes. Information and images (e.g., statistics, magnetic field patterns) that provide convincing evidence of the validity of the source location should also be included.
Neighboring colonies influence uptake of thermotolerant endosymbionts in threatened Caribbean coral recruits
Authors: Williamson Olivia M. , Allen Corinne E. , Williams Dana E. , Johnson Matthew W. , Miller Margaret W. , Baker Andrew C.
Published: November 2020

Intervention strategies to enhance coral resilience include manipulating the association between corals and their algal endosymbionts. While hosting thermotolerantDurusdinium trenchiican increase bleaching thresholds in adults, its effects remain largely unknown during the early life stages of Caribbean corals. Here, we tested ifOrbicella faveolatarecruits could establish symbiosis withD. trenchiisupplied by nearby “donor” colonies and examined the resulting ecological trade-offs to evaluate early Symbiodiniaceae manipulation as a scalable tool for reef restoration. We exposed aposymbiotic recruits to 29°C or 31°C and to fragments of eitherMontastraea cavernosa(containingCladocopium) orSiderastrea siderea(containingD. trenchii). After 60 days, recruits reared withD. trenchiidonors hosted nearly three times moreD. trenchiithan those withCladocopiumdonors, suggesting that recruits can acquire Symbiodiniaceae from nearby corals of different species. Temperature did not affectD. trenchiiuptake. Next, donor colonies were removed and surviving recruits were maintained for three months at ambient temperatures, after which a subset was exposed to a 60-day heat stress trial. Recruits previously reared at 31°C survived twice as long at 34°C as those reared at 29°C, suggesting that pre-exposure to heat can prime recruits to withstand future thermal stress. In addition, recruits hosting primarilyD. trenchiisurvived twice as long at 34°C as those hosting little or noD. trenchii. However, the proportion ofD. trenchiihosted was negatively correlated with polyp size and symbiont density, indicating a trade-off between growth (of both host and symbiont) and heat tolerance. These findings suggest that, while donor colonies may be effective sources for seeding coral recruits with thermotolerant symbionts, practitioners will need to balance the likely benefits and costs of these approaches when designing restoration strategies.
The epithelial splicing regulatorESRP2is epigenetically repressed by DNA hypermethylation in Wilms tumour and acts as a tumour suppressor
Authors: Legge Danny , Li Ling , Moriarty Whei , Lee David , Szemes Marianna , Zahed Asef , Panousopoulus Leonidas , Chung Wan Yun , Aghabi Yara , Barratt Jasmin , Williams Richard , Pritchard-Jones Kathy , Malik Karim T.A. , Oltean Sebastian , Brown Keith W.
Published: November 2020

Wilms tumour (WT), a childhood kidney cancer with embryonal origins, has been extensively characterised for genetic and epigenetic alterations, but a proportion of WTs still lack identifiable abnormalities. To uncover DNA methylation changes critical for WT pathogenesis, we compared the epigenome of fetal kidney with two WT cell lines, using methyl-CpG immunoprecipitation. We filtered our results to remove common cancer-associated epigenetic changes, and to enrich for genes involved in early kidney development. This identified four candidate genes that were hypermethylated in WT cell lines compared to fetal kidney, of whichESRP2(epithelial splicing regulatory protein 2), was the most promising gene for further study.ESRP2was commonly repressed by DNA methylation in WT, and this was shown to occur early in WT development (in nephrogenic rests).ESRP2expression could be reactivated by DNA methyltransferase inhibition in WT cell lines. WhenESRP2was overexpressed in WT cell lines, it acted as an inhibitor of cellular proliferationin vitro,andin vivoit suppressed tumour growth of orthotopic xenografts in nude mice. RNA-seq of the ESRP2-expressing WT cell lines identified several novel splicing targets, in addition to well-characterised targets of ESRP2. We propose a model in which the mesenchymal to epithelial transition that is essential for early kidney development, can be disrupted in to generate WT, either by genetic abnormalities such asWT1mutations, or by epigenetic defects, such asESRP2methylation.
Quantitative assessment of the relationship between behavioral and autonomic dynamics during propofol-induced unconsciousness
Authors: Subramanian Sandya , Purdon Patrick L. , Barbieri Riccardo , Brown Emery N.
Published: November 2020

During general anesthesia, both behavioral and autonomic changes are caused by the administration of anesthetics such as propofol. Propofol produces unconsciousness by creating highly structured oscillations in brain circuits. The anesthetic also has autonomic effects due to its actions as a vasodilator and myocardial depressant. Understanding how autonomic dynamics change in relation to propofol-induced unconsciousness is an important scientific and clinical question since anesthesiologists often infer changes in level of unconsciousness from changes in autonomic dynamics. Therefore, we present a framework combining physiology-based statistical models that have been developed specifically for heart rate variability and electrodermal activity with a robust statistical tool to compare behavioral and multimodal autonomic changes before, during, and after propofol-induced unconsciousness. We tested this framework on physiological data recorded from nine healthy volunteers during computer-controlled administration of propofol. We studied how autonomic dynamics related to behavioral markers of unconsciousness: 1) overall, 2) during the transitions of loss and recovery of consciousness, and 3) before and after anesthesia as a whole. Our results show a strong relationship between behavioral state of consciousness and autonomic dynamics. All of our prediction models showed areas under the curve greater than 0.75 despite the presence of non-monotonic relationships among the variables during the transition periods. Our analysis highlighted the specific roles played by fast versus slow changes, parasympathetic vs sympathetic activity, heart rate variability vs electrodermal activity, and even pulse rate vs pulse amplitude information within electrodermal activity. Further advancement upon this work can quantify the complex and subject-specific relationship between behavioral changes and autonomic dynamics before, during, and after anesthesia. However, this work demonstrates the potential of a multimodal, physiologically-informed, statistical approach to characterize autonomic dynamics.
Automated AI labelling of optic nerve head enables new insights into cross-ancestry glaucoma risk and genetic discovery in over 280,000 images from the UK Biobank and Canadian Longitudinal Study on Aging
Authors: Han Xikun , Steven Kaiah , Qassim Ayub , Marshall Henry N , Bean Cameron , Tremeer Michael , An Jiyuan , Siggs Owen , Gharahkhani Puya , Craig Jamie E , Hewitt Alex W , Trzaskowski Maciej , MacGregor Stuart
Published: November 2020

Cupping of the optic nerve head, a highly heritable trait, is a hallmark of glaucomatous optic neuropathy. Two key parameters are vertical cup-to-disc ratio (VCDR) and vertical disc diameter (VDD). However, manual assessment often suffers from poor accuracy and is time-intensive. Here, we show convolutional neural network models can accurately estimate VCDR and VDD for 282,100 images from both UK Biobank and an independent study (Canadian Longitudinal Study on Aging), enabling cross-ancestry epidemiological studies and new genetic discovery for these optic nerve head parameters. Using the AI approach we perform a systematic comparison of the distribution of VCDR and VDD, and compare these with intraocular pressure and glaucoma diagnoses across various genetically determined ancestries, which provides an explanation for the high rates of normal tension glaucoma in East Asia. We then used the large number of AI gradings to conduct a more powerful genome-wide association study (GWAS) of optic nerve head parameters. Using the AI based gradings increased estimates of heritability by ~50% for VCDR and VDD. Our GWAS identified more than 200 loci for both VCDR and VDD (double the number of loci from previous studies), uncovers dozens of novel biological pathways, with many of the novel loci also conferring risk for glaucoma.
Spatial Profiling of Lung SARS-CoV-2 and Influenza Virus Infection Dissects Virus-Specific Host Responses and Gene Signatures
Authors: Kulasinghe Arutha , Tan Chin Wee , dos Santos Miggiolaro Anna Flavia Ribeiro , Monkman James , Bhuva Dharmesh , Motta Junior Jarbas da Silva , Vaz de Paula Caroline Busatta , Nagashima Seigo , Baena Cristina Pellegrino , Souza-Fonseca-Guimaraes Paulo , de Noronha Lucia , McCulloch Timothy , Rossi Gustavo Rodrigues , Cooper Caroline , Tang Benjamin , Short Kirsty R. , Davis Melissa J , Souza-Fonseca-Guimaraes Fernando , Belz Gabrielle T. , O’Byrne Ken
Published: November 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). Robust blood biomarkers that reflect tissue damage are urgently needed to better stratify and triage infected patients. Here, we use spatial transcriptomics to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19 (10 patients), pandemic H1N1 (pH1N1) influenza (5) and uninfected control patients (4). Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs with few areas of high viral load and these were largely only associated with an increased type I interferon response. A very limited number of genes were differentially expressed between the lungs of influenza and COVID-19 patients. Specific interferon-associated genes (includingIFI27) were identified as candidate novel biomarkers for COVID-19 differentiating this COVID-19 from influenza. Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.
Development and Validation of Early Warning Score Systems for COVID-19 Patients
Authors: Youssef Alexey , Kouchaki Samaneh , Shamout Farah , Armstrong Jacob , El-Bouri Rasheed , Taylor Thomas , Birrenkott Drew , Vasey Baptiste , Soltan Andrew , Zhu Tingting , Clifton David A , Eyre David W
Published: November 2020

COVID-19 is a major, urgent, and ongoing threat to global health. Globally more than 24 million have been infected and the disease has claimed more than a million lives as of October 2020. Predicting which patients will need respiratory support is important to guiding individual patient treatment and also to ensuring sufficient resources are available. We evaluated the ability of six common Early Warning Scores (EWS) to identify respiratory deterioration defined as the need for advanced respiratory support (high-flow nasal oxygen, continuous positive airways pressure, non-invasive ventilation, intubation) within a prediction window of 24 hours. We show these scores perform sub-optimally at this specific task. Therefore, we develop an alternative Early Warning Score based on a Gradient Boosting Trees (GBT) algorithm that is able to predict deterioration within the next 24 hours with high AUROC 94% and an accuracy, sensitivity and specificity of 70%, 96%, 70%, respectively. Our GBT model outperformed the best EWS (LDTEWS:NEWS), increasing the AUROC by 14%. Our GBT model makes the prediction based on the current and baseline measures of routinely available vital signs and blood tests.
Near-Infrared Imaging of Indocyanine Green Identifies Novel Routes of Lymphatic Drainage from Metacarpophalangeal Joints in Healthy Human Hands
Authors: Kenney H. Mark , Dieudonne Gregory , Yee Seonghwan , Maki Jeffrey H. , Wood Ronald W. , Schwarz Edward M. , Ritchlin Christopher T. , Rahimi Homaira
Published: November 2020

Background

Collecting lymphatic vessel (CLV) dysfunction has been implicated in various diseases, including rheumatoid arthritis (RA). Previous studies in the tumor necrosis factor-transgenic (TNF-Tg) mouse model of inflammatory-erosive arthritis have demonstrated reduced joint-draining CLV contractility that correlates with arthritic severity. Clinically, RA patients with active hand arthritis exhibit significantly reduced lymphatic clearance of the web spaces adjacent to the metacarpophalangeal (MCP) joints and a reduction in total and basilic-associated CLVs on the dorsal surface of the hand by dynamic near-infrared (NIR) imaging of indocyanine green (ICG). In this pilot study, we assessed direct lymphatic drainage from MCP joints, and aimed to visualize the total lymphatic anatomy using novel dual-agent relaxation contrast magnetic resonance lymphography (DARC-MRL) in the upper extremity of healthy human subjects.

Methods

Two healthy male subjects participated in the study. We performed NIR imaging following intra-dermal web space and intra-articular MCP joint injections of ICG to visualize the CLV anatomy on the dorsal surface of the hand and antecubital fossa. Subsequently, we performed conventional or DARC-MRL after intra-dermal web space and intra-articular MCP joint injections of gadolinium to evaluate the total lymphatic anatomy of the upper extremity and compare with NIR-ICG imaging.

Results

NIR-ICG imaging demonstrated that web space and MCP lymphatics drain via distinct CLV tributaries. Web space draining CLVs tended to be associated with the cephalic side of the antecubital fossa, while MCP draining CLVs were localized to the basilic side of the forearm. The DARC-MRL methods used in this study did not adequately nullify the contrast in the blood vessels, and limited gadolinium-filled CLVs could be identified.

Conclusion

Through the use of NIR-ICG imaging, we found that MCP joints predominantly drain into basilic CLVs in the forearm, which may explain the reduction in basilic-associated CLVs in the hands of RA patients. In healthy subjects, current DARC-MRL techniques have limited ability in identifying lymphatic structures and further refinement in this technique is necessary.
Revealing the evolutionary history of a reticulate polyploid complex in the genusIsoëtes
Authors: Suissa Jacob S. , Kinosian Sylvia P. , Schafran Peter W. , Bolin Jay F. , Taylor W. Carl , Zimmer Elizabeth A.
Published: November 2020

Polyploidy and hybridization are important processes in the evolution of spore-dispersed plants. Few studies, however, focus these dynamics in heterosporous lycophytes, such asIsoëtes, where polyploid hybrids are common and thought to be important in the generation of their extant diversity. We investigate reticulate evolution in a complex of western North American quillworts (Isoëtes) and provide insights into the evolutionary history of hybrids, and the role of polyploidy in maintaining novel diversity.

We utilize low copy nuclear markers, whole plastomes, restriction site-associated DNA sequencing, cytology, and reproductive status (fertile or sterile) to investigate the reticulate evolutionary history of western North AmericanIsoëtes.

We reconstruct the reticulate evolutionary history and directionality of hybridization events in this complex. The presence of high level polyploids, plus frequent homoploid and interploid hybridization suggests that there are low prezygotic reproductive barriers in this complex, hybridization is common and bidirectional between similar—but not divergent—cytotypes, and that allopolyploidization is important to restore fertility in some hybrid taxa.

Our data provide five lines of evidence suggesting that hybridization and polyploidy can occur with frequency in the genus, and these evolutionary processes may be important in shaping extantIsoëtesdiversity.
Cannabidiol Attenuates Pulmonary Arterial Hypertension by Normalizing the Mitochondrial Function in Vascular Smooth Muscle Cells
Authors: Lu Xiaohui , Zhang Jingyuan , Liu Huijiao , Ma Wenqiang , Yu Leo , Tan Xin , Wang Shubin , Ren Fazheng , Li Xiru , Li Xiangdong
Published: November 2020

Pulmonary artery hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, which was with limited therapeutic options. It has been proved that cannabidiol (CBD) had antioxidant effects in many cardiovascular diseases, whereas the efficacy of CBD in PAH is unknown. To defined the effect of CBD in PAH, we explored the functions of CBD in both PASMCs proliferation test in vitro, and preventive and therapeutic PAH rodent models in vivo. The roles of CBD in mitochondria function and the oxidant stress were assessed in human PASMCs and PAH mice. We found that CBD significantly inhibited hyperproliferation of hypoxia-induced PASMCs, and intragastrically administered CBD could reverse the pathological changes in both Sugen-hypoxia and MCT-induced PAH mice models. Mechanical analysis demonstrated that CBD alleviated PAH by recovering mitochondrial energy metabolism, normalizing the hypoxia-induced oxidant stress, inhibiting abnormal glycolysis and lactate accumulation in cannabinoids receptors-independent manner. Thus, CBD could be a potential drug for PAH.

Graphical Abstracts
Challenges in Undergraduate Synthetic Biology Training: Insights from a Canadian iGEM Student Perspective
Authors: Diep Patrick , Boucinha Austin , Yeung Bi-ru Amy , Kell Brayden , Chen Xingyu , Tsyplenkov Daniel , Serra Danielle , Escobar Andres , Gnanapragasam Ansley , Emond Christian A. , Sajtovich Victoria A. , Mahadevan Radhakrishnan , Kilkenny Dawn M. , Gini-Newman Garfield , Kaern Mads , Ingalls Brian
Published: November 2020

The last two decades have seen vigorous activity in synthetic biology research and ever-increasing applications of synthetic biology technologies. However, pedagogical research on synthetic biology is scarce, especially when compared to some scientific and engineering disciplines. Within Canada, there are only three universities that formally teach synthetic biology programs; two of which are at the undergraduate level. Many Canadian undergraduate students are instead introduced to synthetic biology through participation in the annual International Genetically Engineered Machine (iGEM) competition where they work in design teams to conceive of and execute a synthetic biology project that they present at an international jamboree. We surveyed the Canadian landscape of synthetic biology education through the experience of students from the Canadian iGEM teams of 2019. Using a thematic codebook analysis, we gathered insights to generate recommendations that could empower future iGEM team operations and inform educators about best practices in teaching undergraduate synthetic biology.