bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified decision-making rule supported by scheduled telephone follow-up reduces head computed tomography utilization in children with mild traumatic brain injury
Authors: Zou Liqun , Li Hong , Jiang Zhen , He Bin , Xie Yong , Zhang Wei , Jiang Jingyuan , Nie Hu
Published: May 2020

Unnecessary computed tomography utilization is common in children with a mild traumatic head injury. It is valuable to find a reasonable strategy for the patient's management.

The aim of this study was to investigate the effect of scheduled telephone follow-up on computed tomography utilization in children with a mild head injury.

A 2-year cohort study was performed. Children diagnosed with mild traumatic brain injury (TBI) were evaluated with a scoring system upon their arrival and during 1 month of scheduled telephone follow-ups by nurses. The rates of head computed tomography utilization, delayed imaging, and delayed diagnosis were analyzed.

The rate of computed tomography utilization was 64.3% and 46.1% (P = .00) in the retrospective and prospective study periods, respectively. During the prospective study period, there were no differences in the rates of delayed imaging (2.3% vs. 2.2%, P = .814) or the rates of delayed diagnosis of significant radiological findings (0.1% vs 0.2%, P = .672) in cases with versus without immediate computed tomography.

Adoption of a modified decision-making rule supported by scheduled telephone follow-up can reduce head computed tomography utilization without increasing the rate of missed or delayed diagnosis of clinically significant TBI in children with mild TBI.
Association rule mining for the ordered placement of traditional Chinese medicine containers
Authors: Chen Chih-Wen , Tsai Chih-Fong , Tsai Yi-Hong , Wu Yang-Chang , Chang Fang-Rong
Published: May 2020

In traditional Chinese medicine (TCM) clinics, the pharmacists responsible for dispensing the herbal medicine usually find the desired ingredients based on positions of the shelves (racks; frames; stands). Generally, these containers are arranged in an alphabetical order depending on the herbal medicine they contain. However, certain related ingredients tend to be used together in many prescriptions, even though the containers may be stored far away from each other. This can cause problems, especially when there are many patients and/or the limited number of pharmacists. If the dispensing time takes longer, it is likely to impact the satisfaction of the patients’ experience. Moreover, the stamina of the pharmacists will be consumed quickly.

In this study, we investigate on an association rule mining technology to improve efficiency in TCM dispensing based on the frequent pattern growth algorithm and try to identify which 2 or 3 herbal medicines will match together frequently in prescriptions. Furthermore, 3 experimental studies are conducted based on a dataset collected from a traditional Chinese medicine hospital. The dataset includes information for an entire year (2014), including 4 seasons and doctors. Afterward, a questionnaire on the usefulness of the extracted rules was administered to the pharmacists in the case hospital. The responses showed the mining results to be very valuable as a reference for the placement and ordering of the frames in the TCM pharmacies and drug stores.
Ultrasound and radiological features of abdominal unicentric castleman's disease
Authors: Lv Kun , Zhao Yanan , Xu Wen , Zhang Chao , Huang Pintong
Published: May 2020

This study aimed to improve the diagnostic accuracy of abdominal unicentric Castleman's disease (UCD) by retrospectively summarizes the relatively specific imaging features of UCD.

This study retrospectively collected fifteen patients with abdominal UCD confirmed by pathology. All patients were underwent ultrasound (US), computed tomography (CT), or magnetic resonance imaging (MRI) examination. The imaging findings of UCDs were analyzed by senior radiologists.

Fifteen patients included 7 males and 8 females, aged 30 to 68 years old, with an average age of 51.73 ± 13.57. In the 15 cases, 7 were located around the mesentery, 4 were located in the retroperitoneal space, and 4 in the liver. Fifteen cases contained solid masses, of which 13 had clear margins and 2 had blurred margins. The size of the mass ranged from 1.5 to 14.2 cm, with an average of 6.49 ± 4.16 cm. US showed that 9 lesions were presented with hypo-echogenicity while 5 lesions presented with hyper-echogenicity spots. Unenhanced CT showed that the lesions were comprised of soft tissue while calcified lesions were found in 10 of the cases (66.67%, 10/15). T1-weighted imaging (T1WI) suggested the lesions as iso/hypo-signal, and mildly hyper-signal on T2-weighted imaging (T2WI). Diffusion-weighted imaging (DWI) showed different degrees of hyper-signal. Contrast-enhanced US and CT/MRI showed obvious enhancement at the arterial phase in 12 cases (85.71%, 12/14), most of which (50%, 7/14) showed continuous enhancement at the delayed phase. Feeding vessel could be seen within, or around the lesion in 5 cases (35.71%, 5/14).

The study suggests that abdominal UCD commonly manifests as well-defined, homogeneous, solid, and hypervascular masses. Calcification and the presence of feeding vessel in the tumors are relatively specific features of abdominal UCD.
Characteristics of frequent adult emergency department users
Authors: Lee Ji Han , Park Gwan Jin , Kim Sang Chul , Kim Hoon , Lee Suk Woo
Published: May 2020

Emergency department (ED) crowding is a public health burden that impedes the provision of high-quality emergency care and is related to poor outcomes. Frequent ED visits are known to contribute to ED crowding. This study aimed to identify frequent ED users’ characteristics and risk factors related to frequent ED visits.

A retrospective observational study was conducted using ED-based data derived from adult patients at a university hospital. The main exposure variable was frequent ED visits, which were defined as ≥4 visits within 12 months (January 1–December 31, 2018). Characteristics and risk factors for frequent ED users were evaluated using stepwise regression analysis.

Within the study period, there were 36,932 ED visits involving 29,759 patients. Of these, 3031 (8.2%) visits were from 556 (1.9%) patients classified as frequent ED users. The independent risk factors for frequent ED visits were older patients (≥65 years); the winter season; daytime discharge from ED; patients with medical aid insurance; and patients designated as high acuity at their first visit. Patients with a malignant neoplasm, mental health disorder, alcohol-related liver disease, chronic kidney disease, or chronic obstructive pulmonary disease were associated with more frequent ED visits.

Frequent ED users comprised a significant proportion of total ED visits. Frequent ED users were more likely than occasional ED users to be in poorer health, older, or have a chronic disease or a mental health disorder.
Effects of Baseline Systolic Blood Pressure on Outcome in Ischemic Stroke Patients With Intravenous Thrombolysis Therapy
Authors: Lei Zhihao , Li Shuanglin , Hu Shiyu , Ren Lijie
Published: May 2020

Background:

Baseline systolic blood pressure (SBP) is an important parameter that can significantly influence the outcome in ischemic stroke patients who received intravenous thrombolysis, but the target baseline SBP for optimal outcome is uncertain. This study aimed to assess the relationship between baseline SBP and outcome.

Materials and Methods:

Studies that evaluated the association between the baseline SBP and the outcome of patients undergoing thrombolytic therapy were sought. Data were extracted according to a predefined data extraction form and then analyzed by STATA 12.0 software. The primary endpoint was the occurrence of good outcomes measured by a modified Rankin Scale score at 3 months, while the secondary endpoint was the occurrence of intracranial hemorrhage and death.

Results:

Eleven studies involving a total of 33,263 patients were included. Pooled data suggested that the odds of good outcome was decreased by 7% per 10 mm Hg increase in baseline SBP (odds ratio=0.93; 95% confidence interval: 0.91-0.94;P<0.001). Patients with higher baseline SBP were more likely to have intracranial hemorrhage (odds ratio=1.12 per 10 mm Hg increase; 95% confidence interval: 1.08-1.16,P<0.001).

Conclusions:

This study suggested that lower baseline SBP may be positively associated with a greater chance of good outcome and less chance of intracranial hemorrhage. However, this effect was reliable only when the baseline SBP was within a certain range, which has not been explicitly stated. Therefore, more well-designed studies are needed to define the optimal baseline SBP.
Heart Rate Variability Analysis
Authors: Constantinescu Victor , Matei Daniela , Ignat Bogdan , Hodorog Diana , Cuciureanu Dan I.
Published: May 2020

Background:

Neurogenic heart syndrome represents a phenomenon often encountered in clinical practice after ischemic stroke. Further poststroke cardiovascular complications are possibly related to cardiac autonomic dysregulation. Multiple Trigonometric Regressive Spectral (MTRS) analysis of the heart rate variability (HRV) allows a precise evaluation of cardiovascular modulation under different conditions.

Objectives:

This research aims to evaluate the impact of the middle cerebral artery (MCA) ischemic stroke on cardiac autonomic function, using the MTRS analysis of HRV, during sympathetic and parasympathetic activation tests.

Methods:

The authors analyzed HRV parameters in 20 patients who had a right and 20 who had a left MCA ischemic stroke, under rest condition and during autonomic activation tests (deep breathing and standing tests). Data were compared with 20 age-matched and sex-matched healthy controls.

Results:

Patients who had a right MCA ischemic stroke presented a decreased vagal modulation of the heart rate compared with healthy controls and patients who had a left MCA ischemic stroke, in resting state and during autonomic activation tests. Decreased root mean square of the successive differences, pNN50, high frequency, and high-frequency normalized units values (P<0.05) and increased low frequency/high frequency ratio (P<0.05) in resting state and during autonomic activation tests in patients who had a right MCA stroke indicate a sympathetic predominance in the control of the heart rate. The parasympathetic activation test did not change the sympathovagal balance in this group of patients.

Conclusions:

The autonomic nervous system represents an attractive target for the therapeutic approach. As MCA ischemic stroke, especially in the right hemisphere, seems to cause significant long-lasting autonomic dysregulation, implementing early pharmacological or nonpharmacological intervention for autonomic restoration may improve the outcome of patients who had an ischemic stroke.
Wall-Eyed Bilateral Internuclear Ophthalmoplegia by Ischemic Stroke
Authors: Uzawa Akiyuki , Takeda Yorinobu , Kuwabara Satoshi
Published: May 2020

Introduction:

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a rare symptom. Several studies have reported that a small brainstem lesion could cause WEBINO.

Case Report:

The authors present the case of an 88-year-old female individual who developed sudden-onset diplopia and gait disturbance. Neurological examination revealed WEBINO with convergence impairment, gaze-evoked upward nystagmus on upward gaze, and bilateral limb ataxia. Brain magnetic resonance imaging revealed a small paramedian pontine tegmentum infarction, responsible for the symptoms. A literature review of WEBINO in ischemic stroke revealed that most patients exhibited impaired convergence and other neurological symptoms.

Conclusion:

Gaze-evoked upward nystagmus on upward gaze and bilateral limb ataxia accompanied by WEBINO due to a small brainstem lesion were the characteristic findings of our case.
Angiotensin-Converting Enzyme Inhibitor Angioedema
Authors: Bankston Josh , House David Thomas
Published: May 2020

Angioedema from angiotensin-converting enzyme inhibitors (ACEIs) is a potential, emergent, and frightening problem that presents to the emergency department. This article focuses on angioedema caused by using ACEIs. The presentation, pathology, diagnostic testing, treatment, and patient education of angioedema are explored. This article explores using fresh frozen plasma as an initial approach to the treatment of ACEI angioedema.
Vaping: What Every Emergency Nurse Practitioner Should Know!
Authors: Cerepani Mary Jo , Lynch Michael , Ramponi Denise R.
Published: May 2020

As of December 10, 2019, according to the Centers for Disease Control and Prevention (CDC), more than 2,668 hospitalized cases of lung injury and 60 deaths associated with use of electronic nicotine delivery systems, or “vaping.” In many cases, patients required multiple health care visits prior to diagnosis. Recognition of the risk factors, symptoms, and examination findings that have been consistently reported is critical to making the diagnosis and initiating treatment early in the progression of disease. The precise mechanism and causative agent have yet to be elucidated, but the association with vaping has been established. Multidisciplinary collaboration among health care providers, poison centers, health departments, reference laboratories, and the CDC will be necessary to identify the cause and prevent further harm.
A Review of Central Venous Access Using Ultrasound Guidance Technology
Authors: Crenshaw Nichole A. , Briones Patricia , Gonzalez Juan M. , Ortega Johis
Published: May 2020

More than 5 million central lines are placed in the United States each year. Advanced practice providers place central lines and must understand the importance of ultrasound guidance technology. The use of anatomic landmarks to place central lines has been employed in the past and in some instances is still used. This method may make accessing the target vessel difficult in the patient with anomalous anatomy or in the obese patient. These characteristics decrease successful placement and increase complications. Different organizations have agreed that the use of ultrasound during central venous access has decreased rates of complication and cost. In addition to cannulating and accessing a central vein, ultrasound can be used to rapidly confirm placement and to rule out complications such as pneumothorax. Utilizing ultrasound to assist in performance of procedures, and in assessment of patients, is a skill that should be optimized by nurse practitioners.
Death and Dying in the Emergency Department
Authors: Geller Daniel E. , Evans Dian Dowling
Published: May 2020

The Research to Practice column is intended to improve the research critique skills of the advanced practice registered nurse (APRN) and to assist with the translation of research into practice. For each column, a topic and a particular research study are selected. The stage is set with a case presentation. The research article is then reviewed and critiqued, and the findings are discussed in relation to the case presented. Our current column discusses factors associated with the quality of the death and dying experience in the emergency department (ED) from the perspective of health care providers with implications for APRN practice and strategies using the following study: McCallum, K. J., Jackson, D., Walthall, H., & Aveyard, H. (2018). “Exploring the quality of the dying and death experience in the emergency department: An integrative literature review,” International Journal of Nursing Studies, 85, 106–117. Our case involves a man with metastatic colon cancer where his oncology nurse practitioner recommends no further treatment and tells him he has approximately 6 months to live.
Association of neutrophil-gelatinase-associated lipocalin with microvascular complications in patients with type 2 diabetes: a cross-sectional study
Authors: Aslanhan Erhan , Ojalvo David , Özsenel Ekmek Burak , Ucak Basat Sema , Borlu Fatih
Published: May 2020

Introduction

Diabetic nephropathy and diabetic retinopathy are serious microvascular complications of diabetes mellitus. Recent studies have demonstrated that neutrophil-gelatinase-associated lipocalin (NGAL) may be accompanied by these complications during and before the appearance of microalbuminuria. In this study, we set out to research the role of NGAL in patients with diabetic nephropathy and diabetic retinopathy.

Material and methods

Eighty-two patients with type 2 diabetes were enrolled in our study. Urinary microalbumine and NGAL levels were measured in urine samples over 24 hours. We also studied NGAL levels in serum. All patients went through an ophthalmologic examination. The results were evaluated based on the presence of microalbuminuria and retinopathy.

Results

There were no significant differences in serum and urine NGAL levels between normoalbuminuric (n = 66) and microalbuminuric (n = 16) patients. We also did not find any significant difference in patients with retinopathy (n = 16) or without retinopathy (n = 66).

Conclusion

There are controversial findings about the role of NGAL in diabetic patients in medical literature. Standard values of urine and serum NGAL levels have yet to be determined. Our study suggests that NGAL is not a useful marker to differentiate microalbuminuric patients from normoalbuminuric subjects. We also did not find a relationship between NGAL levels and the presence of retinopathy. Additional studies with larger sample sizes will be required to confirm or refute these findings.
A treatment-based algorithm for identification of diabetes type in the National Health and Nutrition Examination Survey
Authors: Mosslemi Mitra , Park Hannah L. , McLaren Christine E. , Wong Nathan D.
Published: May 2020

Background

In epidemiology studies, identification of diabetes type (type 1 vs. type 2) among study participants with diabetes is important; however, conventional diabetes type identification approaches that include age at diabetes diagnosis as an initial criterion introduces biases. Using data from the National Health and Nutrition Examination Survey, we have developed a novel algorithm which does not include age at diagnosis to identify participants with self-reported diagnosed diabetes as having type 1 vs. type 2 diabetes.

Methods

A total of 5457 National Health and Nutrition Examination Survey participants between cycles 1999–2000 and 2015–2016 reported that a health professional had diagnosed them as having diabetes at a time other than during pregnancy and had complete information on diabetes-related questions. After developing an algorithm based on information regarding the treatment(s) they received, we classified these participants as having type 1 or type 2 diabetes.

Results

The treatment-based algorithm yielded a 6–94% split for type 1 and type 2 diabetes, which is consistent with reports from the Centers for Disease Control and other resources. Moreover, the demographics and clinical characteristics of the assigned type 1 and type 2 cases were consistent with contemporary epidemiologic findings.

Conclusion

Applying diabetes treatment information from the National Health and Nutrition Examination Survey, as formulated in our treatment-based algorithm, may better identify type 1 and type 2 diabetes cases and thus prevent the specific biases imposed by conventional approaches which include the age of diabetes diagnosis as an initial criterion for diabetes type classification.
Comparing inpatient costs of heart failure admissions for patients with reduced and preserved ejection fraction with or without type 2 diabetes
Authors: Olchanski Natalia , Vest Amanda R. , Cohen Joshua T. , DeNofrio David
Published: May 2020

Objective

Both heart failure (HF) and diabetes mellitus (DM) account for major healthcare expenditures. We evaluated inpatient expenditures and cost drivers in patients admitted with HF with and without DM.

Methods

We created a retrospective cohort of acutely decompensated HF patients, using linked data from cost accounting systems and electronic medical records. We stratified patients by LVEF into reduced ejection fraction (HFrEF, LVEF ≤40%) and preserved ejection fraction (HFpEF, LVEF >40%) groups and by DM status at admission.

Results

Our population had 544 people: 285 HFrEF patients (43.5% with DM) and 259 HFpEF patients (43.6% with DM). Patients with HFrEF and DM had the longest hospital stay (5.10 ± 5.21 days). Patients with HFrEF and DM had the highest hospitalization cost ($11 576 ± 15 818). HFrEF and HFpEF patients with DM had the highest cost, and cost per day alive was highest for HFpEF patients with DM [$3153 (95% CI 2332, 4262)].

Conclusion

Overall cost was higher for patients with DM, whether or not they were admitted with acute HF due to HFrEF or HFpEF. Cost per day alive for patients with DM continued to exceed corresponding costs for patients without DM, with HFpEF patients with DM having the highest cost.
Control with uncertain data of socially structured compartmental epidemic models
Authors: Albi Giacomo , Pareschi Lorenzo , Zanella Mattia
Published: May 2020

The adoption of containment measures to reduce the amplitude of the epidemic peak is a key aspect in tackling the rapid spread of an epidemic. Classical compartmental models must be modified and studied to correctly describe the effects of forced external actions to reduce the impact of the disease. In addition, data are often incomplete and heterogeneous, so a high degree of uncertainty must naturally be incorporated into the models. In this work we address both these aspects, through an optimal control formulation of the epidemiological model in presence of uncertain data. After the introduction of the optimal control problem, we formulate an instantaneous approximation of the control that allows us to derive new feedback controlled compartmental models capable of describing the epidemic peak reduction. The need for long-term interventions shows that alternative actions based on the social structure of the system can be as effective as the more expensive global strategy. The importance of the timing and intensity of interventions is particularly relevant in the case of uncertain parameters on the actual number of infected people. Simulations related to data from the recent COVID-19 outbreak in Italy are presented and discussed.
Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence Testing in Idaho
Authors: Bryan Andrew , Pepper Gregory , Wener Mark H. , Fink Susan L. , Morishima Chihiro , Chaudhary Anu , Jerome Keith R. , Mathias Patrick C. , Greninger Alexander L.
Published: May 2020

Background

Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections.

Methods

We evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations.

Results

We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%.

Conclusions

These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.
A study’s got to know its limitations
Authors: Gooch Phil , Warren-Jones Emma
Published: May 2020

Background

All research has room for improvement, but authors do not always clearly acknowledge the limitations of their work. In this brief report, we sought to identify the prevalence of limitations statements in the medRxiv COVID-19 SARS-CoV-2 dataset.

Methods

We combined automated methods with manual review to analyse manuscripts for the presence, or absence, either of a defined limitations section in the text, or as part of the general discussion.

Results

We identified a structured limitations statement in 28% of the manuscripts, and overall 52% contained at least one mention of a study limitation. Over one-third of manuscripts contained none of the terms that might typically be associated with reporting of limitations. Overall our method performed with precision of 0.97 and recall of 0.91.

Conclusion

The presence or absence of limitations statements can be identified with reasonable confidence using automated tools. We suggest that it might be beneficial to require a defined, structured statement about study limitations, either as part of the submission process, or clearly delineated within the manuscript.
LFA-1 signals to promote actin polymerization and upstream migration in T cells
Authors: Roy Nathan H , Kim Sarah Hyun Ji , Buffone Alexander , Blumenthal Daniel , Huang Bonnie , Agarwal Sangya , Schwartzberg Pamela L , Hammer Daniel A , Burkhardt Janis K
Published: May 2020

T cell entry into inflamed tissue requires firm adhesion, cell spreading, and migration along and through the endothelial wall. These events require the T cell integrins LFA-1 and VLA-4 and their endothelial ligands ICAM-1 and VCAM-1, respectively. T cells migrate against the direction of shear flow on ICAM-1 and with the direction of shear flow on VCAM-1, suggesting that these two ligands trigger distinct cellular responses. However, the contribution of specific signaling events downstream of LFA-1 and VLA-4 has not been explored. Using primary mouse T cells, we found that engagement of LFA-1, but not VLA-4, induces cell shape changes associated with rapid 2D migration. Moreover, LFA-1 ligation results in activation of the PI3K and ERK pathways, and phosphorylation of multiple kinases and adaptor proteins, while VLA-4 ligation triggers only a subset of these signaling events. Importantly, T cells lacking Crk adaptor proteins, key LFA-1 signaling intermediates, or the ubiquitin ligase cCbl, failed to migrate against the direction of shear flow on ICAM-1. These studies identify novel signaling differences downstream of LFA-1 and VLA-4 that drive T cell migratory behavior.

Summary Statement

Inflammatory responses require leukocyte migration along the vascular wall. We show that signaling from β2, but not β1, integrins induces cytoskeletal changes needed for upstream migration under shear flow.
Large-scale, in-house production of viral transport media to support SARS-CoV-2 PCR testing in a multi-hospital healthcare network during the COVID-19 pandemic
Authors: Smith Kenneth P , Cheng Annie , Chopelas Amber , DuBois-Coyne Sarah , Mezghani Ikram , Rodriguez Shade , Talay Mustafa , Kirby James E
Published: May 2020

The COVID-19 pandemic has severely disrupted worldwide supplies of viral transport media (VTM) due to widespread demand for SARS-CoV-2 RT-PCR testing. In response to this ongoing shortage, we began production of VTM in-house in support of diagnostic testing in our hospital network. As our diagnostic laboratory was not equipped for reagent production, we took advantage of space and personnel that became available due to closure of the research division of our medical center. We utilized a formulation of VTM described by the CDC that was simple to produce, did not require filtration for sterilization, and used reagents that were available from commercial suppliers. Performance of VTM was evaluated by several quality assurance measures. Based on Ct values of spiking experiments, we found that our VTM supported highly consistent amplification of the SARS-CoV-2 target (coefficient of variation = 2.95%) using the Abbott RealTime SARS-CoV-2 EUA assay on the Abbott m2000 platform. VTM was also found to be compatible with multiple swab types and, based on accelerated stability studies, able to maintain functionality for at least four months at room temperature. We further discuss how we met logistical challenges associated with large-scale VTM production in a crisis setting including use of staged, assembly line for VTM transport tube production.
Validation of an extraction-free RT-PCR protocol for detection of SARS-CoV2 RNA
Authors: Brown Julianne R , Atkinson Laura , Shah Divya , Harris Kathryn
Published: May 2020

In light of supply chain failures for reagents and consumables needed for purification of nucleic acid for detection of SARS-CoV-2 RNA by RT-PCR, we aim to verify the performance and utility of a non-extraction protocol for RT-PCR ("direct RT-PCR"). We report improved sensitivity compared to earlier reports of direct RT-PCR testing of swab samples, in particular at the lower limit of detection (sensitivity 93% overall; 100% for specimens with high to moderate viral titre, Ct <34; 81% for specimens with a low viral titre, Ct ≥34). Sensitivity is improved (from 90 to 93%) by testing in duplicate. We recommend swabs are re-suspended in water to minimise PCR inhibition. A cellular target is necessary to control for PCR inhibition and specimen quality. Direct RT-PCR is best suited to population level screening where results are not clinically actionable, however in the event of a critical supply chain failure direct RT-PCR is fit for purpose for the detection of SARS-CoV-2 infection. The results from our study offer front-line laboratories additional reagent options for performing extraction-free RT-PCR protocols.
Combined Effects of Standing and Passive Heating on Attenuating Sitting-Induced Vascular Dysfunction
Authors: Caldwell Aaron R. , Jansen Lisa T. , Rosa-Caldwell Megan E. , Howie Erin K. , Gallagher Kaitlin M. , Turner Ronna C. , Ganio Matthew S.
Published: May 2020

Recent evidence suggests prolonged sitting strains the arteries through angulations that create turbulent blood flow. This turbulent flow reduces flow-mediated dilation (FMD), a key indicator of vascular health. The purpose of this study was to determine if arterial angulations (through sitting or standing), shear stress (through local heating), or a combination of these factors affected vascular function. In addition, we sought examined the impact of biological sex on these responses.

Methods

Twenty-six healthy, young (18-40 years old) males (n=13) and females (n=13) participated. Participants completed two experimental trials (2-h sitting and 2-h standing), and, in a randomized fashion, one leg was passively heated. Flow-mediated dilation (FMD) at the superficial femoral artery (SFA), and central and peripheral pulse-wave velocity (PWV) were measured using vascular ultrasound.

Results

There was a non-significant decrease in FMD (- 1.48%;p =.06) during sitting and the decline in FMD was not different between biological sexes (−1.96% vs -0.93%;p =.49, males and females respectively). Passive heating (1.42%;p< .05) and standing (1.42%;p< .05) both improved FMD in comparison to sitting. However, standing resulted in a significant increase in peripheral PWV (50 cm/s;p< .05). Interestingly, the standing was not well tolerated among female participants with seven participants having to stop their initial trial early due to lightheadedness.

Conclusions

Both interventions appear to be equally effective at mitigating reductions FMD associated with sitting, but standing increased peripheral PWV. In addition, it does not appear that biological sex moderates these physiological responses.

New Findings

What is the central question of this study?

Prolonged sitting can cause acutely vascular dysfunction while interventions such as local heating or standing have been explored they have not been used in combination and the role of biological sex has not been fully explored.

What is the main finding and its importance?

In this study we demonstrate that either local heating or standing are effective at reducing some of the vascular dysfunction associated with prolonged sitting. Biological sex did not appear appear to play a role in this response. However, standing may also cause some negative effects such as increased arterial stiffness and increase the risk of syncope.
Locating the sex determining region of linkage group 12 of guppy (Poecilia reticulata)
Authors: Charlesworth Deborah , Bergero Roberta , Graham Chay , Gardner Jim , Yong Lengxob
Published: May 2020

We describe new genetic mapping results from 6 full-sib families in the guppy (Poecilia reticulata), two of which included recombinants between the X and Y chromosomes. These recombinants confirm that the guppy sex-determining locus is in the region identified by all previous studies, including a recent report suggesting a candidate sex-determining gene in this fish, close to the pseudo-autosomal region (or PAR) at the chromosome terminus. Our results suggest the presence of some errors in the current assembly of the guppy genome. In males, crossing over occurs at a very high rate in the PAR, and our genetic map of the region allows us to correct the marker order. We also identified two unplaced scaffolds carrying genes that map to the PAR. Genetic mapping cannot be used to order markers in the region where crossing over is infrequent. However, our recombinant male is informative about the order, under the reasonable assumption that crossovers are infrequent. Our mapping families and natural population samples also show that the recently proposed candidate for this species’ sex-determining gene is not completely sex-linked. We detect an association between individuals’ sex and an SNP in the sex-determining region, but not with a marker 0.9 Mb away from it, suggesting that variants in this region may be in linkage disequilibrium with the actual sex-determining factor, but that the factor itself has not yet been identified. So far, no consistently male-specific variant has been identified in the guppy sex-determining region.
Comparing proportional and ordinal dominance ranks reveals multiple competitive landscapes in an animal society
Authors: Levy Emily J , Zipple Matthew N , McLean Emily , Campos Fernando A , Dasari Mauna , Fogel Arielle S , Franz Mathias , Gesquiere Laurence R , Gordon Jacob B , Grieneisen Laura , Habig Bobby , Jansen David J , Learn Niki H , Weibel Chelsea J , Altmann Jeanne , Alberts Susan C , Archie Elizabeth A
Published: May 2020

Across group-living animals, linear dominance hierarchies lead to disparities in access to resources, health outcomes, and reproductive performance. Studies of how dominance rank affects these outcomes typically employ one of several dominance rank metrics without examining the assumptions each metric makes about its underlying competitive processes. Here we compare the ability of two dominance rank metrics—ordinal rank and proportional or ‘standardized’ rank—to predict 20 distinct traits in a well-studied wild baboon population in Amboseli, Kenya. We propose that ordinal rank best predicts outcomes when competition is density-dependent, while proportional rank best predicts outcomes when competition is density-independent. We found that for 75% (15/20) of the traits, one of the two rank metrics performed better than the other. Strikingly, all male traits were better predicted by ordinal than by proportional rank, while female traits were evenly split between being better predicted by proportional or ordinal rank. Hence, male and female traits are shaped by different competitive regimes: males’ competitive environments are largely driven by density-dependent resource access (e.g., access to estrus females), while females’ competitive environments are shaped by both density-independent resource access (e.g. distributed food resources) and density-dependent resource access. However, traits related to competition for social and mating partners are an exception to this sex-biased pattern: these traits were better predicted by ordinal rank than by proportional rank for both sexes. We argue that this method of comparing how different rank metrics predict traits of interest can be used as a way to distinguish between different competitive processes operating in animal societies.
Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number, independent of microglial inflammatory signaling
Authors: Smith Caroline J. , Kingsbury Marcy A. , Dziabis Julia E. , Hanamsagar Richa , Malacon Karen E. , Tran Jessica N. , Norris Haley A. , Gulino Mary , Bilbo Staci D.
Published: May 2020

Decreases in social behavior are a hallmark aspect of acute “sickness behavior” in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling.
Modeling and Analyzing Neural Signals with Phase Variability using the Fisher-Rao Registration
Authors: Zhao Weilong , Xu Zishen , Li Wen , Wu Wei
Published: May 2020

The Dynamic Time Warping (DTW) has recently been introduced to analyze neural signals such as EEG and fMRI where phase variability plays an important role in the data. In this study, we propose to adopt a more powerful method, referred to as the Fisher-Rao Registration (FRR), to study the phase variability. We systematically compare the FRR with the DTW in three aspects: 1) basic framework, 2) mathematical properties, and 3) computational efficiency. We show that the FRR has superior performance in all these aspects and the advantages are well illustrated with simulation examples. We then apply the FRR method to two real experimental recordings – one fMRI and one EEG data set. It is found the FRR method properly removes the phase variability in each set. Finally, we use the FRR framework to examine brain networks in these two data sets and the result demonstrates the effectiveness of the new method.
Macrophages inhibit and enhance endometriosis depending on their origin
Authors: Hogg Chloe , Dhami Priya , Rosser Matthew , Mack Matthias , Soong Daniel , Pollard Jeffrey W , Jenkins Stephen J , Horne Andrew W , Greaves Erin
Published: May 2020

Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increased the number of lesions. We propose a putative model whereby endometrial macrophages are pro-endometriosis whilst newly-recruited monocyte-derived macrophages, possibly in LpM form, are ‘anti-endometriosis’. These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.
Transcriptional profiling reveals a subset of human breast tumors that retain wtTP53but display mutant p53-associated features
Authors: Benor Gal , Fuks Garold , Chin Suet-Feung , Rueda Oscar , Mukherjee Saptaparna , Arandkar Sharathchandra , Aylon Yael , Caldas Carlos , Domany Eytan , Oren Moshe
Published: May 2020

TP53gene mutations are very common in human cancer. While such mutations abrogate the tumor suppressive activities of the wild type (wt) p53 protein, some of them also endow the mutant protein with oncogenic gain-of-function (GOF), facilitating cancer progression. Yet, p53 may acquire altered functionality even without being mutated; in particular, experiments with cultured cells revealed that wt p53 can be rewired to adopt mutant-like features in response to growth factors or cancer-mimicking genetic manipulations. To assess whether such rewiring also occurs in human tumors, we interrogated gene expression profiles and pathway deregulation patterns in the METABRIC breast cancer (BC) dataset as a function ofTP53gene mutation status. Harnessing the power of machine learning, we optimized a gene expression classifier for ER+Her2- patients that distinguishes tumors carryingTP53mutations from those retaining wtTP53. Interestingly, a small subset of wtTP53tumors displayed gene expression and pathway deregulation patterns markedly similar to those ofTP53-mutated tumors. Moreover, similar toTP53mutated tumors, these “pseudomutant” cases displayed a signature for enhanced proliferation and had worse prognosis than typical wt p53 tumors. Notably, these tumors revealed upregulation of genes which, in BC cell lines, were reported to be positively regulated by p53 GOF mutants. Thus, such tumors may benefit from mutant p53-associated activities without having to accrueTP53mutations.
Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest
Authors: Aharon-Hefetz Noa , Frumkin Idan , Mayshar Yoav , Dahan Orna , Pilpel Yitzhak , Rak Roni
Published: May 2020

Different subsets of the tRNA pool in human are expressed in different cellular conditions. The “proliferation-tRNAs” are induced upon normal and cancerous cell division, while the “differentiation tRNAs” are active in non-dividing, differentiated cells. Here we examine the essentiality of the various tRNAs upon cellular growth and arrest. We established a CRISPR-based editing procedure with sgRNAs that each target a tRNA family. We measured tRNA essentiality for cellular growth and found that most proliferation tRNAs are essential compared to differentiation tRNAs in rapidly growing cell lines. Yet in more slowly dividing lines, the differentiation tRNAs were more essential. In addition, we measured these tRNAs roles upon response to cell cycle arresting signals. Here we detected a more complex behavior with both proliferation-tRNAs and differentiation tRNAs showing various levels of essentiality. These results provide the so-far most comprehensive functional characterization of human tRNAs with intricate roles in various proliferation states.
Post-transcriptional regulation of cellulose synthase genes by small RNAs derived from CESA antisense transcripts
Authors: Nething Daniel B. , Mishler-Elmore John W. , Held Michael A.
Published: May 2020

Transcriptional regulatory mechanisms governing plant cell wall biosynthesis are incomplete. Expression programs that activate wall biosynthesis are well understood, but mechanisms that control the attenuation of gene expression networks remain elusive. Previous work has shown that small RNAs (sRNAs) derived from theHvCESA6 (Hordeum vulgare, Hv) antisense transcripts are naturally produced and are capable of regulating aspects of wall biosynthesis. Here, we further test the hypothesis thatCESA-derived sRNAs generated fromCESAantisense transcripts are involved in the regulation of cellulose and broader cell wall biosynthesis. Antisense transcripts were detected for some, but not all members of theCESAgene family in both barley andBrachypodium distachyon. Phylogenetic analysis indicates that antisense transcripts are detected for most primary cell wall CESA genes, suggesting a possible role in the transition from primary to secondary cell wall biosynthesis. Focusing on one antisense transcript,HvCESA1shows dynamic expression throughout development, is correlated with corresponding sRNAs over the same period and is anticorrelated withHvCESA1mRNA expression. To assess the broader impacts ofCESA-derived sRNAs on the regulation of cell wall biosynthesis, transcript profiling was performed on barley tissues overexpressingCESA-derived sRNAs. Together the data support the hypothesis thatCESAantisense transcripts function, through an RNA-induced silencing mechanism, to degradecistranscripts, and may also triggertrans-acting silencing on related genes to alter the expression of cell wall gene networks.
A Novel Efficient L-Lysine Exporter Identified by Functional Metagenomics
Authors: Malla Sailesh , van der Helm Eric , Darbani Behrooz , Wieschalka Stefan , Forster Jochen , Borodina Irina , Sommer Morten O. A.
Published: May 2020

Lack of active export system often limits the industrial bio-based production processes accumulating the intracellular product and hence complexing the purification steps. L-lysine, an essential amino acid, is produced biologically in quantities exceeding two million tons per year; yet, L-lysine production is challenged by efficient export system at high titres during fermentation. To address this issue, new exporter candidates for efficient efflux of L-lysine are needed. Using metagenomic functional selection, we identified 58 genes encoded on 28 unique metagenomic fragments from cow gut microbiome library that improved L-lysine tolerance. These genes include a novel putative L-lysine transporter, belonging to a previously uncharacterized EamA superfamily. Characterization usingXenopus oocyteexpression system as well as anEscherichia colihost demonstrates activity as a L-lysine transporter. This novel exporter improved L-lysine tolerance inE. coliby 40% and enhanced the specific productivity of L-lysine in an industrialCorynebacterium glutamicumstrain by 12%. Our approach allows the sequence-independent discovery of novel exporters and can be deployed to increase titres and productivity of toxicity-limited bioprocesses.