bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Experience of Multiple Hardships and Fetal Growth
Authors: Goin Dana E. , Izano Monika A. , Eick Stephanie M. , Padula Amy M. , DeMicco Erin , Woodruff Tracey J. , Morello-Frosch Rachel
Published: October 2020

Background:

Women can be exposed to a multitude of hardships before and during pregnancy that may affect fetal growth, but previous approaches have not analyzed them jointly as social exposure mixtures.

Methods:

We evaluated the independent, mutually adjusted, and pairwise joint associations between self-reported hardships and birthweight for gestational age z-scores in the Chemicals in Our Bodies-2 prospective birth cohort (N = 510) using G-computation. We examined financial hardship, food insecurity, job strain, poor neighborhood environment, low community standing, caregiving, high burden of stressful life events, and unplanned pregnancy collected via questionnaire administered in the second trimester of pregnancy. We used propensity scores to ensure our analyses had sufficient data support and estimated absolute differences in outcomes.

Results:

Food insecurity was most strongly associated with reduced birthweight for gestational age z-scores individually, with an absolute difference of −0.16, 95% confidence interval (CI) −0.45, 0.14. We observed an unexpected increase in z-scores associated with poor perceived neighborhood environment (0.18, 95% CI −0.04, 0.41). Accounting for coexposures resulted in similar findings. The pairwise joint effects were strongest for food insecurity in combination with unplanned pregnancy (−0.45, 95% CI −0.93, 0.02) and stressful life events (−0.42, 95% CI −0.90, 0.05). Poor neighborhood environment in combination with caregiving was associated with an increase in z-scores (0.47, 95% CI −0.01, 0.95).

Conclusions:

Our results are consistent with the hypothesis that experiencing food insecurity during pregnancy, alone and in combination with stressful life events and unplanned pregnancy, may affect fetal growth.
Circ-HIPK2 Accelerates Cell Apoptosis and Autophagy in Myocardial Oxidative Injury by Sponging miR-485-5p and Targeting ATG101
Authors: Zhou Junling , Li Longwei , Hu Hao , Wu Jiawei , Chen Hongwu , Feng Kefu , Ma Likun
Published: October 2020

Myocardial injury has been deemed as a major cause of heart diseases including myocarditis and coronary heart disease, which have brought multiple mortalities globally. Long non-coding RNAs (lncRNAs) are widely recognized in diverse diseases. However, the role of circular RNA HIPK2 (circ-HIPK2) remains unclear in myocardial injury induced by H2O2. We attempted to investigate the probable role of circ-HIPK2 in myocardial injury induced by H2O2. This study discovered that the treatment of H2O2 inhibited cell proliferation but boosted cell apoptosis and autophagy. ATG101 was upregulated in primary mouse neonatal cardiomyocytes under H2O2 treatment. ATG101 knockdown promoted proliferation and limited apoptosis by attenuating autophagy in H2O2-injured mouse neonatal cardiomyocytes. Furthermore, miR-485-5p was validated to combine with ATG101 and circ-HIPK2, and circ-HIPK2 positively regulated ATG101 expression by sponging miR-485-5p. At last, silenced circ-HIPK2 mediated the promotion of cell proliferation, and repression of cell apoptosis was restored by ATG101 amplification. In a word, circ-HIPK2 facilitates autophagy to accelerate cell apoptosis and cell death in H2O2-caused myocardial oxidative injury through the miR-485-5p/ATG101 pathway, indicating a novel therapeutic target point for patients with myocardial injury.
Identifying women who share patterns of reproductive hormones, vasomotor symptoms, and sleep maintenance problems across the menopause transition: group-based multi-trajectory modeling in the Study of Women's Health Across the Nation
Authors: Matthews Karen A. , Chang Yuefang , Brooks Maria M. , Crawford Sybil L. , Janssen Imke , Joffe Hadine , Kravitz Howard M. , Thurston Rebecca C. , El Khoudary Samar R.
Published: October 2020

Objective:

To identify groups of women who share levels and patterns of change in follicle-stimulating hormone (FSH), self-reported sleep maintenance problems, and frequent vasomotor symptoms (VMS) up to 10 years before and after their final menstrual period and to evaluate their premenopausal characteristics.

Method:

Group-based multi-trajectory modeling grouped 1,407 women from the Study of Women's Health Across the Nation who had an observed natural menopause and did not use hormone therapy, based on repeated measures of FSH, sleep maintenance problems, and frequent VMS relative to final menstrual period. Multivariable analyses assessed race/ethnicity, body mass index, smoking, and depressive symptoms as predictors of group membership.

Results:

Women formed five distinct groups: (1) low symptoms (low VMS/sleep problems)/high FSH rise (N = 552; 39.2%); (2) moderate VMS and sleep problems/low FSH rise (N = 169; 12.0%); (3) dominant sleep problems (lower VMS/high sleep problems)/high FSH rise (N = 203; 14.4%); (4) dominant VMS (high VMS/lower sleep problems)/high FSH rise (N = 297; 21.1%)); and (5) high symptoms (high VMS/high sleep problems)/intermediate FSH rise (N = 186; 13.2%)). Multivariate analyses showed that race/ethnicity, premenopausal body mass index and depressive symptoms, and increasing depressive symptoms during the early phase of the transition predicted group membership.

Conclusions:

Women can be classified based on shared levels and patterns of FSH, sleep maintenance problems, and frequent VMS across the menopause transition. Either VMS or sleep maintenance problems can be dominant in the face of high FSH. Experiencing one menopause-related symptom or hormone profile does not automatically imply that another is also being experienced.
Cryoballoon ablation for extrapulmonary vein targets
Authors: Ling Tian-You , Chen Lin , Su Wilber W. , Wu Li-Qun
Published: October 2020

Purpose of review

Cryoballoon catheter can create large and contiguous lesions with stable contact during ablation. It has proven to be well tolerated and effective in pulmonary vein isolation. But atrial arrhythmias, including atrial fibrillation, atrial tachycardia, and atrial flutter (AFL), also relate to many extrapulmonary vein targets. It is necessary to understand the current evidence for the use of cryoballoon ablation for targets outside of pulmonary veins.

Recent findings

Studies have shown that the cryoballoon ablation can be used in extrapulmonary vein area, including left atrium roof, left atrial appendages, posterior left atrial wall, mitral isthmus, and right atrial appendage. The results indicate cryoballoon ablation is an effective and well-tolerated treatment option for the atrial arrhythmias in these locations outside of pulmonary vein when clinical necessary.

The cryoballoon ablation can safely and effectively perform contiguous linear lesions, structure isolations, and local ablation for targets outside of the pulmonary veins.
Secondary hyperparathyroidism is associated with postpartum blood pressure in preeclamptic women and normal pregnancies
Authors: Colussi GianLuca , Catena Cristiana , Driul Lorenza , Pezzutto Francesca , Fagotto Valentina , Darsiè Daniele , Badillo-Pazmay Gretta V. , Romano Giulio , Cogo Paola E. , Sechi Leonardo A.
Published: October 2020

Background:

Preeclampsia has been associated with features of secondary hyperparathyroidism. In this study, we examine the relationships of calcium metabolism with blood pressure (BP) in preeclamptic women and in a control group of normal (NORM) pregnancies in the postpartum.

Methods:

Sixty-three consecutive preeclamptic women (age 35 ± 6 years) were studied 4 weeks after delivery. We collected clinical and lab information on pregnancy and neonates and measured plasma and urinary calcium and phosphate, plasma parathyroid hormone (PTH) and 25-hydroxy vitamin D [25(OH)D], and performed 24-h ambulatory BP monitoring. BP and calcium metabolism of 51 preeclamptic were compared with 17 NORM pregnant women that matched for age, race, and postpartum BMI.

Results:

25(OH)D deficiency (<10 ng/ml) was found in 3% of preeclamptic women, insufficiency (10–30 ng/ml) in 67%, and NORM values (31–100 ng/ml) in the remaining 30%. Elevated plasma PTH (≥79 pg/ml) was found in 24% of preeclamptic women who had 25(OH)D plasma levels of 21.4 ± 8.3 ng/ml. In these women, PTH levels was independently associated with 24-h SBP and DBP and daytime and night-time DBP. Prevalence of nondippers and reverse dippers was elevated (75% and 33%, respectively). No associations between calcium metabolism and neonates’ characteristics of preeclamptic women were observed. Prevalence of vitamin D deficiency and insufficiency and of elevated plasma PTH levels were comparable in matched groups. Considering preeclamptic women and matched controls as a whole group, office SBP and DBP levels were associated with PTH independently of preeclampsia and other confounders.

Conclusion:

Features of secondary hyperparathyroidism are common in the postpartum. Preeclampsia and increased PTH levels were both independent factors associated with increased BP after delivery, and both might affect the future cardiovascular risk of these women.
Associations of estimated 24-h urinary sodium excretion with mortality and cardiovascular events in Chinese adults: a prospective cohort study
Authors: Liu Xiaoyun , Bai Yinxiao , Li Sidong , O’Donnell Martin , Mente Andrew , Yin Lu , Hu Bo , Cheng Xiaoru , Liu Weida , Bai Xiulin , Wang Yang , Sun Yi , Li Xiaomeng , Liu Lisheng , Yusuf Salim , Li Wei
Published: October 2020

Objective:

To investigate the associations of sodium excretion with blood pressure, mortality and cardiovascular diseases in Chinese population.

Methods:

We studied 39 366 individuals aged 35–70 years from 115 urban and rural communities in 12 centers across mainland China. Trained research staff conducted face-to-face interview to record baseline information of all participants based on questionnaires, and collected their morning fasting urine samples to estimate 24-h sodium excretion (24hUNaE). Multivariable frailty Cox regression accounting for clustering by centre was performed to examine the association between estimated 24hUNaE and the primary composite outcome of death and major cardiovascular events in a Chinese population.

Results:

Mean 24hUNaE was 5.68 (SD 1.69) g/day. After a median follow-up of 8.8 years, the composite outcome occurred in 3080 (7.8%) participants, of which 1426 (3.5%) died and 2192 (5.4%) suffered from cardiovascular events. 24hUNaE was positively associated with increased SBP and DBP. Using the 24hUNaE level of 4–4.99 g/day as the reference group, a 24hUNaE of either lower (<3 g/day) or higher (≥7 g/day) was associated with an increased risk of the composite outcome with a hazard ratio of 1.22 (95% confidence interval: 1.01–1.49) and 1.15 (95% confidence interval: 1.01–1.30), respectively. A similar trend was observed between 24hUNaE level and risk of death or major cardiovascular events.

Conclusion:

These findings support a positive association between estimated urinary sodium excretion and blood pressure, and a possible J-shaped pattern of association between sodium excretion and clinical outcomes, with the lowest risk in participants with sodium excretion between 3 and 5 g/day.
Isolated diastolic hypertension as defined by the 2017 American College of Cardiology/American Heart Association blood pressure guideline and incident cardiovascular events in Chinese
Authors: Wu Shouling , Ji Chunpeng , Shi Jihong , Chen Shuohua , Huang Zhe , Jonas Jost B.
Published: October 2020

Objective:

The new arterial hypertension guidelines by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) changed the definition of isolated diastolic hypertension (IDH). We assessed and compared in a Chinese population the IDH prevalence, newly defined by the 2017 ACC/AHA guidelines versus the former definition by the Joint National Committee 7 (JNC7) criteria, and examined longitudinal associations of IDH with cardiovascular disease (CVD) outcomes.

Methods:

The prospective community-based Kailuan Study included participants aged 18–98 years who underwent a detailed medical examination at baseline in 2006/2007 and who were biennially re-examined till 2017. History of antihypertensive medication at baseline was an exclusion criterion.

Results:

The study population consisted of 87 346 individuals (mean age: 50.9 years; range: 18–98 years). Prevalence of IDH was 7.79% [95% confidence interval (CI): 7.62, 7.97] by JNC7 guidelines and 24.72% (95% CI: 24.43, 25.01) by 2017 ACC/AHA criteria [difference: 19.93% (95% CI: 16.81, 17.04)]. Applying the 2017 ACC/AHA guidelines, the prevalence of IDH-recommended antihypertensive therapy was 7.73% (95% CI: 7.55, 7.90). In multivariable analysis, IDH by JNC7 criteria was significantly associated with incident myocardial infarction [n = 93 events; hazard ratio: 1.30 (95 CI: 1.02, 1.66)], cerebral hemorrhage [n = 73 events; hazard ratio: 1.79 (95% CI: 1.35, 2.38)], and total CVD [n = 373 events; hazard ratio: 1.15 (95% CI: 1.02, 1.30)], when compared with normotension. IDH based on 2017 ACC/AHA guidelines was associated with incident cerebral hemorrhage [n = 129 events; hazard ratio: 1.47 (95% CI: 1.12, 1.94)] and total CVD [n = 828 events; hazard ratio: 1.13 (95% CI: 1.02, 1.26)].

Conclusion:

In this adult Chinese community, 2017 ACC/AHA-defined IDH was associated with the incidence of cerebral hemorrhage and total CVD, and as compared with JNC7-defined IDH, it was more prevalent.
DETECTION OF MORPHOLOGIC PATTERNS OF DIABETIC MACULAR EDEMA USING A DEEP LEARNING APPROACH BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES
Authors: Wu Qiaowei , Zhang Bin , Hu Yijun , Liu Baoyi , Cao Dan , Yang Dawei , Peng Qingsheng , Zhong Pingting , Zeng Xiaomin , Xiao Yu , Li Cong , Fang Ying , Feng Songfu , Huang Manqing , Cai Hongmin , Yang Xiaohong , Yu Honghua
Published: October 2020

Purpose:

To develop a deep learning (DL) model to detect morphologic patterns of diabetic macular edema (DME) based on optical coherence tomography (OCT) images.

Methods:

In the training set, 12,365 OCT images were extracted from a public data set and an ophthalmic center. A total of 656 OCT images were extracted from another ophthalmic center for external validation. The presence or absence of three OCT patterns of DME, including diffused retinal thickening, cystoid macular edema, and serous retinal detachment, was labeled with 1 or 0, respectively. A DL model was trained to detect three OCT patterns of DME. The occlusion test was applied for the visualization of the DL model.

Results:

Applying 5-fold cross-validation method in internal validation, the area under the receiver operating characteristic curve for the detection of three OCT patterns (i.e., diffused retinal thickening, cystoid macular edema, and serous retinal detachment) was 0.971, 0.974, and 0.994, respectively, with an accuracy of 93.0%, 95.1%, and 98.8%, respectively, a sensitivity of 93.5%, 94.5%, and 96.7%, respectively, and a specificity of 92.3%, 95.6%, and 99.3%, respectively. In external validation, the area under the receiver operating characteristic curve was 0.970, 0.997, and 0.997, respectively, with an accuracy of 90.2%, 95.4%, and 95.9%, respectively, a sensitivity of 80.1%, 93.4%, and 94.9%, respectively, and a specificity of 97.6%, 97.2%, and 96.5%, respectively. The occlusion test showed that the DL model could successfully identify the pathologic regions most critical for detection.

Conclusion:

Our DL model demonstrated high accuracy and transparency in the detection of OCT patterns of DME. These results emphasized the potential of artificial intelligence in assisting clinical decision-making processes in patients with DME.
Psychometric Testing of an Indonesian-Version Diabetes Self-Management Instrument
Authors: RAHAYU Henik Tri , CHEN Ching-Min
Published: October 2020

Background

Self-management is one of the vital elements in diabetes management for adults with Type 2 diabetes mellitus (T2DM). Although the number of people with T2DM in Indonesia has risen, clinical understanding of the problems related to practicing diabetes self-management (DSM) is limited because of the lack of a valid measurement instrument. The 35-item Diabetes Self-Management Instrument (DSMI-35) is one instrument widely used in research to assess DSM-related behavior among patients with diabetes.

Purpose

This study was designed to translate the psychometric properties of the Indonesian version of the DSMI-35 and evaluate the efficacy of this instrument in a sample of Indonesian adults with T2DM.

Methods

Forward and backward translation processes were used to translate the DSMI-35 into Indonesian (IDN-DSMI). Then, the translation equivalence, content validity, face validity, construct validity, and internal consistency were assessed using a sample of 222 Indonesian adults with T2DM from eight public health centers. Confirmatory factor analysis was used to test the data.

Results

The confirmatory factor analysis confirmed that the 35 items all had acceptable goodness of fit. Although the analysis supported removing several of the items, removal of these items was not theoretically justified. The average variance extracted was acceptable, and composite reliability was satisfied. The Cronbach's alpha was .96 for the IDN-DSMI and .84–.93 for the subscales. The significant interitem correlations between some items were consistent with the findings of other previous studies.

Conclusions/Implications for Practice

The IDN-DSMI is a valid and reliable instrument that may be used to measure DSM behavior in Indonesian patients with T2DM in primary healthcare settings.
Parkinson Disease and Occupational and Environmental Exposure to Pesticides in a Region of Intense Agribusiness Activity in Brazil
Authors: Silvestre Grasiela Cristina Silva Botelho , Ferreira Marcelo José Monteiro , Figueiredo Sue Ellen Ferreira Modesto Rey de , Silva Cristhiane Almeida Leite da , Siqueira Heloise Helena , Silva Ageo Mário Cândido da
Published: October 2020

Objective:

To evaluate the relationship between occupational and environmental exposure to pesticides and Parkinson disease in a region of intense agribusiness activity in the state of Mato Grosso/Brazil.

Methods:

Case–control study carried out in a referral hospital for chronic neurodegenerative diseases. Non-conditional logistic regression analyses were performed.

Results:

Having performed direct management of pesticides in the workplace (odds ratio [OR]: 3.43; 95% confidence interval [CI]: 1.55 to 7.28), having a family history of Parkinson (OR: 3.42; 95% CI: 1.61 to 7.28) and being men (OR: 3.01; 95% CI: 1.66 to 5.45) were all factors that contributed to a greater chance for the development of the disease.

Conclusion:

Our study reinforces the associations between occupational and environmental exposure to pesticides and the occurrence of Parkinson disease in regions of intense agribusiness activity in Brazil.
Environmental toxicant exposure and menstrual cycle length
Authors: Hammer Karissa C. , Veiga Alexis , Mahalingaiah Shruthi
Published: October 2020

Purpose of review

This review seeks to evaluate the impact of environmental exposures on the menstrual cycle length detailing timing of exposure on pathophysiology.

Recent findings

Recent literature has examined the relationship between menstrual cycle length and environmental exposures including air pollutants, parabens, and polybrominated biphenyls.

Research is limited but suggest importance of further research in evaluating environmental exposures and menstrual cycle length.
Predicting 2-Day Mortality of Thrombocytopenic Patients Based on Clinical Laboratory Data Using Machine Learning
Authors: Lien Frank , Wang Hsin-Yao , Lu Jang-Jih , Wen Ying-Hao , Chiueh Tzong-Shi
Published: October 2020

Background:

Clinical laboratories have traditionally used a single critical value for thrombocytopenic events. This system, however, could lead to inaccuracies and inefficiencies, causing alarm fatigue and compromised patient safety.

Objectives:

This study shows how machine learning (ML) models can provide auxiliary information for more accurate identification of critical thrombocytopenic patients when compared with the traditional notification system.

Research Design:

A total of 50,505 patients’ platelet count and other 26 additional laboratory datasets of each thrombocytopenic event were used to build prediction models. Conventional logistic regression and ML methods, including random forest (RF), artificial neural network, stochastic gradient descent (SGD), naive Bayes, support vector machine, and decision tree, were applied to build different models and evaluated.

Results:

Models using logistic regression [area under the curve (AUC)=0.842], RF (AUC=0.859), artificial neural network (AUC=0.867), or SGD (AUC=0.826) achieved the desired average AUC>0.80. The highest positive predictive value was obtained by the SGD model in the testing data (72.2%), whereas overall, the RF model showed higher sensitivity and total positive predictions in both the training and testing data and outperformed other models. The positive 2-day mortality predictive rate of RF methods is as high as 46.1%—significantly higher than using the traditional notification system at only 14.8% [χ2
(1)=81.66, P<0.001].

Conclusions:

This study demonstrates a data-driven ML approach showing a significantly more accurate 2-day mortality prediction after a critical thrombocytopenic event, which can reinforce the accuracy of the traditional notification system.
Novel approaches to management of hyperkalaemia in kidney transplantation
Authors: Rizk John , Quan David , Gabardi Steven , Rizk Youssef , Kalantar-Zadeh Kamyar
Published: October 2020

Purpose of review

Medications used frequently after kidney transplantation, including calcineurin inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers and antimicrobials, are considered the leading culprit for posttransplant hyperkalaemia in recipients with a well functioning allograft. Other risk factors include comorbidities such as diabetes, hypertension and heart failure; and consumption of a potassium-enriched diet. We review the mechanisms for hyperkalaemia following kidney transplantation that are addressed using nonpharmacological and pharmacological interventions. We also discuss emerging therapeutic approaches for the management of recurrent hyperkalaemia in solid organ transplantation, including newer potassium binding therapies.

Recent findings

Patiromer and sodium zirconium cyclosilicate are emerging potassium binders approved for the treatment of hyperkalaemia. Patiromer is a polymer that exchanges potassium for calcium ions. In contrast, sodium zirconium cyclosilicate is a nonpolymer compound that exchanges potassium for sodium and hydrogen ions. Both agents are efficacious in the treatment of chronic or recurrent hyperkalaemia and may result in fewer gastrointestinal side effects than older potassium binders such as sodium polystyrene sulfonate and calcium polystyrene sulfonate. Large-scale clinical studies have not been performed in kidney transplant patients. Patiromer may increase serum concentrations of tacrolimus, but not cyclosporine. Sodium zirconium cyclosilicate does not appear to compromise tacrolimus pharmacokinetics, although it may have a higher sodium burden.

Patiromer and sodium zirconium cyclosilicate may be well tolerated options to treat asymptomatic hyperkalaemia and have the potential to ease potassium dietary restrictions in kidney transplant patients by maintaining a plant-dominant, heart-healthy diet. Their efficacy, better tolerability and comparable cost with respect to previously available potassium binders make them an attractive therapeutic option in chronic hyperkalaemia following kidney transplantation.
Feasibility of Family-Assisted Severity of Illness Monitoring for Hospitalized Children in Low-Income Settings
Authors: von Saint Andre-von Arnim Amelie O. , Kumar Rashmi K. , Oron Assaf P. , Nguyen Quynh-Uyen P. , Mutonga Daniel M. , Zimmerman Jerry , Walson Judd L.
Published: October 2020

Objectives:

To determine the feasibility of having caregivers assist in recognition of clinical deterioration in children hospitalized with febrile illness in a resource-limited setting.

Design:

Single-center, prospective, interventional pilot study.

Setting:

General pediatric wards at Kenyatta National Hospital, Nairobi, Kenya’s largest public tertiary-care hospital.

Patients:

Children hospitalized with acute febrile illness, accompanied by caregivers available at the bedside for 24 hours soon after hospital admission.

Interventions:

Caregivers were trained to recognize signs of critical illness using the Family-Assisted Severe Febrile Illness Therapy tool, which quantifies patients’ work of breathing, mental status, and perfusion, producing color-coded flags to signal illness severity. Caregivers’ Family-Assisted Severe Febrile Illness Therapy assessments were compared with healthcare professional assessments and to established Pediatric Early Warning Scores (PEWS). An initial study stage was followed by refinement of training and a larger second stage with intervention/control arms.

Measurements and Main Results:

A total of 107 patient/caregiver pairs were enrolled in the interventional arm; 106 caregivers underwent Family-Assisted Severe Febrile Illness Therapy training and were included in the analysis. Patient characteristics included median age 1.1 years (0.2–10 yr), 55 (52%) female, and diagnoses: pneumonia (64 [60%]), meningitis (38 [36%]), gastroenteritis (24 [23%]), and malaria (21 [20%]). Most caregivers had primary (34 [32%]) or secondary (53 [50%]) school education. Fourteen of 106 patients (13%) died during their stay, six within 2 days. Across all severity levels, caregiver Family-Assisted Severe Febrile Illness Therapy assessments matched professionals in 87% and 94% for stages 1 and 2, respectively. Caregiver Family-Assisted Severe Febrile Illness Therapy assessments had a moderate to strong correlation with coinciding Pediatric Early Warning Scores and were sensitive to life-threatening deterioration: for all six patients who died within 2 days of admission, caregiver assessment reached the highest alert level.

Conclusions:

Caregiver involvement in recognition of critical illness in hospitalized children in low-resource settings may be feasible. This may facilitate earlier detection of clinical deterioration where staffing is severely limited by constrained resources. Further validation of the Family-Assisted Severe Febrile Illness Therapy tool is warranted, followed by its application in a larger multisite patient population to assess provider response and associated clinical outcomes.
The impact of within-vector parasite development on the extrinsic incubation period
Authors: Childs Lauren M. , Prosper Olivia F.
Published: October 2020

Mosquito-borne diseases, in particular malaria, have a significant burden worldwide leading to nearly half a million deaths each year. The malaria parasite requires a vertebrate host, such as a human, and a vector host, theAnophelesmosquito, to complete its full life cycle. Here, we focus on the parasite dynamics within the vector to examine the first appearance of sporozoites in the salivary glands, which indicates a first time of infectiousness of mosquitoes. The timing of this period of pathogen development in the mosquito until transmissibility, known as the extrinsic incubation period, remains poorly understood. We develop compartmental models of within-mosquito parasite dynamics fitted with experimental data on oocyst and sporozoite counts. We find that only a fraction of oocysts burst to release sporozoites and bursting must be delayed either via a time-dependent function or a gamma-distributed set of compartments. We use Bayesian inference to estimate distributions of parameters and determine that bursting rate is a key epidemiological parameter. A better understanding of the factors impacting the extrinsic incubation period will aid in the development of interventions to slow or stop the spread of malaria.
Synthesis of mesoporous silicate molecular sieves by the aerosol-assisted method for loading and release of drug
Authors: Hao Liang , Li Xiaojia , Wang Yang
Published: October 2020

The mesoporous silicate molecular sieves were synthesized with polyether F127 as the template by the aerosol-assisted method for loading and release of ibuprofen (IBU). The synthesized samples were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction and N2adsorption–desorption isotherms. The drug IBU was applied as a model drug to investigate the drug release behaviour by ultraviolet spectrophotometry measurements. The investigation results demonstrate that mesoporous silicate molecular sieves by the aerosol-assisted method are spherical with a core–shell structure. As the drug carrier, it has good structural stability and can achieve drug controlled release which is expected. It exhibits safety to a certain degree. Therefore, the aerosol-assisted synthesis method provides a new idea for the synthesis of sustained-release drug carriers.
Development of a specific troponin I detection system with enhanced immune sensitivity using a single monoclonal antibody
Authors: Bozdogan Anıl , El-Kased Reham F. , Jungbluth Vanessa , Knoll Wolfgang , Dostalek Jakub , Kasry Amal
Published: October 2020

Using an immunoassay in combination with surface plasmon fluorescence spectroscopy (SPFS), we report the rapid detection of troponin I, a valuable biomarker for diagnosis of myocardial infarction. We discuss the implementation of (i) direct, (ii) sandwich, and (iii) competitive assay formats, based on surface plasmon resonance and SPFS. To elucidate the results, we relate the experiments to orientation-dependent interaction of troponin I epitopes with respective immunoglobulin G antibodies. A limit of detection (LoD) of 19 pM, with 45 min readout time, was achieved using single monoclonal antibody that is specific for one epitope. The borderline between normal people and patients is 20 pM to 83 pM cTnI concentration, and upon the outbreak of acute myocardial infraction it can raise to 2 nM and levels at 20 nM for 6–8 days, therefore the achieved LoD covers most of the clinically relevant range. In addition, this system allows for the detection of troponin I using a single specific monoclonal antibody, which is highly beneficial in case of detection in real samples, where the protein has a complex form leading to hidden epitopes, thus paving the way towards a system that can improve early-stage screening of heart attacks.
Experimental evidence that hyperthermia limits offspring provisioning in a temperate-breeding bird
Authors: Tapper Simon , Nocera Joseph J. , Burness Gary
Published: October 2020

In many vertebrates, parental care can require long bouts of daily exercise that can span several weeks. Exercise, especially in the heat, raises body temperature, and can lead to hyperthermia. Typical strategies for regulating body temperature during endurance exercise include modifying performance to avoid hyperthermia (anticipatory regulation) and allowing body temperature to rise above normothermic levels for brief periods of time (facultative hyperthermia). Facultative hyperthermia is commonly employed by desert birds to economize on water, but this strategy may also be important for chick-rearing birds to avoid reducing offspring provisioning when thermoregulatory demands are high. In this study, we tested how chick-rearing birds balance their own body temperature against the need to provision dependent offspring. We experimentally increased the heat dissipation capacity of breeding female tree swallows (Tachycineta bicolor) by trimming their ventral feathers and remotely monitored provisioning rates, body temperature and the probability of hyperthermia. Birds with an experimentally increased capacity to dissipate heat (i.e. trimmed treatment) maintained higher feeding rates than controls at high ambient temperatures (greater than or equal to 25°C), while maintaining lower body temperatures. However, at the highest temperatures (greater than or equal to 25°C), trimmed individuals became hyperthermic. These results provide evidence that chick-rearing tree swallows use both anticipatory regulation and facultative hyperthermia during endurance performance. With rising global temperatures, individuals may need to increase their frequency of facultative hyperthermia to maintain nestling provisioning, and thereby maximize reproductive success.
The field of values of Jones matrices: classification and special cases
Authors: Gutiérrez-Vega Julio C.
Published: October 2020

The concept of field of values (FoV), also known as the numerical range, is applied to the 2 × 2 Jones matrices used in polarization optics. We discover the relevant interplay between the geometric properties of the FoV, the algebraic properties of the Jones matrices and the representation of polarization states on the Poincaré sphere. The properties of the FoV reveal hidden symmetries in the relationships between the eigenvectors and eigenvalues of the Jones matrices. We determine the main mathematical properties of the FoV, discuss the special cases that are relevant to polarization optics, and describe its application to calculate the Pancharatnam-Berry phase introduced by an optical system to the input state.
Continent-scale Hiatus Maps for the Atlantic Realm and Australia since the Upper Jurassic and links to mantle flow induced dynamic topography
Authors: Hayek Jorge Nicolas , Vilacís Berta , Bunge Hans-Peter , Friedrich Anke M. , Carena Sara , Vibe Yulia
Published: October 2020

Interregional geological maps hold important information for geodynamic models. Here, we use such maps to visualize major conformable and unconformable contacts at interregional scales and at the level of geologic series from the Upper Jurassic onward across North and South America, Europe, Africa and Australia. We extract hiatus information from these paleogeological maps, which we plot in a paleogeographical reference frame to link the maps to the plate and plume modes of mantle convection. We assume that interregional patterns of hiatus surfaces are proxy records of continent-scale mantle-induced vertical motion of the lithosphere. We find significant differences in the distribution of hiatus across and between continents at the timescale of geologic series, that is ten to a few tens of millions of years (Myrs). This is smaller than the mantle transit time, which, as the timescale of convection, is about 100–200 Myrs. Our results imply that different timescales for convection and topography in convective support must be an integral component of time-dependent geodynamic Earth models, consistent with the presence of a weaker upper mantle relative to the lower mantle. Additional geological constraints together with interregional geological maps at the resolution of stages (1–2 Myrs), are needed to assist in future geodynamic interpretations of interregional geologic hiatus.
Geodesic Loewner paths with varying boundary conditions
Authors: McDonald Robb
Published: October 2020

Equations of the Loewner class subject to non-constant boundary conditions along the real axis are formulated and solved giving the geodesic paths of slits growing in the upper half complex plane. The problem is motivated by Laplacian growth in which the slits represent thin fingers growing in a diffusion field. A single finger follows a curved path determined by the forcing function appearing in Loewner’s equation. This function is found by solving an ordinary differential equation whose terms depend on curvature properties of the streamlines of the diffusive field in the conformally mapped ‘mathematical’ plane. The effect of boundary conditions specifying either piecewise constant values of the field variable along the real axis, or a dipole placed on the real axis, reveal a range of behaviours for the growing slit. These include regions along the real axis from which no slit growth is possible, regions where paths grow to infinity, or regions where paths curve back toward the real axis terminating in finite time. Symmetric pairs of paths subject to the piecewise constant boundary condition along the real axis are also computed, demonstrating that paths which grow to infinity evolve asymptotically toward an angle of bifurcation of
π
/5.
Landmark navigation in a mantis shrimp
Authors: Patel Rickesh N. , Cronin Thomas W.
Published: October 2020

Mantis shrimp commonly occupy burrows in shallow, tropical waters. These habitats are often structurally complex where many potential landmarks are available. Mantis shrimp of the speciesNeogonodactylus oerstediireturn to their burrows between foraging excursions using path integration, a vector-based navigational strategy that is prone to accumulated error. Here, we show thatN. oerstediican navigate using landmarks in parallel with their path integration system, correcting for positional uncertainty generated when navigating using solely path integration. We also report that when the path integration and landmark navigation systems are placed in conflict,N. oerstediiwill orientate using either system or even switch systems enroute. How they make the decision to trust one navigational system over another is unclear. These findings add to our understanding of the refined navigational toolkitN. oerstediirelies upon to efficiently navigate back to its burrow, complementing its robust, yet error prone, path integration system with landmark guidance.
Connectivity analysis of single cell RNA-sequencing derived transcriptional signature of lymphangioleiomyomatosis
Authors: Al Mahi Naim , Zhang Erik Y. , Sherman Susan , Yu Jane J. , Medvedovic Mario
Published: October 2020

Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease affecting women of childbearing age that is characterized by the aberrant proliferation of smooth-muscle (SM)-like cells and emphysema-like lung remodeling. In LAM, mutations in TSC1 or TSC2 genes results in the activation of the mechanistic target of rapamycin complex 1 (mTORC1) and thus sirolimus, an mTORC1 inhibitor, has been approved by FDA to treat LAM patients. Sirolimus stabilizes lung function and improves symptoms. However, the disease recurs with discontinuation of the drug, potentially because of the sirolimus-induced refractoriness of the LAM cells. Therefore, there is a critical need to identify remission inducing cytocidal treatments for LAM. Recently released Library of Integrated Network-based Cellular Signatures (LINCS) L1000 transcriptional signatures of chemical perturbations has opened new avenues to study cellular responses to existing drugs and new bioactive compounds. Connecting transcriptional signature of a disease to these chemical perturbation signatures to identify bioactive chemicals that can “revert” the disease signatures can lead to novel drug discovery. We developed methods for constructing disease transcriptional signatures and performing connectivity analysis using single cell RNA-seq data. The methods were applied in the analysis of scRNA-seq data of naïve and sirolimus-treated LAM cells. The single cell connectivity analyses implicated mTORC1 inhibitors as capable of reverting the LAM transcriptional signatures while the corresponding standard bulk analysis did not. This indicates the importance of using single cell analysis in constructing disease signatures. The analysis also implicated other classes of drugs, CDK, MEK/MAPK and EGFR/JAK inhibitors, as potential therapeutic agents for LAM.
Economic precarity, social isolation, and suicidal ideation during the COVID-19 pandemic
Authors: Raifman Julia , Ettman Catherine K. , Dean Lorraine , Barry Colleen , Galea Sandro
Published: October 2020

Importance

The US population faces stressors associated with suicide brought on by the COVID-19 pandemic. Understanding the relationship between stressors and suicidal ideation may inform policies and programs to prevent suicide.

Objective

To evaluate the relationship between stressors and suicidal ideation during the COVID-19 pandemic.

Design

We compared suicidal ideation in 2017-2018 to suicidal ideation in 2020. We estimated the association between stressors and suicidal ideation in bivariable and multivariable Poisson regression models with robust variance.

Setting

United States

Participants

Participants were from two, nationally representative surveys of US adults: The 2017-2017 National Health and Nutrition Examination Survey and the 2020 COVID-19 and Life Stressors Impact on Mental Health and Well-being study (conducted March 31 to April 13), analyzed April 28 to September 30, 2020.

Exposures

Economic precarity as measured through job loss or difficulty paying rent and social isolation based on reporting “feeling alone.”

Main outcome measure

Suicidal ideation based on reporting “Thoughts that you would be better off dead or of hurting yourself in some way” over the past two weeks.

Results

Suicidal ideation increased more than fourfold, from 3.4% in the 2017-2018 NHANES to 16.3% in the 2020 CLIMB survey, and from 5.8% to 26.4% among participants in low-income households. Suicidal ideation was more prevalent among people facing difficulty paying rent (31.5%), job loss (24.1%), and loneliness (25.1%), with each stressor associated with suicidal ideation in bivariable models. In the multivariable model, difficulty paying rent was associated with suicidal ideation (aPR: 1.5, 95% CI: 1.2 to 2.1), while losing a job was not (aPR: 0.9, 95% CI: 0.6 to 1.2). Feeling alone was associated with suicidal ideation (aPR: 1.9, 95% CI: 1.5 to 2.4).

Conclusions and relevance

Suicidal ideation increased more than fourfold during the COVID-19 pandemic. Difficulty paying rent and loneliness were most associated with suicidal ideation. Policies and programs to support people experiencing economic precarity and loneliness may contribute to suicide prevention.
Developing a Discrete Choice Experiment to Understand Patient Preferences in Resource-Limited Settings: a Six-Step Guide
Authors: Moor Sarah , Tusubira Andrew K. , Akiteng Ann R , Hsieh Evelyn , Ngaruiya Christine , Rabin Tracy L. , Hawley Nicola L. , Armstrong-Hough Mari , Nugent Rachel , Kalyesubula Robert , Nalwadda Christine , Ssinabulya Isaac , Schwartz Jeremy I.
Published: October 2020

A discrete choice experiment (DCE) is a method to quantify preferences for goods and services in a population. Participants are asked to choose between sets of 2 hypothetical scenarios that differ in terms of particular characteristics. Their selections reveal the relative importance of each “attribute”, or characteristic, and the extent to which people consider trade-offs between characteristics. DCEs are increasingly used in healthcare and public health settings as they can inform the design of health-related interventions to achieve maximum impact. Specific efforts must be made in the development process to ensure relevance of DCEs to the communities in which they are administered. Herein, we build upon gaps in the prior literature by offering researchers a step-by-step process to guide DCE development for resource-limited settings, including detailed methodological considerations for each step and a specific actionable approach that we hope will simplify the process for other researchers. We present the 6 steps we followed to develop a DCE to evaluate patient preferences for management of hypertension and diabetes in rural Uganda. These steps are: 1) formative work; 2) attribute selection; 3) attribute level selection; 4) DCE design selection; 5) determination of attribute level combinations; and 6) assessment and enhancement of tool comprehensibility. We describe each of these steps in detail to ease the development process for researchers looking to develop locally contextualized, end-user-centric health interventions.
Antibody reactivity against SARS-CoV-2 in adults from the Vancouver metropolitan area, Canada
Authors: Majdoubi Abdelilah , O’Connell Sarah E. , Michalski Christina , Dada Sarah , Narpala Sandeep , Gelinas Jean , Mehta Disha , Cheung Claire , Basappa Manjula , Görges Matthias , Barakauskas Vilte E , Goldfarb David M. , Douek Daniel C. , McDermott Adrian B. , Lavoie Pascal M.
Published: October 2020

Background

Quantifying antibody reactivity against multiple SARS-CoV-2 antigens at the population level may help understand individual differences in COVID-19 severity. Pre-existing low antibody cross-reactivity may be particularly prevalent among childcare providers, including pediatric health care workers (HCW) who may be more exposed to circulating coronaviruses.

Methods

Cross-sectional study that included adults in the Vancouver area in British Columbia (BC), Canada, between May 17 and June 19, 2020. SARS-CoV-2 seroprevalence was ascertained by measuring total SARS-CoV-2 IgG/M/A antibodies against a recombinant spike (S1) protein and adjusted for bias due to false-positive and false-negative test results. A novel, high sensitivity multiplex assay was also used to profile IgG against four SARS-CoV-2 antigens, SARS-CoV and four circulating coronaviruses.

Findings

Among 276 participants (71% HCW), three showed evidence of direct viral exposure, yielding an adjusted seroprevalence of 0.60% [95%CI 0% – 2.71%], with no difference between HCW and non-HCW, or between paediatric and adult HCW. Among the 273 unexposed individuals, 7.3% [95%CI 4.5% – 11.1%], 48.7 [95%CI 42.7% – 54.8%] and 82.4% [95%CI 77.4% – 86.7%] showed antibody reactivity against SARS-CoV-2 RBD, N or Spike proteins, respectively. SARS-CoV-2 reactivity did not significantly correlate with age, sex, did not significantly differ between HCW and non-HCW (prevalence 1.0% vs 1.0%; P=1.00) and between pediatric and adult HCW (0.7% vs 1.6%; P=0.54), and modestly correlated with reactivity to circulating coronaviruses (Spearman rho range: 0.130 to 0.224 for 7 significant (FDR 5%), out of 16 correlations, from 36 correlations tested).

Interpretation

A substantial proportion of individuals showed low, but detectable antibody reactivity against SARS-CoV-2 antigens in this population despite low evidence of direct SARS-CoV-2 exposure.

Funding

NIAID/NIH
Efficacy of face masks, neck gaiters and face shields for reducing the expulsion of simulated cough-generated aerosols
Authors: Lindsley William G. , Blachere Francoise M. , Law Brandon F. , Beezhold Donald H. , Noti John D.
Published: October 2020

Face masks are recommended to reduce community transmission of SARS-CoV-2. One of the primary benefits of face masks and other coverings is as source control devices to reduce the expulsion of respiratory aerosols during coughing, breathing, and speaking. Face shields and neck gaiters have been proposed as an alternative to face masks, but information about face shields and neck gaiters as source control devices is limited. We used a cough aerosol simulator with a pliable skin headform to propel small aerosol particles (0 to 7 µm) into different face coverings. An N95 respirator blocked 99% of the cough aerosol, a medical grade procedure mask blocked 59%, a 3-ply cotton cloth face mask blocked 51%, and a polyester neck gaiter blocked 47% as a single layer and 60% when folded into a double layer. In contrast, the face shield blocked 2% of the cough aerosol. Our results suggest that face masks and neck gaiters are preferable to face shields as source control devices for cough aerosols.