Predicting the Level of Background Current Noise in Graphene Biosensor through a Non-Covalent Functionalization Process

The rapid worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a series of problems. Detection platforms based on graphene field-effect transistors (GFETs) have been proposed to achieve a rapid diagnosis of SARS-CoV-2 antigen or antibody. For GFET-based biosensors, the graphene surface usually needs to be functionalized to immobilize the bioreceptor and the non-covalent approach is preferred for functionalization because it is believed not to significantly alter the electronic properties of graphene. However, in this work, the non-covalent functionalization introduced by 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE) was determined to lead to different changes in electrical properties in graphene samples with different defect densities. The fabricated graphene biosensor can successfully detect SARS-CoV-2 antigen with a concentration as low as 0.91 pg/mL. Further, by careful comparison, we determined that, for GFET fabricated on graphene with a higher defect density, the current variation caused by PBASE modification is greater and the background current noise in the subsequent antigen detection is also larger. Based on this relationship, we can predict the background current noise of the biosensors by evaluating the current change induced by the modification and screen the devices at an early stage of graphene biosensor fabrication for process optimization.

Mood and activity changes during the COVID-19 pandemic in rural and urban Veterans and their cohabitants.

OBJECTIVES: We aimed to examine the impact of COVID-19 pandemic-related stay-at-home orders on weekly reports of mood and activity before and during COVID-19 in a sample of older Veterans and their cohabitants. METHODS: Urban and rural Veterans and their cohabitants living in the Pacific Northwest ≥62 years old were enrolled as part of the Collaborative Aging Research Using Technology initiative (n = 100, age = 71.2 ± 6.5, 41% women). Participants reported frequency of social activities (e.g., travel away), physical illness, and mood (blue mood and loneliness) via weekly online health forms. RESULTS: A total of 2,441 weekly online health forms (OHFs) were collected from 100 participants. During the COVID-19 pandemic, blue mood (OR = 4.4, p < .0001) and loneliness (OR = 7.2, p < .0001) were significantly higher than before the pandemic, and travel away from home was significantly lower (OR = 0.5, p < .0001). Prevalence of blue mood and loneliness were not associated with rurality. CONCLUSIONS: The current study established that blue mood and loneliness were significantly more prevalent in older Veterans following COVID-19 stay-at-home orders regardless of rurality. CLINICAL IMPLICATIONS: The COVID-19 pandemic associated health precautions, while necessary to curb acute health risks, have created a unique situation that places vulnerable populations at increased risk of low mood.

Diagnostic accuracy of symptoms for an underlying disease: a simulation study.

Symptoms have been used to diagnose conditions such as frailty and mental illnesses. However, the diagnostic accuracy of the numbers of symptoms has not been well studied. This study aims to use equations and simulations to demonstrate how the factors that determine symptom incidence influence symptoms' diagnostic accuracy for disease diagnosis. Assuming a disease causing symptoms and correlated with the other disease in 10,000 simulated subjects, 40 symptoms occurred based on 3 epidemiological measures: proportions diseased, baseline symptom incidence (among those not diseased), and risk ratios. Symptoms occurred with similar correlation coefficients. The sensitivities and specificities of single symptoms for disease diagnosis were exhibited as equations using the three epidemiological measures and approximated using linear regression in simulated populations. The areas under curves (AUCs) of the receiver operating characteristic (ROC) curves was the measure to determine the diagnostic accuracy of multiple symptoms, derived by using 2 to 40 symptoms for disease diagnosis. With respect to each AUC, the best set of sensitivity and specificity, whose difference with 1 in the absolute value was maximal, was chosen. The results showed sensitivities and specificities of single symptoms for disease diagnosis were fully explained with the three epidemiological measures in simulated subjects. The AUCs increased or decreased with more symptoms used for disease diagnosis, when the risk ratios were greater or less than 1, respectively. Based on the AUCs, with risk ratios were similar to 1, symptoms did not provide diagnostic values. When risk ratios were greater or less than 1, maximal or minimal AUCs usually could be reached with less than 30 symptoms. The maximal AUCs and their best sets of sensitivities and specificities could be well approximated with the three epidemiological and interaction terms, adjusted R-squared ≥ 0.69. However, the observed overall symptom correlations, overall symptom incidence, and numbers of symptoms explained a small fraction of the AUC variances, adjusted R-squared ≤ 0.03. In conclusion, the sensitivities and specificities of single symptoms for disease diagnosis can be explained fully by the at-risk incidence and the 1 minus baseline incidence, respectively. The epidemiological measures and baseline symptom correlations can explain large fractions of the variances of the maximal AUCs and the best sets of sensitivities and specificities. These findings are important for researchers who want to assess the diagnostic accuracy of composite diagnostic criteria.

Analysis of Spatial and Temporal Changes of AQI in Wuhan City under the Urban Blockade of COVID-19 Pandemic.

Wuhan was the primary city in the world to adopt lockdown measures during the Coronavirus Disease 2019 pandemic. The influence of the abrupt halt of human activities on the air quality of Wuhan is a subject of considerable attention. This study is based on air quality data from 21 monitoring stations in Wuhan from 2016 to 2020. The lag effect and seasonal factors of AQI were taken into account to analyze the changes in air quality in Wuhan under the influence of the pandemic blockade. The results showed the following during the city closure: (1) A lagging effect is observed in air quality changes, with the change point occurring on the 14th day after the city closure; (2) the air quality index is substantially decreased, demonstrating a reduction in spatial differences; (3) NO2, PM10, and PM2.5 significantly decreased whilst O3 increased, and SO2 and CO did not change significantly; (4) except for the insignificant changes in spatial differences of PM10, all pollutants demonstrated a changing pattern of decreasing geographical differences. This paper provides a reference for studying the influence of human activities on the natural environment.

Type and frequency of social contacts associated with low mood before and during the COVID-19 pandemic in older adults: I-CONECT project.

BACKGROUND: Social isolation is a risk factor for dementia, but the underlying mechanism is not well understood. It is possible that lack of social contacts negatively affects emotional well-being, which leads to cognitive decline. To shed light on this potential mediation mechanism, we examined changes in type and frequency of social contacts and their effects on mood using data collected before and during the COVID-19 pandemic among socially isolated older adults aged 75 and older. METHOD: The data come from an ongoing randomized controlled trial, the Internet-Based Conversational Engagement Clinical Trial (I-CONECT, ClinicalTirals.gov: NCT02871921). One hundred forty-six participants (age=81.0±4.5, 71.9% women) who were in the trial both before and during the pandemic and whose data were available as of November of 2020 were included in the current analysis. Weekly health questionnaires administered on all participants regardless of treatment assignments were collected before and during the COVID-19 pandemic. Low mood ("Blueness") was self-reported as feeling downhearted or blue for three or more days in the past week (YES/NO). Social contacts were self-reported by amount of time they had interacted, with whom (family; friends; others), and via which modalities (in-person; phone/video call; text/email). RESULT: A total of 4,774 weeks of survey data were analyzed (3,047 before COVID 19). The weekly average time spent in-person, on phone/video call, and via text/email were 282, 113, and 44 minutes, respectively. During the COVID-19 pandemic, participants on average spent 82 minutes less in total social contact per week (in-person: reduced 123 minutes, video/call: increased 28 minutes, text/email: increased 13 minutes per week). Generalized estimating equation model revealed that in-person family contact was associated with less blueness regardless of the pandemic (OR=0.91, p=0.04). There was a COVID*text/email time with friends interaction (OR=0.68, p=0.03), suggesting that during the COVID-19 pandemic, an increase of 1 hour of texting/emailing with friends per week was associated with 32% decrease in experiencing blueness three or more days per week. CONCLUSION: In-person family time is beneficial for mental health. While in-person contacts become less frequent during the COVID-19 pandemic, increased text/email time with friends becomes an alternative to maintain mental health for socially isolated older adults.

Can changes in social contact (frequency and mode) mitigate low mood before and during the COVID-19 pandemic? The I-CONECT project.

BACKGROUND/OBJECTIVES: The coronavirus disease 2019 (COVID-19) global outbreak allowed a natural experiment to observe how older adults changed social patterns and how it affected their emotional well-being. We studied the frequency and modes of social contact and their effects on older adults' mood before and during the COVID-19 pandemic. DESIGN: Phone-based surveys were administered weekly before and during the COVID-19 pandemic. SETTING: Participants were recruited from Portland, Oregon, and Detroit, Michigan. PARTICIPANTS: Older adults ≥75 years old (n = 155, age = 81.0 ± 4.5, 72.3% women) were included in a randomized controlled trial, the Internet-Based Conversational Engagement Clinical Trial (I-CONECT). MEASUREMENTS: Low mood was self-reported as feeling downhearted or blue for three or more days in the past week. Social contact was self-reported by the amount of time spent in interactions, with whom (family, friends, others), and via which modes (in-person, phone/video call, text/email/letter). RESULTS: A total of 5525 weeks of data were derived from 155 participants. Before the COVID-19 pandemic, average social interaction time spent in-person, on phone/video call, and via text/email/letter was 406, 141, and 68 min/week, respectively. During the COVID-19 pandemic, time spent in-person was reduced by 135 min/week, while time spent via phone/video call and writing increased by 33 and 26 mins/week, respectively. In-person family contact was associated with less low mood regardless of the pandemic (odds ratio = 0.92, p < 0.05). There was a COVID-19 × text/email/letter with friends interaction (odds ratio = 0.77, p = 0.03), suggesting that during the COVID-19 pandemic, an increase of 1 h of writing with friends per week was associated with a 23% decrease in the likelihood of experiencing low mood. CONCLUSION: The lost in-person time relating to COVID-19 restrictions tended to be partially compensated for with increased calls and writing time, although overall social interaction time decreased. During the COVID-19 pandemic, at least two types of social interactions (writing to friends and in-person family time) showed promise for mitigating low mood for older adults with limited social resources.

Using a 360° Virtual Reality or 2D Video to Learn History Taking and Physical Examination Skills for Undergraduate Medical Students: Pilot Randomized Controlled Trial.

BACKGROUND: Learning through a 360° virtual reality (VR) or 2D video represents an alternative way to learn a complex medical education task. However, there is currently no consensus on how best to assess the effects of different learning materials on cognitive load estimates, heart rate variability (HRV), outcomes, and experience in learning history taking and physical examination (H&P) skills. OBJECTIVE: The aim of this study was to investigate how learning materials (ie, VR or 2D video) impact learning outcomes and experience through changes in cognitive load estimates and HRV for learning H&P skills. METHODS: This pilot system-design study included 32 undergraduate medical students at an academic teaching hospital. The students were randomly assigned, with a 1:1 allocation, to a 360° VR video group or a 2D video group, matched by age, sex, and cognitive style. The contents of both videos were different with regard to visual angle and self-determination. Learning outcomes were evaluated using the Milestone reporting form. Subjective and objective cognitive loads were estimated using the Paas Cognitive Load Scale, the National Aeronautics and Space Administration Task Load Index, and secondary-task reaction time. Cardiac autonomic function was assessed using HRV measurements. Learning experience was assessed using the AttrakDiff2 questionnaire and qualitative feedback. Statistical significance was accepted at a two-sided P value of <.01. RESULTS: All 32 participants received the intended intervention. The sample consisted of 20 (63%) males and 12 (38%) females, with a median age of 24 (IQR 23-25) years. The 360° VR video group seemed to have a higher Milestone level than the 2D video group (P=.04). The reaction time at the 10th minute in the 360° VR video group was significantly higher than that in the 2D video group (P<.001). Multiple logistic regression models of the overall cohort showed that the 360° VR video module was independently and positively associated with a reaction time at the 10th minute of ≥3.6 seconds (exp B=18.8, 95% CI 3.2-110.8; P=.001) and a Milestone level of ≥3 (exp B=15.0, 95% CI 2.3-99.6; P=.005). However, a reaction time at the 10th minute of ≥3.6 seconds was not related to a Milestone level of ≥3. A low-frequency to high-frequency ratio between the 5th and 10th minute of ≥1.43 seemed to be inversely associated with a hedonic stimulation score of ≥2.0 (exp B=0.14, 95% CI 0.03-0.68; P=.015) after adjusting for video module. The main qualitative feedback indicated that the 360° VR video module was fun but caused mild dizziness, whereas the 2D video module was easy to follow but tedious. CONCLUSIONS: Our preliminary results showed that 360° VR video learning may be associated with a better Milestone level than 2D video learning, and that this did not seem to be related to cognitive load estimates or HRV indexes in the novice learners. Of note, an increase in sympathovagal balance may have been associated with a lower hedonic stimulation score, which may have met the learners' needs and prompted learning through the different video modules. TRIAL REGISTRATION: ClinicalTrials.gov NCT03501641; https://clinicaltrials.gov/ct2/show/NCT03501641.

Older Adults' Daily Activity and Mood Changes Detected During the COVID-19 Pandemic Using Remote Unobtrusive Monitoring Technologies.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has limited older adults' access to in-person medical care, including screenings for cognitive and functional decline. Remote, technology-based tools have shown recent promise in assessing changes in older adults' daily activities and mood, which may serve as indicators of underlying health-related changes (e.g., cognitive decline). This study examined changes in older adults' driving, computer use, mood, and travel events prior to and following the COVID-19 emergency declaration using unobtrusive monitoring technologies and remote online surveys. As an exploratory aim, the impact of mild cognitive impairment (MCI) on these changes was assessed. RESEARCH DESIGN AND METHODS: Participants were 59 older adults (41 cognitively intact and 18 MCI) enrolled in a longitudinal aging study. Participants had their driving and computer use behaviors recorded over a 5-month period (75 days pre- and 76 days post-COVID emergency declaration) using unobtrusive technologies. Measures of mood, overnight guests, and frequency of overnight travel were also collected weekly via remote online survey. RESULTS: After adjusting for age, gender, and education, participants showed a significant decrease in daily driving distance, number of driving trips, highway driving, and nighttime driving, post-COVID-19 as compared to pre-COVID-19 (p < .001) based on generalized estimating equation models. Further, participants spent more time on the computer per day post-COVID-19 (p = .03). Participants endorsed increases in blue mood (p < .01) and loneliness (p < .001) and decreases in travel away from home and overnight visitors (p < .001) from pre- to post-COVID-19. Cognitive status did not impact these relationships. DISCUSSION AND IMPLICATIONS: From pre- to post-COVID-19 emergency declaration, participants drove and traveled less, used their computer more, had fewer overnight visitors, and reported greater psychological distress. These results highlight the behavioral and psychological effects of stay-at-home orders on older adults who are cognitively intact and those with MCI.

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array ("ePatch") for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin's epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.