Analyzing Google COVID-19 Vaccine Intent Search Trends and Vaccine Readiness in the United States: Panel Data Study.

BACKGROUND: Factors such as anxiety, worry, and perceptions of insufficient knowledge about a topic motivate individuals to seek web-based health information to guide their health-related decision-making. These factors converged during the COVID-19 pandemic and were linked to COVID-19 vaccination decision-making. While research shows that web-based search relevant to COVID-19 was associated with subsequent vaccine uptake, less is known about COVID-19 vaccine intent search (which assesses vaccine availability, accessibility, and eligibility) as a signal of vaccine readiness. OBJECTIVE: To increase knowledge about vaccine intent search as a signal of vaccine readiness, we investigated the relationship between COVID-19 vaccine readiness and COVID-19 vaccine intent relative search volume on Google. METHODS: We compiled panel data from several data sources in all US counties between January 2021 and April 2023, a time during which those with primary COVID-19 vaccinations increased from <57,000 to >230 million adults. We estimated a random effects generalized least squares regression model with time-fixed effects to assess the relationship between county-level COVID-19 vaccine readiness and COVID-19 vaccine intent relative search volume. We controlled for health care capacity, per capita COVID-19 cases and vaccination doses administered, and sociodemographic indicators. RESULTS: The county-level proportions of unvaccinated adults who reported that they would wait and see before getting a COVID-19 vaccine were positively associated with COVID-19 vaccine intent relative search volume (ß=9.123; Z=3.59; P<.001). The county-level proportions of vaccine-enthusiast adults, adults who indicated they were either already vaccinated with a primary COVID-19 vaccine series or planned to complete the vaccine series soon, were negatively associated with COVID-19 vaccine intent relative search volume (ß=-10.232; Z=-7.94; P<.001). However, vaccine intent search was higher in counties with high proportions of people who decided to wait and see and lower in counties with high proportions of vaccine enthusiasts. CONCLUSIONS: During this period of steep increase in COVID-19 vaccination, web-based search may have signaled differences in county-level COVID-19 vaccine readiness. More vaccine intent searches occurred in high wait-and-see counties, whereas fewer vaccine intent searches occurred in high vaccine-enthusiast counties. Considering previous research that identified a relationship between vaccine intent search and subsequent vaccine uptake, these findings suggest that vaccine intent search aligned with people's transition from the wait-and-see stage to the vaccine-enthusiast stage. The findings also suggest that web-based search trends may signal localized changes in information seeking and decision-making antecedent to vaccine uptake. Changes in web-based search trends illuminate opportunities for governments and other organizations to strategically allocate resources to increase vaccine uptake. Resource use is part of the larger public policy decisions that influence vaccine uptake, such as efforts to educate the public during evolving public health crises, including future pandemics.

The Association Between the We Can Do This Campaign and Vaccination Beliefs in the United States, January 2021-March 2022.

Public health campaigns addressing COVID-19 vaccination beliefs may be effective in changing COVID-19 vaccination behaviors, particularly among people who remain vaccine hesitant. The "We Can Do This" COVID-19 public education campaign (the Campaign) was designed to increase COVID-19 vaccine confidence and uptake. This study aims to evaluate whether Campaign dose was associated with changes in vaccination beliefs related to COVID-19 vaccine concerns and perceived risks, the importance of COVID-19 vaccines, the perceived benefits of COVID-19 vaccination, normative beliefs about COVID-19 vaccination, and perceptions about general vaccine safety and effectiveness. The study linked data from four waves of a nationally representative longitudinal panel of U.S. adults (January 2021-March 2022) with Campaign paid digital media data (April 2021-May 2022). We used mixed-effects linear regressions to examine the association between Campaign paid digital impressions and changes in vaccination beliefs. The results provide evidence that Campaign digital impressions were significantly associated with changes in respondent beliefs regarding COVID-19 vaccine concerns and perceived risks, perceived benefits of COVID-19 vaccination, and perceptions about general vaccine safety and effectiveness. Findings suggest that public education campaigns may influence vaccine confidence and uptake by increasing positive vaccination beliefs and reducing vaccine concerns.

Persistent Listeria monocytogenes Cerebritis Mimicking Cerebral Metastases Due to Melanoma.

Listeria cerebritis is a rare yet serious central nervous system infection, which can present with leptomeningeal enhancement, abscess, and seizures. An adult patient with a history of metastatic melanoma presented with left-sided weakness, later identified as postictal Todd's paralysis due to focal motor seizures. Further diagnostic workup revealed a leptomeningeal abscess in the setting of listeria cerebritis. The patient's condition improved after treatment with a prolonged course of ampicillin, gentamicin, and linezolid over eight weeks. Leptomeningeal disease in patients with cancer history is often thought to be metastatic disease but infections, such as listeria, should be considered even if cerebrospinal fluid is bland. Treatment of listeria may need to be prolonged in patients who are immunocompromised.

Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology.

INTRODUCTION: The entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology. METHODS: We imaged post mortem human tissue at 100 µm3 with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean = 270 slices/case). Vessel density was quantified and compared per EC subfield, between EC and PC, and in relation to tau and TAR DNA-binding protein 43 (TDP-43) semiquantitative scores. RESULTS: PC was more vascularized than EC and vessel densities were higher in posterior EC subfields. Tau and TDP-43 strongly correlated with vasculature density and subregions with severe tau at the preclinical stage had significantly greater vessel density than those with low tau burden. DISCUSSION: These data impact cerebrovascular maps, quantification of subfield vasculature, and correlation of vasculature and pathology at early stages. The ordered association of vessel density, and tau or TDP-43 pathology, may be exploited in a predictive context. HIGHLIGHTS: Vessel density correlates with phosphorylated tau (p-tau) burden in entorhinal and perirhinal cortices. Perirhinal area 35 and posterior entorhinal cortex showed greatest p-tau burden but also the highest vessel density in the preclinical phase of Alzheimer's disease. We combined an ex vivo magnetic resonance imaging model and histopathology to demonstrate the 3D reconstruction of intracortical vessels and its spatial relationship to the pathology.

Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology.

We present open-source tools for three-dimensional (3D) analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (1) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (2) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable financial resources. We tested our tools on synthetic and real data from two NIH Alzheimer's Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected differences between post mortem confirmed Alzheimer's disease cases and controls. The tools are available in our widespread neuroimaging suite 'FreeSurfer' (https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools).

Every year, thousands of human brains are donated to science. These brains are used to study normal aging, as well as neurological diseases like Alzheimer's or Parkinson's. Donated brains usually go to 'brain banks', institutions where the brains are dissected to extract tissues relevant to different diseases. During this process, it is routine to take photographs of brain slices for archiving purposes. Often, studies of dead brains rely on qualitative observations, such as 'the hippocampus displays some atrophy', rather than concrete 'numerical' measurements. This is because the gold standard to take three-dimensional measurements of the brain is magnetic resonance imaging (MRI), which is an expensive technique that requires high expertise ­ especially with dead brains. The lack of quantitative data means it is not always straightforward to study certain conditions. To bridge this gap, Gazula et al. have developed an openly available software that can build three-dimensional reconstructions of dead brains based on photographs of brain slices. The software can also use machine learning methods to automatically extract different brain regions from the three-dimensional reconstructions and measure their size. These data can be used to take precise quantitative measurements that can be used to better describe how different conditions lead to changes in the brain, such as atrophy (reduced volume of one or more brain regions). The researchers assessed the accuracy of the method in two ways. First, they digitally sliced MRI-scanned brains and used the software to compute the sizes of different structures based on these synthetic data, comparing the results to the known sizes. Second, they used brains for which both MRI data and dissection photographs existed and compared the measurements taken by the software to the measurements obtained with MRI images. Gazula et al. show that, as long as the photographs satisfy some basic conditions, they can provide good estimates of the sizes of many brain structures. The tools developed by Gazula et al. are publicly available as part of FreeSurfer, a widespread neuroimaging software that can be used by any researcher working at a brain bank. This will allow brain banks to obtain accurate measurements of dead brains, allowing them to cheaply perform quantitative studies of brain structures, which could lead to new findings relating to neurodegenerative diseases.

Gal - T Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.

BACKGROUND: Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout (GalT-KO) pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. In this study, we compare outcomes between autografts and cold preserved xenografts in a rat sciatic model of nerve gap repair. METHODS: Fifty male Lewis rats had a 1 cm sciatic nerve defect repaired using either: autograft and suture (n=10); 1-week or 4-week cold preserved xenograft and suture (n=10 per group); 1-week or 4-week cold preserved xenograft and photochemical tissue bonding using a human amnion wrap (PTB/HAM) (n=10 per group). Rats with xenografts were given tacrolimus until 4 months post-operatively. At 4 and 7 months, rats were euthanized and nerve sections harvested. Monthly sciatic functional index (SFI) scores were calculated. RESULTS: All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the 1-week cold preserved PTB/HAM group. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold preserved groups had significantly lower scores than the 4-week cold preserved suture group. CONCLUSIONS: Our results in the rat sciatic model suggest that GalT-KO nerve xenografts may be viable alternatives to autografts and demonstrate the need for further studies of long-gap repair and comparison with acellular nerve allografts. CLINICAL RELEVANCE: This proof-of-concept study in the rat sciatic model demonstrates that cold preserved GalT-KO porcine xenografts support axonal regeneration, as well as axonal viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.

Differences in social media use by COVID-19 vaccination status.

The near-ubiquitous use of social media in the United States (U.S.) highlights the utility of social media for encouraging vaccination. Vaccination campaigns have used social media to reach audiences, yet research linking the use of specific social media platforms and vaccination uptake is nascent. This descriptive study assesses differences in social media use by COVID-19 vaccination status among adults overall and those who reported baseline vaccine hesitancy. We used data from a nationally representative longitudinal survey of U.S. adults administered between January 2021-August 2022 (n = 2,908). Results indicated a positive association between frequent Instagram and/or Twitter use and vaccination status (p <.05). Among baseline vaccine hesitant adults, results indicated a positive association between frequent TikTok, Instagram, and/or Twitter use and vaccination status (p <.05). Findings have implications for research that examines the content of social media platforms and their environment on vaccine attitudes and uptake.

Association Between the "We Can Do This" Campaign and COVID-19 Booster Uptake, U.S., 2021-2022.

Introduction: Monovalent COVID-19 boosters lower the risk of COVID-19 disease, infection, hospitalization, and death. This study examined associations between exposure to a booster public education campaign (the booster campaign) and the increases in booster uptake and reduced length of time until booster uptake among U.S. adults. Methods: Data included a national survey panel of U.S. adults and booster campaign paid media (i.e., digital impressions and TV gross rating points) from September 2021 to May 2022. Multilevel logistic regression models examined the association between exposure to the booster campaign and the likelihood of booster uptake. A Cox proportional hazard model evaluated the association between the booster campaign and booster uptake timing. Interaction terms between the booster campaign media variables and first-dose COVID-19 vaccine date examined differential effects of the booster campaign based on when individuals received their first dose. Results: Interactions between first-dose vaccination date and the booster campaign were statistically significant for cumulative digital impressions (ß=4.75e-08; 95% CIs=5.93e-09, 8.90e-08) and TV gross rating points (ß = 4.62e-05; 95% CIs=5.09e-06, 8.73e-05), suggesting that booster uptake was strongest among those who received their first-dose COVID-19 vaccine later. Booster campaign cumulative digital impressions and TV gross rating points were associated with accelerated booster uptake among those with later first-dose vaccination dates (digital: ß=9.98e-08; 95% CIs=2.70e-08, 1.73e-07; TV: ß=0.0001; 95% CIs=2.80e-05, 0.0002), relative to those with earlier first-dose vaccination dates. Conclusions: The booster campaign may have increased monovalent booster uptake and reduced how long individuals waited until getting their booster. Public education campaigns show promise in stemming the tide of pandemic fatigue and increasing booster confidence.

Racial and ethnic differences in COVID-19 vaccine readiness among adults in the United States, January 2021-April 2023.

Racial and ethnic minority groups have been disproportionately affected by COVID-19 and have experienced systemic, attitudinal, and access-related barriers to COVID-19 vaccination. We examined differences in COVID-19 vaccine readiness-a composite measure of vaccination intention and behavior-between non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic Asian American/Pacific Islander, and American Indian/Alaska Native U.S. adults. Using data from a cross-sectional survey administered to nationally representative samples of âˆ¼ 5,000 U.S. adults each month from January 2021 to April 2023 (n = 135,989), we conducted weighted ttests comparing the monthly percentage of participants from racial/ethnic groups who were "Vaccine Ready." Initial racial/ethnic disparities in vaccine readiness were attenuated within a 7-month period, after which adults from most minority racial/ethnic groups became equally or more vaccine ready compared to non-Hispanic White adults (p < 0.05). Findings suggest that barriers to vaccine readiness that were more prevalent in non-White racial/ethnic groups may have largely been addressed.

Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology.

We present open-source tools for 3D analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (i) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (ii) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable financial resources. We tested our tools on synthetic and real data from two NIH Alzheimer's Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected differences between post mortem confirmed Alzheimer's disease cases and controls. The tools are available in our widespread neuroimaging suite "FreeSurfer" ( https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools ).

Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients.

The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue. This tumour-specific shift in FLT can be used to distinguish tumours from normal tissue with an accuracy of over 97% across tumour types, and can be visualized at the cellular level using microscopy and in larger specimens through wide-field imaging. Unlike fluorescence intensity, which depends on imaging-system parameters, tissue depth and the amount of dye taken up by tumours, FLT is a photophysical property that is largely independent of these factors. FLT imaging with indocyanine green may improve the accuracy of cancer surgeries.

Bedside Clinician's Guide to Pulmonary Artery Catheters.

BACKGROUND: Pulmonary artery catheters provide important information about cardiac function, mixed venous oxygenation, and right-sided pressures and potentially provide temporary pacing ability. OBJECTIVE: To provide bedside clinicians with guidance for techniques to insert right heart monitors and devices, describe risk factors for difficult insertion and contraindications to placement, and provide updates on new technologies that may be encountered in the intensive care unit. METHODS: An extensive literature review was performed. Experienced clinicians were asked to identify topics not addressed in the literature. RESULTS: Advanced imaging techniques such as transesophageal echocardiography or fluoroscopy can supplement traditional pressure waveform-guided insertion when needed, and several other techniques can be used to facilitate passage into the pulmonary artery. Caution is warranted when attempting insertion in patients with right-sided masses or preexisting conduction abnormalities. New technologies include a pacing catheter that anchors to the right ventricle and a remote monitoring device that is implanted in the pulmonary artery. DISCUSSION: Bedside clinicians should be aware of risk factors such as atrial fibrillation with dilated atria, decreased ventricular function, pulmonary hypertension, and right-sided structural abnormalities that can make pulmonary artery catheter insertion challenging. Clinicians should be familiar with advanced techniques and imaging options to facilitate placement. CONCLUSION: The overall risk of serious complications with right heart catheter placement and manipulation is low and often outweighed by its benefits, specifically pressure monitoring and pacing.

Cry1 expression during postnatal development is critical for the establishment of normal circadian period.

The mammalian circadian system generates an approximate 24-h rhythm through a complex autoregulatory feedback loop. Four genes, Period1 (Per1), Period2 (Per2), Cryptochrome1 (Cry1), and Cryptochrome2 (Cry2), regulate the negative feedback within this loop. Although these proteins have distinct roles within the core circadian mechanism, their individual functions are poorly understood. Here, we used a tetracycline trans-activator system (tTA) to examine the role of transcriptional oscillations in Cry1 and Cry2 in the persistence of circadian activity rhythms. We demonstrate that rhythmic Cry1 expression is an important regulator of circadian period. We then define a critical period from birth to postnatal day 45 (PN45) where the level of Cry1 expression is critical for setting the endogenous free running period in the adult animal. Moreover, we show that, although rhythmic Cry1 expression is important, in animals with disrupted circadian rhythms overexpression of Cry1 is sufficient to restore normal behavioral periodicity. These findings provide new insights into the roles of the Cryptochrome proteins in circadian rhythmicity and further our understanding of the mammalian circadian clock.