bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison between Automated Subjective Refraction and Traditional Subjective Refraction in Keratoconus Patients
Authors: Carracedo Gonzalo , Carpena-Torres Carlos , Pastrana Cristina , Privado-Aroco Ana , Serramito María , Espinosa-Vidal Teresa María , Rodríguez-Lafora María
Published: June 2021

SIGNIFICANCE

The performance of the Eye Refract (Luneau Technology, Chartres, France), a new instrument to perform aberrometry-based automated subjective refraction, has been previously evaluated in healthy subjects. However, its clinical implications in other ocular conditions are still unknown.

PURPOSE

The purpose of this study was to evaluate the agreement between the Eye Refract and the traditional subjective refraction, as the criterion standard, in keratoconus patients with and without intracorneal ring segments (ICRSs).

METHODS

A total of 50 eyes of 50 keratoconus patients were evaluated, dividing the sample into 2 groups: 27 eyes without ICRS (37.78 ± 9.35 years) and 23 eyes with ICRS (39.26 ± 13.62 years). An optometrist conducted the refraction with the Eye Refract, and another different optometrist conducted the traditional subjective refraction on the same day. Spherical equivalent (M), cylindrical vectors (J
0 and J
45), and corrected distance visual acuity were compared between both methods of refraction. In addition, Bland-Altman analysis was performed to assess the agreement between both methods of refraction.

RESULTS

There were no statistically significant differences (P ≥ .05) between the Eye Refract and the traditional subjective refraction for all the variables under study in either group. Without ICRS, the mean difference and 95% limits of agreement (upper, lower) were −0.20 (+1.50, −1.89) D for M, −0.14 (+1.40, −1.68) D for J
0, and +0.05 (+1.23, −1.14) D for J
45. With ICRS, these values worsened to −0.62 (+3.89, −5.12) D for M, +0.06 (+2.46, −2.34) D for J
0, and −0.02 (+2.23, −2.28) D for J
45.

CONCLUSIONS

The Eye Refract seems to offer similar results compared with the traditional subjective refraction in keratoconus patients not implanted with ICRS. However, some patients could show abnormal measurements, especially those with ICRS, who should be treated with caution in clinical practice.
Multifaceted Public Health Response to a COVID-19 Outbreak Among Meat-Processing Workers, Utah, March-June 2020
Authors: Rogers Tia M. , Robinson Susan J. , Reynolds Laura E. , Ladva Chandresh N. , Burgos-Garay Maria , Whiteman Ari , Budge Holly , Soto Natalie , Thompson Mariela , Hunt Estee , Barson Todd , Boyd Andrew T.
Published: June 2021

Objective:

To identify potential strategies to mitigate COVID-19 transmission in a Utah meat-processing facility and surrounding community.

Design/Setting:

During March-June 2020, 502 workers at a Utah meat-processing facility (facility A) tested positive for SARS-CoV-2. Using merged data from the state disease surveillance system and facility A, we analyzed the relationship between SARS-CoV-2 positivity and worker demographics, work section, and geospatial data on worker residence. We analyzed worker survey responses to questions regarding COVID-19 knowledge, beliefs, and behaviors at work and home.

Participants:

(1) Facility A workers (n = 1373) with specimen collection dates and SARS-CoV-2 RT-PCR test results; (2) residential addresses of all persons (workers and nonworkers) with a SARS-CoV-2 diagnostic test (n = 1036), living within the 3 counties included in the health department catchment area; and (3) facility A workers (n = 64) who agreed to participate in the knowledge, attitudes, and practices survey.

Main Outcome Measures:

New cases over time, COVID-19 attack rates, worker characteristics by SARS-CoV-2 test results, geospatially clustered cases, space-time proximity of cases among workers and nonworkers; frequency of quantitative responses, crude prevalence ratios, and counts and frequency of coded responses to open-ended questions from the COVID-19 knowledge, attitudes, and practices survey.

Results:

Statistically significant differences in race (P = .01), linguistic group (P < .001), and work section (P < .001) were found between workers with positive and negative SARS-CoV-2 test results. Geographically, only 6% of cases were within statistically significant spatiotemporal case clusters. Workers reported using handwashing (57%) and social distancing (21%) as mitigation strategies outside work but reported apprehension with taking COVID-19–associated sick leave.

Conclusions:

Mitigating COVID-19 outbreaks among workers in congregate settings requires a multifaceted public health response that is tailored to the workforce.

Implications for Policy and Practice:

Tailored, multifaceted mitigation strategies are crucial for reducing COVID-19–associated health disparities among disproportionately affected populations.
Evaluating and Assessing Radon Testing in Multifamily Housing
Authors: Kitto Michael E. , Murphy Calvin , Dixon Sherry L. , Jacobs David E. , Wilson Jonathan , Malone Jane
Published: June 2021

Context:

To determine if radon mitigation is needed to protect occupants of multifamily housing, reliable testing procedures are needed. Yet, protocols on how many ground-contact housing units must be tested vary from 10% to 25% to 100%.

Objectives:

To estimate the probability of failing to identify a building containing at least one unit with elevated radon level when all ground-contact units are not tested.

Design:

Retrospective analysis of previously collected data from licensed (ie, certified) radon measurement professionals using hypergeometric and Monte Carlo statistical methods to estimate the confidence that there are no units with radon levels of 4 picoCuries/liter of air (pCi/L) or more based on various testing percentages.

Setting:

Testing data were obtained from 29 US states for 7892 ground-contact units in 687 multifamily buildings, primarily 5 to 20 units per building.

Main Outcome Measure:

Probability of failing to identify elevated radon levels in untested units.

Results:

About 15% (n = 1163) of the units had radon levels of more than 4 pCi/L (the EPA action level); 59 units had more than 20 pCi/L (maximum of 96 pCi/L). For building sizes of 5 to 20 ground-contact units, the 2018 federal testing protocols that currently require testing of 10% and 25% of ground-contact units in each building failed to identify 47%-69% and 32%-46% of the units, respectively, depending on building size.

Conclusions:

Measurement of 90% of the ground-contact units in buildings with 5 to 20 ground-contact units results in up to 4% of the units with elevated radon levels being missed. To achieve 95% confidence that no units in the building have radon levels of 4 pCi/L or more in buildings up to 20 units, 100% sampling is required. For the vast majority of multifamily buildings, all ground-contact units in multifamily buildings should be tested for radon.
Willingness to Get a COVID-19 Vaccine and Reasons for Hesitancy Among Medicare Beneficiaries: Results From a National Survey
Authors: Luo Huabin , Qu Haiyan , Basu Rashmita , Rafferty Ann P. , Patil Shivajirao P. , Cummings Doyle M.
Published: June 2021

Objectives:

To assess (1) the willingness to get a COVID-19 vaccine among Medicare beneficiaries, (2) the associated factors, and (3) the reasons for vaccine hesitancy.

Methods:

Data were taken from the Medicare Current Beneficiary Survey (MCBS) 2020 Fall COVID-19 Supplement, conducted October-November 2020. Willingness to get a COVID-19 vaccine was measured by respondents' answer to whether they would get a COVID-19 vaccine when available. We classified responses of “definitely” and “probably” as “willing to get,” and responses “probably not,” “definitely not,” and “not sure” as “vaccine hesitancy.” Reasons for vaccine hesitancy were assessed by a series of yes/no questions focusing on 10 potential reasons. The analytical sample included 6715 adults 65 years and older. We conducted a logistic regression model to assess demographic factors and other factors associated with the willingness to get a COVID-19 vaccine. All analyses were conducted in Stata 14 and accounted for the complex survey design of MCBS.

Results:

Overall, 61.0% (95% confidence interval [CI], 59.1-63.0) of Medicare beneficiaries would be willing to get a vaccine when available. Among those who were hesitant, more than 40% reported that mistrust of the government and side effects as the main reasons. Logistic regression model results showed that non-Hispanic Blacks (adjusted odds ratio [AOR] = 0.33; 95% CI, 0.24-0.44) and Hispanics (AOR = 0.60; 95% CI, 0.47-0.77) were less willing to get a vaccine than non-Hispanic Whites; beneficiaries with an income of less than $25 000 (AOR = 0.71; 95% CI, 0.62-0.81) were less willing to get the vaccine than those with an income of $25 000 or more; those who did not think that the COVID-19 virus was more contagious (AOR = 0.53; 95% CI, 0.41-0.69) or more deadly (AOR = 0.51; 95% CI, 0.41-0.65) were also less willing to get the vaccine than those who thought that the virus was more contagious or more deadly than the influenza virus.

Conclusions:

The 2020 MCBS survey data showed that close to 40% of Medicare beneficiaries were hesitant about getting a COVID-19 vaccine, and the hesitancy was greater in racial/ethnic minorities. Medicare beneficiaries were concerned about the safety of the vaccine, and some appeared to be misinformed. Evidence-based educational and policy-level interventions need to be implemented to further promote COVID-19 vaccination.
Interrelationships Between Oxidative Stress, Cytokines, and Psychotic Symptoms and Executive Functions in Patients With Chronic Schizophrenia
Authors: Wu Zhi Wei , Yu Hong Hua , Wang Xuan , Guan Heng Yong , Xiu Mei Hong , Zhang Xiang Yang
Published: June 2021

Objective

Accumulating evidence has demonstrated that the pathophysiology of schizophrenia is involved in various abnormalities in oxidative stress markers and cytokines closely related to synaptic plasticity. However, the interactive effects among key cytokines, oxidative stress, and executive dysfunction and symptoms of schizophrenia have not been investigated yet.

Methods

A total of 189 patients with chronic schizophrenia and 60 controls were recruited in the current study. Tumor necrosis factor α (TNF-α), interleukin (IL)-8, IL-6, and IL-2 levels; catalase, glutathione peroxidase, and superoxide dismutase (SOD) activities; and malondialdehyde (MDA) levels were determined in patients and controls. Executive function was evaluated by the Wisconsin card sorting tests, the verbal fluency tests, and the Stroop word-color test. Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale.

Results

Relative to the controls, the patients had lower activities of SOD and glutathione peroxidase and levels of TNF-α, but higher levels of MDA, IL-8, IL-6, and IL-2 (all p values < .05). A significant negative relationship between SOD activity and IL-8 levels was found only in patients (β = −0.44, p = .008). Furthermore, we found that an interactive effect of low TNF-α level and high MDA level was associated with negative symptoms (β = −0.02, p = .01). Moreover, the interactive effects of IL-8 and MDA or IL-8 and SOD were correlated with executive function only in patients (β = 0.23, p = .02; β = 0.09, p = .03).

Conclusions

Our findings suggest that the interrelationships between oxidative stress markers and cytokines occur in schizophrenia patients, which may be the basis of their pathological mechanisms underlying clinical symptoms and cognitive dysfunction.
Prognostic Role of Paravalvular Spread on Computed Tomography in Suspected Prosthetic Valve Endocarditis
Authors: Sandhu Gurmandeep S. , Velangi Pratik S. , Kharoud Harmeet , Nijjar Prabhjot S.
Published: June 2021

We aimed to assess the prognostic value of computed tomography assessment of paravalvular spread in suspected prosthetic valve endocarditis.
Technique for Reduced Trocar Decapsulation of a Giant Nonparasitic Splenic Cyst
Authors: Dapri Giovanni , Arts Sophie
Published: June 2021

Background:

Minimally invasive surgery is adopted for patients presenting benign splenic cysts. Reduced port laparoscopy is an evolution of conventional laparoscopy, which can be applied for splenic cysts as well. In this video, a 3-trocar laparoscopic decapsulation of a giant nonparasitic splenic cyst is reported.

Case Report:

A 16-year-old man, without history of trauma or abdominal surgery, suddenly presented abdominal pain in the left hypochondrium, associated to fever and hyperleukocytosis. A thoracoabdominal computed tomography scan showed a giant cyst of the upper pole of the spleen; serum tumor markers carcinoembryonic antigen and carbohydrate antigen 19-9 were negatives. Any preoperative vaccine was prescribed.

Results:

Operative time was 130 minutes, and operative bleeding 10 mL. No additional trocar or conversion to laparotomy was necessary. Postoperatively, 4 g of paracetamol were used for 2 days, when the patient was discharged. Pathology confirmed the nonparasitic epidermoid splenic cyst. At 18 months, the patient is fine, without symptoms and without disease’s recurrence.

Conclusions:

Decapsulation of a giant nonparasitic splenic cyst is feasible to be performed by 3-trocar laparoscopy. This technique allows to improve the patient’s comfort and the cosmetic results, to reduce the postoperative pain and to finally avoid a preoperative vaccine.
Aberrant cerebral intrinsic activity and cerebro-cerebellar functional connectivity in right temporal lobe epilepsy: a resting-state functional MRI study
Authors: Zhou Xia , Liu Jinping , Zhang Zhao , Qin Lu , Pang Xiaomin , Yu Lu , Zheng Jinou
Published: June 2021

Objective

Numerous neuroimaging studies have demonstrated that functional brain aberrations are associated with cognitive impairments in temporal lobe epilepsy (TLE). Here, we aimed to investigate the neural substrates of attention deficits by combining assessment of regional intrinsic brain activities with large-scale functional connectivity in patients with right TLE (rTLE).

Methods

Thirty-five patients with rTLE and 33 matched healthy controls were recruited. All participants completed the Attention Network Test (ANT) and resting-sate functional MRI (rs-fMRI) scans. The z-standardized fractional amplitude of the low-frequency fluctuation (zfALFF) approach was applied to evaluate the brain’s intrinsic activity. The cerebral regions with significant zfALFF values were selected as seeds for subsequent functional connectivity analyses. A correlation analysis was performed between functional activity and clinical variables.

Results

Compared with the healthy control group, the patients showed decreased zfALFF in the right inferior temporal gyrus and bilateral superior parietal gyrus, and the right inferior temporal gyrus exhibited increased functional connectivity with the bilateral cerebellum-6/vermis-6 and decreased functional connectivity with right superior frontal gyrus. The ANT indicated that the rTLE group exhibited attention deficits. Furthermore, a positive correlation was found between the zfALFF value of the left superior parietal gyrus and alerting performance, while a negative correlation between the zfALFF value of the right superior parietal gyrus and disease duration.

Conclusion

This study demonstrated aberrant intrinsic cerebral activity and functional connectivity in the whole brain network, which may act as responsible and compensatory factors in attention deficits, especially further profoundly illuminated the compensatory role of cerebellum in patients with rTLE.
The Female Predominant Persistent Immune Dysregulation of the Post COVID Syndrome: A Cohort Study
Authors: Ganesh Ravindra , Grach Stephanie L , Bierle Dennis M. , Salonen Bradley R , Collins Nerissa M , Joshi Avni Y , Boeder Neal , Anstine Christopher V , Mueller Michael R , Wight Elizabeth C , Croghan Ivana T , Badley Andrew D , Carter Rickey E , Hurt Ryan T
Published: June 2021

Objective

To describe the clinical data from the first 107 patients seen in the Mayo Clinic Post COVID-19 Care Clinic (PCOCC).

Patients and Methods

After IRB approval, we reviewed the charts of 107 patients seen between January 19, 2021 and April 29, 2021 in the Mayo Clinic Post COVID Care Clinic (PCOCC) in order to describe the first 107 patients treated through the Mayo Clinic PCOCC. Data was abstracted from the electronic medical record into a standardized database to facilitate analysis. Phenotypes of patients seen in the PCOCC clinic were identified by expert review of predominant symptom clusters.

Results

The majority of patients seen in our clinic were female (75%, 80/107), and the median age at presentation was 47 years (interquartile range [IQR] 37, 55). All had Post Acute Sequelae of SARS-CoV-2 infection (PASC) with six clinical phenotypes being identified – fatigue predominant (n=68), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women (84%, p=0.006) and the dyspnea-predominant phenotype was more common in men (52%, p=0.002). IL-6 was elevated in 61% of patients (69% of women, p=0.0046) which was statistically discordant with elevation in CRP and ESR which was identified in 17% and 20% of cases respectively (p<0.001). Four PASC phenotypes (fatigue-predominant, myalgia-predominant, orthostasis predominant, and headache-predominant) were associated with central sensitization (CS), and higher IL-6 levels than those phenotypes not associated with CS (p=0.013). Patients with CS phenotypes after COVID-19 infection (post COVID syndrome) were predominantly female (80%, p=0.0085).

Conclusion

In our post COVID clinic, we observed several distinct clinical phenotypes. Fatigue-predominance was the most common presentation and was associated with elevated IL-6 levels and female gender. Dyspnea-predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were significantly elevated in patients with PASC and discordant with ESR and CRP, particularly in those with central sensitization phenotypes.
Clinical validation of colorimetric RT-LAMP, a fast, highly sensitive and specific COVID-19 molecular diagnostic tool that is robust to detect SARS-CoV-2 variants of concern
Authors: Alves Pedro A. , Oliveira de Ellen G. , Franco-Luiz Ana Paula M. , Almeida Letícia T. , Gonçalves Amanda B. , Borges Iara A. , Rocha Flávia de S. , Rocha Raissa P. , Bezerra Matheus F. , Miranda Pâmella , Capanema Flávio D. , Martins Henrique R. , Weber Gerald , Teixeira Santuza M. R. , Wallau Gabriel Luz , do Monte-Neto Rubens L.
Published: June 2021

The COVID-19 pandemics unfolded due to the widespread SARS-CoV-2 transmission reinforced the urgent need for affordable molecular diagnostic alternative methods for massive testing screening. We present the clinical validation of a pH-dependent colorimetric RT-LAMP (reverse transcription loop-mediated isothermal amplification) for SARS-CoV-2 detection. The method revealed a limit of detection of 19.3 ± 2.7 viral genomic copies/μL when using RNA extracted samples obtained from nasopharyngeal swabs collected in guanidine-containing viral transport medium. Typical RT-LAMP reactions were performed at 65 ºC for 30 min. When compared to RT-qPCR, up to Ct value 32, RT-LAMP presented 97% (87.4-99.4% 95% CI) sensitivity and 100% (86.2-100%) specificity for SARS-CoV-2 RNA detection targeting N gene. No cross-reactivity was detected when testing other non-SARS-CoV virus, confirming high specificity. The test is compatible with primary RNA extraction free samples. We also demonstrated that colorimetric RT-LAMP can detect SARS-CoV-2 variants of concern (VOC) and variants of interest (VOI), such as variants occurring in Brazil named P.1, P.2, B.1.1.374 and B.1.1.371. The method meets point-of-care requirements and can be deployed in the field for high-throughput COVID-19 testing campaigns, especially in countries where COVID-19 testing efforts are far from ideal to tackle the pandemics. Although RT-qPCR is considered the gold standard for SARS-CoV-2 RNA detection, it requires expensive equipments, infrastructure and highly trained personnel. In contrast, RT-LAMP emerges as an affordable, inexpensive and simple alternative for SARS-CoV-2 molecular detection that can be applied to massive COVID-19 testing campaigns and save lives.
The Impact of COVID-19 Lockdowns on Mental Health Patient Populations: Evidence from Medical Claims Data
Authors: Ferwana Ibtihal , Varshney Lav R.
Published: June 2021

Background

Social distancing policies were enacted during March 2020 to limit the spread of COVID-19. Lockdowns and movement restrictions increased the potential of negative impact on population mental health, in which depression and anxiety symptoms were frequently reported by different population groups during COVID-19 lockdown. However, the causal relationship of mitigation policies on national-wide mental health resource usage is lacking.

Objective

This study investigates the effect of COVID-19 mitigation measures on mental health across the United States, on county and state levels. It examines the effect on mental health facility usage and the prevalence of mental illnesses on the total population, different age and gender groups, and patients of selected mental health diagnoses.

Methods

We used large-scale medical claims data for mental health patients dated from September 1, 2019 to December 31, 2020, with publicly available state- and county-specific COVID-19 cases from first case in January to December 31, 2020, and used publicly available lockdown dates for states and counties. We designed a difference-in-differences (DID) model, which infers the causal effect of a policy intervention by comparing pre-policy and post-policy periods in different regions. We mainly focused on two types of social distancing policies, stay-at-home and school closure orders.

Results

Based on common pre-treatment trend assumption of regions, we find that lockdown has significantly and causally increased the usage of mental health in regions with lockdowns in comparison to regions without. In regions with lockdown orders the resource usage increased by 18% compared to 1% decline in regions without a lockdown. Also, female populations have been exposed to a larger lockdown effect on their mental health with 24% increase in regions with lockdowns compared to 3% increase in regions without. While male mental health patients decreased by 5% in regions without lockdowns. Patients diagnosed withpanic disordersandreaction to severe stressboth were significantly exposed to a significant large effect of lockdowns. Also,life management difficultypatients doubled in regions with stay-at-home orders but increased less with school closures. Contrarily,attention-deficit hyperactivitypatients declined in regions without stay-at-home orders. Patients older than 80 used mental health resources less in regions with lockdowns. Adults between (21 – 40) years old were exposed to the greatest lockdown effect with increase between 20% to 30% in regions with lockdown.

Conclusion

Although non-pharmaceutical intervention policies were effective in containing the spread of COVID-19, our results show that mitigation policies led to population-wide increase in mental health patients. Our results suggest the need for greater mental health treatment resources in the face of lockdown policies.
Incidence of chikungunya virus infections among Kenyan children with neurological disease: a prospective cohort study
Authors: Nyamwaya Doris K. , Otiende Mark , Mwango Lilian , Kariuki Symon M. , Otieno Berrick , Omuoyo Donwilliams O. , Githinji George , Kitsao Barnes S. , Karanja Henry K. , Gitonga John N. , de Laurent Zaydah R. , Davies Alun , Mwarumba Salim , Agoti Charles N. , Thumbi Samuel M. , Hamaluba Mainga M. , Newton Charles R. , Bejon Philip , Warimwe George M.
Published: June 2021

Background

Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown.

Methods

We estimated the incidence of CHIKV infection among children hospitalised with neurological disease in coastal Kenya. We used reverse-transcriptase polymerase chain reaction (RT-PCR) to systematically test for CHIKV in cerebrospinal fluid (CSF) samples from children aged <16 years hospitalised with symptoms of neurological disease at Kilifi County Hospital between January 2014 and December 2018. Clinical records were linked to the Kilifi Health and Demographic Surveillance System and population incidence rates of CHIKV infection estimated.

Findings

There were 18,341 paediatric admissions during the 5-year study period, of which 4,332 (24%) had CSF collected. The most common clinical reasons for CSF collection were impaired consciousness, seizures and coma (47%, 22% and 21% of all collections, respectively). After acute investigations done for immediate clinical care, CSF samples were available for 3,980 admissions, of which 367 (9.2%) were CHIKV RT-PCR positive. The annual incidence of CHIKV-associated neurological disease varied between 13 to 58 episodes per 100,000 person-years among all children <16 years old. Among children aged <5 years, the incidence of CHIKV-associated neurological disease was 77 per 100,000 person-years, compared with 20 per 100,000 for cerebral malaria and 7 per 100,000 for bacterial meningitis during the study period.

Interpretation

Although not previously recognized, CHIKV-associated neurological disease is common in coastal Kenya and a significant public health burden.
Chronic distress in male mice impairs motivation compromising both effort and reward processing with altered anterior insular cortex and basolateral amygdala neural activation
Authors: Cabeza Lidia , Ramadan Bahrie , Cramoisy Stephanie , Houdayer Christophe , Haffen Emmanuel , Risold Pierre-Yves , Fellmann Dominique , Peterschmitt Yvan
Published: June 2021

In humans and mammals, effort-based decision-making for monetary or food rewards paradigms contribute to the study of adaptive goal-directed behaviours acquired through reinforcement learning. Chronic distress modelled by repeated exposure to glucocorticoids in rodents induces suboptimal decision-making under uncertainty by impinging on instrumental acquisition and prompting negative valence behaviours. In order to further disentangle the motivational tenets of adaptive decision-making, this study addressed the consequences of enduring distress on relevant effort and reward processing dimensions. Experimentally, appetitive and consummatory components of motivation were evaluated in adult C57BL/6JRj male mice experiencing chronic distress induced by oral corticosterone (CORT), using multiple complementary discrete behavioural tests. Behavioural data (from Novelty Supressed Feeding, operant effort-based choice, Free Feeding and Sucrose Preference tasks) collectively show that behavioural initiation, effort allocation and hedonic appreciation and valuation are altered in mice exposed to several weeks of oral CORT treatment. Additionally, data analysis from FosB immunohistochemical processing of postmortem brain samples highlight a CORT-dependent dampening of neural activation in the anterior insular cortex (aIC) and basolateral amygdala (BLA), key telencephalic brain regions involved in cue appetitive and consummatory motivational processing. Combined, these results suggest that chronic distress-induced irregular aIC and BLA neural activations with reduced effort production and attenuated reward value processing during reinforcement-based instrumental learning could result in maladaptive decision-making under uncertainty. The current study further illustrates how the stoichiometry of effort and reward processing contributes to dynamically adjust the motivational threshold triggering goal-directed behaviours in versatile environments.
Performance evaluation of virus concentration methods for implementing SARS-CoV-2 wastewater based epidemiology emphasizing quick data turnaround
Authors: Juel Md Ariful Islam , Stark Nicholas , Nicolosi Bridgette , Lontai Jordan , Lambirth Kevin , Schlueter Jessica , Gibas Cynthia , Munir Mariya
Published: June 2021

Wastewater based epidemiology (WBE) has drawn significant attention as an early warning tool to detect and predict the trajectory of COVID-19 cases in a community, in conjunction with public health data. This means of monitoring for outbreaks has been used at municipal wastewater treatment centers to analyze COVID-19 trends in entire communities, as well as by universities and other community living environments to monitor COVID-19 spread in buildings. Sample concentration is crucial, especially when viral abundance in raw wastewater is below the threshold of detection by RT-qPCR analysis. We evaluated the performance of a rapid ultrafiltration-based virus concentration method using InnovaPrep Concentrating Pipette (CP) Select and compared this to the established electronegative membrane filtration (EMF) method. We evaluated sensitivity of SARS-CoV-2 quantification, surrogate virus recovery rate, and sample processing time. Results suggest that the CP Select concentrator is more efficient at concentrating SARS-CoV-2 from wastewater compared to the EMF method. About 25% of samples that tested negative when concentrated with the EMF method produced a positive signal with the CP Select protocol. Increased recovery of the surrogate virus control using the CP Select confirms this observation. We optimized the CP Select protocol by adding AVL lysis buffer and sonication, to increase the recovery of virus. Sonication increased Bovine Coronavirus (BCoV) recovery by 19%, which seems to compensate for viral loss during centrifugation. Filtration time decreases by approximately 30% when using the CP Select protocol, making this an optimal choice for building surveillance applications where quick turnaround time is necessary.
COVID-19 vaccine acceptance and its socio-demographic and emotional determinants: a multi-country cross-sectional study
Authors: de Figueiredo A. , Simas C. , Larson H. J.
Published: June 2021

Background

Multiple COVID-19 vaccines have now been licensed for human use, with other candidate vaccines in different stages of development. Effective and safe vaccines against COVID-19 are essential to achieve global control of the pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), but multiple factors, including vaccine supply and vaccine confidence, will be key for high rates of global uptake. Confidence in COVID-19 vaccines, socio-demographic status, and recent emotional status are likely to be key drivers of COVID-19 vaccine acceptance. In this study, we explore these determinants of COVID-19 vaccination intent across17 countries worldwide.

Methods

In this large-scale multi-country study, we explore intent to accept a COVID-19 vaccine and the socio-demographic and emotional determinants of uptake for 17 countries and over 19,000 individuals surveyed in June and July 2020 via nationally representative samples. We used Bayesian ordinal logistic regressions to probe the relationship between intent to accept a COVID-19 vaccine and individuals’ socio-demographic status, their confidence in COVID-19 vaccines, and their recent emotional status. Gibbs sampling was used for Bayesian model inference, with 95% Bayesian highest posterior density intervals used to capture uncertainty.

Findings

Intent to accept a COVID-19 vaccine is highest in India, where 77.8% (95% HPD, 75.5 to 80.0%) of respondents strongly agreeing that they would take a new COVID-19 vaccine if it were available. The Democratic Republic of Congo (15.5%, 12.2 to 18.6%) and France (26.4%, 23.7 to 29.2%) have the lowest share of respondents who strongly agree that they would accept a COVID-19. Confidence in the safety, importance, and effectiveness of COVID-19 vaccines are the most widely informative determinants of vaccination intent. Socio-demographic and emotional determinants played a lesser role, with being male and having higher education was associated with increased uptake intent in five countries and being fearful of catching COVID-19 also a strong determinant of uptake intent.

Interpretation

Barriers to COVID-19 vaccine acceptance will be highly country and context dependent. These findings highlight the importance of regular monitoring of COVID-19 vaccine confidence to identify groups less likely to vaccinate and to monitor the impact of vaccination policies on uptake behaviour.
IL10RB as a key regulator of COVID-19 host susceptibility and severity
Authors: Voloudakis Georgios , Hoffman Gabriel , Venkatesh Sanan , Lee Kyung Min , Dobrindt Kristina , Vicari James M. , Zhang Wen , Beckmann Noam D. , Jiang Shan , Hoagland Daisy , Bian Jiantao , Gao Lina , Corvelo André , Cho Kelly , Lee Jennifer S. , Iyengar Sudha K. , Luoh Shiuh-Wen , Akbarian Schahram , Striker Robert , Assimes Themistocles L. , Schadt Eric E. , Merad Miriam , tenOever Benjamin R. , Charney Alexander W. ,   Mount Sinai COVID-19 Biobank,   VA Million Veteran Program COVID-19 Science Initiative, Brennand Kristen J. , Lynch Julie A. , Fullard John F. , Roussos Panos
Published: June 2021

Background

Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes and readily available compounds that reduce COVID-19 host susceptibility is a critical next step.

Methods

We integrate COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX) and perturbargen signatures to identify candidate genes and compounds that reverse the predicted gene expression dysregulation associated with COVID-19 susceptibility. The top candidate gene is validated by testing both its GReX and observed blood transcriptome association with COVID-19 severity, as well as byin vitroperturbation to quantify effects on viral load and molecular pathway dysregulation. We validate thein silicodrug repositioning analysis by examining whether the top candidate compounds decrease COVID-19 incidence based on epidemiological evidence.

Results

We identifyIL10RBas the top key regulator of COVID-19 host susceptibility. Predicted GReX up-regulation ofIL10RBand higherIL10RBexpression in COVID-19 patient blood is associated with worse COVID-19 outcomes.In vitroIL10RB overexpression is associated with increased viral load and activation of immune-related molecular pathways. Azathioprine and retinol are prioritized as candidate compounds to reduce the likelihood of testing positive for COVID-19.

Conclusions

We establish an integrative data-driven approach for gene target prioritization. We identify and validateIL10RBas a suitable molecular target for modulation of COVID-19 host susceptibility. Finally, we provide evidence for a few readily available medications that would warrant further investigation as drug repositioning candidates.
A comparison of four commercially available RNA extraction kits for wastewater surveillance of SARS-CoV-2 in a college population
Authors: O’Brien Megan , Rundell Zachary C. , Nemec Michelle D. , Langan Laura M. , Back Jeffrey A. , Lugo Joaquin N.
Published: June 2021

Localized wastewater surveillance has allowed for public health officials to gain a broader understanding of SARS-CoV-2 viral prevalence in the community allowing public health officials time to prepare for impending outbreaks. Given variable levels of virus in the population through public health interventions, proper concentration and extraction of viral RNA is a key step in ensuring accurate detections. With many commercial RNA extraction kits and methodologies available, the performance of 4 different kits were evaluated for SARS-CoV-2 RNA detection in wastewater, specifically focusing on their applicability to lower population densities such as those at university campus dorms. Raw wastewater samples were collected at 4 sites on a college campus over a 24 hour period as a composite sample. Included in these sites was an isolation site that housed students that tested positive for Covid-19 via nasopharyngeal swabs. These samples were analyzed using the following kits: Qiagen All Prep PowerViral DNA/RNA kit, New England BioLabs Monarch RNA MiniPrep Kit, and Zymo Quick RNA-Viral Kit, and the Zymo Quick-RNA Fecal/Soil Microbe MicroPrep Kit. All four sites were processed according to the manufacturer’s guidelines. Extractions were then quantified with RT-qPCR one-step reactions using an N2 primer and a linearized plasmid standard. While the Zymo Quick-RNA Fecal/Soil Microbe MicroPrep Kit (also known as the Zymo Environ Water RNA Kit) only recovered approximately 73% (+/- 38%) SARS-CoV-2 RNA compared to the Zymo Quick-RNA Viral kit, it was the most time efficient kit to yield comparable results. This extraction kit had a cumulative processing time of approximately five hours compared, while the other three kits had processing times between approximately 9 and 9.5 hours. Based on the current research, the most effective kits for smaller population densities are pellet based and include a homogenization, inhibitor removal, and RNA preservation step.

Highlights

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Samples from smaller population densities make concentrating RNA vital for detection

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Pelleting may provide for more timely concentration and extraction of SARS-CoV-2 RNA

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RNA shields and PCR inhibitor removal may increase detection of RNA during RT-qPCR

Abstract Figure
The COVID-19 pandemic storm in India subsides, but the calm is still far away
Authors: Nesteruk Igor
Published: June 2021

In May 2021, the number of new COVID-19 patients in India began to decline, as predicted by the generalized SIR-model (susceptible-infected-removed). The calculations of the final size of this pandemic wave and its duration probably were too pessimistic. New SIR simulations with the use of fresher datasets are necessary in order to update the predictions and to calculate the difference between the registered (laboratory-confirmed) and real number of cases.
Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19: an observational cohort
Authors:   ISARIC Clinical Characterisation Group, Hall Matthew
Published: June 2021

Background

There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an ongoing infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high density unit (HDU), while novel treatment modalities may reduce the time course of illness. On the other hand, limited resources at times of high demand may lead to rationing of resources, with less beneficial consequences. Despite little evidence on how the values of such variables change over the course of a crisis (such as the current COVID-19 pandemic), they may nevertheless be used as proxies for disease severity, outcome measures for clinical trials, and to inform planning and logistics. We hypothesise that variation of this kind has been present over the first year of the pandemic.

Methods and Findings

We investigate such time trends in an extremely large international cohort of 142,540 patients with symptom onset of, or hospital admission for, COVID-19 during 2020. The variables investigated are time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, case fatality ratio (CFR) and total length of hospital stay. Time from hospital symptom onset to hospital admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December. ICU/HDU admission was more frequent from June to August, while there were only modest time trends in time from hospital admission to ICU/HDU. The CFR was lowest from June to August, a trend mostly driven by patients with no ICU/HDU admission. Raw numbers for overall hospital stay showed little overall variation over the time period, but further examination reveals a clear decline in time to discharge for ICU/HDU survivors. The main limitations are that these are predominantly severe COVID-19 cases, and that there are temporal, spatial and demographic biases present in an observational study of this kind.

Conclusions

Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly-evolving situation.
BrainXcan identifies brain features associated with behavioral and psychiatric traits using large scale genetic and imaging data
Authors: Liang Yanyu , Melia Owen , Caroll Timothy J. , Brettin Thomas , Brown Andrew , Im Hae Kyung
Published: June 2021

Advances in brain MRI have enabled many discoveries in neuroscience. Comparison of brain MRI features between cases and controls have highlighted potential causes of psychiatric and behavioral disorders (complex traits). However, due to the cost of collecting MRI data and the difficulty in recruiting particular patient groups, most studies have small sample sizes, limiting their reliability. Furthermore, reverse causality complicates interpretation because many observed brain differences are the result rather than the cause of the disease. Here we propose a method (BrainXcan) that leverages the power of large-scale genome-wide association studies (GWAS) and reference brain MRI data to discover new mechanisms of disease etiology and validate existing ones. BrainXcan tests the association with genetic predictors of brain MRI-derived features and complex traits to pinpoint relevant region-specific and cross-brain features. As this approach requires only genetic data, BrainXcan allows us to test a host of hypotheses on mental illness, across many disorders and MRI modalities, using existing public data resources. For example, our method shows that reduced axonal density across the brain is associated with the risk of schizophrenia, consistent with the disconnectivity hypothesis. We also find structural features in the hippocampus, amygdala, and anterior cingulate cortex, among others associated with schizophrenia risk highlighting the potential of our approach, which uses orthogonal lines of evidence to inform the biology of complex traits.
SHORTENING TIME FOR ALCOHOL ACCESS DRIVES UP FRONT-LOADING BEHAVIOR, BRINGING CONSUMPTION IN MALE RATS TO THE LEVEL OF FEMALES
Authors: Flores-Bonilla A. , De Oliveira B. , Silva-Gotay A. , Lucier K. , Richardson H.N.
Published: June 2021

Alcohol can have more detrimental effects on mental health in women, even when intake is comparable or higher in men. This may relate to a differential pattern of drinking, e.g., how rapidly alcohol is consumed. We used operant procedures to gain insight into sex differences in the drinking dynamics of rats. Adult male and female Wistar rats underwent operant training to promote voluntary drinking of 10% (w/v) alcohol (8 rats/sex). We tested how drinking patterns changed after manipulating the effort required for alcohol (fixed ratio, FR), as well as the length of time in which animals had access to alcohol (self-administration session length). Rats were tested twice within the 12 hours of the dark cycle, at 2 hours (early sessions) and 10 hours into the dark cycle (late sessions). As expected, adult females consumed significantly more alcohol than males in the 30-minute sessions with the FR1 paradigm. Alcohol consumption within females was higher in the late sessions compared to early sessions, whereas this difference was not found within males. “Front-loading” of alcohol (heavier drinking in the first five minutes of the session) was the primary factor underlying higher consumption in females, and this sex difference was accentuated in the late sessions. Increasing the effort required from FR1 to FR3 reduced alcohol drinking in both sexes. Front-loading behavior remained in females in both early and late sessions, whereas males exhibited minimal front-loading behavior only in the early sessions. Compressing drinking access to 15-minutes drove up front-loading behavior, producing total alcohol intake levels that were comparable in both sexes. This strategy could be useful for exploring sex differences in the effect of voluntary alcohol drinking on the brain. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior.

Highlights

Voluntary alcohol drinking is higher in adult female rats compared to adult male rats. This sex difference is most pronounced in the later phase of the dark cycle, and when the operant effort is minimal (when 1 lever press gives 1 reward: fixed ratio 1, FR1).

Higher alcohol intake in females is primarily due to “front-loading,” or the rapid consumption of alcohol within the first 5 minutes of access.

Increasing the effort required to obtain alcohol from FR1 to FR3 dampens “front-loading” drinking behavior, resulting in similar levels of total intake in males and females.

Compressing the time of access to 15 minutes drives up “front-loading” to such a degree that animals end up consuming more alcohol in total than they do in 30-minute sessions. In males, this increase in drinking is large enough that it eliminates the sex difference in total alcohol intake.

Visual Abstract
CeLINC, a fluorescence-based protein-protein interaction assay in C. elegans
Authors: Kroll Jason R , Remmelzwaal Sanne , Boxem Mike
Published: June 2021

Interactions among proteins are fundamental for life and determining whether two particular proteins physically interact can be essential for fully understanding a protein’s function. We present C. elegans light-induced co-clustering (CeLINC), an optical binary protein-protein interaction assay to determine whether two proteins interact in vivo. Based on CRY2/CIB1 light-dependent oligomerization, CeLINC can rapidly and unambiguously identify protein-protein interactions between pairs of fluorescently tagged proteins. A fluorescently tagged bait protein is captured using a nanobody directed against the fluorescent protein (GFP or mCherry) and brought into artificial clusters within the cell. Co-localization of a fluorescently tagged prey protein in the cluster indicates a protein interaction. We tested the system with an array of positive and negative reference protein pairs. Assay performance was extremely robust with no false positives detected in the negative reference pairs. We then used the system to test for interactions among apical and basolateral polarity regulators. We confirmed interactions seen between PAR-6, PKC-3, and PAR-3, but observed no physical interactions among the basolateral Scribble module proteins LET-413, DLG-1, and LGL-1. We have generated a plasmid toolkit that allows use of custom promoters or CRY2 variants to promote flexibility of the system. The CeLINC assay is a powerful and rapid technique that can be widely applied in C. elegans due to the universal plasmids that can be used with existing fluorescently tagged strains without need for additional cloning or genetic modification of the genome.

We have developed a protein-protein interaction assay for C. elegans to investigate whether pairs of proteins interact in vivo. C. elegans light-induced co-clustering (CeLINC) is based on trapping a fluorescently-tagged bait protein into artificial clusters, and observing whether candidate interacting prey proteins co-cluster with the bait protein. CeLINC can be widely applied as a single set of universal plasmids can be used with existing strains expressing fluorescently-tagged proteins.