bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the Peri-oral Mimic Muscles on Cadaver Slices and 3 and 7 Tesla MRI Scans
Authors: Schutte Hilde , Muradin Marvick S.M. , Seubring Karlien , Bleys Ronald L.A.W. , Pameijer Frank A. , Rosenberg Antoine J.W.P.
Published: February 2022

Background:

Decreased smile dynamics is reported as an unwanted side effect after Le Fort I osteotomies. It is assumed that this negative sequela might be caused by postoperative changes in the anatomy of peri-oral mimic muscles. Due to a lack of specific anatomical knowledge, the exact mechanism is not yet clarified. This makes prevention of the undesired changes in smile dynamics difficult. The first aim of this study is to increase basic anatomical and radiological MRI knowledge of the peri-oral mimic muscles. The second aim is to investigate if 7 Tesla MRI scans are better suited to identify these muscles than 3 Tesla MRI scans.

Methods:

Eleven peri-oral mimic muscles were chosen as subjects of the present study. Three and 7 Tesla MRI scans of a cadaver head were made. The same head was cut in axial slices using a cryomacrotome. Every second slice was digitally photographed. A three-dimensional model was created utilizing EMAC software, which served as gold standard for the identification and comparison of the chosen peri-oral mimic muscles on both MRI scans.

Results:

All predetermined peri-oral mimic muscles could be identified in the cadaver head, and a detailed radiological atlas was created. The ease of identification and separation of the peri-oral mimic muscles was significantly higher on the 7 Tesla MRI than on the 3 Tesla MRI scan (P < 0.001).

Conclusion:

A 7 Tesla MRI scanner offers great improvement in the identification of peri-oral mimic muscles compared with a 3 Tesla scanner.
BRIDGE ARCH–SHAPED SUBRETINAL FLUID IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Venkatesh Ramesh , Mangla Rubble , Mishra Pranjal , Nahata Harshita , Yadav Naresh K. , Chhablani Jay
Published: February 2022

Purpose:

To study factors leading to bridge arch–shaped subretinal fluid (SRF) on optical coherence tomography in wet age-related macular degeneration and evaluate its anatomical and functional outcomes.

Methods:

In this single-center, retrospective study, patients with bridge arch–shaped SRF and choroidal neovascular membrane (CNVM) were included.

Results:

Overall, 623 eyes in 431 patients with chronic CNVM were identified, and 24 eyes (4%) in 21 patients showed bridge arch–shaped SRF. Mean age of patients was 69.19 ± 12.0 years. Type-1 CNVM was noted in 79% cases before development of bridge arch-shaped SRF. Mean early treatment diabetic retinopathy letters visual acuity was 53.93 ± 32.19. Time interval to develop bridge arch–shaped SRF was 21.9 ± 30.63 months. Mean number of intravitreal anti–vascular endothelial growth factor injections given before developing bridge arch–shaped SRF was 6.5 ± 7.09. During the development of bridge arch–shaped SRF, visual acuity reduced by −20.57 ± 31.13 letters (P = 0.033) and fibrotic Type-2 CNVM (n = 18, 75%) was noted. Retinal pigment epithelium tear was noted in 8 eyes (33%). At the final visit, further reduction in visual acuity of −7.136 ± 13.73 early treatment diabetic retinopathy letters (P = 0.011) after developing bridge arch–shaped SRF was seen. Mean number of injections given after developing bridge arch–shaped SRF was 4.76 ± 3.76.

Conclusion:

Bridge arch–shaped SRF is an uncommon finding seen in eyes with Type-2 chronic CNVMs. Presence of retinal pigment epithelium breach and tear and nonaggressive treatment regimen with intravitreal anti–vascular endothelial growth factor injections could be responsible for its pathogenesis. It is a marker of fibrotic enlargement, leading to poor visual outcomes despite showing favorable therapeutic response.
Developing and Pilot Testing of a Mini Massive Open Online Course (MOOC) on Occupational Epidemiology
Authors: Braeckman Lutgart , Hermans Linda , D’Hulster Leon , Van de Cauter Joy , Verbrugghe Mathieu
Published: February 2022

Objective:

Massive Open Online Courses (MOOCs) offer a flexible method of providing education to large numbers of people around the world. This study aimed to develop and pilot test a mini MOOC in order to teach knowledge and skills in occupational epidemiology.

Methods:

Using instructional design principles, an open online course was developed.

Results:

Four modules have been designed and delivered in a pilot version requiring an 8-hour time commitment. Thirty postgraduate students evaluated different aspects of the MOOC. They appreciated the active learning approach, gave high rates of approval for learning effects and structure but would welcome more feedback and interaction.

Conclusions:

Although students were satisfied, developing the MOOC entailed a considerable amount of time. A multi-institutional approach and international collaboration would be beneficial to improve the present MOOC and develop new ones.
Compliance versus Risk Awareness with Contact Lens Storage Case Hygiene and Replacement
Authors: Cardona Genis , Alonso Silvia , Yela Sandra
Published: February 2022

SIGNIFICANCE

Compliance with hygiene and replacement of contact lens (CL) storage cases is key to avoid CL contamination and anterior ocular surface complications. However, compliance levels with these accessories remain low, even in patients with awareness of the risk associated with noncompliance.

PURPOSE

This study aimed to determine level of compliance with common practices regarding CL storage case hygiene and replacement, type of information provided by practitioners, and risk perception.

METHODS

An ad hoc self-reported survey was used to collect demographic and CL wear details, compliance with storage case care, type of received information, and risk perception (in a 1-to-5 scale). Inferential statistics explored the relationship of demographic details and type of received information with compliance and risk perception.

RESULTS

Nondaily disposable wearing participants returned 299 completed surveys, with a median age of 24 years (76.9% females). Monthly replacement silicone hydrogel CLs and multipurpose solutions were predominant. Self-reported compliance with storage case care was poor, with 19.1% of respondents never cleaning their cases, 68.6% exposing them to tap water, and 26.4% failing to replace them within 6 months of acquisition. Two-thirds of respondents received specific information on case maintenance, mainly in oral form. Perceived risk associated with poor-compliance practices was high (median values of 4 and 5), and increased with educational level (P = .02, regarding handwashing; P = .03, regarding case hygiene), with years of CL wear experience (P < .001, regarding handwashing), in those patients provided with specific information on CL case care (P = .01, regarding case replacement).

CONCLUSIONS

Compliance with CL storage case hygiene and replacement was generally poor, although awareness of risk associated with noncompliance was high and influenced by factors related to demographic details, CL experience, and patient-practitioner communication. Strategies must be explored to increase risk awareness through education because this may lead to better compliance practices.
Investigation of Predictors of Successful Replantation of Distal Digits at the Nail Bed Level: The Contribution of Digital Nerve Repair to Survival Rate
Authors: Usami Satoshi , Inami Kohei , Kawahara Sanshiro , Hirase Yuichi , Shimizu Hiroaki , Mori Hiroki
Published: February 2022

Background:

Replantation of amputated digits at the nail bed level is surgically challenging and differs from replantation at a more proximal amputation level. This study aimed to determine the predictors influencing the success rate of fingertip replantation.

Methods:

Overall, 239 digits of 226 patients who underwent replantation surgery from August of 2009 to March of 2020 were considered. A total of 15 independent variables (i.e., sex; age; injured hand; digit; history of smoking; history of hypertension or diabetes; injury mechanism; amputation level; ischemia duration; surgeon’s expertise; numbers of repaired arteries, veins, and nerves; and the need for a vein graft) were investigated for their effects on the survival of the replanted digits.

Results:

Of all 239 digits, 190 (79.5 percent) survived. Univariate analysis indicated that non–crush-avulsion injury, expertise and experience of the surgeon, vein repair, and nerve repair contributed to increasing the survival rate. Binary logistic regression analysis demonstrated that injury mechanism, vein repair, and nerve repair were significant predictive factors. In addition, in non–vein-repaired, blunt cut, or Ishikawa subzone II cases, digital nerve repair contributed significantly to promote the success rate relative to vein-repaired, crush-avulsion–type injury, and subzone I cases.

Conclusions:

Vein repair, nerve repair, non–crush-avulsion injury, and surgeon’s expertise and experience were the predictors for successful replantation. Intraoperative vein and nerve repair are recommended to improve the survival rate of fingertip replantation at the nail bed level.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Reconstruction of Temporomandibular Joint and Skull Base Defect Following Osteosarcoma Resection
Authors: Machoň Vladimír , Vlachopulos Vasilis , Beňo Michal
Published: February 2022

Osteosarcoma of the jaw is uncommon, occurring in about 6% to 8% of cases. The authors present the case report of a (woman 72-year-old) with osteosarcoma involving the temporomandibular joint (TMJ). Radical surgery was chosen with resection of the tumor together with the condyle, the coronoid process, the zygomatic arch and eroded bone of the skull base at the site of the joint cavity. Contact of the tumor with the dura mater was not confirmed perioperatively.

Reconstruction of the TMJ was 24 months after resection. The fossa component was concurrently formed in such a way as to cover the defect in the skull base and allow the reconstruction of the fossa and resected zygomatic arch. Four years after tumor resection there are no signs of local recurrence or metastases. Two years after TMJ reconstruction, the patient is symptom-free-occlusion is satisfactory, jaw movement is within normal range.
Exploring neural correlates of behavioral and academic resilience among children in poverty
Authors: Ellwood-Lowe M.E. , Irving C.N. , Bunge S.A.
Published: February 2022

Children in poverty must contend with systems that do not meet their needs. We explored what, at a neural level, helps explain children’s resilience in these contexts. Lower coupling between lateral frontoparietal network (LFPN) and default mode network (DMN)—linked, respectively, to externally- and internally-directed thought—has previously been associated with better cognitive performance. However, we recently found the opposite pattern for children in poverty. Here, we probed ecologically-valid assessments of performance. In a pre-registered study, we investigated trajectories of network coupling over ages 9-13 and their relation to school grades and attention problems. We analyzed longitudinal data from ABCD Study (N=8366 children at baseline; 1303 below poverty). The link between cognitive performance and grades was weaker for children in poverty, highlighting the importance of ecologically-valid measures. As predicted, higher LFPN-DMN connectivity was linked to worse grades and attentional problems for children living above poverty, while children below poverty showed opposite tendencies. This interaction between LFPN-DMN connectivity and poverty related to children’s grades two years later; however, it was attenuated when controlling for baseline grades and was not related to attention longitudinally. Together, these findings suggest network connectivity is differentially related to performance in real-world settings for children above and below poverty.
Does the Heart Fall Asleep? – Diurnal Variations of Heart Rate Variability in Patients with Disorders of Consciousness
Authors: Angerer Monika , Wilhelm Frank H. , Liedlgruber Michael , Pichler Gerald , Angerer Birgit , Scarpatetti Monika , Blume Christine , Schabus Manuel
Published: February 2022

The current study investigated heart rate (HR) and heart rate variability (HRV) across day and night in patients with disorders of consciousness (DOC). We recorded 24-h ECG in 26 patients with DOC (i.e., unresponsive wakefulness syndrome [UWS; n=16] and (exit) minimally conscious state [(E)MCS; n=10]). To examine diurnal variations, HR and HRV indices in the time, frequency, and entropy domains were computed for periods of clear day- (forenoon: 8am-2pm; afternoon: 2pm-8pm) and nighttime (11pm-5am). Results indicate that patients’ interbeat intervals (IBIs) were larger during the night than during the day indicating HR slowing. Additionally, higher HRV entropy was associated with higher EEG entropy during the night. Patients in UWS showed larger IBIs compared to patients in (E)MCS, and patients with non-traumatic brain injury showed lower ECG entropy than patients with traumatic brain injury. Thus, cardiac activity varies with a diurnal pattern in patients with DOC and can differentiate between patients’ diagnoses and etiologies. Moreover, also the interaction of heart and brain appears to follow a diurnal rhythm. Thus, HR and HRV seem to mirror the integrity of brain functioning and consequently might serve as supplementary measures for improving the validity of assessments in patients with DOC.
Half the picture: Word frequencies reveal racial differences in clinical documentation, but not their causes
Authors: Penn Jacqueline A. , Newman-Griffis Denis
Published: February 2022

Clinical notes are the best record of a provider’s perceptions of their patients, but their use in studying racial bias in clinical documentation has typically been limited to manual evaluation of small datasets. We investigated the use of computational methods to scale these insights to large, heterogeneous clinical text data. We found significant differences in negative emotional tone and language implying social dominance in clinical notes between Black and White patients, but identified multiple contributing factors in addition to potential provider bias, including mis-categorization of some healthcare vocabulary as emotion-related. We further found that notes for Black patients were significantly less likely to mention opioids than for White patients, potentially reflecting both inequitable access to medication and provider bias. Our analysis showed that computational tools have significant potential for studying racial bias in large clinical corpora, and identified key challenges to providing a nuanced analysis of bias in clinical documentation.
Neonatal and Maternal Outcome of COVID-19 positive women in Sri Lanka: Secondary Analysis using National COVID-19 Positive Pregnant Women Surveillance
Authors: Kumarasinghe Malith , Kasturiaratchi Kaushalya , Jayakody Hemali , Irfaan Shakira , Samarasinghe Wasana , Dassanayake Harendra , Godakandage Sanjeeva , de Silva Chithramalee
Published: February 2022

Objectives

This study aims to describe the population level data on neonatal and maternal outcomes of COVID-19 positive pregnant women of Sri Lanka by secondary analysis using National COVID-19 Positive Pregnant Women Surveillance.

Design

Secondary analysis of surveillance data from the National COVID-19 positive pregnant women surveillance, Sri Lanka. Data of all pregnant women whose maternal and neonatal outcomes were reported in National Surveillance from 1st March 2020 to 31st October 2021 were included in the study. Associated factors for maternal and neonatal outcomes, namely POA at delivery, mode of delivery, birthweight, immediate place of newborn care, congenital abnormalities, and condition of neonate at completion of one month were calculated using univariate and multivariate Odds ratios.

Results

Maternal COVID-19 infection reported preterm birth rate of 11.9%, LSCS rate of 54.5%, low birthweight rate16.5% and 8.3% of the newborns requiring intensive care. Neonatal mortality rate was 9 per 1000 live births. Pre-pregnancy overweight and obesity increased the risk of preterm delivery compared to pregnant women with normal BMI by 46.7% (AOR=1.467, CI=1.111-1.938, P=0.007). In contrast, the risk of preterm delivery reduced by 82.4% (AOR=0.176, CI=0.097-0.317, p<0.001) and presence of any type of congenital abnormalities in newborns by 72.4% among the COVID-19 positive women who required only inward treatment in comparison to women with severe COVID-19 infection requiring intensive care (AOR=0.276, CI=0.112-0.683, p=0.005).

Conclusion

Increased severity of maternal COVID-19 infection and pre-pregnancy overweight/ obesity were associated with many adverse pregnancy and neonatal outcomes. Therefore, close observation and aggressive management of COVID-19 among the pregnant women should be considered to reduce the risk of progressing to severe illness.
COVID-19 in Japan: insights from the first three months of the epidemic
Authors: Imai Natsuko , Gaythorpe Katy AM , Bhatia Sangeeta , Mangal Tara D , Cuomo-Dannenburg Gina , Unwin H Juliette T , Jauneikaite Elita , Ferguson Neil M
Published: February 2022

Background

Understanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data.

Methods

We conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs.

Results

The corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period, Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients <20 years old developing pneumonia or severe respiratory symptoms.

Conclusions

Information collected in the early phases of an outbreak are important in characterising any novel pathogen. Timely recognition of key symptoms and high-risk settings for transmission can help to inform response strategies. The data analysed here were the result of robust and timely investigations and demonstrate the improvements to epidemic control as a result of such surveillance.
Evaluating the effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control teams: the COG-UK hospital-onset COVID-19 infection study
Authors: Stirrup Oliver , Blackstone James , Mapp Fiona , MacNeil Alyson , Panca Monica , Holmes Alison , Machin Nicholas , Shin Gee Yen , Mahungu Tabitha , Saeed Kordo , Saluja Tranprit , Taha Yusri , Mahida Nikunj , Pope Cassie , Chawla Anu , Cutino-Moguel Maria-Teresa , Tamuri Asif , Williams Rachel , Darby Alistair , Robertson David , Flaviani Flavia , Nastouli Eleni , Robson Samuel , Smith Darren , Loose Matthew , Laing Kenneth , Monahan Irene , Kele Beatrix , Haldenby Sam , George Ryan , Bashton Matthew , Witney Adam , Byott Matthew , Coll Francesc , Chapman Michael , Peacock Sharon ,   COG-UK HOCI Investigators,   The COVID-19 Genomics UK (COG-UK) consortium, Hughes Joseph , Nebbia Gaia , Partridge David G , Parker Matthew , Price James , Peters Christine , Roy Sunando , Snell Luke B , de Silva Thushan I , Thomson Emma , Flowers Paul , Copas Andrew , Breuer Judith
Published: February 2022

Introduction

Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.

Methods

We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of ‘rapid’ (<48h) and 4 weeks of ‘longer-turnaround’ (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs; detected ≥48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated.

Results

A total of 2170 HOCI cases were recorded from October 2020-April 2021, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (IRR 1.60, 95%CI 0.85-3.01; P=0.14) or rapid (0.85, 0.48-1.50; P=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a per-protocol sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days.

Conclusion

While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.
Excess COVID-19-associated deaths among the unvaccinated population ≥18 years old in the United States, May 30 – December 4, 2021
Authors: Jia Katherine M. , Hanage William P. , Lipsitch Marc , Swerdlow David L.
Published: February 2022

Vaccines against SARS-CoV-2 were authorized at the end of 2020 and are effective in preventing deaths; however, many persons remain unvaccinated. Using weekly publicly available CDC data of COVID-19-associated death rates by age and vaccination status from 26 US jurisdictions, we estimated the number of excess deaths that might have been averted by vaccination among unvaccinated persons ≥ 18 years old from May 30 to December 4, 2021. We subtracted the death rate in the vaccinated from rates in the unvaccinated to estimate the death rate each week that could be attributable to non-vaccination and multiplied this rate difference by the number of people in the unvaccinated group for each age group and each week, to estimate the excess mortality among the unvaccinated. Then, we extrapolated the number of deaths due to non-vaccination in the 26 jurisdictions to the whole US population using 2020 census estimates. In the 26 participating jurisdictions there were an estimated 83,400 excess deaths among the unvaccinated from May 30 to December 4, 2021. The largest number of excess deaths occurred in those 65–79 years old (n=28,900; 34.7% of total), followed by those 50-64 years old (n=25,900; 31.1%). Extrapolated to the US population we estimated approximately 135,000 excess deaths during the study period in persons ≥18 years old. Our estimates are an underestimate of all excess deaths that have occurred since vaccine became available because our analysis period was limited to May 30 to December 4, 2021, and many excess deaths occurred before and after this period. In summary, we used retrospective data to estimate the substantial number of COVID-19-associated deaths among the unvaccinated illustrating the importance of vaccination to prevent further unnecessary mortality during this pandemic.
Correlation between post-vaccination titres of combined IgG, IgA, and IgM anti-Spike antibodies and protection against breakthrough SARS-CoV-2 infection: a population-based longitudinal study (COVIDENCE UK)
Authors: Vivaldi Giulia , Jolliffe David A , Faustini Sian , Holt Hayley , Perdek Natalia , Talaei Mohammad , Tydeman Florence , Chambers Emma S , Cai Weigang , Li Wenhao , Gibbons Joseph M , Pade Corinna , McKnight Áine , Shaheen Seif O , Richter Alex G , Martineau Adrian R
Published: February 2022

In this population-based cohort of 7530 adults, combined IgG/A/M anti-Spike titres measured after SARS-CoV-2 vaccination were predictive of protection against breakthrough SARS-CoV-2 infection. Discrimination was significantly improved by adjustment for factors influencing risk of SARS-CoV-2 exposure including household overcrowding, public transport use, and visits to indoor public places.
Clinico epidemiological profile of Omicron variant of SARS CoV2 in Rajasthan
Authors: Sharma Ravi Prakash , Gautam Swati , Sharma Pratibha , Singh Ruchi , Sharma Himanshu , Parsoya Dinesh , Deba Farah , Bhomia Neha , pal Nita , Potdar Varsha A , Yadav Pragya D , Gupta Nivedita , Bhandari Sudhir , Malhotra Bharti
Published: February 2022

Background

Omicron a new variant of SARS COV2 was first detected in November 2021. This was believed to be highly transmissible and evade immunity as a result urgent need was felt to screen all positive, identify Omicron cases and isolate them to prevent spread of infection and study their clinico-epidemiological profile.

Methodology

All positive cases detected in state of Rajasthan during November to January beginning were selected for next generation sequencing. Processing was done as per protocol on Ion Torrent S5 system for 1210 samples and bioinformatics analysis was done.

Results

Among the 1210 samples tested 762(62.9%) were Delta/Delta like and other lineages, 291(24%) were Omicron and 157(12.9%) were invalid or repeat samples. Within a month the proportion of Delta and other variants was reversed, from zero omicron became 81% and delta and other variants 19%, initially all omicron cases were international travelers and their contacts but soon community transmission was seen. Majority of omicron patients were asymptomatic (56.7%) or had mild disease (33%), 9.2% had moderate symptoms and 2(0.7%) had severe disease requiring hospitalization, of which one (0.3%) died and rest (99.7%) recovered. History of vaccination was seen in 81.1%, of previous infection in 43.2%. Among the Omicron cases BA.1 (62.8%) was the predominant lineage followed by BA.2(23.7%) and B.1.529 (13.4%), however rising trends were seen initially for BA.1 and later for BA.2 also.

Conclusion

In very short time Omicron has spread in community and has taken over the preexisting Delta/Delta like and other lineages, it evades immunity, but the good part is most of the cases were asymptomatic or had mild disease and mortality rate was very low.
Socio-economic deprivation and cancer incidence in England: Quantifying the role of smoking
Authors: Payne Nick W. S. , Brown Katrina F. , Delon Christine , Kotrotsios Yannis , Soerjomataram Isabelle , Shelton Jon
Published: February 2022

Background

More deprived populations typically experience higher cancer incidence rates and smoking prevalence compared to less deprived populations. We calculated the proportion of cancer cases attributable to smoking by socio-economic deprivation in England and estimated the impact smoking has on the deprivation gap for cancer incidence.

Methods

Data for cancer incidence (2013-2017), smoking prevalence (2003-2007) and population estimates (2013-2017) were split by sex, age-group and deprivation quintile. Relative risk estimates from meta-analyses were used to estimate the population attributable fraction (PAF) for 15 cancer types associated with smoking. The deprivation gap was calculated using age-specific incidence rates by deprivation quintile.

Results

Smoking-related cancer PAFs in England are 2.2 times larger in the most deprived quintile compared to the least deprived quintile (from 9.7% to 21.1%). If everyone had the same smoking prevalence as the least deprived quintile, 20% of the deprivation gap in cancer incidence could have been prevented. If nobody smoked, 61% of the deprivation gap could have been prevented.

Conclusions

The majority of the deprivation gap in cancer incidence could have been prevented in England between 2013-2017 if nobody had smoked. Policy makers should ensure that tobacco control policies reduce overall smoking prevalence by tackling smoking inequalities.
Persistence of SARS-CoV-2 immunity, Omicron’s footprints, and projections of epidemic resurgences in South African population cohorts
Authors: Sun Kaiyuan , Tempia Stefano , Kleynhans Jackie , Gottberg Anne von , McMorrow Meredith L , Wolter Nicole , Bhiman Jinal N. , Moyes Jocelyn , Plessis Mignon du , Carrim Maimuna , Buys Amelia , Martinson Neil A , Kahn Kathleen , Tollman Stephen , Lebina Limakatso , Wafawanaka Floidy , du Toit Jacques D. , Gómez-Olivé Francesc Xavier , Mkhencele Thulisa , Viboud Cécile , Cohen Cheryl ,   the PHIRST group
Published: February 2022

Understanding the build-up of immunity with successive SARS-CoV-2 variants and the epidemiological conditions that favor rapidly expanding epidemics will facilitate future pandemic control. High-resolution infection and serology data from longitudinal household cohorts in South Africa reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the cohort’s history of past exposures to different SARS-CoV-2 variants and vaccination, we use mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modelling suggests the Omicron wave infected a large fraction of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. Future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection.

One Sentence Summary

Closely monitored population in South Africa reveal high cumulative infection rates and durable protection by prior infection against pre-Omicron variants. Modelling indicates that a large fraction of the population has been infected with Omicron; yet epidemic resurgences are plausible under a wide range of epidemiologic scenarios.
Development and validation of radiomics nomograms for preoperative prediction of characteristics in non-small cell lung cancer and circulating tumor cells
Authors: Wang Yang , Zhu Junkai , Cheng Wenxuan , Xu Li , Wang Xin , Wang Jian , Yang Jun , Niu Fengnan , li Wenyi , Wen Zhibo , Lu Xiaofan , Yan Fangrong
Published: February 2022

Purpose

To develop and validate three radiomics nomograms for preoperative prediction of pathological and progression diagnosis in non-small cell lung cancer (NSCLC) as well as circulating tumor cells (CTCs).

Patients and methods

A total of 224 and 134 patients diagnosed with NSCLC were respectively gathered in 2018 and 2019 in this study. There were totally 1,197 radiomics features that were extracted and quantified from the images produced by computed tomography (CT). Then we selected the radiomics features with predictive value by LASSO and combined them into radiomics signature. Logistic regression models were built using radiomics signature as the only predictor, which were then converted to nomograms for individualized predictions. Finally, the performance of the nomograms was assessed on both two cohorts.

Results

As for discrimination, the AUC of pathological diagnosis nomogram and progression diagnosis nomogram in NSCLC were both higher than 90% in the training cohort and higher than 80% in the validation cohort. The performance of the CTC-diagnosis nomogram was somehow unexpected where the AUC were range from 60% to 70% in both two cohorts. As for calibration, nonsignificant statistics (p>0.05) yielded by Hosmer-Lemeshow tests suggested no departure between model prediction and perfect fit. Additionally, decision curve analyses demonstrated the clinically usefulness of the nomograms.

Conclusion

We developed radiomics-based nomograms for pathological, progression and CTC diagnosis prediction in NSCLC, respectively. Nomograms for pathological and progression diagnosis were demonstrated well performed to facilitate the preoperative individualized prediction, while the nomogram for CTC-diagnosis prediction needed improvement.
Food intake patterns, social determinants and emotions during COVID-19 confinement
Authors: Rios Maritza , Subinas Jon , Delgado Celestina , Torres Eliecer , Goodridge Amador , Cubilla-Batista Idalina
Published: February 2022

Objective

The COVID-19 pandemic was accompanied by varying movement restriction measures across populations worldwide. These restrictions altered daily activities at all levels, including food access and intake, as well as psychological feelings during lockdown. The main objective of the present study was to evaluate health, and nutrition behaviors during confinement during the first wave of the COVID-19 pandemic.

Method

We conducted a cross-sectional study using an online survey for data collection; a total of 1,561 surveys were validated.

Results

The majority of respondents were women (74.2%) between 18 and 49 years old. Among the respondents, 83.3% indicated a university education level, and 49.9% reported a monthly family income equal to or less than 1,000 USD. In addition, more than 50% self-reported overweight or obesity. Responses were analyzed using k-means algorithms to identify food intake patterns; we found three patterns: a healthy food intake pattern, a non-healthy food intake pattern and a mixed food intake pattern. The respondents with healthy food intake and non-healthy food intake patterns reported better socioeconomic conditions. Individuals classified as having mixed food intake patterns had lower incomes, less education and higher unemployment rates. Regarding emotions, we found that women experienced more negative emotions, such as fear, worry and anxiety, during the lockdown period.

Conclusions

Taken together, these results suggest that the mobility restriction measures imposed during the COVID-19 pandemic affected food intake patterns by exacerbating existing inequalities. We believe that directing resources towards strategies with the greatest positive impacts on public health remains key, especially in critical situations such as the COVID-19 pandemic.
Omicron-Specific and Bivalent Omicron-Containing Vaccine Candidates Elicit Potent Virus Neutralisation in the Animal Model
Authors: Abdoli Asghar , Jamshidi Hamidreza , Taqavian Mohammad , Baghal Mehdi Lari , Jalili Hasan
Published: February 2022

Background

Omicron variant (B. 1.1.529) is able to escape from naturally acquired and vaccine-induced immunity, which mandates updating the current COVID-19 vaccines. Here, we investigated and compared the neutralising antibody induction of the ancestral variant-based BIV1-CovIran vaccine, the Omicron variant-based BIV1-CovIran Plus vaccine, and the novel bivalent vaccine candidate, BBIV1-CovIran, against the Omicron and ancestral Wuhan variants on the rat model.

Methods

Viruses were isolated from a clinical specimen and virus characterisation performed. After inactivating the viral particles, the viruses were purified and formulated. Bivalent vaccines were a composition of 2.5 μg (5 μg total) or 5 μg (10 μg total) doses of each ansectral-based and Omicron-based monovalent vaccine. Subsequently, the potency of the monovalent and bivalent vaccines was investigated using the virus neutralisation test (VNT).

Results

The group that received three doses of the Omicron-specific vaccine demonstrated neutralisation activity against the Omicron variant with a geometric mean titer of 337.8. However, three doses of the Wuhan variant-specific vaccine could neutralise the Omicron variant at a maximum of 1/32 serum dilution. The neutralisation activity of the Omicron-specific vaccine, when administered as the booster dose after two doses of the Wuhan variant-specific vaccine, was 100% against the Omicron variant and the Wuhan variant at 1/64 and 1/128 serum dilution, respectively. Three doses of 5 μg bivalent vaccine could effectively neutralise both variants at the minimum of 1/128 serum dilution. The 10 μg bivalent vaccine at three doses showed even higher neutralisation titers: geometric mean titer of 338.0 against Omicron and 445.7 against Wuhan).

Conclusion

It is shown that the candidate bivalent vaccine could elicit a potent immune response against both Wuhan-Hu-1 and Omicron BA.1 variants. Therefore, we plan to evaluate the updated vaccine in the clinical trial setting.
Workplace infection control measures and romantic activities of workers during COVID-19 pandemic: a prospective cohort study in Japan
Authors: Fujino Yoshihisa , Okawara Makoto , Hino Ayako , Muramatsu Keiji , Nagata Tomohisa , Ikegami Kazunori , Tateishi Seiichiro , Tsuji Mayumi , Ishimaru Tomohiro ,   the CORoNaWork project
Published: February 2022

Background

Due to the COVID-19 pandemic, non-married people are at high risk of loneliness. With social interactions restricted, it is important for non-married people to acquire a new romantic partner for their mental health and quality of life. We hypothesized that infection control efforts in the workplace influence people’s social interactions, including romantic activities.

Methods

We conducted an internet-based prospective cohort study from December 2020 (baseline) to December 2021, using self-administered questionnaires. Briefly, 27,036 workers completed the questionnaires at baseline, and when followed up after one year, 18,560 (68.7%) participated. A total of 6,486 non-married individuals with no romantic relationship at baseline were included in the analysis. At baseline they were asked about the implementation of infection control measures in the workplace, and at follow-up they were asked about activities they performed with a view to romantic relationships during the period from baseline to follow-up.

Results

Compared to workers in workplaces with no infection control measures, the OR associated with romance-related activities for those in workplaces with seven or more infection control measures was 1.90 (95% CI: 1.45-2.48, p<0.001), and the OR associated with having a new romantic partner was 1.79 (95% CI: 1.20-2.66, p=0.004).

Conclusions

Under the COVID-19 pandemic, the implementation of infection control measures in the workplace and the expressed satisfaction with those measures promoted romantic relationships among non-married, single individuals.
CT-Guided Direct Current Cardioversion for Atrial Arrhythmias During the COVID-19 Pandemic
Authors: Veillet-Chowdhury Mahdi , Dabbagh Ghaith Sharaf , Benton Stewart M. , Hill April M. , Lee Jefferson H. , Singleton Matthew J. , Fazio Gregory P. , Harvey James E. , Samady Habib , Singh David , Khanji Mohammed Y. , Nazarian Saman , Pugliese Francesca , Obeng-Gyimah Edmond , Schuler Brian T. , Chahal C. Anwar A.
Published: February 2022

Objective

To assess left atrial appendage (LAA) thrombus detection using a novel cardiac computed tomography (CT) protocol specifically prior to direct current cardioversion (DCCV).

Background

Transesophageal echocardiography (TEE) is the gold standard in evaluating the LAA prior to DCCV for atrial fibrillation (AF) or flutter (AFL). The COVID-19 pandemic has restricted availability of TEE and anesthesia support.

Methods

Prospective cohort of consecutive patients with uncontrolled AF/AFL referred for DCCV from March 2020 to March 2021 were enrolled. CT evaluation of LAA was performed with an initial arterial and subsequent 30-second delayed acquisition to exclude thrombus prior to DCCV. Primary end points were to assess safety and outcomes.

Results

A total of 161 patients were included; mean age 69.8 ± 11.1 years; mean CHA2DS2-VASc 3.4 ± 1.7; and HAS-BLED 1.8 ± 0.9. Median follow-up 175 (105-267) days with zero cardiac-related deaths, and no episodes of TIA or embolic stroke. There was no statistically significant change in mean glomerular filtration rate (GFR) in the study population between the pre- and post-GFR measurements (73.9 ± 21.0 vs 72.7 ± 20.3; p=0.104). Overall mean total dose length product (DLP) was 1042.8 ± 447.5 mGy*cm. Modifying the CT protocol to a narrower 8-cm axial coverage had a statistically significant decrease in total DLP (from 1130.6 ± 464.1 mGy*cm to 802.1 ± 286.4 mGy*cm; P<0.0001).

Conclusion

Cardiac CT is both a safe and feasible alternative imaging to TEE for patients prior to DCCV.

Perspectives

Competency in Medical Knowledge

Cardiac CT is a powerful tool for the evaluation of left atrial appendage and detection of thrombus prior to direct current cardioversion.

Translational Outlook

Our protocol was implemented with the restrictions during COVID-19 in mind, yet CT can be a viable tool beyond the pandemic; future randomized clinical trials can bridge the gap between CT and TEE in the setting of cardioversion and help elucidate its safety profile further.
SARS-CoV-2 Permissive Glioblastoma Cell Line for High Throughput Antiviral Screening
Authors: Vanhulle Emiel , Stroobants Joren , Provinciael Becky , Camps Anita , Noppen Sam , Maes Piet , Vermeire Kurt
Published: February 2022

Despite the great success of the administered vaccines against SARS-CoV-2, the virus can still spread, as evidenced by the current circulation of the highly contagious Omicron variant. This emphasizes the additional need to develop effective antiviral countermeasures. In the context of early preclinical studies for antiviral assessment, robust cellular infection systems are required to screen drug libraries. In this study, we reported the implementation of a human glioblastoma cell line, stably expressing ACE2, in a SARS-CoV-2 cytopathic effect (CPE) reduction assay. These glioblastoma cells, designated as U87.ACE2+, expressed ACE2 and cathepsin B abundantly, but had low cellular levels of TMPRSS2 and cathepsin L. The U87.ACE2+ cells fused highly efficiently and quickly with SARS-CoV-2 spike expressing cells. Furthermore, upon infection with SARS-CoV-2 wild-type virus, the U87.ACE2+ cells displayed rapidly a clear CPE that resulted in complete cell lysis and destruction of the cell monolayer. By means of several readouts we showed that the U87.ACE2+ cells actively replicate SARS-CoV-2. Interestingly, the U87.ACE2+ cells could be successfully implemented in an MTS-based colorimetric CPE reduction assay, providing IC50 values for Remdesivir in the low nanomolar range. Lastly, the U87.ACE2+ cells were consistently permissive to all tested SARS-CoV-2 variants of concern, including the current Omicron variant. Thus, ACE2 expressing glioblastoma cells are highly permissive to SARS-CoV-2 with productive viral replication and with the induction of a strong CPE that can be utilized in high-throughput screening platforms.
Brain endothelial STING1 activation by Plasmodium-sequestered heme promotes cerebral malaria via type I IFN response
Authors: Pais Teresa F. , Ali Hajrabibi , Moreira da Silva Joana , Duarte Nádia , Neres Rita , Chhatbar Chintan , Acúrcio Rita C. , Guedes Rita C. , Moraes Maria Carolina Strano , Silva Bruno Costa , Kalinke Ulrich , Penha-Gonçalves Carlos
Published: February 2022

Cerebral malaria (CM) is a life-threatening form of Plasmodium falciparum infection caused by brain inflammation. Brain endothelium dysfunction is a hallmark of CM pathology, which is also associated with the activation of the type I interferon (IFN) inflammatory pathway. The molecular triggers and sensors eliciting brain type I IFN cellular responses during CM remain largely unknown. We herein identified the stimulator of interferon response cGAMP interactor 1 (STING1) as the key innate immune sensor that induces Ifnβ1 transcription in the brain of mice infected with Plasmodium berghei (Pba). This STING1/IFNβ-mediated response increases brain CXCL10 governing the extent of brain leucocyte infiltration and blood-brain barrier (BBB) breakdown, and determining CM lethality. The critical role of brain endothelial cells (BECs) in fueling type I IFN-driven brain inflammation was demonstrated in brain endothelial-specific IFNβ-reporter and STING1-deficient Pba-infected mice, which are significantly protected from CM lethality. Moreover, extracellular particles (EPs) released from Pba-infected erythrocytes activated STING1-dependent type I IFN response in BECs, a response requiring intracellular acidification. Fractionation of the EPs enabled us to identify a defined fraction carrying hemoglobin degradation remnants that activates STING1/IFNβ in the brain endothelium, a process correlated with heme content. Notably, stimulation of STING1-deficient BECs with heme, docking experiments and in vitro binding assays unveiled that heme is a putative STING1 ligand. This work shows that heme resultant from the parasite heterotrophic activity operates as an alarmin triggering brain endothelial inflammatory responses via STING1/IFNβ/CXCL10 axis crucial to CM pathogenesis and lethality.

Significance

CM results from loss of blood-brain endothelial barrier function caused by unrestrained inflammatory response in the natural course of infection by Plasmodium parasites. However, the role of brain endothelium in triggering inflammatory mechanisms is still undetermined. We found that the innate immune sensor STING1 is crucial for production of IFNβ in brain endothelial cells in Plasmodium-infected mice. This in turn stimulates CXCL10-mediated recruitment of leukocytes and subsequent brain inflammation and tissue damage. We identified within extracellular particles released from Plasmodium-infected erythrocytes, a fraction containing products of hemoglobin degradation, namely heme, which we show can bind STING1. Our results unravel a new angle of CM pathogenesis: heme contained in particles triggers the STING/IFNβ/CXCL10 axis in brain endothelial cells.
Genomic profiling of HIV-1 integration in microglia links viral insertions to TAD organization
Authors: Rheinberger Mona , Costa Ana Luisa , Kampmann Martin , Glavas Dunja , Shytaj Iart Luca , Penzo Carlotta , Tibroni Nadine , Fackler Oliver T. , Vlahovicek Kristian , Lucic Bojana , Herrmann Carl , Lusic Marina
Published: February 2022

HIV-1 persists in anatomically distinct cellular and tissue reservoirs as a stably integrated provirus that is a major barrier to HIV-1 cure. Proviral insertions are largely characterized in blood cells, while HIV-1 integration patterns remain unexplored in microglia, the major brain reservoir. Here, we employ genomics approaches to obtain the first HIV-1 integration site (IS) profiling in microglia and perform in-depth analysis of transcriptome, specific histone signatures and chromatin accessibility on different genomic scales. We show that HIV-1 follows genic insertion patterns into introns of actively transcribed genes, characteristic of blood reservoirs. HIV-1 insertional hotspot analysis by non-negative matrix factorization (NMF)-based approach clusters IS signatures with genic- and super-enhancers. Chromatin accessibility transcription factor (TF) footprints reveal that increased CTCF binding marks latently infected microglia compared to productively infected one. We identify CTCF-enriched topologically associated domain (TAD) borders with signatures of active chromatin as a neighborhood for HIV-1 integration in microglia and CD4+T cells. Our findings further strengthen the notion that HIV-1 follows the patterns of host cell genome organization to integrate and to establish the silent proviral state and reveal that these principles are largely conserved in different anatomical latent reservoirs.