bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the allosteric effects that define functional activity of SARS-CoV-2 specific antibodies
Authors: Tulsian Nikhil K. , Raghuvamsi Palur V. , Qian Xinlei , Yue Gu , D/O Shunmuganathan Bhuvaneshwari , Samsudin Firdaus , Hwa Wong Yee , Jianqing Lin , Purushotorman Kiren , Kozma Mary M. , Wang Bei , Lescar Julien , Wang Cheng-I , Anand Ganesh S. , Bond Peter J. , MacAry Paul A.
Published: January 2022

Previous studies on the structural relationship between human antibodies and SARS-CoV-2 have focused on generating static snapshots of antibody complexes with the Spike trimer. However, antibody-antigen interactions are dynamic, with significant binding-induced allosteric effects on conformations of antibody and its target antigen. In this study, we employ hydrogen-deuterium exchange mass spectrometry, in vitro assays, and molecular dynamics simulations to investigate the allosteric perturbations linked to binding events between a group of human antibodies with differential functional activities, and the Spike trimer from SARS-CoV-2. Our investigations have revealed key dynamic features that define weakly or moderately neutralizing antibodies versus those with strong neutralizing activity. These results provide mechanistic insights into the functional modes of human antibodies against COVID-19, and provide a rationale for effective antiviral strategies.

Teaser

Different neutralizing antibodies induce site-specific allosteric effects across SARS-CoV-2 Spike protein
Perceived Timing of Cutaneous Vibration and Intracortical Microstimulation of Human Somatosensory Cortex
Authors: Christie Breanne , Osborn Luke E. , McMullen David P. , Pawar Ambarish S. , Thomas Tessy M. , Bensmaia Sliman J. , Celnik Pablo A. , Fifer Matthew S. , Tenore Francesco V.
Published: January 2022

Background

Electrically stimulating the somatosensory cortex can partially restore the sense of touch. Though this technique bypasses much of the neuroaxis, prior studies with non-human primates have found that conscious detection of touch elicited by intracortical microstimulation (ICMS) lags behind the detection of vibration applied to the skin. These findings may have been influenced by a mismatch in stimulus intensity; typically, vibration is perceived as more intense than ICMS, which can significantly impact temporal perception.

Objective

The goal of this study was to evaluate the relative latency at which intensity-matched vibration and ICMS are perceived in a human subject.

Methods

A human participant implanted with microelectrode arrays in somatosensory cortex performed a reaction time task and a temporal order judgment (TOJ) task. In the reaction time task, the participant was presented with vibration or ICMS and verbal response times were obtained. In the TOJ task, the participant was sequentially presented with a pair of stimuli – vibration followed by ICMS or vice versa – and reported which stimulus occurred first.

Results

When vibration and ICMS were matched in intensity at a “high” stimulus level, the reaction time to vibration was 48 ms faster than ICMS. When both stimuli were perceived as lower in intensity, the difference in reaction time was even larger: vibration was perceived 90 ms before ICMS. However, in the TOJ task, vibratory and ICMS sensations arose at comparable latencies, with points of subjective simultaneity that were not significantly different from zero.

Conclusions

Because the perception of ICMS is slower than that of intensity-matched vibration, it may be necessary to stimulate at stronger ICMS intensities (thus decreasing reaction time) when incorporating ICMS sensory feedback into neural prostheses.
The Effect of Weather Pattern on the Second Wave of Coronavirus: A cross study between cold and tropical climates of France, Italy, Colombia, and Brazil
Authors: Islam Ahmed
Published: January 2022

This study aims to explore and understand the common belief that COVID infection rate is highly dependent on either the outside temperature and/or the humidity. Thirty-six regions/states from two humid-tropical countries, namely Brazil and Colombia and two countries with temperate climate, France and Italy, are studied over the period of October to December. Daily outside temperature, relative humidity and hospitalization/cases are analyzed using Spearman’s correlation. The eighteen cold regions of France and Italy has seen an average drop in temperature from 10°C to 6°C and 17°C to 7°C, respectively, and France recorded an addition of 2.3 million cases, while Italy recorded an addition of 1.8 million cases. Outside temperature did not fluctuate much in tropical countries, but Brazil and Colombia added 4.17 million and 1.1 million cases, respectively. Köppen–Geiger classification showed the differences in weather pattern between the four countries, and the analysis showed that there is very weak correlation between either outside weather and/or relative humidity alone to the COVID-19 pandemic.
Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine
Authors: Coléon Séverin , Wiedemann Aurélie , Surénaud Mathieu , Lacabaratz Christine , Hue Sophie , Prague Mélanie , Cervantes-Gonzalez Minerva , Wang Zhiqing , Ellis Jerome , Sansoni Amandine , Pierini Camille , Bardin Quentin , Fabregue Manon , Sharkaoui Sarah , Hoest Philippe , Dupaty Léa , Picard Florence , Centlivre Mireille , Ghosn Jade ,   French COVID Cohort Study Group, Thiébaut Rodolphe , Cardinaud Sylvain , Malissen Bernard , Zurawski Gérard , Zarubica Ana , Zurawski Sandra M , Godot Véronique , Lévy Yves
Published: January 2022

The emergence of SARS-CoV-2 variants of concern (VOCs) that escape pre-existing antibody neutralizing responses increases the need for vaccines that target conserved epitopes and induce cross-reactive B- and T-cell responses. We used a computational approach and sequence alignment analysis to design a new-generation subunit vaccine targeting conserved sarbecovirus B- and T-cell epitopes from Spike (S) and Nucleocapsid (N) to antigen-presenting cells expressing CD40 (CD40.CoV2). We demonstrate the potency of CD40.CoV2 to elicit high levels of cross-neutralizing antibodies against SARS-CoV-2, VOCs, and SARS-CoV-1 in K18-hACE2 transgenic mice, associated with improved viral control and survival after challenge. In addition, we demonstrate the potency of CD40.CoV2 in vitro to recall human multi-epitope, functional, and cytotoxic SARS-CoV-2 S- and N-specific T-cell responses that are unaffected by VOC mutations and cross-reactive with SARS-CoV-1 and, to a lesser extent, MERS epitopes. Overall, these findings provide a framework for a pan-sarbecovirus vaccine.
Leveraging global multi-ancestry meta-analysis in the study of Idiopathic Pulmonary Fibrosis genetics
Authors: Partanen Juulia J. , Häppölä Paavo , Zhou Wei , Lehisto Arto Aleksanteri , Ainola Mari , Sutinen Eva , Allen Richard J , Stockwell Amy D , Oldham Justin M , Guillen-Guio Beatriz , Flores Carlos , Noth Imre , Yaspan Brian L , Jenkins R. Gisli , Wain Louise V , Ripatti Samuli , Pirinen Matti ,   Global Biobank Meta-analysis Initiative (GBMI), Kaarteenaho Riitta , Myllärniemi Marjukka , Daly Mark J , Koskela Jukka T.
Published: January 2022

The research of rare and devastating orphan diseases such as Idiopathic Pulmonary Fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor – the prevalence of IPF is only ∼4-times the incidence of the condition, limiting the recruitment of patients to trials and studies of the underlying biology of the disease. However, global biobanking efforts can dramatically alter the future of IPF research.

Here we describe the largest meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine the meta-analysis with the largest available meta-analysis of IPF so far, reaching 11,160 patients and 1,364,410 population controls in analysis.

We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection, beyond what is known to date. We also note a significant unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.
Long-lasting cellular immunity to SARS-CoV-2 following infection or vaccination and implications for booster strategies
Authors: Mazzoni Alessio , Vanni Anna , Spinicci Michele , Lamacchia Giulia , Kiros Seble Tekle , Rocca Arianna , Capone Manuela , Di Lauria Nicoletta , Salvati Lorenzo , Carnasciali Alberto , Mantengoli Elisabetta , Farahvachi Parham , Zammarchi Lorenzo , Lagi Filippo , Colao Maria Grazia , Liotta Francesco , Cosmi Lorenzo , Maggi Laura , Bartoloni Alessandro , Rossolini Gian Maria , Annunziato Francesco
Published: January 2022

Immunization against SARS-CoV-2, the causative agent of coronavirus disease-19 (COVID-19) occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last. We performed a longitudinal evaluation of immunological memory to SARS-CoV-2 following mRNA vaccination in naïve and COVID-19 recovered individuals. We found that cellular immunity is still detectable 8 months after vaccination, while antibody levels decline significantly especially in naïve subjects. We also found that a booster injection is more efficacious in reactivating immunological memory to spike protein in naïve than in previously SARS-CoV-2 infected subjects. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to one year following natural infection in a cohort of unvaccinated individuals. Short-term persistence of humoral immunity may account for reinfections and breakthrough infections, although long-lived memory B and CD4+ T cells may protect from severe disease. A booster dose restores optimal anti-spike immunity in naïve subjects, while the need for vaccinated COVID-19 recovered subjects has yet to be defined.
A cohort study of the effect of SARS-CoV-2 point of care rapid RT-PCR at the Emergency Department on targeted admission
Authors: Mortazavi Susanne E , Inghammar Malin , Christiansen Claus , Pesola Anne-Katrine , Stenkilsson Mikael , Paulsson Magnus
Published: January 2022

(ii)

Background

To prevent nosocomial transmission of SARS-CoV-2, infection control measures are implemented for patients with symptoms compatible with COVID-19 until reliable test results are available. This delay targeted admission to the most appropriate ward based on the medical condition. SARS-CoV-2 rapid antigen detection (RAD) tests and point of care (POC) rapid RT-PCR were introduced at emergency departments (EDs) in late 2020, but the consequence on targeted admission is unknown.

Objectives

To assess the effect of RAD tests and POC rapid RT-PCR (VitaPCR, Credo Diagnostics, Singapore) on targeted admission.

Methods

Patients presenting at the ED of a referral hospital (N = 2,940) between 13-Nov-2020 and 12-Jan-2021 were included. The study period was delimited by introduction of RAD tests and VitaPCR. Participant data was collected retrospectively, and outcome variables were length-of-stay (LoS), intrahospital transfers and targeted admission to COVID-19 ward.

Results

RAD tests reduced ED LoS for participants with positive tests or that were not tested. Negative VitaPCR results reduced mean hospital LoS by 1.5 (95%CI: 0.3–2.7) days and admissions to COVID-19 wards from 34.5 (95%CI: 28.9-40.5) to 14.7 (95%CI: 11.1-19.1) per 100 admissions. Introduction of VitaPCR reduced transfers between hospital wards in the first 5 days from 50.0 (95%CI: 45.0-55.0) to 34.0 (95%CI: 30.3-37.9) per 100 admissions.

Conclusion

RAD tests enabled rapid detection of SARS-CoV-2 infection which had pronounced effects on LoS at the ED. VitaPCR added the possibility of exclusion of the infection which increased targeted admissions, reduced intrahospital transfers and lead to shorter stay at the hospital.
COVID-19 vaccine effectiveness among immunocompromised populations: a targeted literature review of real-world studies
Authors: Di Fusco Manuela , Lin Jay , Vaghela Shailja , Lingohr-Smith Melissa , Nguyen Jennifer L , Sforzolini Thomas Scassellati , Judy Jennifer , Cane Alejandro , Moran Mary M
Published: January 2022

Introduction

From July through October of 2021, several countries issued recommendations for increased COVID-19 vaccine protection for individuals with one or more immunocompromised (IC) conditions. It is critically important to understand the vaccine effectiveness (VE) of COVID-19 vaccines among IC populations as recommendations are updated over time in response to the evolving COVID-19 pandemic.

Areas covered

A targeted literature review was conducted to identify real-world studies that assessed COVID-19 VE in IC populations between December 2020 and September 2021. A total of 10 studies from four countries were identified and summarized in this review.

Expert opinion/commentary

VE of the widely available COVID-19 vaccines, including BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), and ChAdOx1 nCoV-19 (Oxford/AstraZeneca), ranged from 64%-90% against SARS-CoV-2 infection, 73%-84% against symptomatic illness, 70%-100% against severe illness, and 63%-100% against COVID-19-related hospitalization among the fully vaccinated IC populations included in the studies. COVID-19 VE for most outcomes in the IC populations included in these studies was lower than in the general populations. These findings provide preliminary evidence that the IC population requires greater protective measures to prevent COVID-19 infection and associated illness, hence should be prioritized while implementing recommendations of additional COVID-19 vaccine doses.
Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions
Authors: Panovska-Griffiths J. , Swallow B. , Hinch R. , Cohen J. , Rosenfeld K. , Stuart R. M. , Ferretti L. , Lauro F. Di , Wymant C. , Izzo A. , Waites W. , Viner R. , Bonell C. ,   The COVID-19 Genomics UK (COG-UK) consortium, Fraser C. , Klein D. , Kerr C. C.
Published: January 2022

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and calibration of an stochastic agent-based model Covasim to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. We used these estimates in Covasim (calibrated between September 01, 2020 and June 20, 2021), in June 2021, to explore whether planned relaxation of restrictions should proceed or be delayed. We found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination.
Comparison of outcomes from COVID infection in pediatric and adult patients before and after the emergence of Omicron
Authors: Wang Lindsey , Berger Nathan A. , Kaelber David C. , Davis Pamela B. , Volkow Nora D. , Xu Rong
Published: January 2022

Background

The Omicron SARS-CoV-2 variant is rapidly spreading in the US since December 2021 and is more contagious than earlier variants. Currently, data on the severity of the disease caused by the Omicron variant compared with the Delta variant is limited. Here we compared 3-day risks of emergency department (ED) visit, hospitalization, intensive care unit (ICU) admission, and mechanical ventilation in patients who were first infected during a time period when the Omicron variant was emerging to those in patients who were first infected when the Delta variant was predominant.

Method

This is a retrospective cohort study of electronic health record (EHR) data of 577,938 first-time SARS-CoV-2 infected patients from a multicenter, nationwide database in the US during 9/1/2021–12/24/2021, including 14,054 who had their first infection during the 12/15/2021–12/24/2021 period when the Omicron variant emerged (“Emergent Omicron cohort”) and 563,884 who had their first infection during the 9/1/2021–12/15/2021 period when the Delta variant was predominant (“Delta cohort”). After propensity-score matching the cohorts, the 3-day risks of four outcomes (ED visit, hospitalization, ICU admission, and mechanical ventilation) were compared. Risk ratios, and 95% confidence intervals (CI) were calculated.

Results

Of 14,054 patients in the Emergent Omicron cohort (average age, 36.4 ± 24.3 years), 27.7% were pediatric patients (<18 years old), 55.4% female, 1.8% Asian, 17.1% Black, 4.8% Hispanic, and 57.3% White. The Emergent Omicron cohort differed significantly from the Delta cohort in demographics, comorbidities, and socio-economic determinants of health. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities, medications and vaccination status, the 3-day risks in the Emergent Omicron cohort outcomes were consistently less than half those in the Delta cohort: ED visit: 4.55% vs. 15.22% (risk ratio or RR: 0.30, 95% CI: 0.28-0.33); hospitalization: 1.75% vs. 3.95% (RR: 0.44, 95% CI: 0.38-0.52]); ICU admission: 0.26% vs. 0.78% (RR: 0.33, 95% CI:0.23-0.48); mechanical ventilation: 0.07% vs. 0.43% (RR: 0.16, 95% CI: 0.08-0.32). In children under 5 years old, the overall risks of ED visits and hospitalization in the Emergent Omicron cohort were 3.89% and 0.96% respectively, significantly lower than 21.01% and 2.65% in the matched Delta cohort (RR for ED visit: 0.19, 95% CI: 0.14-0.25; RR for hospitalization: 0.36, 95% CI: 0.19-0.68). Similar trends were observed for other pediatric age groups (5-11, 12-17 years), adults (18-64 years) and older adults (≥ 65 years).

Conclusions

First time SARS-CoV-2 infections occurring at a time when the Omicron variant was rapidly spreading were associated with significantly less severe outcomes than first-time infections when the Delta variant predominated.
Performance on verbal fluency tasks depends on the given category/letter: Preliminary data from a multivariable analysis
Authors: Gabrić Petar , Vandek Mija
Published: January 2022

Verbal fluency tasks are often used in neuropsychological research and may have predictive and diagnostic utility in psychiatry and neurology. However, researchers using verbal fluency have uncritically assumed that there are no category-or phoneme-specific effects on verbal fluency performance. We recruited 16 healthy young adult subjects and administered two semantic (animals, trees) and phonemic (K, M) fluency tasks. Because of the small sample size, results should be regarded as preliminary and exploratory. On the animal compared to the tree task, subjects produced significantly more legal words, had a significantly lower intrusion rate, significantly shorter first-response latencies and final silence periods, as well as significantly shorter between-cluster response latencies. These differences may be explained by differences in the category sizes, integrity of the categories’ borders, and efficiency of the functional connectivity between subcategories. On the K compared to the M task, subjects produced significantly more legal words and had significantly shorter between-cluster response times. Counterintuitively, a corpus analysis revealed there are more words starting with ⟨m⟩ compared to ⟨k⟩ in the experimental language. Our results potentially have important implications for research utilizing verbal fluency, including decreased reproducibility, questionable reliability of diagnostic and predictive tools based on verbal fluency, decreased knowledge accumulation, and increased number of publications with potentially misleading clinical interpretations.
Baptism of fire: Modeling the effects of prescribed fire on tick-borne disease
Authors: Guo Emily , Agusto Folashade B.
Published: January 2022

Recently, tick-borne illnesses have been trending upward and are an increasing source of risk to people’s health in the United States. This is due to range expansion in tick habitats as a result of climate change. Thus, it is imperative to find a practical and cost-efficient way of managing tick populations. Prescribed burns are a common form of land management that can be cost efficient if properly managed and can be applied across large amounts of land. In this study, we present a compartmental model for ticks carrying Lyme disease and uniquely incorporate the effects of prescribed fire using an impulsive system to investigate the effects of prescribed fire intensity (high and low) and the duration between burns. Our study found that fire intensity has a larger impact in reducing tick population than the frequency between burns. Furthermore, burning at high intensity is preferable to burning at low intensity whenever possible, although high intensity burns may be unrealistic due to environmental factors. Annual burns resulted in the most significant reduction of infectious nymphs, which are the primary carriers of Lyme disease.
How To Enhance Empathy Nursing Students In Education: Literature Review
Authors: Permana Bhakti , Pandin Moses Glorino Rumambo
Published: January 2022

Introduction

The tendency of reducing student empathy requires efforts to improve it through education or training. The purpose of this review is to identify education, learning, or teaching that is used to increase student empathy.

Method

The design used a Literature Systematic Review. Articles were conducted in three electronic databases guided by The PRISMA. Articles published in English and in 2019 to 2021.

Results

The result obtained 20 articles and will be reviewed. Eighteen articles show an effect or relationship between intervention and empathy. Training materials that can increase student empathy are the concept of empathy, communication, mindfulness, and transcultural nursing education. Education and training using patients/patient simulations to help improve student empathy, namely: expert patients, ECARE Program, polypharmacy effects; clinical Simulation of Inpatients, Lectures in class, Virtual Dementia Tour, living in poverty, and games for team interaction. Another method is through the KSS module, mannequin simulator experience, and peers.

Conclusion

Education and training on the concepts of empathy, communication, meditation, and cultural competence using Simulation and immersion methods with patients, being like patients, using mannequins, or interacting with vulnerable groups can increase student empathy. Faculty and lecturers can apply experiential learning methods with Simulation and immersion in learning or training courses.
SARS-CoV-2 screening in patients in need of urgent inpatient treatment in the Emergency Department (ED) by digitally integrated point-of-care PCR: A clinical cohort study
Authors: Möckel Martin , Bolanaki Myrto , Hofmann Jörg , Stein Angela , Hitzek Jennifer , Holert Fabian , Fischer-Rosinský Antje , Slagman Anna
Published: January 2022

Patients in need of urgent inpatient treatment were recruited prospectively. A rapid point of care PCR test (POC-PCR; Liat®) for SARS-CoV2 was conducted in the ED and a second PCR-test from the same swab was ordered in the central laboratory (CL-PCR). POC-PCR analyzers were digitally integrated in the laboratory information system.

Overall, 160 ED patients were included. A valid POC-PCR-test result was available in 96.3% (n=154) of patients. N=16 patients tested positive for SARS-CoV-2 (10.0%). The POC PCR test results were available within 102 minutes (median, IQR: 56-211), which was significantly earlier compared to the CL PCR (811 minutes; IQR: 533-1289, p < 0.001). The diagnostic accuracy of the POC-PCR test was 100%. The implementation and digital LIS integration was successfully done. Staff satisfaction with the POC process was high.

The POC-PCR testing in the emergency department is feasible and shows a very high diagnostic performance.

Trial registration: DRKS00019207
Up-regulated tumor intrinsic growth potential and decreased immune function orchestrate the evolution of lung adenocarcinoma
Authors: Zhao Yue , Shang Jun , Gao Jian , Han Han , Gao Zhendong , Yan Yueren , Zheng Qiang , Ye Ting , Fu Fangqiu , Deng Chaoqiang , Ma Zelin , Zhang Yang , Zheng Difan , Zheng Shanbo , Li Yuan , Cao Zhiwei , Shi Leming , Chen Haiquan
Published: January 2022

Introduction

Lung adenocarcinoma is the most common pathological subtype of lung cancer. Precursors of lung adenocarcinoma, namely adenocarcinoma in situ and minimally invasive adenocarcinoma, have a superb 5-year survival rate after surgical resection. A deeper understanding of the key genetic changes driving the progression of lung adenocarcinoma is needed.

Methods

In this study, we performed whole-exome sequencing and RNA-sequencing on surgically resected 24 AIS, 74 MIA, 99 LUAD specimens and their adjacent paired normal tissues. Radiological, clinical, and pathological characteristics were recorded. Gene expression patterns were identified to find key pathways driving the progression of lung adenocarcinoma. Furthermore, genomic alterations and differential expression analyses were performed to compare tumors with different radiological manifestations. Finally, a progressive index was developed to quantitatively measure the level of imbalance between tumor intrinsic growth potential and immune microenvironment.

Results

12 patterns of gene expression were identified. Pathways associated with tumor growth and metastasis were found to be up-regulated as tumors progressed, while pathways associated with immune function were found to be down-regulated. Deconvolution of RNA-seq data also showed a decrease of CD8+ T cells and an increase of Tregs as the tumors progressed. Furthermore, tumors with more solid components on CT scan had a higher mutation frequency of tumor suppressor genes, higher tumor mutation burden and higher frequency of somatic copy number alterations. Finally, tumor progressive index demonstrated an increasing trend with the progression of lung adenocarcinoma.

Discussion

Our results reveal the imbalance of tumor intrinsic factors and immune function orchestrate the progression of lung adenocarcinoma.
Use of Andrographis paniculata (Burm.f.) Wall. ex Nees and risk of pneumonia in hospitalised patients with mild COVID-19: a retrospective cohort study
Authors: Tanwettiyanont Jeeranan , Piriyachananusorn Napacha , Sangsoi Lilit , Boonsong Benjawan , Sunpapoa Chamlong , Tanamatayarat Patcharawan , Na-Ek Nat , Kanchanasurakit Sukrit
Published: January 2022

Background

Andrographis paniculata (Burm.f.) Wall. ex Nees (AP) has been widely used in Thailand to treat mild COVID-19 infections since early 2020; however, supporting evidence is scarce and ambiguous. Thus, this study aimed to examine whether the use of AP is associated with a decreased risk of pneumonia in hospitalised mild COVID-19 patients.

Methods

We collected data between March 2020 and August 2021 from COVID-19 patients admitted to one hospital in Thailand. Patients whose infection was confirmed by real-time polymerase chain reaction, had normal chest radiography and did not receive favipiravir at admission were included and categorised as either AP (deriving from a dried and ground aerial part of the plant), given as capsules with a total daily dose of 180 mg of andrographolide for five days or standard of care. They were followed for pneumonia confirmed by chest radiography. Multiple logistic regression was used for the analysis controlling for age, sex, diabetes, hypertension, statin use, and antihypertensive drug use.

Results

A total of 605 out of 1,054 patients (mostly unvaccinated) were included in the analysis. Of these, 59 patients (9.8%) developed pneumonia during the median follow-up of 7 days. The incidence rates of pneumonia were 13.93 (95% CI 10.09, 19.23) and 12.47 (95% CI 8.21, 18.94) per 1,000 person-days in the AP and standard of care groups, respectively. Compared to the standard of care group, the odds ratios of having pneumonia in the AP group were 1.24 (95% CI 0.71, 2.16; unadjusted model) and 1.42 (95% CI 0.79, 2.55; fully adjusted model). All sensitivity analyses were consistent with the main results.

Conclusions

The use of AP was not significantly associated with a decreased risk of pneumonia in mild COVID-19 patients. While waiting for insights from ongoing trials, AP’s use in COVID-19 should be done with caution.
The NILS study protocol - a retrospective validation study of a preoperative decision-making tool for non-invasive lymph node staging in women with primary breast cancer [ISRCTN14341750]
Authors: Skarping Ida , Dihge Looket , Bendahl Pär-Ola , Huss Linnea , Ellbrant Julia , Ohlsson Mattias , Rydén Lisa
Published: January 2022

Background

Routine preoperative axillary ultrasonography has proven insufficient for detecting low-burden nodal metastatic deposits. For the majority of newly diagnosed breast cancer patients presenting with clinical T1-T2 N0 disease, the standard axillary staging by sentinel lymph node biopsy is not therapeutic. The pilot non-invasive lymph node staging (NILS) artificial neural network (ANN) model to predict nodal status was published in 2019. The aim of the current study is to assess the performance measures of the model for the prediction of healthy lymph nodes in clinically N0 breast cancer patients at two breast cancer centers in Sweden.

Methods

This bicenter, observational, retrospective study has been designed to validate the NILS prediction model for nodal status using preoperatively collected clinicopathological and radiological data. A web-based implementation of the nodal status classifier has been developed and will be used in this study, resulting in an estimated probability of healthy lymph nodes for each study participant. Our primary endpoint is to report on the performance of the NILS prediction model to distinguish between healthy and metastatic lymph nodes (discrimination, N0 vs. N+) and compare the observed and predicted event rates of benign axillary nodal status (calibration).

Discussion

Internationally, there are numerous artificial intelligence projects involving non-invasive identification of N0 breast cancer. Here, we present a robust validation study based on external cohorts of our ANN model. Although validation is necessary to show generalizability, it is often overlooked. If the accuracy and discrimination reach a satisfactory level, our prediction tool can be implemented to assist medical professionals and breast cancer patients in shared decision-making on omitting sentinel node biopsy in patients predicted to be node-negative. In future, this may potentially save healthcare resources and reduce costs and adverse side effects. In addition, our study might prompt future studies of nodal metastases of malignancies in other organs, and thus might have implications beyond breast cancer.

Trial registration

This study has been prospectively registered in the ISRCTN registry, identification number: 14341750
Large household reduces dementia mortality
Authors: You Wenpeng , Henneberg Maciej
Published: January 2022

Background

Large households/families create more positive psychological well-being which may offer a life course protection against dementia development and deliver more comprehensive healthcare to dementia patients.

Methods

Dementia specific mortality rates of the 183 member states of World Health Organization were calculated and matched with the respective country data on household size, Gross Domestic Product (GDP), urban and ageing. Scatter plots were produced to explore and visualize the correlations between household size and dementia mortality rates. Pearson’s and nonparametric correlations were used to evaluate the strength and direction of the associations between household size and all other variables. Partial correlation of Pearson’s moment-product approach was used to identify that household size protects against dementia regardless of the competing effects from ageing, GDP and urbanization. Multiple regression identified large household was a significant predictor of dementia mortality.

Results

Household size was in a negative and moderately strong correlation (r = -0.6034, p < 0.001) with dementia mortality. This relationship was confirmed in both Pearson r (r= - 0.524, p<0.001) and nonparametric (rho□=□-0.579, p□<□0.001) analyses. Regardless of the contribution of ageing, SES and urban lifestyle to dementia mortality, large household was an independent predictor of dementia mortality (r = -0.331, p <0.001) in partial correlation analysis. Stepwise multiple regression analysis selected large household as the variable having the greatest contribution to dementia mortality with R2 = 0.263 while ageing was placed second increasing R2 to 0.259. GDP and urbanization were removed as having no statistically significant influence on dementia mortality.

Conclusions

Independent of ageing, urbanization and GDP, large household protects against dementia mortality. As part of dementia prevention, healthcare practitioners should encourage people to increase their positive interactions with persons from their neighbourhood or other fields where large household/family size is hard to achieve.
Cognitive predictors of vaccine hesitancy and COVID-19 mitigation behaviors in a population representative sample
Authors: Hudson Anna , Hall Peter A. , Hitchman Sara C. , Meng Gang , Fong Geoffrey T.
Published: January 2022

With the continued threat of COVID-19, predictors of vaccination hesitancy and mitigation behaviors are critical to identify. Prior studies have found that cognitive factors are associated with some COVID-19 mitigation behaviors, but few studies employ representative samples and to our knowledge no prior studies have examined cognitive predictors of vaccine hesitancy. The purpose of the present study, conducted among a large national sample of Canadian adults, was to examine associations between cognitive variables (executive function, delay discounting, and temporal orientation) and COVID-19 mitigation behaviors (vaccination, mask wearing, social distancing, and hand hygiene). Findings revealed that individuals with few executive function deficits, limited delay discounting and who adopted a generally future-orientation mindset were more likely to be double-vaccinated and to report performing COVID-19 mitigation behaviors with high consistency. The most reliable findings were for delay discounting and future orientation, with executive function deficits predicting mask wearing and hand hygiene behaviors but not distancing and vaccination. These findings identify candidate mediators and moderators for health communication messages targeting COVID-19 mitigation behaviors and vaccine hesitancy.
Vaccines Elicit Highly Cross-Reactive Cellular Immunity to the SARS-CoV-2 Omicron Variant
Authors: Liu Jinyan , Chandrashekar Abishek , Sellers Daniel , Barrett Julia , Lifton Michelle , McMahan Katherine , Sciacca Michaela , VanWyk Haley , Wu Cindy , Yu Jingyou , Collier Ai-ris Y. , Barouch Dan H.
Published: January 2022

The highly mutated SARS-CoV-2 Omicron (B.1.1.529) variant has been shown to evade a substantial fraction of neutralizing antibody responses elicited by current vaccines that encode the WA1/2020 Spike immunogen1, resulting in increased breakthrough infections and reduced vaccine efficacy. Cellular immune responses, particularly CD8+ T cell responses, are likely critical for protection against severe SARS-CoV-2 disease2-6. Here we show that cellular immunity induced by current SARS-CoV-2 vaccines is highly cross-reactive against the SARS-CoV-2 Omicron variant. Individuals who received Ad26.COV2.S or BNT162b2 vaccines demonstrated durable CD8+ and CD4+ T cell responses that showed extensive cross-reactivity against both the Delta and Omicron variants, including in central and effector memory cellular subpopulations. Median Omicron-specific CD8+ T cell responses were 82-84% of WA1/2020-specific CD8+ T cell responses. These data suggest that current vaccines may provide considerable protection against severe disease with the SARS-CoV-2 Omicron variant despite the substantial reduction of neutralizing antibody responses.
Optogenetic Manipulation of Cell Migration with High Spatiotemporal Resolution Using Lattice Lightsheet Microscopy
Authors: Tang Wei-Chun , Liu Yen-Ting , Yeh Cheng-Han , Lin Yi-Ling , Lin Yu-Chun , Hsu Tsui-Ling , Gao Liang , Chang Shu-Wei , Chen Peilin , Chen Bi-Chang
Published: January 2022

Lattice lightsheet microscopy (LLSM) is modified with the aim of manipulating cellular behavior with subcellular resolution through three-dimensional (3D) optogenetic activation. In this study, we report a straightforward implementation of the activation source in LLSM in which the stimulating light can be generated by changing the spatial light modulator (SLM) patterns and the annual masks. As a result, a Bessel beam as a stimulation source is integrated into the LLSM without changing the optical configuration, achieving better spatiotemporal control of photoactivation. We show that the energy power required for optogenetic reactions is lower than 1 nW (or 24 mW/cm2), and membrane ruffling can be activated at different locations within a cell with subcellular resolution. We also demonstrate guided cell migration using optogenetic stimulation for up to 6 h, where 463 imaging volumes are collected, without noticeable damage to cells.
The Layer 7 Cortical Interface: A Scalable and Minimally Invasive Brain–Computer Interface Platform
Authors: Hettick Mark , Ho Elton , Poole Adam J. , Monge Manuel , Papageorgiou Demetrios , Takahashi Kazutaka , LaMarca Morgan , Trietsch Daniel , Reed Kyle , Murphy Mark , Rider Stephanie , Gelman Kate R. , Byun Yoon Woo , Hanson Timothy , Tolosa Vanessa , Lee Sang-Ho , Bhatia Sanjay , Konrad Peter E. , Mager Michael , Mermel Craig H. , Rapoport Benjamin I.
Published: January 2022

Progress toward the development of brain–computer interfaces has signaled the potential to restore, replace, and augment lost or impaired neurological function in a variety of disease states. Existing approaches to developing high-bandwidth brain–computer interfaces rely on invasive surgical procedures or brain-penetrating electrodes, which limit addressable applications of the technology and the number of eligible patients. Here we describe a novel approach to constructing a neural interface, comprising conformable thin-film electrode arrays and a minimally invasive surgical delivery system that together facilitate bidirectional communication with large portions of the cortical surface (enabling both recording and stimulation). We demonstrate the feasibility and safety of delivering reversible implants containing over 2,000 microelectrodes to multiple functional regions in both hemispheres of the brain simultaneously, without requiring a craniotomy or damaging the cortical surface, at an effective insertion rate faster than 40 ms per channel. We further evaluate the performance of this system immediately following implantation for high-density neural recording and visualizing cortical surface activity at spatial and temporal resolutions and extents not previously possible in multiple preclinical large animal studies as well as in a five-patient pilot clinical study involving both anesthetized and awake neurosurgical patients. We characterize the spatial scales at which sensorimotor activity and speech are represented at the cortical surface, demonstrate accurate neural decoding of somatosensory, visual, and volitional walking activity, and achieve precise neuromodulation through cortical stimulation at sub-millimeter scales. The resulting system generates 90 Gb/h of electrophysiologic data, and demonstrates the highly scalable nature of micro-electrocorticography and its utility for next-generation brain-computer interfaces that may expand the patient population that could benefit from neural interface technology.
Retrieval context determines whether event boundaries impair or enhance temporal order memory
Authors: Wen Tanya , Egner Tobias
Published: January 2022

Meaningful changes in context create “event boundaries”, segmenting continuous experience into distinct episodes in memory. A foundational finding in this literature is that event boundaries impair memory for the temporal order of stimuli spanning a boundary compared to equally spaced stimuli within an event. This seems surprising in light of intuitions about memory in everyday life, where the order of within-event experiences (did I have coffee before the first bite of bagel?) often seems more difficult to recall than the order of events per se (did I have breakfast or do the dishes first?). Here, we aimed to resolve this discrepancy by manipulating whether stimuli carried information about their encoding context during retrieval, as they often do in everyday life (e.g., bagel-breakfast). In Experiments 1 and 2, we show that stimuli inherently associated with a unique encoding context produce a “flipped” order memory effect, whereby temporal memory was superior for cross-boundary than within-event item pairs. In Experiments 3 and 4, we added context information at retrieval to a standard laboratory event memory protocol where stimuli were encoded in the presence of arbitrary context cues (colored frames). We found that whether temporal order memory for cross-boundary stimuli was enhanced or impaired relative to within-event items depended on whether the context was present or absent during the memory test. Taken together, we demonstrate that the effect of event boundaries on temporal memory is malleable, and determined by the availability of context information at retrieval.
Intestinal Mucin Is a Chaperone of Multivalent Copper
Authors: Reznik Nava , Gallo Annastassia D. , Rush Katherine W. , Javitt Gabriel , Fridmann-Sirkis Yael , Ilani Tal , Nairner Noa A. , Chacón Kelly N. , Franz Katherine J. , Fass Deborah
Published: January 2022

Mucus protects the body by many mechanisms, but a role in managing toxic transition metals was not previously known. Here we report that secreted mucins, the major mucus glycoproteins coating the respiratory and intestinal epithelia, are specific copper-binding proteins. Most remarkably, the intestinal mucin, MUC2, has two juxtaposed copper binding sites, one that accommodates Cu2+and the other Cu1+, which can be formedin situby reduction with vitamin C. Copper is an essential trace metal because it is a cofactor for a variety of enzymes catalyzing electron transfer reactions, but copper damages macromolecules when unregulated. We observed that MUC2 protects against copper toxicity while permitting nutritional uptake into cells. These findings introduce mucins, produced in massive quantities to guard extensive mucosal surfaces, as extracellular copper chaperones and potentially important players in physiological copper homeostasis.
Determinants of entrepreneurial alertness: towards sustainable agribusiness development
Authors: Shiri Nematollah , Mehdizadeh Hossein , Khoshmaram Mojgan , Azadi Hossein
Published: January 2022

Purpose

Entrepreneurship is known to be important to the economy, and many scholars across the globe have researched it from a number of viewpoints. Currently, there is a need for an academic study to explore this area by combining sustainability value creating practices and the efforts of current entrepreneurs towards the said target, particularly in the case of the agricultural sector. While the entrepreneurship studies have mostly focused on the determinants of entrepreneurial opportunity recognition, few studies have attempted to analyze the factors influencing the entrepreneurial alertness (EA) of students, especially in relation to agricultural students. To fill this gap, this work investigated the impact of human and social capital on EA among the students of agricultural higher education in Iran.

Design/methodology/approach

The sample consisted of 254 agricultural students in higher education from Ilam province in the Islamic Republic of Iran, selected by the stratified random sampling method for the study. Modeling of structural equations was used in inferential statistics.

Findings

According to the results of the trial, human resources and social capital (SC) have been seen to have a strong, optimistic and measurable impact on EA. Key findings also show that human capital (HC) has an indirect, optimistic and important effect on EA through the mediator role of SC. Establishing higher education science teams, groups, networks and associations can foster opportunities to create and develop relationships and communication between agricultural students and entrepreneurs.

Originality/value

These findings illustrate the value of human and social resources in fostering entrepreneurship alertness among Iranian students of agricultural higher education. Considering the research results, the authors recommend some theoretical and realistic implications and suggestions for ways of promoting and increasing EA among farm students to encourage sustainable growth of agricultural careers in western Iran.
The emotional cost-of-carry: Chinese investor sentiment and equity index futures basis
Authors: Cao Song , Li Ziran , Koedijk Kees G. , Gao Xiang
Published: January 2022

Purpose

While the classic futures pricing tool works well for capital markets that are less affected by sentiment, it needs further modification in China's case as retail investors constitute a large portion of the Chinese stock market participants. Their expectations of the rate of return are prone to emotional swings. This paper, therefore, explores the role of investor sentiment in explaining futures basis changes via the channel of implied discount rates.

Design/methodology/approach

Using Chinese equity market data from 2010 to 2019, the authors augment the cost-of-carry model for pricing stock index futures by incorporating the investor sentiment factor. This design allows us to estimate the basis in a better way that reflects the relationship between the underlying index price and its futures price.

Findings

The authors find strong evidence that the measure of Chinese investor sentiment drives the abnormal fluctuations in the basis of China's stock index futures. Moreover, this driving force turns out to be much less prominent for large-cap stocks, liquid contracting frequencies, regulatory loosening periods and mature markets, further verifying the sentiment argument for basis mispricing.

Originality/value

This study contributes to the literature by relying on investor sentiment measures to explain the persistent discount anomaly of index futures basis in China. This finding is of great importance for Chinese investors with the intention to implement arbitrage, hedging and speculation strategies.