bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Opioid-Minimizing Pain Protocols After Burn Injury
Authors: Donthula Deepanjli , Conner Christopher R , Truong Van Thi Thanh , Green Charles , Jiang Chuantao , Wandling Michael W , Komak Spogmai , Huzar Todd F , Adams Sasha D , Freet Daniel J , Wainwright David J , Wade Charles E , Kao Lillian S , Harvin John A
Published: July 2021

In 2019, we implemented a pill-based, opioid-minimizing pain protocol and protocolized moderate sedation for dressing changes in order to decrease opioid exposure in burn patients. We hypothesized that these interventions would reduce inpatient opioid exposure without increasing acute pain scores. Two groups of consecutive patients admitted to the burn service were compared: Pre-group (from January 1, 2018 to July 31, 2019) and Post-group (from January 1, 2020 to June 30, 2020) from before and after the implementation of the protocols (from August 1, 2019 to December 31, 2019). We abstracted patient demographics and burn injury characteristics from the burn registry. We obtained opioid exposure and pain scale scores from the electronic medical record. The primary outcome was total morphine milligram equivalents (MMEs). Secondary outcomes included MMEs/day, pain domain-specific MMEs, and pain scores. Pain was estimated by creating a normalized pain score (range 0–1), which incorporated three different pain scales (Numeric Rating Scale, Behavioral Pain Scale, and Behavioral Pain Assessment Scale). Groups were compared using Wilcoxon rank-sum and chi-square tests. Treatment effects were estimated using Bayesian generalized linear models. There were no differences in demographics or burn characteristics between the Pre-group (n = 495) and Post-group (n = 174). The Post-group had significantly lower total MMEs (Post-group 110 MMEs [32, 325] vs Pre-group 230 [60, 840], P < .001), MMEs/day (Post-group 33 MMEs/day [15, 54] vs Pre-group 52 [27, 80], P < .001), and domain-specific total MMEs. No difference in average normalized pain scores was seen. Implementation of opioid-minimizing protocols for acute burn pain was associated with a significant reduction in inpatient opioid exposure without an increase in pain scores.
TheAedes aegypti(Diptera: Culicidae)hsp83Gene Promoter Drives Strong Ubiquitous DsRed and ZsGreen Marker Expression in Transgenic Mosquitoes
Authors: Webster Sophia H , Scott Maxwell J
Published: July 2021

Transgenic strains of the mosquito disease vector Aedes aegypti (L.) are being developed for population suppression or modification. Transgenic mosquitoes are identified using fluorescent protein genes. Here we describe DsRed and ZsGreen marker genes driven by the constitutive Ae. aegypti heat shock protein 83 (hsp83) promoter in transgenic mosquitoes. Transgenic larvae and pupae show strong full body expression of the red and green fluorescent proteins. This greatly assists in screening for transgenic individuals while making new or maintaining already established lines. Transient marker gene expression after embryo microinjection was readily visible in developing larvae allowing the separation of individuals that are more likely to produce transgenic offspring. The strongly expressed marker genes developed in this study should facilitate the detection of transgenic Ae. aegypti larvae or pupae in the field.
In situ observation of the chemical bonding state of Si in the molten state of eutectic Au–Si alloy of Au81Si19 by using a soft X-ray emission spectroscopy electron microscope
Authors: Terauchi Masami , Umemoto Naoya , K. Sato Yohei , Ageishi Masaki , Tsai An-Pang
Published: July 2021

Phase diagram of Au–Si binary alloy system shows a large drop in melting temperature of about 1000K compared with that of Si at a composition of Au:Si = 81:19, where the melting temperature is about 636K. Mixing of Au and Si below the melting temperature was observed by transmission electron microscopy experiment, and it was found that the mixed region shows a diffraction pattern of a diffuse ring intensity indicating an amorphous structure of the mixed area. Si L-emission spectra, which reflect the energy state of bonding electrons of Si atom, of molten Au81Si19 alloy were measured for the first time to investigate the energy state of valence electrons of Si. The Si L-emission spectrum showed a characteristic loss of L1 peak, which is related to sp3 directional bonding in crystalline Si. The intensity profile is also different from that of molten Si reported. This suggests a characteristic atomic arrangement that exists in the molten state. The intensity profile also indicated a small density of state in the molten state at Fermi energy. The obtained spectrum was compared with the calculated density of state of possible crystal structures reported. The comparison suggested that Si atoms are surrounded by eight Au atoms in the molten state of Au81Si19 alloy. The formation of this local atomic arrangement can be an origin of a large drop of melting temperature at about Au:Si = 81:19.
Rank-Based Inference for Survey Sampling Data
Authors: Adekpedjou Akim , Bindele Huybrechts F
Published: July 2021

For regression models where data are obtained from sampling surveies, the statistical analysis is often based on approaches that are either non-robust or inefficient. The handling of survey data requires more appropriate techniques, as the classical methods usually result in biased and inefficient estimates of the underlying model parameters. This article is concerned with the development of a new approach of obtaining robust and efficient estimates of regression model parameters when dealing with survey sampling data. Asymptotic properties of such estimators are established under mild regularity conditions. To demonstrate the performance of the proposed method, Monte Carlo simulation experiments are carried out and show that the estimators obtained from the proposed methodology are robust and more efficient than many of those obtained from existing approaches, mainly if the survey data tend to result in residuals with heavy-tailed or skewed distributions and/or when there are few gross outliers. Finally, the proposed approach is illustrated with a real data example.
A co-designed integrated kidney and diabetes model of care improves mortality, glycaemic control and self-care
Authors: Zimbudzi Edward , Lo Clement , Ranasinha Sanjeeva , Earnest Arul , Teede Helena , Usherwood Tim , Polkinghorne Kevan R , Fulcher Gregory , Gallagher Martin , Jan Stephen , Cass Alan , Walker Rowan , Russell Grant , Johnson Greg , Kerr Peter G , Zoungas Sophia
Published: July 2021

Background

Current healthcare models are ill-equipped for managing people with diabetes and chronic kidney disease (CKD). We evaluated the impact of a new diabetes and kidney disease service (DKS) on hospitalization, mortality, clinical and patient-relevant outcomes.

Methods

Longitudinal analyses of adult patients with diabetes and CKD (Stages 3a–5) were performed using outpatient and hospitalization data from January 2015 to October 2018. Data were handled according to whether patients received the DKS intervention (n = 196) or standard care (n = 7511). The DKS provided patient-centred, coordinated multidisciplinary assessment and management of patients. Primary analyses examined hospitalization and mortality rates between the two groups. Secondary analyses evaluated the impact of the DKS on clinical target attainment, changes in estimated glomerular filtration rate (eGFR), glycated haemoglobin A1c (HbA1c), self-care and patient activation at 12 months.

Results

Patients who received the intervention had a higher hospitalization rate {incidence rate ratio [IRR] 1.20 [95% confidence interval (CI) 1.13–1.30]; P < 0.0001}, shorter median length of stay {2 days [interquartile range (IQR) 1–6] versus 4 days [IQR 1–9]; P < 0.0001} and lower all-cause mortality rate [IRR 0.4 (95% CI 0.29–0.64); P < 0.0001] than those who received standard care. Improvements in overall self-care [mean difference 2.26 (95% CI 0.83–3.69); P < 0.001] and in statin use and eye and feet examinations were observed. The mean eGFR did not change significantly after 12 months [mean difference 1.30 mL/min/1.73 m2 (95% CI −4.17–1.67); P = 0.40]. HbA1c levels significantly decreased by 0.40, 0.35, 0.34 and 0.23% at 3, 6, 9 and 12 months of follow-up, respectively.

Conclusions

A co-designed, person-centred integrated model of care improved all-cause mortality, kidney function, glycaemic control and self-care for patients with diabetes and CKD.
Thalamic Deep Brain Stimulation Ameliorates Mixed and Abductor Spasmodic Dysphonia: Case Reports and Proof of Concept
Authors: Honey C Michael , Hart Michael G , Rammage Linda A , Morrison Murray D , Hu Amanda , Honey Christopher R
Published: July 2021

BACKGROUND AND IMPORTANCE

Spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. A recent randomized controlled trial showed that thalamic deep brain stimulation (DBS) was safe and could improve this condition in the most common subtype—adductor SD. We investigated if thalamic DBS could also improve the other subtypes of abductor SD and mixed SD. These prospective blinded trials of 1 were designed to assess the safety of thalamic DBS in mixed and abductor SD and to quantify the magnitude of any benefit from unilateral or bilateral thalamic stimulation.

CLINICAL PRESENTATION

One patient with mixed SD and one patient with abductor SD received bilateral thalamic DBS. After optimizing their DBS settings for vocal improvement, they were blinded and prospectively randomized to receive 1 mo of left, right, both, or neither hemisphere stimulation. Outcome was assessed by a speech language pathologist, blinded to the settings, rating voice recordings with the Unified Spasmodic Dysphonia Rating Scale, and by patient self-reported quality-of-life questionnaires. Additional outcomes included scores of mood and cognition. There were no complications. Both patients reported a subjective improvement of their voice and quality of life with blinded left thalamic DBS. The quality of their voice was also objectively rated as improved with blinded left thalamic DBS.

CONCLUSION

This small proof-of-concept study suggests that left thalamic DBS can improve the quality of voice and quality of life of patients with mixed SD and abductor SD.
Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study
Authors: Burke Rebecca M , Chen Ching-Jen , Ding Dale , Buell Thomas J , Sokolowski Jennifer , Sheehan Kimball A , Lee Cheng-Chia , Sheehan Darrah E , Kano Hideyuki , Kearns Kathryn N , Tzeng Shih-Wei , Yang Huai-che , Huang Paul P , Kondziolka Douglas , Ironside Natasha , Mathieu David , Iorio-Morin Christian , Grills Inga S , Feliciano Caleb , Barnett Gene , Starke Robert M , Lunsford L Dade , Sheehan Jason P ,   on behalf of the International Radiosurgery Research Foundation
Published: July 2021

BACKGROUND

Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood.

OBJECTIVE

To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs.

METHODS

We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC).

RESULTS

The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%,  < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013).

CONCLUSION

Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role.
ADD It Up: An Evaluation of Antibiotic Duration at Hospital Discharge at a Community Hospital
Authors: Conner Morgan , Harris William H , Bomkamp John P
Published: July 2021

Background

According to the Centers for Disease Control and Prevention, patients admitted to the hospital are commonly discharged on antibiotic therapy with prolonged courses of therapy, which contributes to excessive antibiotic exposure and adverse events. The purpose of this study was to evaluate total antibiotic duration of therapy at hospital discharge at Indiana University Health Arnett, White Memorial, and Frankfort hospitals.

Methods

A multicenter, retrospective electronic health record review was conducted from 1 January to 30 June 2019. Patients were included if they were at least 18 years of age, began antibiotic therapy while admitted, and continued antibiotic therapy at hospital discharge for 1 of the following indications: skin/soft tissue infection (SSTI), urinary tract infection (UTI), community-acquired pneumonia (CAP), or acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The number of days of therapy (DOT) of each inpatient and outpatient antibiotic prescribed was collected to calculate the total DOT, which was utilized to determine the appropriateness of the duration of therapy.

Results

Of the 547 patients included, 233 patients (42.6%) had CAP, 120 (21.9%) had UTI, 101 (18.5%) had SSTI, and 93 (17%) had AECOPD. The median duration of antibiotic therapy across all indications was 9 days (interquartile range [IQR], 7–11). Median duration for CAP was 9 days (IQR, 7–10), AECOPD was 7 days (IQR, 5–9), UTI was 8 days (IQR, 6–10), and SSTI was 12 days (IQR, 10–14).

Conclusions

Excess antimicrobial duration at hospital discharge represents an unmet need of antimicrobial stewardship programs.
Machine learning-enabled phenotyping for GWAS and TWAS of WUE traits in 869 field-grown sorghum accessions
Authors: Ferguson John N , Fernandes Samuel B , Monier Brandon , Miller Nathan D , Allen Dylan , Dmitrieva Anna , Schmuker Peter , Lozano Roberto , Valluru Ravi , Buckler Edward S , Gore Michael A , Brown Patrick J , Spalding Edgar P , Leakey Andrew D B
Published: July 2021

Sorghum (Sorghum bicolor) is a model C4 crop made experimentally tractable by extensive genomic and genetic resources. Biomass sorghum is studied as a feedstock for biofuel and forage. Mechanistic modeling suggests that reducing stomatal conductance (gs) could improve sorghum intrinsic water use efficiency (iWUE) and biomass production. Phenotyping to discover genotype-to-phenotype associations remains a bottleneck in understanding the mechanistic basis for natural variation in gs and iWUE. This study addressed multiple methodological limitations. Optical tomography and a machine learning tool were combined to measure stomatal density (SD). This was combined with rapid measurements of leaf photosynthetic gas exchange and specific leaf area (SLA). These traits were the subject of genome-wide association study and transcriptome-wide association study across 869 field-grown biomass sorghum accessions. The ratio of intracellular to ambient CO2 was genetically correlated with SD, SLA, gs, and biomass production. Plasticity in SD and SLA was interrelated with each other and with productivity across wet and dry growing seasons. Moderate-to-high heritability of traits studied across the large mapping population validated associations between DNA sequence variation or RNA transcript abundance and trait variation. A total of 394 unique genes underpinning variation in WUE-related traits are described with higher confidence because they were identified in multiple independent tests. This list was enriched in genes whose Arabidopsis (Arabidopsis thaliana) putative orthologs have functions related to stomatal or leaf development and leaf gas exchange, as well as genes with nonsynonymous/missense variants. These advances in methodology and knowledge will facilitate improving C4 crop WUE.
Capturing in-field root system dynamics with RootTracker
Authors: Aguilar Jeffrey J , Moore Matt , Johnson Logan , Greenhut Rachel F , Rogers Eric , Walker Drew , O’Neil Fletcher , Edwards Jake L , Thystrup Jake , Farrow Sam , Windle Jesse B , Benfey Philip N
Published: July 2021

Optimizing root system architecture offers a promising approach to developing stress tolerant cultivars in the face of climate change, as root systems are critical for water and nutrient uptake as well as mechanical stability. However, breeding for optimal root system architecture has been hindered by the difficulty in measuring root growth in the field. Here, we describe the RootTracker, a technology that employs impedance touch sensors to monitor in-field root growth over time. Configured in a cylindrical, window shutter-like fashion around a planted seed, 264 electrodes are individually charged multiple times over the course of an experiment. Signature changes in the measured capacitance and resistance readings indicate when a root has touched or grown close to an electrode. Using the RootTracker, we have measured root system dynamics of commercial maize (Zea mays) hybrids growing in both typical Midwest field conditions and under different irrigation regimes. We observed rapid responses of root growth to water deficits and found evidence for a “priming response” in which an early water deficit causes more and deeper roots to grow at later time periods. Genotypic variation among hybrid maize lines in their root growth in response to drought indicated a potential to breed for root systems adapted for different environments. Thus, the RootTracker is able to capture changes in root growth over time in response to environmental perturbations.
Chlamydomonas as a model for reactive oxygen species signaling and thiol redox regulation in the green lineage
Authors: Wakao Setsuko , Niyogi Krishna K.
Published: July 2021

One-sentence summary: Advances in proteomic and transcriptomic studies have made Chlamydomonas a powerful research model in redox and reactive oxygen species regulation with unique and overlapping mechanisms with plants.
International Police Liaison Officers: An Examination of the Experiences of New Zealand Police International Liaison Officers
Authors: den Heyer Garth
Published: July 2021

Since the early 1970s, international police liaison officers have been a pivotal resource in building and maintaining relationships and cooperation between the police and other law enforcement organizations. Their role and their contribution to investigating transnational crime and terrorism have not been examined. This research includes a survey of 18 serving police officers, who were, or had been appointed to international liaison posts, by the New Zealand Police. The participants claimed that their role was to establish networks, gather information and intelligence followed by undertaking inquiries in relation to criminal and drug investigations. To a lesser extent, the participants thought that the purpose of their role was to counter terrorism, undertake immigration inquiries, and to attend social events.
Bisphenol A and Male Murine Reproductive System: Finding a Link between Plasticizer and Compromised Health
Authors: Mondal Shirsha , Bandyopadhyay Arindam
Published: July 2021

The global burden of male infertility is rising at an alarming rate affecting the lives of millions in terms of physical, emotional, and societal perspectives. Among several existing endocrine-disrupting chemicals, bisphenol A (BPA) has been reported by many to inflict male reproductive toxicity in different experimental models, especially in mice. This review article critically discusses the overall reproductive toxicity of BPA with a special note to its ubiquitous existence, contamination route, effects on the reproductive system, and toxicity mechanisms in male mice. Disturbed redox status in germ cells and spermatozoa plays a pivotal role in BPA-induced male reproductive toxicity. In this context, the involvement of mitochondria and endoplasmic reticulum is also of grave importance. Induction of caspase-dependent apoptosis is the extreme consequence that leads to deterioration of cellular parameters. Besides the oxidative cellular and histoarchitectural damages, perturbed endocrine regulation, subsequent impaired hormonal and cellular genesis program, epigenetic alterations, and inflammation cumulatively reflect poor sperm quality leading to compromised reproduction. Moreover, several key issues have also been highlighted that, if addressed, will strengthen our understanding of BPA-mediated male reproductive toxicity.
Association of lipid-lowering drugs with COVID-19 outcomes: A Mendelian Randomization study
Authors: Huang Wuqing , Xiao Jun , Ji Jianguang , Chen Liang-Wan
Published: July 2021

Background

Lipid metabolism plays an important role in viral infections. Large cohort study suggested a protective potential of lipid-lowering drugs in COVID-19 outcomes, but the nature of observational study precludes it to draw a causal inference.

Objectives

To assess the causal effect of lipid-lowering drugs (HMGCR inhibitors, PCSK9 inhibitors and NPC1L1 inhibitors) on COVID-19 outcomes using 2-sample Mendelian Randomization (MR) study.

Methods

We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including expression quantitative trait loci (eQTLs) of drugs target genes, and genetic variants within or nearby drugs target genes associated with low-density lipoprotein (LDL) cholesterol from genome-wide association study (GWAS). GWASs of COVID-19 outcomes (susceptibility, hospitalization and very severe disease) were obtained from the COVID-19 Host Genetics Initiative. Summary-data-based MR (SMR) and inverse-variance weighted MR (IVW-MR) were used to calculate the effect estimates.

Results

SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (OR=1.38, 95%CI=1.06-1.81; P=0.019). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR=1.32, 95%CI=1.00-1.74; P=0.049). No consistent evidence from both SMR and IVW-MR analyses was found for the association of HMGCR inhibitors with COVID-19 susceptibility or very severe disease, or for the association of PCSK9 inhibitors and NPC1L1 inhibitor with COVID-19 outcomes.

Conclusions

In this 2-sample MR study, we found potential causal evidence that HMGCR inhibitors could reduce the risk of COVID-19 hospitalization. Further research is needed to explore the therapeutic role of statins for COVID-19.
Incidence of Lyme disease in the United Kingdom and association with fatigue: a population-based, historical cohort study
Authors: Brellier Florence , Pujades-Rodriguez Mar , Powell Emma , Mudie Kathleen , Lacerda Eliana , Nacul Luis , Wing Kevin
Published: July 2021

Objectives

To evaluate incidence rates of Lyme disease in the UK and to investigate a possible association with subsequent fatigue

Design

Population-based historical cohort study with a comparator cohort matched by age, sex, and general practice

Setting

Patients treated in UK general practices contributing to IQVIA Medical Research Data

Participants

2,130 patients with a first diagnosis of Lyme disease between 2000 and 2018, and 8,510 randomly-sampled matched comparators, followed-up for a median time of 3 years and 8 months.

Main outcome measures

Time from Lyme disease diagnosis to consultation for any fatigue-related symptoms or diagnosis and for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Adjusted hazard ratios (HRs) were estimated from Cox models.

Results

Average incidence rate for Lyme disease across the UK was 5.18 per 100,000 py between 2000 and 2018, increasing from 2.55 in 2000 to 9.33 in 2018. In total 929 events of any types of fatigue were observed, i.e. an incidence rate of 307.90 per 10,000 py in the Lyme cohort (282 events) and 165.60 in the comparator cohort (647 events). Effect of Lyme disease on any subsequent fatigue varied by index season with highest adjusted HRs in autumn [3.14 (95%CI: 1.92 to 5.13)] and winter [2.23 (1.21 to 4.11)]. Incidence rates of ME/CFS were 11.16 per 10,000 py in Lyme patients (12 events) and 1.20 in comparators (5 events), corresponding to an adjusted HR of 16.95 (5.17 to 55.60). Effect on any types of fatigue and ME/CFS was attenuated 6 months after diagnosis but still clearly visible.

Conclusions

UK primary care records provided strong evidence that Lyme disease was associated with acute and chronic fatigue. Albeit weaker, these effects persisted beyond 6 months, suggesting that patients and healthcare providers should remain alert to fatigue symptoms months to years following Lyme disease diagnosis.

Key messages box

What is already known on this topic

Incidence rates of Lyme disease in the UK are increasing but estimations vary according to data sources used.

Reports investigating the association between Lyme disease and long-term fatigue are contradictory.

What this study adds

Average incidence rate for Lyme disease across the UK was estimated at 5.18 per 100,000 py between 2000 and 2018, and followed an increasing trend.

In patients with Lyme disease, a 2- and 3-fold increase in any subsequent fatigue was observed in winter and autumn, respectively, and a 16-fold increase in ME/CFS (all seasons combined), compared to a non-Lyme cohort matched by sex, age, and general practice.
Change in Symptoms and Immune Response in People with Post-Acute Sequelae of SARS-Cov-2 Infection (PASC) After SARS-Cov-2 Vaccination
Authors: Massey Daisy , Berrent Diana , Akrami Athena , Assaf Gina , Davis Hannah , Harris Karen , McCorkell Lisa , Ring Aaron M , Schulz Wade L , Wei Hannah , Krumholz Harlan M , Iwasaki Akiko
Published: July 2021

As more people are vaccinated against SARS-CoV-2, many of those already infected are still suffering from Post-Acute Sequelae (PASC). Although there is no current treatment for PASC, reports from patients that the vaccine itself improves, and in some reports, worsens, PASC symptoms may lead to a deeper understanding of the causes of PASC symptoms and viable treatments. As such, we are conducting a study that measures the changes in PASC symptoms after vaccination. We are collecting baseline self-report and biospecimens for immune assays and then are following up with participants to collect the same data at 2-weeks, 6-weeks, and 12-weeks post-vaccination (first dose). Immune assays using blood specimens will include B-cell, T-cell, and myeloid cell panels; evaluation of T-cell responsiveness to SARS-CoV-2 peptides and antigen specific response; autoantibody screening (of IgG, IgM, and IgA antibodies that attack human proteins); and TCR sequencing and antigen mapping of CD8+ T-cells. Mucosal immunity will be measured using saliva specimens. The study aims to provide answers for people with PASC, especially regarding the causes of their symptoms and how the vaccine may affect them, and clues for PASC treatment.
Hospitalization Data Supports Correlation of Lower Covid-19 Severity vs. Universal BCG Immunization in the Early Phase of the Pandemic
Authors: Dolgikh Serge
Published: July 2021

The possibility of a correlation between universal administration of the bacillus Calmette-Guerin (BCG) tuberculosis vaccine and lower severity of Covid-19 by national jurisdiction has been pointed out previously. In this work we examined hospitalization data attributed to Covid-19 cause reported by European national jurisdictions with the conclusion of a clear negative correlation between current or recent BCG vaccination program and reduced impact of the epidemics on the population measured in hospital admissions per capita in the early phase of the pandemic, before variants and vaccines. While there is no evidence that BCG vaccination provides strong individual level protection, the results of this work in combination with the results of other studies appear to support the hypothesis of a certain population-wide protection effect that is correlated with BCG immunization.
Upregulation of TBX1 by genetic variants are associated with human congenital heart disease
Authors: Yu Liwei , Li Binbin , Wang Hongyan
Published: July 2021

Congenital heart disease (CHD) is the most common human birth defect worldwide and also an important cause of childhood morbidity and mortality. The transcription factor of TBX1 early expressed in embryonic cardiac progenitor cells underlys embryo cardiogenesis in a dosage-dependent manner. Imbalanced TBX1 level has been shown to lead to cardiac defects. To study the association of TBX1 genetic variants with CHD susceptibility, we screened genetic variants in 409 CHD patients and 203 healthy controls. One single nucleotide polymorphism (SNP), rs41260844, in TBX1 promotor region was identified to be associated with CHD. Functional studies showed the minor allele of rs41260844 is associated with higher CHD risk and increases TBX1 promoter activity through attenuating TBX1 promoter binding affinity with nuclear protein(s). In addition, a novel case-specific missense rare mutation of p.P164L in TBX1 T-box domain was identified and predicted as deleterious mutation, which showed a trend of increased protein function. In summary, we concluded that a higher TBX1 expression level or activity is associated with CHD susceptibility, which could affect TBX1 downstream targets and thus disrupt the balance of the complex regulation network during cardiogenesis. This study deepens our current understanding of embryo cardiogenesis and CHD etiology.
Proteomic and metabolomic signatures associated with the immune response in healthy individuals immunized with an inactivated SARS-CoV-2 vaccine
Authors: Wang Yi , Wang Xiaoxia , Wai Luu Laurence Don , Chen Shaojin , Jin Fu , Wang Shufang , Huang Xiaolan , Wang Licheng , Zhou Xiaocui , Chen Xi , Cui Xiaodai , Li Jieqiong , Tai Jun , Zhu Xiong
Published: July 2021

Summery

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results suggest that protective immunity against SARS-CoV-2 can be achieved via multiple mechanisms and highlights the utility of a systems biology approach in defining molecular correlates of protection to vaccination.
Cerebral coherence in task-based fMRI hyperscanning: A new trick to an old dog
Authors: Wang Le-Si , Cheng Jen-Tang , Hsu I-Jeng , Liu Shyhnan , Kung Chun-Chia , Chen Der-Yow , Weng Ming-Hung
Published: July 2021

This study features an fMRI hyperscanning experiment, mapping the brains of the dyads from two fMRI sites, 305 km apart. There are two conditions: in half of the trials (the cooperation condition), the dyad had to collaborate to win and then split the reward, whereas in the other half (the competition condition), the winner took all the reward, thereby resulting in dynamic strategic interactions. Each subject took alternating turns as senders and receivers. To calculate the cerebral coherence in such jittered event-related fMRI tasks, we first estimated the feedback-related BOLD responses of each trial, using 8 finite impulse response functions (16 seconds), and then concatenated the beta volume series. With the right temporal-parietal junction (rTPJ) as the seed, the interpersonal connected brain areas in the cooperation and competition conditions were separately identified: the former condition with the right superior temporal gyrus (rSTG) and the latter with the left precuneus (lPrecuneus) (as well as some other regions of interest), both peaking at the designated frequency bin (1/16 s = 0.0625 Hz), but not in permuted pairs. In addition, the extended coherence analyses on shorter (12 s, or .083 Hz) and longer (20 s, or .05 Hz) concatenated volumes verified that only approximately in the trial length were the rTPJ-rSTG and rTPJ-lPrecuneus couplings found. In sum, our approach both showcases a flexible analysis method that widens the applicability of interpersonal coherence in the rapid event-related fMRI hyperscanning, and reveals a context-based interpersonal coupling between pairs in cooperation vs. competition.

Author summary

Social neuroscience is gaining momentum, while coherence analysis as one of the interpersonal connectivity measures is rarely applied to the rapid event-related fMRI. The reason could be that the inherent task design (such as the periodicity constraint for Fourier transformation), among others, limits its applicability and usage. In this fMRI hyperscanning study of a two-person strategic interactions, we independently estimated the feedback-related BOLD responses of each trial, and concatenated the beta time series for interpersonal coherence. The main advantage of this method is in its flexibility against the constraints of jittered experimental trials intermixing several task conditions in most task-based fMRI runs. In addition, our coherence results, which highlight two inter-brain couplings (e.g., rTPJ-rSTG between collaborating, and rTPJ-lPrecuneus for competing dyads) among other brain regions, plus its temporal specificity of such seed-brain couplings only between pairs, both replicate previous run-wide fMRI coherence results, and hold great promise in extending its applicability in task-based fMRI hyperscanning.
Linearly polarized excitation enhances signals from fluorescent voltage indicators
Authors: Bloxham William , Brinks Daan , Kheifets Simon , Cohen Adam E.
Published: July 2021

Voltage imaging in cells requires high-speed recording of small fluorescent signals, often leading to low signal-to-noise ratios. Because voltage indicators are membrane-bound, their orientations are partially constrained by the plane of the membrane. We explored whether tuning the linear polarization of excitation light could enhance voltage indicator fluorescence. We tested a panel of dye and protein-based voltage indicators in mammalian cells. The dye BeRST1 showed a 73% increase in brightness between the least and most favorable polarizations. The protein-based reporter ASAP1 showed a 22% change in brightness, and QuasAr3 showed a 14% change in brightness. In very thin neurites expressing QuasAr3, improvements were anomalously large, with a 170% increase in brightness between polarization parallel vs perpendicular to the dendrite. Signal-to-noise ratios of optically recorded action potentials were increased by up to 50% in neurites expressing QuasAr3. These results demonstrate that polarization control can be a facile means to enhance signals from fluorescent voltage indicators, particularly in thin neurites or in high-background environments.
Untangling the ecological signal in the dental morphology in the bat superfamily Noctilionoidea
Authors: López-Aguirre Camilo , Hand Suzanne J , Simmons Nancy B , Silcox Mary T
Published: July 2021

Diet has been linked to the diversification of the bat superfamily Noctilionoidea, a group that underwent an impressive ecological adaptive radiation within Mammalia. For decades, studies have explored morphological adaptations and diversity of noctilionoid bats to reveal traits associated with their ecological diversity. Surprisingly, despite such interest and recent application of novel techniques, ecomorphological studies have failed to fully resolve the link between diet and a critical component of the feeding apparatus: dental morphology. Using multivariate dental topographic analysis and phylogenetic comparative methods, we examined the phylogenetic, biological and ecological signal in the dental morphology of noctilionoid bats. Analysing the lower first molars of 110 species, we explored relationships between diet and dental morphology, accounting for three different dimensions of diet (guild, composition and breadth). Phylogenetic and size-dependent structuring of the dental topography data shows it does not correlate only to diet, highlighting the need to account for multiple sources of variation. Frugivorous noctilionoids have sharper molars than other previously reported frugivorous mammals. Nectarivorous noctilionoids showed reduced lower molar crown height and steepness, whereas animalivorous species had larger molars. Dietary composition suggested that the intensity of exploitation of a resource is also linked to different dimensions of dental morphology. Increasing carnivory positively correlated with MA, explaining the highest proportion of its variation, and increasing frugivory explained the highest proportion of variation in all other variables. Dietary breadth showed generalist species have sharper, more topographically-complex molars, whereas specialist herbivores and specialist animalivores fell at opposite ends in the range of tooth steepness and crown height. Together, the results suggest that adaptations affecting different attributes of dental morphology likely facilitated the dietary diversity and specialisation found in Noctilionoidea.
Individual difference in addiction-like behaviors and choice between cocaine versus food in Heterogeneous Stock rats
Authors: Sedighim Sharona , Carrette Lieselot LG , Venniro Marco , Shaham Yavin , de Guglielmo Giordano , George Olivier
Published: July 2021

Rationale and objectives

Recent studies reported that when given a mutually exclusive choice between cocaine and palatable food, most rats prefer the non-drug reward over cocaine. However, these studies used rat strains with limited genetic and behavioral diversity. Here, we used a unique outbred strain of rats (Heterogeneous Stock, HS) that mimic the genetic variability of humans.

Methods

We first identified individual differences in addiction-like behaviors (low and high). Next, we tested choice between cocaine and palatable food using a discrete choice procedure. We characterized the individual differences using an Addiction score that incorporates key features of addiction: escalated intake, highly motivated responding (progressive ratio), and responding despite adverse consequences (footshock punishment). We assessed food vs. cocaine choice at different drug-free days (without pre-trial cocaine self administration) during acquisition of cocaine self-administration or after escalation of cocaine self-administration. We also assessed drug vs. food choice immediately after 1-, 2-, or 6-h cocaine self-administration.

Results

Independent of the addiction score, without pre-trial coccaine (1 or more abstinence days) HS rats strongly preferred the palatable food over cocaine, even if the food reward was delayed or its size was reduced. However, rats with high but not low addiction score modestly increased cocaine choice immediately after 1-, 2- or 6-h cocaine self-administration.

Conclusions

Like other strains, HS rats strongly prefer palatable food over cocaine. Individual differences in addiction score were associated with increased drug choice in the presence but not absence (abstinence) of cocaine. The HS strain may be useful in studies on mechanisms of addiction vulnerability.
Cytolytic memory CD4+ T cell clonotypes are expanded during Plasmodium falciparum infection
Authors: Furtado Raquel , Delahaye Fabien , Zhang Jinghang , Sung Joowhan , Karell Paul , Kim Ryung S. , Caillat-Zucman Sophie , Liang Li , Felgner Philip , Bauleni Andy , Gama Syze , Buchwald Andrea , Taylor Terrie , Seydel Karl , Laufer Miriam , Daily Johanna P. , Lauvau Grégoire
Published: July 2021

Plasmodium falciparum (Pf) malaria causes high rates of morbidity and mortality and lacks a sufficiently effective vaccine. Clinical immunity develops in residents of malaria endemic regions which confers reduced clinical symptoms during infection and protection against severe disease. We hypothesized that understanding the immune mechanisms of clinical immunity could inform vaccine design to improve efficacy. We compared the peripheral blood cellular and humoral immune responses during a mild episode of Pf malaria infection. Participants were classified as either clinically susceptible or clinically protected, based on the number of recurrent clinical infections over an 18-month longitudinal study in a malaria endemic region in Malawi. Susceptible participants had three or more recurrent clinical episodes while clinically immune individuals had one or none. Protected participants exhibited higher plasma immunoglobulin G (IgG) breadth and titers against Pf antigens, and greater antibody (Ab)-dependent Pf opsonization compared to susceptible participants. Using high dimensional mass cytometry (CyTOF), spectral flow cytometry and single-cell transcriptomic analyses, we identified expanded memory CD4+ T cell clones sharing identical T cell receptor clonotypes in the blood of protected participants during malaria infection. These cells express a strong cytolytic T helper 1 effector program with transcripts encoding granzymes (A, B, H, M), granulysin, NKG7 and the Zeb2 master transcriptional regulator of terminally differentiated effector T cells. Memory CD4+ T cells expressing Zeb2+ were CD39hiTIGIThi and expressed multiple chemotactic and checkpoint inhibitory receptors, although the cellular levels of several of these receptors were reduced in protected compared to susceptible individuals. We propose that clonally expanded Zeb2+ cytolytic memory CD4+ Th1 cells could represent essential contributors to clinical immunity against Pf malaria.

One Sentence Summary

A population of cytolytic memory CD4+ T cells is clonally expanded in patients with Plasmodium falciparum malaria and has reduced chemotactic and inhibitory receptor expression in patients with naturally acquired clinical malaria immunity.
Development of Visual Response Selectivity in Cortical GABAergic Interneurons
Authors: Chang Jeremy T. , Fitzpatrick David
Published: July 2021

The visual cortex of carnivores and primates displays a high degree of modular network organization characterized by local clustering and structured long-range correlations of activity and functional properties. Excitatory networks display modular organization before the onset of sensory experience, but the developmental timeline for modular networks of GABAergic interneurons, remains under-explored. Using in vivo calcium imaging of the ferret visual cortex, we find evidence that before visual experience, interneurons display weak orientation tuning and widespread non-specific activation in response to visual stimuli. Modular organization and orientation tuning are evident with as little as one week of visual experience. Furthermore, we find that the development of orientation tuning requires visual experience, while the reduction in widespread network activity does not. Thus, the maturation of inhibitory cortical networks occurs in a delayed, parallel process relative to excitatory neurons.
Breakout Rooms, Polling, and Chat, Oh My! The Development and Validation of Online COPUS
Authors: Pusey Téa S. , Valencia Andrea Presas , Signorini Adriana , Kranzfelder Petra
Published: July 2021

We developed and validated a new classroom observation protocol, Online COPUS (E-COPUS), to measure teaching and learning practices in the online learning environment. We collected COPUS and E-COPUS data from 40 STEM courses before, during the transition, and continuation of emergency remote teaching (ERT). Through weekly discussions among observers, we adjusted six of the original instructor COPUS code descriptions and six of the original student code descriptions to fit the online learning environment. We trained 23 observers to conduct E-COPUS utilizing both in-person and online lecture recordings. To validate E- COPUS, we consulted an expert panel of science educators and education researchers to provide feedback on our code descriptions and complete a matching activity with our E-COPUS code descriptions. We further examined E-COPUS by analyzing the teaching and learning practices of 6 instructors across in-person and online instruction and found that the online functions of breakout rooms, polling, and the chat were utilized to promote active learning activities in the online learning environment. As we prepare for teaching in the future, it is important to have formative assessment tools designed for all course formats to support assessment and improvement of teaching practices in college STEM classrooms.
hECA: the cell-centric assembly of a cell atlas
Authors: Chen Sijie , Luo Yanting , Gao Haoxiang , Li Fanhong , Li Jiaqi , Chen Yixin , You Renke , Hao Minsheng , Bian Haiyang , Xi Xi , Li Wenrui , Li Weiyu , Ye Mingli , Meng Qiuchen , Zou Ziheng , Li Chen , Li Haochen , Zhang Yangyuan , Cui Yanfei , Wei Lei , Chen Fufeng , Wang Xiaowo , Lv Hairong , Hua Kui , Jiang Rui , Zhang Xuegong
Published: July 2021

Single-cell omics data can characterize multifaceted features of massive cells and bring significant insights to biomedical researches. The accumulation of single-cell data provides growing resources for constructing atlases for all cells of a human organ or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We proposed a unified information framework enabling seamless cell-centric data assembly and developed a human Ensemble Cell Atlas (hECA) as an instance. hECA version 1.0 assembled scRNA-seq data across multiple studies into one orchestrated data repository. It contains 1,093,299 labeled cells and metadata from 116 published human single-cell studies, covering 38 human organs and 11 systems. We invented three methods of applications based on the cell-centric assembly: “In data” cell sorting enables targeted data retrieval in the full atlas with customizable logic expressions; The “quantitative portraiture” system provides a multi-view presentation of biological entities (organs, cell types, and genes) of multiple granularities; The customizable reference creation allows users to use the cell-centric assembly to generate references for their own cell type annotations. Case studies on agile construction of user-defined sub-atlases and “in data” investigation of CAR-T off-targets in multiple organs showed the great potential of cell-centric atlas assembly.