bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian Calibration of Using CO2Sensors to Assess Ventilation Conditions and Associated COVID-19 Airborne Aerosol Transmission Risk in Schools
Authors: Hou Danlin , Katal Ali , Wang Liangzhu (Leon)
Published: February 2021

Ventilation rate plays a significant role in preventing the airborne transmission of diseases in indoor spaces. Classrooms are a considerable challenge during the COVID-19 pandemic because of large occupancy density and mainly poor ventilation conditions. The indoor CO2level may be used as an index for estimating the ventilation rate and airborne infection risk. In this work, we analyzed a one-day measurement of CO2levels in three schools to estimate the ventilation rate and airborne infection risk. Sensitivity analysis and Bayesian calibration methods were applied to identify uncertainties and calibrate key parameters. The outdoor ventilation rate with a 95% confidence was 1.96 ± 0.31ACH for Room 1 with mechanical ventilation and fully open window, 0.40 ± 0.08 ACH for Rooms 2, and 0.79 ± 0.06 ACH for Room 3 with only windows open. A time-averaged CO2level < 450 ppm is equivalent to a ventilation rate > 10 ACH in all three rooms. We also defined the probability of the COVID-19 airborne infection risk associated with ventilation uncertainties. The outdoor ventilation threshold to prevent classroom COVID-19 aerosol spreading is between 3 – 8 ACH, and the CO2threshold is around 500 ppm of a school day (< 8 hr) for the three schools.

Practical Implications

The actual outdoor ventilation rate in a room cannot be easily measured, but it can be calculated by measuring the transient indoor CO2level. Uncertainty in input parameters can result in uncertainty in the calculated ventilation rate. Our three classrooms study shows that the estimated ventilation rate considering various input parameters’ uncertainties is between ± 8-20 %. As a result, the uncertainty of the ventilation rate contributes to the estimated COVID-19 airborne aerosol infection risk’s uncertainty up to ± 10 %. Other studies can apply the proposed Bayesian and MCMC method to estimating building ventilation rates and airborne aerosol infection risks based on actual measurement data such as CO2levels with uncertainties and sensitivity of input parameters identified. The outdoor ventilation rate and CO2threshold values as functions of exposure times could be used as the baseline models to develop correlations to be implemented by cheap/portable sensors to be applied in similar situations to monitor ventilation conditions and airborne risk levels.
Successful spermatogonial stem cells transplantation within Pleuronectiformes: first breakthrough at inter-family level in marine fish
Authors: Zhou Li , Wang Xueying , Liu Qinghua , Yang Jingkun , Xu Shihong , Wu Zhihao , Wang Yanfeng , You Feng , Song Zongcheng , Li Jun
Published: January 2021

As a promising biotechnology, fish germ cell transplantation shows potentials in conservation germplasm resource, propagation of elite species, and generation of transgenic individuals. In this study, we successfully transplanted the Japanese flounder (P. olivaceus), summer flounder (P. dentatus), and turbot (S. maximus) spermatogonia into triploid Japanese flounder larvae, and achieved high transplantation efficiency of 100%, 75-95% and 33-50% by fluorescence tracking and molecular analysis, respectively. Eventually, donor-derived spermatozoa produced offspring by artificial insemination. We only found male and intersex chimeras in inter-family transplantations, while male and female chimeras in both intra-species and intra-genus transplantations. Moreover, the intersex chimeras could mature and produce turbot functional spermatozoa. We firstly realized inter-family transplantation in marine fish species. These results demonstrated successful spermatogonial stem cells transplantation within Pleuronectiformes, suggesting the germ cells migration, incorporation and maturation within order were conserved across a wide range of teleost species.
SiCEP3, a C-terminally encoded peptides fromSetaria italica, promotes ABA import and signaling pathway
Authors: Zhang Lei , Ren Yue , Wan Yiman , Xu Qian , Yang Guodong , Zhang Shizhong , Huang Jinguang , Yan Kang , Zheng Chengchao , Wu Changai
Published: January 2021

C-terminally encoded peptides (CEPs) are small peptides, typically post-translationally modified, and highly conserved in many species. CEPs are known to play roles in inhibition of plant growth and regulation of development, but the mechanisms are not well understood. In this study, we searched for CEP peptides in foxtail millet (Setaria italica). The 14 peptides we identified are divided into two subfamilies. The transcripts of mostSiCEPs were more abundant in roots than in other tissues.SiCEP3,SiCEP4,andSiCEP5were also expressed at high levels in panicles. Moreover, expression of allSiCEPswas induced by biotic stress and phytohormones.SiCEP3overexpression and application of biosynthetic SiCEP3 both inhibited the growth of seedlings. In the presence of ABA, growth inhibition and ABA content of seedlings increased with the concentration of SiCEP3. Transcripts encoding two ABA transporters and one ABA receptor were induced by SiCEP3, ABA, and the two in combination. Further analysis revealed that SiCEP3 promoted ABA transport via NRT1.2 and ABCG40. In addition, SiCEP3, ABA, or the combination inhibited the kinase activities of CEP receptors CEPR1/2. Taken together, our results indicated that the CEP–CEPR module mediates ABA signaling by regulating ABCG40, NRT1.2, and PYL4in planta.

Highlight

SiCEP3, a C-terminally encoded peptide, can promote ABA import and signaling pathway by inhibiting the kinase activity of its receptors under abiotic stress inSetaria italica.
Mixology: a tool for calculating required masses and volumes for laboratory solutions
Authors: Sanderson Theo
Published: January 2021

We have created a tool to calculate the amount of each ingredient required to make up a custom solution with defined concentrations. It can convert between many kinds of volumetric, mass and concentration units. This includes the ability to convert between molarities and mass-based concentrations, using molecular masses retrieved from the ChEBI database. Mixology can be accessed athttp://mixology.science.
Single Molecule Mass Photometry Reveals Dynamic Oligomerization of Plant and Human Peroxiredoxins for Functional Conservation and Diversification
Authors: Liebthal Michael , Kushwah Manish Singh , Kukura Philipp , Dietz Karl-Josef
Published: January 2021

Single molecule mass photometry was used to study the dynamic equilibria of the ubiquitous and highly abundant 2-Cysteine peroxiredoxins (2-CysPRX). 2-CysPRXs adopt distinct functions in all cells dependent on their oligomeric conformation ranging from dimers to decamers and high molecular weight aggregates (HMW). The oligomeric state depends on the redox state of their catalytic cysteinyl residues. To which degree they interconvert, how the interconversion is regulated, and how the oligomerisation propensity is organism specific remains, however, poorly understood. The dynamics differs between wild-type and single point mutants affecting the oligomerization interfaces, with concomitant changes to function. Titrating concentration and redox state ofArabidopsis thalianaand human 2-CysPRXs revealed features conserved among all 2-CysPRX and clear differences concerning oligomer transitions, the occurrence of transition states and the formation of HMW which are associated with chaperone activity or storage. The results indicate functional differentiation of human 2-CysPRXs. Our results point to a diversified functionality of oligomerization for 2-CysPRXs and illustrate the power of mass photometry to non-invasively quantify oligomer distributions in a redox environment. This knowledge is important to fully address and model PRX function in cell redox signaling e.g., in photosynthesis, cardiovascular and neurological diseases or carcinogenesis.
Who should be first in line for the COVID-19 vaccine? Surveys in 13 countries of the public’s preferences for prioritisation
Authors: Duch Raymond , Roope Laurence S J , Violato Mara , Becerra Matias Fuentes , Robinson Thomas , Bonnefon Jean-Francois , Friedman Jorge , Loewen Peter , Mamidi Pavan , Melegaro Alessia , Blanco Mariana , Vargas Juan , Seither Julia , Candio Paolo , Cruz Ana Gibertoni , Hua Xinyang , Barnett Adrian , Clarke Philip M
Published: February 2021

How does the public want a COVID-19 vaccine to be allocated? We conducted a conjoint experiment asking 15,536 adults in 13 countries to evaluate 248,576 profiles of potential vaccine recipients that varied randomly on five attributes. Our sample includes diverse countries from all continents. The results suggest that in addition to giving priority to health workers and to those at high risk, the public favours giving priority to a broad range of key workers and to those on lower incomes. These preferences are similar across respondents of different education levels, incomes, and political ideologies, as well as across most surveyed countries. The public favoured COVID-19 vaccines being allocated solely via government programs, but were highly polarized in some developed countries on whether taking a vaccine should be mandatory. There is a consensus among the public on many aspects of COVID-19 vaccination which needs to be taken into account when developing and communicating roll-out strategies.
Returning to a normal life via COVID-19 vaccines in the USA: a large-scale agent-based simulation study
Authors: Li Junjiang , Giabbanelli Philippe J.
Published: February 2021

Background

In 2020, COVID-19 has claimed more than 300,000 deaths in the US alone. While non-pharmaceutical interventions were implemented by federal and state governments in the USA, these efforts have failed to contain the virus. Following the FDA approval of two COVID-19 vaccines, however, the hope for the return to normalcy is renewed. This hope rests on an unprecedented nation-wide vaccine campaign, which faces many logistical challenges and is also contingent on several factors whose values are currently unknown.

Objective

We study the effectiveness of a nation-wide vaccine campaign in response to different vaccine efficacies, the willingness of the population to be vaccinated, and the daily vaccine capacity under two different federal plans. To characterize the possible outcomes most accurately, we also account for the interactions between non-pharmaceutical interventions and vaccines, through six scenarios that capture a range of possible impact from non-pharmaceutical interventions.

Methods

We use large-scale cloud-based agent-based simulations by implementing the vaccination campaign using Covasim, an open-source ABM for COVID-19 that has been used in several peer-reviewed studies and accounts for individual heterogeneity as well as a multiplicity of contact networks. Several modifications to the parameters and simulation logic were made to better align the model with current evidence. We chose six non-pharmaceutical intervention scenarios and applied the vaccination intervention following both the plan proposed by Operation Warp Speed (former Trump administration) and the plan of one million vaccines per day, proposed by the Biden administration. We accounted for unknowns in vaccine efficacies and levels of population compliance by varying both parameters. For each experiment, the cumulative infection growth is fitted to a logistic growth model, and the carrying capacities and the growth rates are recorded.

Results

For both vaccination plans and all non-pharmaceutical intervention scenarios, the presence of the vaccine intervention considerably lowers the total number of infections when life returns to normal, even when the population compliance to vaccines is as low at 20%. We noted an unintended consequence: given the vaccine availability estimates under both federal plans and the focus on vaccinating individuals by age categories, a significant reduction in non-pharmaceutical interventions results in a counterintuitive situation in which higher vaccine compliance then leads to more total infections.

Conclusions

Although potent, vaccines alone cannot effectively end the pandemic given the current availability estimates and the adopted vaccination strategy. Non-pharmaceutical interventions need to continue and be enforced to ensure high compliance, so that the rate of immunity established by vaccination outpaces that induced by infections.
Multimodal sensorimotor integration of visual and kinaesthetic afferents modulates motor circuits in humans
Authors: Zschorlich Volker R. , Behrendt Frank , de Lussanet Marc H.E.
Published: January 2021

Optimal motor control requires the effective integration of multi-modal information. Visual information of movement performed by others even enhances potentials in the upper motor neurons, through the mirror-neuron system. On the other hand, it is known that motor control is intimately associated with afferent proprioceptive information. Kinaesthetic information is also generated by passive, external-driven movements. In the context of sensory integration, its an important question, how such passive kinaesthetic information and visually perceived movements are integrated. We studied the effects of visual and kinaesthetic information in combination, as well as isolated, on sensorimotor-integration – compared to a control condition. For this, we measured the change in the excitability of motor cortex (M1) using low-intensity TMS. We hypothesised that both visual motoneurons and kinaesthetic motoneurons could enhance the excitability of motor responses. We found that passive wrist movements increase the motor excitability, suggesting that kinaesthetic motoneurons do exist. The kinaesthetic influence on the motor threshold was even stronger than the visual information. Moreover, the simultaneous visual and passive kinaesthetic information increased the cortical excitability more than each of them independently. Thus, for the first time, we found evidence for the integration of passive kinaesthetic- and visual-sensory stimuli.
Zebrafish spinal cord oligodendrocyte formation requiresbocfunction
Authors: Kearns Christina A. , Walker Macie , Ravanelli Andrew M. , Scott Kayt , Arzbecker Madeline R. , Appel Bruce
Published: January 2021

The axis of the vertebrate neural tube is patterned, in part, by a ventral to dorsal gradient of Shh signaling. In the ventral spinal cord, Shh induces concentration-dependent expression of transcription factors, subdividing neural progenitors into distinct domains that subsequently produce distinct neuronal and glial subtypes. In particular, progenitors of the pMN domain express the bHLH transcription factor Olig2 and produce motor neurons followed by oligodendrocytes, the myelinating glial cell type of the central nervous system. In addition to its role in patterning ventral progenitors, Shh signaling must be maintained through development to specify pMN progenitors for oligodendrocyte fate. Using a forward genetic screen in zebrafish for mutations that disrupt development of oligodendrocytes, we identified a new mutant allele ofboc, which encodes a type I transmembrane protein that functions as a coreceptor for Shh. Embryos homozygous for thebocco25allele, which creates a missense mutation in a Fibronectin type III domain that binds Shh, have normally patterned spinal cords but fail to maintain pMN progenitors, resulting in a deficit of oligodendrocytes. Using a sensitive fluorescent detection method for in situ RNA hybridization, we found that spinal cord cells expressbocin a graded fashion that is inverse to the gradient of Shh signaling activity and thatbocfunction is necessary to maintain pMN progenitors by shaping the Shh signaling gradient.
Increased circulating levels of angiotensin-(1-7) in severely ill COVID-19 patients
Authors: Martins Ana Luiza Valle , da Silva Filipe Alex , Bolais-Ramos Lucas , de Oliveira Gisele Capanema , Ribeiro Renata Cunha , Pereira Danilo Augusto Alves , Annoni Filippo , Diniz Mirella Monique Lana , Silva Thuanny Granato Fonseca , Zivianni Bruna , Cardoso Alexandre Carvalho , Martins Juliana Carvalho , Motta-Santos Daisy , José Campagnole-Santos Maria , Taccone Fabio Silvio , Verano-Braga Thiago , Santos Robson Augusto Souza
Published: February 2021

The mono-carboxypeptidase Angiotensin-Converting Enzyme 2 (ACE2) is an important “player” of the renin-angiotensin system (RAS). ACE2 is also the receptor for SARS-CoV-2, the new coronavirus that causes COVID-19. It has been hypothesized that following SARS-CoV-2/ACE2 internalization Ang II level would increase in parallel to a decrease of Ang-(1-7) in COVID-19 patients. In this preliminary report, we analyzed the plasma levels of angiotensin peptides in 19 severe COVID-19 patients and 19 non-COVID-19 volunteers, to assess potential outcome associations. Unexpectedly, a significant increase in circulating Ang-(1-7) and lower Ang II plasma level were found in critically ill COVID-19 patients. Accordingly, an increased Ang-(1-7)/ Ang II ratio was observed in COVID-19 suggesting a RAS dysregulation toward an increased formation of Ang-(1-7) in these patients.
Towards a COVID-19 symptom triad: The importance of symptom constellations in the SARS-CoV-2 pandemic
Authors: Melms Leander , Falk Evelyn , Schieffer Bernhard , Jerrentrup Andreas , Wagner Uwe , Matrood Sami , Schaefer Jürgen R. , Müller Tobias , Hirsch Martin
Published: February 2021

Pandemic scenarios like SARS-Cov-2 require rapid information aggregation. In the age of eHealth and data-driven medicine, publicly available symptom tracking tools offer efficient and scalable means of collecting and analyzing large amounts of data. As a result, information gains can be communicated to front-line providers. We have developed such an application in less than a month and reached more than 500 thousand users within 48 hours. The dataset contains information on basic epidemiological parameters, symptoms, risk factors and details on previous exposure to a COVID-19 patient. Exploratory Data Analysis revealed different symptoms reported by users with confirmed contacts vs. no confirmed contacts. The symptom combination of anosmia, cough and fatigue was the most important feature to differentiate the groups, while single symptoms such as anosmia, cough or fatigue alone were not sufficient. A linear regression model from the literature using the same symptom combination as features was applied on all data. Predictions matched the regional distribution of confirmed cases closely across Germany, while also indicating that the number of cases in northern federal states might be higher than officially reported. In conclusion, we report that symptom combinations anosmia, fatigue and cough are most likely to indicate an acute SARS-CoV-2 infection.
Single-cell spatial analysis of tumor immune architecture in diffuse large B cell lymphoma
Authors: Colombo Anthony , Hav Monirath , Gerdtsson Erik , Singh Mohan , Xu Alexander , Gamboa Alicia , Chen Denaly , Houldsworth Jane , Shaknovich Rita , Aoki Tomohiro , Chong Lauren , Takata Katsuyoshi , Chavez Elizabeth A , Steidl Christian , Hicks James , Kuhn Peter , Siddiqi Imran , Merchant Akil
Published: February 2021

Multiplexed immune cell profiling of the tumor microenvironment (TME) in cancer has improved our understanding of cancer immunology, but complex spatial analyses of tumor-immune interactions in lymphoma are lacking. Here we used imaging mass cytometry (IMC) on 33 cases of diffuse large B cell lymphoma (DLBCL) to characterize tumor and immune cell architecture and correlate it to clinicopathological features such as cell of origin, gene mutations, and responsiveness to chemotherapy. To understand the poor response of DLBCL to immune check point inhibitors (ICI), we compared our results to IMC data from Hodgkin lymphoma (HL), a cancer highly responsive to ICI, and observed differences in the expression of PD-L1, PD-1, and TIM-3. We created a spatial classification of tumor cells and identified sub-regions of immune activation, immune suppression, and immune exclusion within the topology of DLBCL. Finally, the spatial analysis allowed us to identify markers such as CXCR3, which are associated with penetration of immune cells into immune desert regions, with important implications for engineered cellular therapies.

SIGNIFICANCE

This is the first study to integrate tumor mutational profiling, cell of origin classification, and multiplexed immuno-phenotyping of the TME into a spatial analysis of DLBCL at the single cell level. We demonstrate that, far from being histo-pathologically monotonous, DLBCL has a complex tumor architecture, and that changes in tumor topology can be correlated with clinically relevant features. This analysis identifies candidate biomarkers and therapeutic targets such as TIM-3, CCR4, and CXCR3 that are relevant for combination treatment strategies in immuno-oncology and cellular therapies such as CAR-T cells.
Optimal time to return to normality: parallel use of COVID-19 vaccines and circuit breakers
Authors: Bonsall Michael B. , Huntingford Chris , Rawson Thomas
Published: February 2021

By January 2020, the COVID-19 illness has caused over two million deaths. Countries have restricted disease spread through non-pharmaceutical interventions (e.g., social distancing). More severe “lockdowns” have also been required. Although lockdowns keep people safer from the virus, they substantially disrupt economies and individual well-being. Fortunately, vaccines are becoming available. Yet, vaccination programs may take several months to implement, requiring further time for individuals to develop immunity following inoculation. To prevent health services being overwhelmed it may be necessary to implement further lockdowns in conjunction with vaccination. Here, we investigate optimal approaches for vaccination under varying lockdown lengths and/or severities to prevent COVID-19-related deaths exceeding critical thresholds. We find increases in vaccination rate cause a disproportionately larger decrease in lockdowns: with vaccination, severe lockdowns can reduce infections by up to 89%. Notably, we include demographics, modelling three groups: vulnerable, front-line workers, and non-vulnerable. We investigate the sequence of vaccination. One counter-intuitive finding is that even though the vulnerable group is high risk, demographically, this is a small group (per person, vaccination occurs more slowly) so vaccinating this group first achieves limited gains in overall disease control. Better disease control occurs by vaccinating the non-vulnerable group with longer and/or more severe lockdowns.
Diagnostic performance of standard and inverted grey-scale CXR in detection of lung lesions in COVID-19 patients. A single institution study in the region of Abu Dhabi
Authors: AlHelali Abeer Ahmed , Kukkady Mohamed Ashfaque , Saeed Ghufran Aref , Elholiby Tamer Ibrahim , Mansoori Rabab Abdulrahman Al , Ahmed Luai A
Published: February 2021

Purpose

To evaluate diagnostic performance of greyscale and inverted greyscale Chest X-ray (CXR) using Computed Tomography (CT) scan as a gold standard.

Methods

In this retrospective study, electronic medical records of 120 patients who had valid CXR and High-resolution CT (HRCT) within less than 24 hours after having a positive COVID-19 RT-PCR test during the period from May 19 th to May 23 rd 2020 in a single tertiary care center were reviewed.

PA chest radiographs were presented on 2 occasions to 5 radiologists to evaluate the role and appropriateness of greyscale and inverted greyscale chest radiographs (CXR). The images were viewed on high-specification viewing systems using a primary display monitors and compared it to computed tomography (CT) findings for screening and management of suspected or confirmed COVID-19 patients.

Results

Ninety-six (80%) patients had positive CT findings, 81 (67.5%) had positive grey scale CXR lesions, and 25 (20.8%) had better detection in the inverted grey scale CXR. The CXR sensitivity for COVID-19 pneumonia was 93.8% (95% CI (86.2% - 98.0%) and the specificity was 48.7% (95% CI (32.4% - 65.2%). The CXR sensitivity of detection of lung lesions was slightly higher in male (95.1% (95% CI (86.3% - 99.0%)) than female (90.0% (95% CI (68.3% - 98.8%)), while the specificity was 48.0% (95% CI (27.8% - 68.7%) and 50.0% (95% CI (23.0% - 77.0%) in males and females, respectively. However, no significant difference was detected in ROC area between men and women.

Conclusions

The sensitivity of detection of lung lesions of CXR was relatively high, particularly in men. The results of the study support the idea of considering conventional radiographs as an important diagnostic tool in suspected COVID-19 patients especially in healthcare facilities where there is no access to HRCT scans.

Highlights

CXR shows high sensitivity for detecting lung lesions in HRCT confirmed COVID-19 patients.

Better detection of lesions was noted in the inverted grey scale CXR in (20.8%) of cases with positive findings in standard greyscale CXR.

Conventional radiographs can be used as diagnostic tools in suspected COVID-19 patients especially in healthcare facilities where there is no access to HRCT scans.
How lifestyle changes within the COVID-19 global pandemic have affected the pattern and symptoms of the menstrual cycle
Authors: Bruinvels Georgie , Goldsmith Esther , Blagrove Richard C. , Martin Dan , Shaw Laurence , Piasecki Jessica
Published: February 2021

Background

The coronavirus 2019 (COVID-19) pandemic has caused significant changes to homes, working life and stress. The purpose of this research was to investigate the implications that the COVID-19 pandemic has had on the menstrual cycle and any contributing factors to these changes.

Methods

A questionnaire was completed by 749 participants, whom ranged from ‘physically active’ to elite, in their training status. The questionnaire captured detail on menstrual cycle symptoms and characteristics prior to and during the COVID-19 pandemic lockdown period, as well as lifestyle, stress, exercise and nutrition. Descriptive statistics and frequency distribution were reported and decision tree analysis performed. Statistical significance was assumed at p<0.05.

Results

Fifty-two point six percent of females experienced a change in their menstrual cycle during the lockdown period. Psychosocial symptoms had changed in over half of all participants. Participants who reported increased stress/worry in family and personal health were significantly associated with changes in menstrual symptoms. Similarly, job security stress was associated with increases in bleeding time (p<0.05).

Conclusions

It is important that females and practitioners become aware of the implications of stressful environments and the possible long-term implications on fertility, particularly given the uncertainty around a second wave of the global pandemic.
Microscopic dynamics modeling unravels the role of asymptomatic virus carriers in SARS-CoV-2 epidemics at the interplay between biological and social factors
Authors: Tadić Bosiljka , Melnik Roderick
Published: February 2021

The recent experience of SARS-CoV-2 epidemics spreading revealed the importance of passive forms of infection transmissions. Apart from the virus survival outside the host, the latent infection transmissions caused by asymptomatic and presymptomatic hosts represent major challenges for controlling the epidemics. In this regard, social mixing and various biological factors play their subtle, but often critical, role. For example, a life-threatening condition may result in the infection contracted from an asymptomatic virus carrier. Here, we use a new recently developed microscopic agent-based modelling framework to shed light on the role of asymptomatic hosts and to unravel the interplay between the biological and social factors of these nonlinear stochastic processes. The model accounts for each human actor’s susceptibility and the virus survival time, as well as traceability along the infection path. These properties enable an efficient dissection of the infection events caused by asymptomatic carriers from those which involve symptomatic hosts before they develop symptoms and become removed to a controlled environment. Consequently, we assess how their relative proportions in the overall infection curve vary with changing model parameters. Our results reveal that these proportions largely depend on biological factors in the process, specifically, the virus transmissibility and the critical threshold for developing symptoms, which can be affected by the virus pathogenicity. Meanwhile, social participation activity is crucial for the overall infection level, further modulated by the virus transmissibility.
Identifying Heart Failure from Electronic Health Records: A Systematic Evidence Review
Authors: Levinson Rebecca T. , Malinowski Jennifer R. , Bielinski Suzette J. , Rasmussen Luke V. , Wilson Melissa P. , Manemann Sheila M. , Wells Quinn S. , Roger Veronique L. , Wiley Laura K.
Published: February 2021

Background

Heart failure (HF) is a complex syndrome associated with significant morbidity, mortality, and healthcare costs. Electronic health records (EHRs) are widely used to identify patients with HF. Despite the development of many HF phenotyping algorithms, it is unclear if the characteristics of identified populations reflect the known spectrum of disease in HF patients.

Methods

We performed a systematic evidence review to assess the methods used for HF algorithm development from US based data sources and the relevant information facilitating their application to research and clinical care. We queried PubMed for articles published up to November 2021. Out of 428 studies screened, 35 articles were included for primary analysis and 23 studies using only International Classification of Diseases (ICD) codes were evaluated for secondary analysis. Results are reported descriptively.

Results

HF algorithms were most often developed at academic medical centers, though these were not evenly distributed across the US. HF and congestive HF were the most frequent labels for observed phenotypes. Diagnoses were the most common data type used to identify HF patients and echocardiography was the second most frequent. Most studies used rule-based algorithms. Validation of algorithms varied considerably with 36% of HF subtype algorithms validated and 67% of acute HF algorithms validated. Demographics of any study population were reported in 57% of algorithm studies and 70% of ICD-only studies, however fewer than half (40% of algorithm and 46% of ICD-only) of studies reported demographics of the HF population identified by their computable phenotype. Of those reporting, most identified majority (>50%) male populations, including both algorithms for HF with preserved ejection fraction identified in this study.

Conclusion

There is significant heterogeneity in phenotyping algorithms used to ascertain HF from EHRs. Validation of algorithms is inconsistent and largely relies on manual review of medical records. The concentration of algorithm development at a few sites limits their generalizability to identify HF patients in other settings. Differences between the reported demographics of algorithm-identified HF populations and those expected based on HF epidemiology suggest that current algorithms do not reflect the full spectrum of HF in the general population.
Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders
Authors: Nakua Hajer , Hawco Colin , Forde Natalie J. , Jacobs Grace R. , Joseph Michael , Voineskos Aristotle , Wheeler Anne L. , Lai Meng-Chuan , Szatmari Peter , Kelley Elizabeth , Liu Xudong , Georgiades Stelios , Nicolson Rob , Schachar Russell , Crosbie Jennifer , Anagnostou Evdokia , Lerch Jason P. , Arnold Paul D. , Ameis Stephanie H.
Published: February 2021

Background

Externalizing and internalizing behaviors are common and contribute to impairment in children with neurodevelopmental disorders (NDDs). Associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in children with and without clinically significant internalizing/externalizing behaviors. This study examined whether such associations are present across children with different NDDs.

Methods

Multi-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6-18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (n range=157-346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined.

Results

No significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results.

Conclusions

The current study provides evidence in favour of the absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with various NDDs and TDC. Detecting shared brain-behavior relationships in children with NDDs may benefit from the use of different methodological approaches, including incorporation of multi-dimensional behavioral data (i.e. behavioral assessments, neurocognitive tasks, task-based fMRI) or clustering approaches to delineate whether subgroups of individuals with different brain-behavior profiles are present within heterogeneous cross-disorder samples.
Hydrogen peroxide modulates lignin and silica deposits in sorghum roots
Authors: Zexer Nerya , Elbaum Rivka
Published: February 2021

Hydrated silica (SiO2·nH2O) aggregates in the root endodermis of grasses. Application of soluble silicates (Si) to roots is associated with variations in the balance of reactive oxygen species (ROS), increased tolerance to a broad range of stresses affecting ROS levels, and early lignin deposition. In sorghum (Sorghum bicolorL.), silica aggregation is patterned in an active silicification zone (ASZ) by a special type of lignin. Since lignin polymerization is mediated by ROS, we studied the formation of root lignin and silica under varied conditions of ROS by modulating hydrogen peroxide (H2O2) concentration in the growth solution. Sorghum seedlings were grown hydroponically and supplemented with Si, H2O2, and KI, a salt that catalyzes H2O2decomposition. Lignin and silica deposits in the endodermis were studied by histology, scanning electron and Raman microscopies. Cell wall composition was quantified by thermal gravimetric analysis. We found that the endodermal H2O2concentration regulated the extent of ASZ lignin deposition along the root, but not its patterning in spots. Our results show that ASZ lignin is necessary for root silica aggregation in sorghum, and that silicification is enhanced under oxidative stress as a result of increased deposition of the ASZ lignin.

One sentence summary

Lignin with carbonyl modifications is patterned by the activity of H2O2to nucleate silica aggregations in sorghum roots.
RIM and RIM-binding protein localize synaptic CaV2 channels to differentially regulate transmission in neuronal circuits
Authors: Jánosi Barbara , Liewald Jana F. , Yu Szi-chieh , Umbach Simon , Alcantara Ivan C. , Bergs Amelie C.F. , Schneider Martin , Shao Jiajie , Gottschalk Alexander
Published: February 2021

At chemical synapses, voltage-gated Ca2+-channels (VGCCs) translate electrical signals into a trigger for synaptic vesicle (SV) fusion. VGCCs and the Ca2+microdomains they elicit must be located precisely to primed SVs, to evoke rapid transmitter release. Localization is mediated by Rab3 interacting molecule (RIM) and RIM-binding proteins (RIM-BPs), which interact and bind to the C-terminus of the CaV2 VGCC α-subunit. We studied this machinery at the mixed cholinergic/GABAergic neuromuscular junction (NMJ) ofCaenorhabditis elegans. rimb-1mutants had mild synaptic defects, through loosening the anchoring of UNC-2/CaV2 and delaying the onset of SV fusion. UNC-10/RIM deletion much more severely affected transmission. Even though postsynaptic depolarization was reduced,rimb-1mutants had increased cholinergic (but reduced GABAergic) transmission, to compensate for the delayed release. This did not occur when the excitation-inhibition balance was altered by removing GABA transmission. RIMB-1 thus may differentially regulate transmission in mixed circuits. Untethering the UNC-2/CaV2 channel by removing its C-terminal PDZ ligand exacerbated therimb-1defects, and similar phenotypes resulted from acute degradation of the CaV2 β-subunit CCB-1. Therefore, untethering of the CaV2 complex is as severe as its elimination, yet does not abolish transmission, likely due to compensation by CaV1. Thus, robustness and flexibility of synaptic transmission emerges from VGCC regulation.
Kv1.1 subunits localize to cardiorespiratory brain networks in mice where their absence induces astrogliosis and microgliosis
Authors: Dhaibar Hemangini A , Hamilton Kathryn A , Glasscock Edward
Published: February 2021

Cardiorespiratory collapse following a seizure is a suspected cause of sudden unexpected death in epilepsy (SUDEP), the leading cause of epilepsy-related mortality. In the commonly usedKcna1gene knockout (Kcna1−/−) mouse model of SUDEP, cardiorespiratory profiling reveals an array of aberrant breathing patterns that could contribute to risk of seizure-related mortality. However, the brain structures mediating these respiratory abnormalities remain unknown. We hypothesize that Kv1.1 deficiency in respiratory control centers of the brain contribute to respiratory dysfunction inKcna1−/−mice leading to increased SUDEP risk. Thus, in this study, we first used immunohistochemistry to map expression of Kv1.1 protein in cardiorespiratory brain regions of wild-typeKcna1+/+(WT) mice. Next, GFAP and Iba1 immunostaining was used to test for the presence of astrogliosis and microgliosis, respectively, in the cardiorespiratory centers ofKcna1−/−mice, which could be indicative of seizure-related brain injury that could impair breathing. In WT type mice, we detected Kv1.1 protein in all cardiorespiratory centers examined, including the basolateral amygdala, dorsal respiratory group, dorsal motor nucleus of vagus, nucleus ambiguus, ventral respiratory column, and pontine respiratory group, as well as chemosensory centers including the retrotrapezoid and median raphae nuclei. Extensive gliosis was observed in the same areas inKcna1−/−mice suggesting that seizure-associated brain injury could contribute to respiratory abnormalities.
Colonization at birth with human CST IV cervicovaginal microbiota alters development and increases neonatal mortality in mice
Authors: Jašarević Eldin , Hill Elizabeth M. , Kane Patrick J. , Rutt Lindsay , Gyles Trevonn , Folts Lillian , Rock Kylie D. , Howard Christopher D. , Morrison Kathleen E. , Ravel Jacques , Bale Tracy L.
Published: February 2021

Profound racial health disparities contribute to maternal-infant morbidity and mortality. An emergent risk factor is the maternal microbiota, whereby compositional alterations impact maternal health and offspring development during pregnancy and beyond. The presence of a nonoptimal CST IV cervicovaginal microbiota, more common in Black and Hispanic women, is associated with increased risk of preterm birth and adverse birth outcomes. Through examination of the biological mechanisms by which vertical transmission of microbiota from mother to offspring influences postnatal development, we found that exposing cesarean delivered mice with CST IV cervicovaginal microbiota from pregnant women produced lasting effects on offspring metabolic, immune, and neural outcomes. We then examined how compounding effects of a typical high-risk, proinflammatoryin uteroenvironment, characterized by a maternal obesogenic state and the presence ofG. vaginalis, would affect the offspring response to CST IV microbial gut colonization. The resultant developmental immaturity, coupled with an exaggerated immune response induced by exposure to risk-associated maternal microbiota, resulted in a profound increase in neonatal mortality, supporting the critical importance of elucidating the multifactorial biological mechanisms involved in high-risk pregnancies.

Highlights

Gut colonization by nonoptimal human cervicovaginal microbiota had sex-specific effects on postnatal development.

A high-riskin uteroenvironment increased offspring mortality risk.

Heightened innate immune response associated with mortality risk.

Developmental immaturity, premature birth, and exposure to CST IV contribute to increased offspring mortality risk.
Isolation andin vitroculture of primarypia matercells
Authors: Saadeh Fadi , Remsik Jan , Derderian Camille , Chi Yudan , Boire Adrienne
Published: February 2021

The meninges remain an unexplored area of neurobiology. These structures play host to dozens of morbid pathologies. This protocol provides a reliable way to identify and isolate pial cells from mice using robust markers of pial identity in mouse and human tissues. We describe a protocol for the extraction ofpia matercells from mice and their culture as primary cellsin vitro. Using an array of transcriptomic, histological, and flow cytometric analyses, we identified Icam1 and Slc38a2 as two novelpia matermarkersin vitroandin vivo. Our results confirm the fibroblastoid nature of pial cells and their ability to form a sheet-like layer that covers the brain parenchyma. To our knowledge, this is the first published protocol for the isolation, tissue culture, and marker identification of pial cells from mice. These findings will enable researchers in CNS barriers to describe pial cell functions in both health and disease.
Molecular mechanism underlying the non-essentiality of Bub1 for the fidelity of chromosome segregation in human cells
Authors: Chen Qinfu , Zhang Miao , Pan Xuan , Zhou Linli , Yan Haiyan , Wang Fangwei
Published: February 2021

The multi-task protein kinase Bub1 has long been considered important for chromosome alignment and spindle assembly checkpoint signaling during mitosis. However, recent studies provide surprising evidence that Bub1 may not be essential in human cells, with the underlying mechanism unknown. Here we show that Bub1 plays a redundant role with the non-essential CENP-U complex in recruiting Polo-like kinase 1 (Plk1) to the kinetochore. While disrupting either pathway of Plk1 recruitment does not affect the accuracy of whole chromosome segregation, loss of both pathways leads to a strong reduction in the kinetochore accumulation of Plk1 under a threshold level required for proper chromosome alignment and segregation. Thus, parallel recruitment of Plk1 to kinetochores by Bub1 and the CENP-U complex ensures high fidelity of mitotic chromosome segregation. This study may have implications for targeted treatment of cancer cells harboring mutations in either Bub1 or the CENP-U complex.
Voluntary alcohol consumption disrupts coupling of prefrontal cortical activity to arousal
Authors: Sipe Grayson , Linares-Garcia Ivan , Nguyen My , Vazey Elena , Huda Rafiq
Published: February 2021

Alcohol use disorder (AUD) exacts a major personal, societal, and economic toll. Top-down control from the prefrontal cortex (PFC), a critical hub for decision making, executive, and other cognitive functions, is key for the regulation of alcohol consumption. Arousal exerts profound effects on cortical processing, allowing it to potentially modulate PFC functions relevant for alcohol consumption and AUD. Despite this, it is unclear whether and how arousal-mediated modulation of PFC circuits relates to voluntary alcohol drinking behaviors. Two-photon microscopy is ideally suited for dissecting the neural circuit mechanisms underlying the effect of alcohol on intact circuits in behaving animals. We addressed a major limitation of this technology by developing a novel behavioral paradigm for voluntary drinking in head-fixed mice. We recorded responses of layer 2/3 excitatory neurons in the anterior cingulate cortex (ACC) subdivision of the PFC as mice voluntarily consumed ethanol, along with video recording of the pupil to track momentary fluctuations in arousal. Ethanol consumption bidirectionally modified the activity of subsets of ACC neurons, both at slow (minutes) and fast (sub-second) time scales. Remarkably, we found that the coupling of arousal to ACC activity before drinking was associated with subsequent ethanol engagement behavior. In turn, ethanol consumption modulated neuronal-arousal coupling. Together, our results suggest neuronal-arousal coupling as a key biomarker for alcohol drinking and lays the groundwork for future studies to dissect the therapeutic potential of this process for AUD and other substance use disorders.
Rampant prophage movement among transient competitors drives rapid adaptation during infection
Authors: Marshall Christopher W. , Gloag Erin S. , Lim Christina , Wozniak Daniel J. , Cooper Vaughn S.
Published: February 2021

Interactions between bacteria, their close competitors, and viral parasites are common in infections but understanding of these eco-evolutionary dynamics is limited. Most examples of adaptations caused by phage lysogeny are through the acquisition of new genes. However, integrated prophages can also insert into functional genes and impart a fitness benefit by disrupting their expression, a process called active lysogeny. Here, we show that active lysogeny can fuel rapid, parallel adaptations in establishing a chronic infection. These recombination events repeatedly disrupted genes encoding global regulators, leading to increased cyclic-di-GMP levels and elevated biofilm production. The implications of prophage-mediated adaptation are broad, as even transient members of microbial communities can alter the course of evolution and generate persistent phenotypes associated with poor clinical outcomes.

One Sentence Summary

Bacteriophage act as genetic regulators that are key to establishing chronic infections and are rapidly shared among co-infecting strains.
Sequence-specific minimizers via polar sets
Authors: Zheng Hongyu , Kingsford Carl , Marçais Guillaume
Published: February 2021

Minimizers are efficient methods to samplek-mers from genomic sequences that unconditionally preserve sufficiently long matches between sequences. Well-established methods to construct efficient minimizers focus on sampling fewerk-mers on a random sequence and use universal hitting sets (sets ofk-mers that appear frequently enough) to upper bound the sketch size. In contrast, the problem of sequence-specific minimizers, which is to construct efficient minimizers to sample fewerk-mers on a specific sequence such as the reference genome, is less studied. Currently, the theoretical understanding of this problem is lacking, and existing methods do not specialize well to sketch specific sequences. We propose the concept of polar sets, complementary to the existing idea of universal hitting sets. Polar sets arek-mer sets that are spread out enough on the reference, and provably specialize well to specific sequences. Link energy measures how well spread out a polar set is, and with it, the sketch size can be bounded from above and below in a theoretically sound way. This allows for direct optimization of sketch size. We propose efficient heuristics to construct polar sets, and via experiments on the human reference genome, show their practical superiority in designing efficient sequence-specific minimizers. A reference implementation and code for analyses under an open-source license are athttps://github.com/kingsford-group/polarset.