bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing Comorbid Attention Deficit Hyperactivity Disorder (ADHD) in Adults With Substance Use Disorder (SUD): What the Addiction Specialist Needs to Know
Authors: Johnson Joe , Morris Sarah , George Sanju
Published: December 2020

Attention deficit hyperactivity disorder (ADHD) and substance use disorder (SUD) often co-exist and the link between the 2 is bidirectional, with higher rates of ADHD symptoms found in the SUD population and higher rates of SUD found among the ADHD population. Some possible mechanisms which could explain the increased risk of developing a SUD in those who have ADHD include self-medication, both ADHD and SUD arising from dysregulation of 1 or more of the dopaminergic circuits, genetic factors as well exposure to parental SUD. Given the complex relationship between ADHD and SUD, those working in SUD services should be vigilant to ADHD as a possible comorbid diagnosis and refer to a specialist ADHD service for further assessment where appropriate. On the basis of a detailed clinical assessment, it has to be decided whether SUD or ADHD should be the priority for treatment or if they both ought to be; in either case, ADHD and SUD treatment services must work collaboratively. The recommended first line pharmacological treatment option for adolescents and adults with ADHD is a stimulant medication, with nonstimulants being reserved as a second or third line option. In the brief review paper, the authors further discuss the various medications for treatment of ADHD, the benefits and risks of treating ADHD in those with SUD, discuss the role of specialist ADHD treatment services, and illustrate these with the help of 2 anonymized case vignettes.
Naturalistic Decision Making in Everyday Self-care Among Older Adults With Heart Failure
Authors: Daley Carly N. , Cornet Victor P. , Toscos Tammy R. , Bolchini Davide P. , Mirro Michael J. , Holden Richard J.
Published: December 2020

Background

Every day, older adults living with heart failure make decisions regarding their health that may ultimately affect their disease trajectory. Experts describe these decisions as instances of naturalistic decision making influenced by the surrounding social and physical environment and involving shifting goals, high stakes, and the involvement of others.

Objective

This study applied a naturalistic decision-making approach to better understand everyday decision making by older adults with heart failure.

Methods

We present a cross-sectional qualitative field research study using a naturalistic decision-making conceptual model and critical incident technique to study health-related decision making. The study recruited 24 older adults with heart failure and 14 of their accompanying support persons from an ambulatory cardiology center. Critical incident interviews were performed and qualitatively analyzed to understand in depth how individuals made everyday health-related decisions.

Results

White, male (66.7%), older adults' decision making accorded with a preliminary conceptual model of naturalistic decision making occurring in phases of monitoring, interpreting, and acting, both independently and in sequence, for various decisions. Analyses also uncovered that there are barriers and strategies affecting the performance of these phases, other actors can play important roles, and health decisions are made in the context of personal priorities, values, and emotions.

Conclusions

Study findings lead to an expanded conceptual model of naturalistic decision making by older adults with heart failure. In turn, the model bears implications for future research and the design of interventions grounded in the realities of everyday decision making.
Management of Anticoagulation Therapy in Patients With Thromboembolism in the Context of Renal Dysfunction: Challenging Cases and Practical Algorithms
Authors: Bahabri Aban , Chan Anthony K.C. , Belostosky Vladimir , Bhatt Mihir D.
Published: December 2020

Background:

Low–molecular-weight heparin is cleared through the kidneys and is commonly used for anticoagulation in the pediatric population.

Observation:

We present 3 challenging cases of children requiring anticoagulation in the context of acute kidney injury, nephrotic syndrome, and hemodialysis.

Conclusions:

A significant change in anti-factor Xa (anti-Xa) levels—used for drug monitoring—should prompt an assessment of renal function. In nephrotic syndrome, anti-Xa levels should be closely monitored when there is a change in the status of nephrotic disease activity. In hemodialysis patients, enoxaparin at once daily reduced dosing should be considered with trough and peak anti-Xa levels monitoring.
A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer
Authors: Hewitt Daniel Brock , Nissen Nicholas , Hatoum Hassan , Musher Benjamin , Seng John , Coveler Andrew L. , Al-Rajabi Raed , Yeo Charles J. , Leiby Benjamin , Banks Joshua , Balducci Lodovico , Vaccaro Gina , LoConte Noelle , George Thomas J. , Brenner Warren , Elquza Emad , Vahanian Nicholas , Rossi Gabriela , Kennedy Eugene , Link Charles , Lavu Harish
Published: December 2020

Objectives:

To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC).

Summary Background Data:

To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene.

Methods:

A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival.

Results:

Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (interquartile range) overall survival was 14.9 (12.2–17.8) months in the standard group (N = 158) and 14.3 (12.6–16.3) months in the experimental group (N = 145) [hazard ratio (HR) 1.02, 95% confidence intervals 0.66–1.58; P = 0.98]. Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% confidence intervals 0.72–1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05).

Conclusions:

Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation.

Trial Registration:

ClinicalTrials.gov Identifier: NCT01836432
Mapping the probability of forest snow disturbances in Finland
Authors: Suvanto S , Lehtonen A , Nevalainen S , Lehtonen I , Viiri H , Strandström M , Peltoniemi M
Published: December 2020

The changing forest disturbance regimes emphasize the need for improved damage risk information. Here, our aim was to (1) improve the current understanding of snow damage risks by assessing the importance of abiotic factors, particularly the modelled snow load on trees, versus forest properties in predicting the probability of snow damage, (2) produce a snow damage probability map for Finland. We also compared the results for winters with typical snow load conditions and a winter with exceptionally heavy snow loads. To do this, we used damage observations from the Finnish national forest inventory (NFI) to create a statistical snow damage occurrence model, spatial data layers from different sources to use the model to predict the damage probability for the whole country in 16 x 16 m resolution. Snow damage reports from forest owners were used for testing the final map. Our results showed that best results were obtained when both abiotic and forest variables were included in the model. However, in the case of the high snow load winter, the model with only abiotic predictors performed nearly as well as the full model and the ability of the models to identify the snow damaged stands was higher than in other years. The results showed patterns of forest adaptation to high snow loads, as spruce stands in the north were less susceptible to damage than in southern areas and long-term snow load reduced the damage probability. The model and the derived wall-to-wall map were able to discriminate damage from no-damage cases on a good level. The damage probability mapping approach identifies the drivers of snow disturbances across forest landscapes and can be used to spatially estimate the current and future disturbance risks in forests, informing practical forestry and decision-making and supporting the adaptation to the changing disturbance regimes.
Patterns of within-host genetic diversity in SARS-CoV-2
Authors: Tonkin-Hill Gerry , Martincorena Inigo , Amato Roberto , Lawson Andrew R J , Gerstung Moritz , Johnston Ian , Jackson David K , Park Naomi R , Lensing Stefanie V , Quail Michael A , Gonçalves Sónia , Ariani Cristina , Chapman Michael Spencer , Hamilton William L , Meredith Luke W , Hall Grant , Jahun Aminu S , Chaudhry Yasmin , Hosmillo Myra , Pinckert Malte L , Georgana Iliana , Yakovleva Anna , Caller Laura G , Caddy Sarah L , Feltwell Theresa , Khokhar Fahad A , Houldcroft Charlotte J , Curran Martin D , Parmar Surendra ,   The COVID-19 Genomics UK (COG-UK) Consortium, Alderton Alex , Nelson Rachel , Harrison Ewan , Sillitoe John , Bentley Stephen D , Barrett Jeffrey C , Torok M. Estee , Goodfellow Ian G , Langford Cordelia , Kwiatkowski Dominic ,   Wellcome Sanger Institute COVID-19 Surveillance Team
Published: December 2020

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1,181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within and between host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.
Remdesivir-ivermectin combination displays synergistic interaction with improvedin vitroantiviral activity against SARS-CoV-2
Authors: Jeffreys Laura N , Pennington Shaun H , Duggan Jack , Caygill Claire H , Lopeman Rose C , Breen Alastair F , Jinks Jessica B , Ardrey Alison , Donnellan Samantha , Patterson Edward I , Hughes Grant L , Hong David W , O’Neill Paul M , Aljayyoussi Ghaith , Owen Andrew , Ward Stephen A , Biagini Giancarlo A
Published: December 2020

A key element for the prevention and management of COVID-19 is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer several advantages over monotherapies, including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Here, we report on thein vitrosynergistic interaction between two FDA approved drugs, remdesivir and ivermectin resulting in enhanced antiviral activity against SARS-CoV-2. These findings warrant further investigations into the clinical potential of this combination, together with studies to define the underlying mechanism.
Genomic signature of shifts in selection and alkaline adaptation in highland fish
Authors: Tong Chao , Li Miao , Tang Yongtao , Zhao Kai
Published: December 2020

Understanding how organisms adapt to aquatic life at high altitude is fundamental in evolutionary biology. This objective has been addressed primarily related to hypoxia adaptation by recent comparative studies, whereas highland fish has also long suffered extreme alkaline environment, insight into the genomic basis of alkaline adaptation has rarely been provided. Here, we compared the genomes or transcriptomes of 15 fish species, including two alkaline tolerant highland fish species and their six alkaline intolerant relatives, three alkaline tolerant lowland fish species and four alkaline intolerant species. We found putatively consistent patterns of molecular evolution in alkaline tolerant species in a large number of shared orthologs within highland and lowland fish taxa. Remarkably, we identified consistent signatures of accelerated evolution and positive selection in a set of shared genes associated with ion transport, apoptosis, immune response and energy metabolisms in alkaline tolerant species within both highland and lowland fish taxa. This is one of the first comparative studies that began to elucidate the consistent genomic signature of alkaline adaptation shared by highland and lowland fish. This finding also highlights the adaptive molecular evolution changes that support fish adapting to extreme environments at high altitude.

Significance Statement

Little is known about how wild fish responds to extreme alkaline stress besides hypoxia at high altitude. Comparative genomics has begun to elucidate the genomic basis of alkaline adaptation in lowland fish, such as killifish, but insight from highland fish has lagged behind. The common role of adaptive molecular evolution during alkaline adaptation in highland and lowland fish has rarely been discussed. We address this question by comparing 15 fish omics data. We find numbers of shared orthologs exhibited consistent patterns of molecular evolution in alkaline tolerant species relative to intolerant species. We further identify remarkably consistent signatures of rapidly evolving and positive selection in a substantial shared core of genes in both highland and lowland alkaline tolerant species.
Heterologous flavivirus exposure provides varying degrees of cross-protection from Zika virus in a mouse model of infection
Authors: Hassert Mariah , Scroggins Stephen , Coleman Abigail K. , Shacham Enbal , Brien James D. , Pinto Amelia K.
Published: December 2020

The 2015/16 Zika virus epidemic in South and Central America left the scientific community urgently trying to understand the disease and the factors which modulate Zika virus pathogenesis. Multiple other flaviviruses are endemic in areas where Zika virus emerged in 2015/16. Therefore, it is hypothesized that a key to understanding how Zika virus infection and disease progresses, is to study Zika virus infection in the context of prior flavivirus exposure. Humans and animal studies have highlighted the idea that having been previously exposed to a heterologous flavivirus may modulate the immune response to Zika virus. However, it is still unclear 1) how this impacts viral burden and pathology, and 2) the factors which correlate with the multiple metrics of disease. In this murine study, we longitudinally examine multiple factors involved in Zika disease, linking viral burden over time with increased neurological disease severity and weight loss. We show that prior heterologous flavivirus exposure with dengue virus type 2 or 3, or the vaccine strain of yellow fever, provides protection from mortality in a lethal Zika challenge. Reduction in viral burden and Zika disease in the context of prior flavivirus exposure varies depending on the infecting primary virus; with primary Zika infection being most protective from Zika challenge, followed by dengue 2, yellow fever, and dengue 3. This study demonstrates a protective effect of prior heterologous flavivirus exposure on Zika virus pathogenesis, and defines the relationship between prior flavivirus exposure and the potential for Zika virus disease.

IMPORTANCE

The emergence and re-emergence of various vector-borne diseases in recent years highlights the need to understand the mechanisms of protection for each pathogen. In this study, we investigated the impact of prior exposure to Zika, dengue serotypes 2, 3, and the vaccine strain of yellow fever on pathogenesis and disease outcomes in a mouse model of Zika virus infection. We found that prior exposure to a heterologous flavivirus was protective from mortality, neurological disease, weight loss, and severe viral burden during a lethal Zika challenge. Using a longitudinal study design, we were able to link multiple disease parameters including viral burden over time with neurological disease severity and weight loss in the context of heterologous infection.This study demonstrates a role for heterologous flavivirus exposure in modulating flavivirus pathophysiology. Given the cyclic nature of most flavivirus outbreaks, this work will contribute to the forecasting of disease severity for future outbreaks.
Detection and molecular characterisation of SARS-CoV-2 in farmed mink (Neovision vision) in Poland
Authors: Rabalski Lukasz , Kosinski Maciej , Smura Teemu , Aaltonen Kirsi , Kant Ravi , Sironen Tarja , Szewczyk Boguslaw , Grzybek Maciej
Published: December 2020

SARS-CoV-2 is the aetiological agent of COVID-19 disease and has been spreading worldwide since December 2019. The virus has been shown to infect different animal species under experimental conditions. Also, minks have been found to be susceptible to SARS-CoV-2 infection in fur farms in Europe and the USA. Here we investigated 91 individual minks from a farm located in Northern Poland. Using RT-PCR, antigen detection and NGS, we confirmed 15 animals positive for SARS-CoV-2. The result was verified by sequencing of full viral genomes, confirming SARS-CoV-2 infection in Polish mink. Country-scale monitoring conducted by veterinary inspection so far has not detected the presence of SARS-CoV-2 on other mink farms. Taking into consideration that Poland has a high level of positive diagnostic tests among its population, there is a high risk that more Polish mink farms become a source for SARS-CoV-2. Findings reported here and from other fur producing countries urge the assessment of SARS-CoV-2 prevalence in animals bred in Polish fur farms.
Effector-independent brain network for auditory-motor integration: fMRI evidence from singing and cello playing
Authors: Segado Melanie , Zatorre Robert J. , Penhune Virginia B.
Published: December 2020

Many everyday tasks share high-level sensory goals but differ in the movements used to accomplish them. One example of this is musical pitch regulation, where the same notes can be produced using the vocal system or a musical instrument controlled by the hands. Cello playing has previously been shown to rely on brain structures within the singing network for performance of single notes, except in areas related to primary motor control, suggesting that the brain networks for auditory feedback processing and sensorimotor integration may be shared (Segado et al. 2018). However, research has shown that singers and cellists alike can continue singing/playing in tune even in the absence of auditory feedback (Chen et al. 2013, Kleber et al. 2013), so different paradigms are required to test feedback monitoring and control mechanisms. In singing, auditory pitch feedback perturbation paradigms have been used to show that singers engage a network of brain regions including anterior cingulate cortex (ACC), anterior insula (aINS), and intraparietal sulcus (IPS) when compensating for altered pitch feedback, and posterior superior temporal gyrus (pSTG) and supramarginal gyrus (SMG) when ignoring it (Zarate et al. 2005, 2008). To determine whether the brain networks for cello playing and singing directly overlap in these sensory-motor integration areas, in the present study expert cellists were asked to compensate for or ignore introduced pitch perturbations when singing/playing during fMRI scanning. We found that cellists were able to sing/play target tones, and compensate for and ignore introduced feedback perturbations equally well. Brain activity overlapped for singing and playing in IPS and SMG when compensating, and pSTG and dPMC when ignoring; differences between singing/playing across all three conditions were most prominent in M1, centered on the relevant motor effectors (hand, larynx). These findings support the hypothesis that pitch regulation during cello playing relies on structures within the singing network and suggests that differences arise primarily at the level of forward motor control.

Highlights

Expert cellists were asked to compensate for or ignore introduced pitch perturbations when singing/playing during fMRI scanning.

Cellists were able to sing/play target tones, and compensate for and ignore introduced feedback perturbations equally well.

Brain activity overlapped for singing and playing in IPS and SMG when compensating, and pSTG and dPMC when ignoring.

Differences between singing/playing across were most prominent in M1, centered around the relevant motor effectors (hand, larynx)

Findings support the hypothesis that pitch regulation during cello playing relies on structures within the singing network with differences arising primarily at the level of forward motor control
Assembly and Validation of Two Gap-free Reference Genomes forXian/indicaRice Reveals Insights into Plant Centromere Architecture
Authors: Song Jia-Ming , Xie Wen-Zhao , Wang Shuo , Guo Yi-Xiong , Koo Dal-Hoe , Kudrna Dave , Huang Yicheng , Feng Jia-Wu , Zhang Wenhui , Zhou Yong , Zuccolo Andrea , Long Evan , Lee Seunghee , Talag Jayson , Zhou Run , Zhu Xi-Tong , Yuan Daojun , Udall Joshua , Xie Weibo , Wing Rod A. , Zhang Qifa , Poland Jesse , Zhang Jianwei , Chen Ling-Ling
Published: December 2020

Rice (Oryza sativa), a major staple throughout the world and a model system for plant genomics and breeding, was the first crop genome completed almost two decades ago. However, all sequenced genomes to date contain gaps and missing sequences. Here, we report, for the first time, the assembly and analyses of two gap-free reference genome sequences of the eliteO. sativa xian/indicarice varieties ‘Zhenshan 97 (ZS97)’ and ‘Minghui 63 (MH63)’ that are being used as a model system to study heterosis. Gap-free reference genomes also provide global insights into the structure and function of centromeres. All rice centromeric regions share conserved centromere-specific satellite motifs but with different copy numbers and structures. Importantly, we demonstrate that >1,500 genes are located in centromere regions, of which ~15.6% are actively transcribed. The generation and release of both the ZS97 and MH63 gap-free genomes lays a solid foundation for the comprehensive study of genome structure and function in plants and breed climate resilient varieties for the 21stcentury.
In vivovisualization of pig vagus nerve ‘vagotopy’ using ultrasound
Authors: Settell Megan L. , Kasole Maïsha , Skubal Aaron C. , Knudsen Bruce E. , Nicolai Evan N. , Huang Chengwu , Zhou Chenyun , Trevathan James K. , Upadhye Aniruddha , Kolluru Chaitanya , Shoffstall Andrew J. , Williams Justin C. , Suminski Aaron J. , Grill Warren M. , Pelot Nicole A. , Chen Shigao , Ludwig Kip A.
Published: December 2020

Background

Placement of the clinical vagus nerve stimulating cuff is a standard surgical procedure based on anatomical landmarks, with limited patient specificity in terms of fascicular organization or vagal anatomy. As such, the therapeutic effects are generally limited by unwanted side effects of neck muscle contractions, demonstrated by previous studies to result from stimulation of 1) motor fibers near the cuff in the superior laryngeal and 2) motor fibers within the cuff projecting to the recurrent laryngeal.

Objective

The use of patient-specific visualization of vagus nerve fascicular organization could better inform clinical cuff placement and improve clinical outcomes.

Methods

The viability of ultrasound, with the transducer in the surgical pocket, to visualize vagus nerve fascicular organization (i.e. vagotopy) was characterized in a pig model. Ultrasound images were matched to post-mortem histology to confirm the utility of ultrasound in identifying fascicular organization.

Results

High-resolution ultrasound accurately depicted the vagotopy of the pig vagus nerve intra-operatively, as confirmed via histology. The stereotypical pseudo-unipolar cell body aggregation at the nodose ganglion was identifiable, and these sensory afferent fascicular bundles were traced down the length of the vagus nerve. Additionally, the superior and recurrent laryngeal nerves were identified via ultrasound.

Conclusions

Intraoperative visualization of vagotopy and surrounding nerves using ultrasound is a novel approach to optimize stimulating cuff placement, avoid unwanted activation of motor nerve fibers implicated in off-target effects, and seed patient-specific models of vagal fiber activation to improve patient outcomes.
Response of Soil Microbiome Structure to Biological Control Agents (BCAs) in Strawberry Greenhouse
Authors: Liu Senlin , Hassan Khan Muzammil , Yuan Zhongyuan , Hussain Sarfraz , Cao Hui , Liu Yabo
Published: December 2020

Continuous cropping always leads to severe abiotic and biotic problems, especially the high-intensity land utilization in greenhouses, which causes widespread concern. Effective Microorganisms (EM) andBacillus subtilis(BS) have been widely used to promote plant growth and increase yields as biological control agents (BCAs). However, their effects on soil microbes are obscure. To regulate the microbial community in continuous cropping strawberry soils, we developed four soil amendments by combining EM and BS with compost. The amplicon sequencing of bacterial and fungal ribosomal markers was applied to study the response of the soil microbiome structure. We noticed a sharp increase in bacterial diversity after the addition of EM-treated high compost and BS-treated low compost, while there was no significant change in fungal diversity among treatments. Interestingly, both the relative abundance and FUNGuild predictions was consistent in revealing that BCAs may inhibit fungal pathogens in soils. Correlation analysis indicated that soil microbial community was indirectly driven by soil properties. Co-occurrence networks demonstrated that BCAs could be microecologically homogeneous through enhancing bacterial network complexity and modularity. Collectively, EM-treated high compost and BS-treated low compost can well regulate the microbial community structure and thus maintain soil health.
Cega: A Single Particle Segmentation Algorithm to Identify Moving Particles in a Noisy System
Authors: Masucci Erin M. , Relich Peter K. , Ostap E. Michael , Holzbaur Erika L. F. , Lakadamyali Melike
Published: December 2020

Improvements to particle tracking algorithms are required to effectively analyze the motility of biological molecules in complex or noisy systems. A typical single particle tracking (SPT) algorithm detects particle coordinates for trajectory assembly. However, particle detection filters fail for datasets with low signal-to-noise levels. When tracking molecular motors in complex systems, standard techniques often fail to separate the fluorescent signatures of moving particles from background noise. We developed an approach to analyze the motility of kinesin motor proteins moving along the microtubule cytoskeleton of extracted neurons using the Kullback-Leibler (KL) divergence to identify regions where there are significant differences between models of moving particles and background signal. We tested our software on both simulated and experimental data and found a noticeable improvement in SPT capability and a higher identification rate of motors as compared to current methods. This algorithm, called Cega, for ‘find the object’, produces data amenable to conventional blob detection techniques that can then be used to obtain coordinates for downstream SPT processing. We anticipate that this algorithm will be useful for those interested in tracking moving particles in complex in vitro or in vivo environments.
Single cell RNA analysis of trunk neural crest cells in zebrafish identifies pre-migratory populations expressing markers of differentiated derivatives
Authors: Lencer Ezra , Prekeris Rytis , Artinger Kristin Bruk
Published: December 2020

The neural crest is a migratory population of stem-like cells that contribute to multiple traits including the bones of the skull, peripheral nervous system, and pigment. How neural crest cells differentiate into diverse cell types is a fundamental question in the study of vertebrate biology. Here, we use single cell RNA sequencing to characterize transcriptional changes associated with neural crest cell development in the zebrafish trunk during the early stages of migration. We show that neural crest cells are transcriptionally diverse, and identify pre-migratory populations already expressing genes associated with differentiated derivatives. Further, we identify a population of Rohon-Beard neurons that are shown to be sources of Fgf signaling in the zebrafish trunk. The data presented identify novel genetic markers for multiple trunk neural crest cell populations and Rohon-Beard neurons providing insight into previously uncharacterized genes critical for vertebrate development.
Single cell multi-omic analysis identifies aTbx1-dependent multilineage primed population in the murine cardiopharyngeal mesoderm
Authors: Nomaru Hiroko , Liu Yang , De Bono Christopher , Righelli Dario , Cirino Andrea , Wang Wei , Racedo Silvia E. , Dantas Anelisa G. , Cai Chenleng , Angelini Claudia , Christiaen Lionel , Kelly Robert G. , Baldini Antonio , Zheng Deyou , Morrow Bernice
Published: December 2020

The poles of the heart and branchiomeric muscles of the face and neck are formed from the cardiopharyngeal mesoderm (CPM) within the pharyngeal apparatus. The formation of the cardiac outflow tract and branchiomeric muscles are disrupted in patients with 22q11.2 deletion syndrome (22q11.2DS), due to haploinsufficiency ofTBX1, encoding a T-box transcription factor. Here, using single cell RNA-sequencing, we identified a multilineage primed population (MLP) within the CPM, marked by theTbx1lineage, which has bipotent properties to form cardiac and skeletal muscle cells. The MLPs are localized within the nascent mesoderm of the caudal lateral pharyngeal apparatus and provide a continuous source of progenitors that undergo TBX1-dependent progression towards maturation.Tbx1also regulates the balance between MLP maintenance and maturation while restricting ectopic non-mesodermal gene expression. We further show that TBX1 confers this balance by direct regulation of MLP enriched genes and downstream pathways, partly through altering chromatin accessibility. Our study thus uncovers a new cell population and reveals novel mechanisms by whichTbx1directs the development of the pharyngeal apparatus, which is profoundly altered in 22q11.2DS.
An open source platform for presenting dynamic visual stimuli
Authors: Swanson Kyra , White Samantha R. , Preston Michael W. , Wilson Joshua , Mitchell Meagan , Laubach Mark
Published: December 2020

Operant behavior procedures often rely on visual stimuli to cue the initiation or secession of a response, and to provide a means for discriminating between two or more simultaneously available responses. While primate and human studies typically use LCD or OLED monitors and touch screens, rodent studies use a variety of methods to present visual cues ranging from traditional incandescent light bulbs, single LEDs, and, more recently, touch screen monitors. Commercially available systems for visual stimulus presentation are costly, challenging to customize, and are typically closed source. We developed an open-source, highly-modifiable visual stimulus presentation platform that can be combined with a 3D-printed operant response device. The device uses an eight by eight matrix of LEDs, and can be expanded to control much larger LED matrices. Implementing the platform is low-cost (<$70 USD per device in the year 2020). Using the platform, we trained rats to make nosepoke responses and discriminate between two distinct visual cues in a location-independent manner. This visual stimulus presentation platform is a cost-effective way to implement complex visually-guided operant behavior, including the use of moving or dynamically changing visual stimuli.

Significance Statement

The design of an open source and low cost device for presenting visual stimuli is described. It is capable of presenting complex visual patterns and dynamically changing stimuli. A practical demonstration of the device is also reported, from an experiment in which rats performed a luminance based visual discrimination. The device has utility for studying visual processing, psychophysics, and decision making in a variety of species.
Quantitative genetics of phosphorus content in the freshwater herbivore, Daphnia pulicaria
Authors: Sherman Ryan E. , Hartnett Rachel , Kiehnau Emily L. , Weider Lawrence J. , Jeyasingh Punidan D.
Published: December 2020

Phosphorus (P) is essential for growth of all organisms, and P content is correlated with growth in most taxa. Although P content was initially considered to be a trait fixed at the species level, there is growing evidence for considerable intraspecific variation. Selection on such variation can thus alter the rates at which P fluxes through food webs.

Nevertheless, prior work describing the sources and extent of intraspecific variation in P content were not genetically explicit, confounded by unknown genetic background and evolutionary history. We constructed an F2 recombinant population of the dominant freshwater grazer, Daphnia pulicaria to mitigate such issues.

F2 recombinants exhibited considerable variation in growth rate, P content (0.49%–1.97%), P use efficiency (PUE; 51–208 mg biomass/mg P), and correlated traits such as hatching time of resting eggs, in common garden conditions.

These results clearly demonstrate the scope of genetic recombination in generating variation in ecologically relevant traits. The absence of environmental selection is a likely component driving such variation not observed in natural settings.

Although phosphoglucose isomerase (PGI) genotype was significantly associated with variation in hatching time of resting eggs, contrary to prior work with less rigorous designs, and allelic variation at the PGI locus did not explain variation in P content and PUE of Daphnia, indicating that such quantitative traits are under polygenic control.

Together, these results suggest that although there is considerable genetic scope for variation in key ecologically relevant traits, such as P content and efficiency of P use, these traits are likely under strong stabilizing selection, most likely due to selection on growth rate and size. Importantly, our observations suggest that anthropogenic alterations to P supply due to eutrophication could alter selection on these traits, thereby rapidly altering the role Daphnia plays in the P cycle of lakes.
Bumblebee colony density on farmland is influenced by late‐summer nectar supply and garden cover
Authors: Timberlake Thomas P. , Vaughan Ian P. , Baude Mathilde , Memmott Jane
Published: December 2020

Floral resources are important in limiting pollinator populations, but they are often highly variable across time and space and the effect of this variation on pollinator population dynamics is not well understood. The phenology (timing) of floral resources is thought to be important in structuring pollinator populations, but few studies have directly investigated this.

Our study quantifies the landscape composition, seasonal nectar and pollen supply and Bombus terrestris colony density of 12 farms in southwest UK to investigate how landscape composition influences the phenology of floral resources and how both these factors affect colony density. We use this information in a spatially explicit predictive model to estimate the effect of different farmland management scenarios on seasonal resource supplies and colony density.

We find that farmland nectar supply during September is a strong predictor of B. terrestris colony density in the following year, explaining over half of all the variation in colony density; no other period of resource availability showed a significant association. Semi‐natural habitat cover was not a good proxy for nectar or pollen supply and showed no significant association with colony density. However, the proportional cover of gardens in the landscape was significantly associated with colony density.

The predictive model results suggest that increasing the area of semi‐natural flowering habitat has limited effect on bumblebee populations. However, improving the quality of these habitats through Environmental Stewardship and other management options is predicted to reduce the late‐summer resource bottleneck and increase colony density.

Synthesis and Applications. Our study demonstrates the importance of considering the phenology of resources, rather than just total resource availability, when designing measures to support pollinators. Late summer appears to be a resource bottleneck for bumblebees in UK farmland, and consequently management strategies which increase late‐summer nectar availability may be the most effective. These include mowing regimes to delay flowering of field margins until September, planting late‐flowering cover crops such as red clover and supporting late‐flowering wild plant species such as Hedera helix. Our results also suggest that rural gardens may play an important role in supporting farmland bumblebee populations.
Just what is critical race theory, and what is it doing in British sociology? From “BritCrit” to the racialized social system approach
Authors: Meghji Ali
Published: December 2020

Critical race theory is growing in popularity in Britain. However, critics and advocates of critical race theory (CRT) in Britain have neglected the racialized social system approach. Through ignoring this approach, critics have thus “missed the target” in their rebuttals of CRT, while advocates of CRT have downplayed the strength of critical race analysis. By contrast, in this paper, I argue that that through the racialized social system approach, critical race theory has the conceptual flexibility to study British society. As a practical social theory, critical race theory provides us with the tools to study the realities and reproduction of racial inequality. To demonstrate this strength of CRT, and to demonstrate its theoretical nature, I discuss the conceptual framework of the racialized social system approach, paying specific attention to the notions of social space, the racial structure and racial interests; the racialized interaction order, racialized emotions, and structure and agency; and racial ideology, racial grammar, and racialized cognition.
Craft beer: An overview
Authors: Baiano Antonietta
Published: December 2020

The purpose of the work was to provide an overview on craft beer. Details and issues concerning history and legal definition market, fiscal policy, innovation, safety, healthiness, consumer profile, and sustainability are supplied. The term “craft brewery” generally refers to a brewery able to produce low volumes of beer, often made with traditional ingredients—for emulating historic styles—but also with the addition of nontraditional ingredients as a distinctiveness sign of the master brewer. In many countries, the importance of the company size is related to the opportunity to take advantage of reduced excise rates for low production volumes. In several countries, another important requisite of a craft brewery is represented by its independence from other alcohol industry members. Even in the presence of a great heterogeneity of the size of craft breweries in the various countries, their number in the world is around 17,000. Craft beer is mainly consumed in restaurants and bars. Innovation of craft beer concerns aspects, such as ingredients, alcohol content, aging, and packaging, and the profile of the typical craft beer drinker is that of a young man, with a higher education and a medium‐high income. Craft beers are often not filtered/not pasteurized and, for these reasons, they are beverages rich in health compounds but with a reduced shelf life. As in the case of larger breweries, the environmental impact of craft breweries is mainly represented by water consumption and production of liquid and solid wastes.
Novel biomarkers for the diagnosis and prognosis of gallbladder cancer
Authors: Lin Hong Ze , Zhang Tao , Chen Ming Yu , Shen Ji Liang
Published: December 2020

Gallbladder cancer (GBC) is the most common form of biliary tract malignancy with a dismal prognosis. A poor outcome in patients with GBC is related to the aggressive nature of the tumor, delayed diagnosis, and a lack of reliable biomarkers and effective treatment. Therefore, early diagnosis and accurate disease assessment are crucial to prolonging the patient survival. Identification of novel prognostic and diagnostic biomarkers may help improve the early diagnostic rate and develop specific targeted treatments for patients with GBC. We herein review the novel biomarkers that may be associated with the diagnosis and prognosis in GBC and their potential clinical significance in the management of GBC.
Courting Informal Workers: Exclusion, Forbearance, and the Left
Authors: Feierherd Germán
Published: December 2020

Leftist governments with strong links to organized labor are expected to increase the number of people protected by job security rules. But do they? I explore whether the Left in power at the local level in Brazil cracks down on enterprises that employ noncontract, informal‐sector workers, and implements policies aimed at reducing the size of the informal sector. With a close‐election regression‐discontinuity design, I show that mayors from the Workers' Party (PT) in fact slow down enforcement and improve conditions in the informal sector, rather than encouraging a shift to formal jobs. This reflects a challenge that leftist parties face across the world: how to simultaneously improve the employment prospects and conditions of workers in precarious employment and those in full‐time jobs in the context of increased global competition, segmented labor markets and, in Latin America, truncated welfare states.
Effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST‐segment elevation myocardial infarction: A pilot test
Authors: Xu Yan , Zhang Wenying , Zhong Xinbo , Yan Shaodi , Chen Haijun , Guo Ruirui , Luo Xinlin , Liu Qiang
Published: December 2020

Objective

To investigate the effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST‐segment elevation myocardial infarction (STEMI).

Methods

A total of 66 STEMI patients with sinus rhythm and the resting heart rate ≥80 bpm after successful emergency PCI were included. The patients in the test group were treated with ivabradine combined with metoprolol at 12 hr after PCI, while the control group was given only metoprolol orally. Their resting heart rate was controlled to <70 bpm at discharge and followed for 180 days. Heart rate and blood pressure were measured regularly. Echocardiogram was performed. N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), high sensitivity troponin T, high sensitivity troponin I, and high sensitivity C‐reactive protein were measured. The major adverse cardiovascular events during hospitalization and follow‐up period were recorded.

Results

Compared with the control group, the heart rate of the test group decreased significantly (p < .05). Compared with the control group, the left ventricular end‐diastolic volume and left ventricular end‐systolic volume were significantly decreased while left ventricular ejection fraction was significantly increased in the test group at 90 days after operation. NT‐proBNP of the test group was significantly lower than that of the control group at 7 days after operation (p < .05).

Conclusion

For STEMI patients, early use of ivabradine combined with standard therapy such as β‐blocker after successful reperfusion can achieve effective heart rate control, with great safety and tolerance. But the effect of ivabradine on left ventricular remodeling is uncertain.
MicroRNA‐2355‐5p regulates γ‐globin expression in human erythroid cells by inhibiting KLF6
Authors: Cheng Yi , Shang Xuan , Chen Diyu , Pang Dejian , Zhao Cunyou , Xu Xiangmin
Published: December 2020

Krüppel‐like factors (KLFs) are a highly conserved family of transcription factors. We analysed expression profile data of KLFs and identified KLF6 as a new potential regulator of erythropoiesis. Knocking down the expression of KLF6 significantly raised γ‐globin mRNA and protein levels in the erythroid cell line HUDEP‐2 and haematopoietic progenitor (CD34+) cells. We found that overexpression of microRNA (miR)‐2355‐5p in HUDEP‐2 and CD34+ cells correlated with increased γ‐globin synthesis by suppressing expression of KLF6. Our discovery that the interaction between miR‐2355‐5p and KLF6 affects the expression of γ‐globin may provide more information for the clinical management of β‐thalassaemia patients.
Memory at Play: Examining Relations Between Episodic and Semantic Memory in a Children’s Museum
Authors: Sipe Sarah J. , Pathman Thanujeni
Published: December 2020

The relation between episodic and semantic memory was examined by testing how semantic knowledge influences children’s episodic memory for events and their locations. Five‐, six‐, and seven‐year‐olds (N = 87) engaged in events in a children’s museum designed as a town. Events were semantically congruent or incongruent with the spatial location (e.g., sorting mail at post office vs. grocery store). In addition to this experimental paradigm, a semantic interview assessed children’s semantic knowledge about real‐world locations. Accuracy in the experimental paradigm showed that children’s semantic memory influenced memory for locations. Interviews revealed age‐related improvements in children’s semantic knowledge. Regression analyses examined factors that best supported episodic memory. These results provide novel insights and highlight the utility of research in naturalistic settings.