bluuebunny/crossref_metadata_2025 huggingface dataset:
Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy
Authors: Zhang Yuguo , Gabere Musa , Taylor Mika , Simoes Camila C. , Dumbauld Chelsae , Barro Oumar , Chamcheu Jean Christopher , Post Steven R. , Kelly Thomas J. , Borad Mitesh J. , Cannon Martin J. , Basnakian Alexei , Nagalo Bolni M.
Published: March 2022

Despite its rising promise, cancer immunotherapy remains out of reach for many patients because of the extensive cost of manufacturing immunotherapy products. In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulates a potent cytotoxic T-cell antitumor immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma and colorectal cancer. Using an integrated transcriptomic and proteomic approach, we demonstrated that mechanistically, MMR exerts its antitumor activity by priming innate and adaptive antitumor immune responses, leading to immunologically coordinated cancer cells death. Our findings highlight a promising potential for LAVs, such as MMR, to be repurposed as cost-effective cancer immunotherapy.
Studies for searching factors relating rumination time around the heat season in Holstein milking cows
Authors: Seto Takahiro , Toba Yuichi
Published: March 2022

To identify factors affecting rumination time (RT), factorial analyses in a dairy farm were performed. In univariate analyses, differences in distribution were observed between low (< 45 kg/d) and high (≥ 45 kg/d) milk yield (MY) before the heat season, early and peak lactation periods and mid and late at the start of the heat season, and 1-2 and ≥ 3 parity at the start of the heat season. Multiple regression analysis confirmed that RT was affected by low MY, early to peak and 1-2 parity cows, low MY, mid to late and 1-2 parity cows, and low MY, early to peak and ≥ 3 parity cows (coefficients = −37.039, −25.353, −44.805 respectively,P< 0.05). When the cows were classified by MY before the heat season, the RT and MY of the high-MY group remained higher than the low-MY group until before the severe heat (THI ≥ 84 continued). However, when cows were classified by RT before the heat season, there was no difference in MY between the low-RT (< 485 min/d) and the high-RT group (> 485 min/d). In conclusions, MY is a factor affecting RT up to moderate heat but RT is not a sufficient condition affecting MY.
The Development of 2-stage Microfermentation Protocols for High Throughput Cell Factory Evaluations
Authors: Li Shuai , Ye Zhixia , Moreb Eirik A. , Menacho-Melgar Romel , Lynch Michael D.
Published: March 2022

Cell based factories can be engineered to produce a wide variety of products. Advances in DNA synthesis and genome editing have greatly simplified the design and construction of these factories. It has never been easier to generate hundreds or even thousands of cell factory strain variants for evaluation. These advances have amplified the need for standardized, higher throughput means of evaluating these designs. Toward this goal, we have previously reported the development of engineered E. coli strains and associated 2-stage production processes to simplify and standardize strain engineering, evaluation and scale up. This approach relies on decoupling growth (stage 1), from production, which occurs in stationary phase (stage 2). Phosphate depletion is used as the trigger to stop growth as well as induce heterologous expression. Here, we describe in detail the development of optimal protocols used for the evaluation of engineered E. coli strains in 2-stage microfermentations. These protocols are readily adaptable to the evaluation of strains producing a wide variety of protein as well as small molecule products. Additionally, the development approach described is adaptable to additional cellular hosts, as well as other 2-stage processes with various additional triggers.
Mucosal microbiomes and Fusobacterium genomics in Vietnamese colorectal cancer patients
Authors: Tran Hoang N. H. , Hoang Thu Trang Nguyen , Nguyen Phu Huu , Vo Chi Nguyen , Van Doan Khanh , Ngoc Minh Chau Nguyen , Nguyen Ngoc Tuan , Duc Ta Van Ngoc , Vu Khuong An , Hua Thanh Danh , Thi Nguyen To Nguyen , Van Tan Trinh , Duc Trung Pham , Duong Ba Lap , Nguyen Phuc Minh , Hoang Vinh Chuc , Pham Duy Thanh , Thwaites Guy E. , Hall Lindsay J. , Slade Daniel J. , Baker Stephen , Tran Vinh Hung , The Hao Chung
Published: March 2022

Perturbations in the gut microbiome have been linked to the promotion and prognosis of colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite the increasing health burden inflicted by CRC in low- and middle-income countries like Vietnam, the CRC-specific microbiome in these populations remains underexplored. Here we conducted a study in Vietnam to enrol 43 CRC patients (cases) and 25 patients with non-cancerous colorectal polyps (controls) between December 2018 and January 2020. Our study investigated the mucosal microbiome signature and genomic diversity of Fusobacterium in Vietnamese CRC patients, using a combination of 16S rRNA gene profiling, anaerobic microbiology, and whole genome sequencing. We found that several oral bacteria, including F. nucleatum and Leptotrichia, were significantly more abundant in the tumour mucosa, and these two bacteria were also more enriched in tumours of advanced CRC stages (III-IV). We obtained 53 Fusobacterium genomes from the saliva, tumour and non-tumour mucosa of six CRC patients. Isolates from the gut mucosa belonged to diverse F. nucleatum subspecies (nucleatum, animalis, vincentii, polymorphum) and a potential new subspecies of F. periodonticum. The Fusobacterium population within each individual was distinct and in many cases diverse, with minimal intra-clonal variation. Phylogenetic analyses showed that within each individual, tumour-associated Fusobacterium were clonal to those isolated from non-tumour mucosa, but distantly related to those isolated from saliva. Genes encoding major virulence factors (Fap2 and RadD) showed variability in length and evidence of horizontal gene transfer. Our work provides a framework to understand the genomic diversity of Fusobacterium within the CRC patients, which can be exploited for the development of CRC diagnostic and therapeutic options targeting this oncobacterium.
Photizo: an open-source library for cross-sample analysis of FTIR spectroscopy data
Authors: Grant-Peters Melissa , Rich-Griffin Charlotte , Grant-Peters Jonathan E. , Cinque Gianfelice , Dendrou Calliope A.
Published: March 2022

With continually improved instrumentation, Fourier transform infrared (FTIR) microspectroscopy can now be used to capture thousands of high-resolution spectra for chemical characterisation of a sample. The spatially resolved nature of this method lends itself well to histological characterisation of complex biological specimens. However, commercial software currently available can make joint analysis of multiple samples challenging and, for large datasets, computationally infeasible. In order to overcome these limitations, we have developed Photizo - an open-source Python library for spectral analysis which includes functions for pre-processing, visualisation and downstream analysis, including principal component analysis, clustering, macromolecular quantification and biochemical mapping. This library can be used for analysis of spectroscopy data without a spatial component, as well as spatially-resolved data, such as data obtained via infrared (IR) microspectroscopy in scanning mode and IR imaging by focal plane array (FPA) detector.

Contact

cdendrou@well.ox.ac.uk
LabNet: hardware control software for the Raspberry Pi
Authors: Schatz Alexej , Winter York
Published: March 2022

Single-board computers such as the Raspberry Pi make it easy to control hardware setups for laboratory experiments. GPIOs and expansion boards (HATs) give access to a whole range of sensor and control hardware. However, controlling such hardware can be challenging, when many experimental setups run in parallel and the time component is critical. LabNet is a C++ optimized control layer software to give access to the Raspberry Pi connected hardware over a simple network protocol. LabNet was developed to be suitable for time-critical operations, and to be simple to expand. It leverages the actor model to simplify multithreading programming and to increase modularity. The message protocol is implemented in Protobuf and offers performance, small message size, and supports a large number of programming languages on the client side. It shows good performance compared to locally executed tools like Bpod or pyControl, outperforms Autopilot and reaches sub-millisecond range in network communication latencies. LabNet itself does not provide support for the design of experimental tasks. This is left to the client. LabNet can be used for general automation in experimental laboratories with its control PC located at some distance. LabNet is open source and under continuing development.
Dark kinase annotation, mining and visualization using the Protein Kinase Ontology
Authors: Soleymani Saber , Gravel Nathan , Huang Liang-Chin , Yeung Wayland , Bozorgi Elika , Bendzunas Nathaniel G. , Kochut Krzysztof J. , Kannan Natarajan
Published: March 2022

The Protein Kinase Ontology (ProKinO) is an integrated knowledge graph that conceptualizes the complex relationships connecting protein kinase sequence, structure, function, and disease in a human and machine-readable format. Here we extend the scope of ProKinO as a discovery tool by including new classes and relationships capturing information on kinase ligand binding sites, expression patterns, and functional features, and demonstrate its application in uncovering new knowledge regarding understudied members of the protein kinase family. Specifically, through graph mining and aggregate SPARQL queries, we identify the p21-activated protein kinase 5 (PAK5) as one of the most frequently mutated dark kinase in human cancers with abnormal expression in multiple cancers, including an unappreciated role in acute myeloid leukemia. We identify recurrent oncogenic mutations in the PAK5 activation loop predicted to alter substrate binding and phosphorylation and identify common ligand/drug binding residues in PAK family kinases, highlighting the potential application of ProKinO in drug discovery. The updated ontology browser and a web component, ProtVista, which allows interactive mining of kinase sequence annotations in 3D structures and Alphafold models, provide a valuable resource for the signaling community. The updated ProKinO database is accessible athttp://prokino.uga.edu/browser/.
Flexible Control as Surrogate Reward or Dynamic Reward Maximization
Authors: Liljeholm Mimi
Published: March 2022

The utility of a given experience, like interacting with a particular friend or tasting a particular food, fluctuates continually according to homeostatic and hedonic principles. Consequently, to maximize reward, an individual must be able to escape or attain outcomes as preferences change, by switching between actions. Recent work on human and artificial intelligence has defined such flexible instrumental control in information theoretic terms and postulated that it may serve as a reward surrogate. Another possibility, however, is that the adaptability afforded by flexible control is tacitly implemented by planning for dynamic changes in outcome values. In the current study, an expected utility model that computes decision values over a range of possible monetary gains and losses associated with sensory outcomes provided the best fit to behavioral choice data and performed best in terms of earned rewards. Moreover, consistent with previous work on perceived control and personality, individual differences in dimensional schizotypy were correlated with behavioral choice preferences in conditions with the greatest and lowest levels of flexible control. These results contribute to a growing literature on the role of instrumental control in goal-directed choice.
Lower limb in sprinters with larger relative mass but not larger normalized moment of inertia
Authors: Sado Natsuki , Ichinose Hoshizora , Kawakami Yasuo
Published: March 2022

Purpose

Sprinters exhibit inhomogeneous muscularity corresponding to musculoskeletal demand for sprinting execution. An inhomogeneous morphology would affect the mass distribution, which in turn may affect the mechanical difficulty in moving from an inertia perspective; however, the morphological characteristics of sprinters from the inertia perspective have not been examined. Here we show no corresponding differences in the normalized mass and normalized moment of inertia between the sprinters and untrained non-sprinters.

Methods

We analyzed fat- and water-separated magnetic resonance images from the lower limbs of 11 male sprinters (100 m best time of 10.44–10.83 s) and 12 untrained non-sprinters. We calculated the inertial properties by identifying the tissue of each voxel and combining the literature values for each tissue density.

Results

The lower-limb relative mass was significantly larger in sprinters (18.7 ± 0.7% body mass) than in non-sprinters (17.6 ± 0.6% body mass), while the normalized moment of inertia of the lower limb around the hip in the anatomical position was not significantly different (0.044 ± 0.002 vs. 0.042 ± 0.002 [a. u.]). The thigh relative mass in sprinters (12.9 ± 0.4% body mass) was significantly larger than that in non-sprinters (11.9 ± 0.4% body mass), whereas the shank and foot relative masses were not significantly different.

Conclusion

We revealed that the mechanical difficulty in swinging the lower limb is not relatively larger in sprinters in terms of inertia, even though the lower-limb mass is larger, reflecting their muscularity. We provide practical implications that sprinters can train without paying close attention to the increase in lower-limb mass and moment of inertia.
Japanese national well-being survey shows that living alone results in lower satisfaction and affects other relationships, while social networking service usage is related to life satisfaction: A cross-sectional study
Authors: Miyaki Koichi , Kawamura Takashi , Takano Hirohisa , Suzuki Kan Hiroshi
Published: March 2022

This study examined how social isolation and subjective loneliness impacted subjective well-being across Japan, with the aim of offering policy recommendations. We analyzed data (N = 5,234, age:15-89) obtained through a Japanese population-based national survey conducted in March 2021. First, we found that mean life satisfaction was statistically lowest among the subgroup of respondents who lived alone (approximately 20% of the total), with more pronounced impacts in males. We also found that the frequency of social networking site (SNS) usage was significantly associated with overall life satisfaction, exhibiting a J-curve (three to four times per week was better than everyday usage). The frequency of interaction with others, number of SNS friends, employment/wage satisfaction, family budget/asset satisfaction, subjective health satisfaction, and subjective connectedness were also related to well-being in a dose-dependent manner (Trend P<0.001). Second, our multiple logistic regression model showed that the above relationships were independently and statistically significant (p<0.05). Moreover, a stratified analysis showed that living alone significantly affected these relationships, which suggests that this condition should specifically be addressed in the context of efforts aimed at enhancing subjective well-being. In addition, respondents who lived alone had low subjective connectedness, which also independently influenced well-being, as shown by our multivariate logistic model. In sum, these findings indicate that national well-being enhancement policies should particularly consider social isolation and loneliness, including issues stemming from low social connectedness.
An Immunobridging study to evaluate the neutralizing antibody titer in adults immunized with two doses of either ChAdOx1-nCov-19 (AstraZeneca) or MVC-COV1901
Authors: Estrada Josue Antonio , Cheng Chien-Yu , Ku Shin-Yen , Hu Hui-Chun , Yeh Hsiu-Wen , Lin Yi-Chun , Chen Cheng-Pin , Cheng Shu-Hsing , Lin I-Feng
Published: March 2022

Background

Rapid development and deployment of vaccine is crucial to control the continuously evolving COVID-19 pandemic. Placebo-controlled phase 3 efficacy trial is still standard for authorizing vaccines in majority of the world. However, due to lack of cases or participants in parts of the world, this has not always been feasible. An alternative to efficacy trial is immunobridging, in which the immune response or correlates of protection of a vaccine candidate is compared against an approved vaccine. Here we describe a case study where our candidate vaccine, MVC-COV1901, has been granted for emergency use authorization (EUA) locally based on the non-inferiority immunobridging process.

Methods

The per protocol immunogenicity (PPI) subset from the MVC-COV1901 phase 2 trial was used for this study and consisted of 903 subjects who have received two doses of MVC-COV1901 as scheduled in the clinical trial. The comparator set of population consisted of 200 subjects of ≥ 20 years of age who were generally healthy and have received two doses of AstraZeneca ChAdOx nCOV-19 (AZD1222) recruited from Taoyuan General Hospital, Ministry of Health and Welfare.

Results

MVC-COV1901 was shown to have a geometric mean titer (GMT) ratio lower bound 95% confidence interval (CI) of 3.4 against the comparator vaccine and a seroconversion rate of 95.5% at the 95% CI lower bound, which both exceeded the criteria set by the Taiwan regulatory authority for EUA approval. These results supported the EUA approval of MVC-COV1901 by the Taiwanese regulatory authority in July 2021. Following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), countries from the Access Consortium has recently adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data.

Conclusion

The data presented in the study showed that it is reasonably likely that the vaccine efficacy of MVC-COV1901 is similar or superior to that of AZ. Data could be used in support of further vaccine development and regulatory approval.
Optimal protocol design for diffusion-weighted imaging of the prostate: an estimation theory examination of parameter estimate variance
Authors: Conlin Christopher C , Seibert Tyler M , Dale Anders M
Published: March 2022

Diffusion-weighted imaging (DWI) is routinely used to aid in the detection and characterization of prostate cancer. Given imaging time constraints in a clinical setting, it is important to maximize the statistical efficiency of a DWI examination of the prostate. The objective is to maximize the accuracy with which microstructural information about the prostate can be obtained while minimizing diffusion scan time.

In this study, we apply estimation theory to evaluate the statistical efficiency of different DWI acquisitions and methods. Specifically, we show that the variance of DWI parameters estimated using nonlinear multiexponential signal models is considerably higher than the variance observed using linear signal models. We then derive a simple analytical expression for the efficiency of a linear estimator and use it to optimize b-value sampling for DWI of the prostate.
Converting cropping systems into seasonal habitat functionality reveals the hump-shaped responses of carabid beetles to agricultural management
Authors: Muneret Lucile , Ricci Benoit , Vialatte Aude , Aviron Stéphanie , Ducourtieux Chantal , Biju-Duval Luc , Petit Sandrine
Published: March 2022

Understanding effects on the huge diversity of cropping systems on local biodiversity is challenging but necessary to implement agroecological systems. Through a functional approach, the translation of cropping systems into resource and disturbance gradients is promising to decipher the relationship between cropping systems and biodiversity but has never been implemented for arthropods.

To investigate contributions of resource and disturbance gradients arising from cropping systemsvsenvironmental context (regional effect, meteorological conditions and landscape characteristics) on beneficial arthropod communities, we used a dataset collected in 60 crop fields from three French areas over a five-years period. It includes all farmers interventions, crop sequences, meteorological data, landscape composition and carabid samplings.

We found that the environmental context contributed to about 75% of explained carabid variations on average, while resource and disturbance gradients contributed to about 25% of explained carabid variations. The resource and disturbance gradients were particularly important in winter and spring preceding the spring-summer period to determine carabid variations.

Moreover, we identified thresholds above which resource and disturbance gradients start being beneficial or detrimental for carabids. For example, a Treatment Frequency Index above 2.07 in spring decreased the total activity density of carabids during the spring-summer period.

Synthesis and application. While implementing for the first time a functional approach to understand the effects of different facets of cropping systems on arthropods, our study also allows us to identify periods and thresholds above which specific practices affect carabids. The identification of such thresholds can guide the provision of recommendations for policy, stakeholders and farmers about how to reduce cropping systems’ impact on arthropods.
Environmental DNA reflects common haplotypic variation
Authors: Adams Clare I M , Hepburn Christopher , Jeunen Gert-Jan , Cross Hugh , Taylor Helen R , Gemmell Neil J , Bunce Michael , Knapp Michael
Published: March 2022

Analysis of environmental DNA (eDNA) has gained widespread usage for taxonomically based biodiversity assessment. While interest in applying non-invasive eDNA monitoring for population genetic assessments has grown, its usage in this sphere remains limited. One barrier to uptake is that the effectiveness of eDNA detection below the species level remains to be determined for multiple species and environments. Here, we test the utility of this emergent technology in a population genetic framework using eDNA samples derived from water along New Zealand’s South Island (Otago Coast: n=9; Kaikōura: n=7) and DNA obtained from tissue samples (n=76) of individual blackfoot pāua (Haliotis iris)sampled from New Zealand’s Otago coast. We recovered four mitochondrial haplotypes from eDNA versus six from the tissue samples collected. Three common haplotypes were recovered with both eDNA and tissue samples, while only one out of three rare haplotypes – represented in tissue samples by one individual each – was recovered with our eDNA methods. We demonstrate that eDNA monitoring is an effective tool for recovering common genetic diversity from pāua, although rare (< 5%) haplotypes are seldom recovered. Our results show the potential of eDNA to identify population-level haplotypes for gastropods in the marine environment identification below the species level and for studying the population genetic diversity of gastropods. This work supports eDNA methods as effective, non-invasive tools for genetic monitoring. Non-invasive eDNA sampling could minimize target organism stress and human interaction enabling population genetic research for hard-to-sample, delicate, or sensitive species.
Assessing temporal and geographic contacts across the Adriatic Sea through the analysis of genome-wide data from Southern Italy
Authors: Raveane Alessandro , Molinaro Ludovica , Aneli Serena , Capodiferro Marco Rosario , Ongaro Linda , Migliore Nicola Rambaldi , Soffiati Sara , Scarano Teodoro , Torroni Antonio , Achilli Alessandro , Ventura Mario , Pagani Luca , Capelli Cristian , Olivieri Anna , Bertolini Francesco , Semino Ornella , Montinaro Francesco
Published: March 2022

Southern Italy was characterised by a complex prehistory that started with different Palaeolithic cultures, later followed by the Neolithic transition and the demic dispersal from the Pontic-Caspian Steppe during the Bronze Age. Archaeological and historical evidence points to demic and cultural influences between Southern Italians and the Balkans, starting with the initial Palaeolithic occupation until historical and modern times. To shed light on the dynamics of these contacts, we analysed a genome-wide SNP dataset of more than 700 individuals from the South Mediterranean area (102 from Southern Italy), combined with ancient DNA from neighbouring areas. Our findings revealed high affinities of South-Eastern Italians with modern Eastern Peloponnesians, and a closer affinity of ancient Greek genomes with those from specific regions of South Italy than modern Greek genomes. The higher similarity could be associated with the presence of a Bronze Age component ultimately originating from the Caucasus and characterised by high frequencies of Iranian and Anatolian Neolithic ancestries. Furthermore, to reveal possible signals of natural selection, we looked for extremely differentiated allele frequencies among Northern and Southern Italy, uncovering putatively adapted SNPs in genes involved in alcohol metabolism, nevi features and immunological traits, such as ALDH2,NID1andCBLB.
Salient 40 Hz sounds probe affective aversion and neural excitability
Authors: Schneefeld F , Doelling K , Marchesotti S , Schwartz S , Igloi K , Giraud A-L , Arnal LH
Published: March 2022

The human auditory system is not equally reactive to all frequencies of the audible spectrum. Emotional and behavioral reactions to loud or aversive acoustic features can vary from one individual to another, to the point that some exhibit exaggerated or even pathological responses to certain sounds. The neural mechanisms underlying these interindividual differences remain unclear. Whether distinct aversion profiles map onto neural excitability at the individual level needs to be tested. Here, we measured behavioral and EEG responses to click trains (from 10 to 250 Hz, spanning the roughness and pitch perceptual ranges) to test the hypothesis that interindividual variability in aversion to rough sounds is reflected in neural response differences between participants. Linking subjective aversion to 40 Hz steady-state EEG responses, we demonstrate that participants experiencing enhanced aversion to roughness also show stronger neural responses to this attribute. Interestingly, this pattern also correlates with inter-individual anxiety levels, suggesting that this personality trait might interact with subjective sensitivity and neural excitability to these sounds. These results support the idea that 40 Hz sounds can probe the excitability of non-canonical auditory systems involved in exogenous salience processing and aversive responses at the individual level. By linking subjective aversion to neural excitability, 40 Hz sounds provide neuromarkers relevant to a variety of pathological conditions, such as those featuring enhanced emotional sensitivity (hyperacusis, anxiety) or aberrant neural responses at 40 Hz (autism, schizophrenia).
UPP2: Fast and Accurate Alignment Estimation of Datasets with Fragmentary Sequences
Authors: Park Minhyuk , Ivanovic Stefan , Chu Gillian , Shen Chengze , Warnow Tandy
Published: March 2022

Motivation

Multiple sequence alignment (MSA) is a basic step in many bioinformatics pipelines. However, achieving highly accurate alignments on large datasets, especially those with sequence length heterogeneity, is a challenging task. UPP (Ultra-large multiple sequence alignment using Phylogeny-aware Profiles) is a method for MSA estimation that builds an ensemble of Hidden Markov Models (eHMM) to represent an estimated alignment on the full length sequences in the input, and then adds the remaining sequences into the alignment using selected HMMs in the ensemble. Although UPP provides good accuracy, it is computationally intensive on large datasets.

Results

We present UPP2, a direct improvement on UPP. The main advance is a fast technique for selecting HMMs in the ensemble that allows us to achieve the same accuracy as UPP but with greatly reduced runtime. We show UPP2 produces more accurate alignments compared to leading MSA methods on datasets exhibiting substantial sequence length heterogeneity, and is among the most accurate otherwise.

Availability

https://github.com/gillichu/sepp

Contact

warnow@illinois.edu
The role of floral traits in community assembly process at high elevations in Lesser Himalaya
Authors: Ahmad Mustaqeem , Rosbakh Sergey , Bucher Solveig Franziska , Sharma Padma , Rathee Sonia , Uniyal Sanjay Kr. , Batish Daizy R. , Singh Harminder P.
Published: March 2022

Ecological theory postulates that plant trait research should consider multiple traits related to different organs and/or ontogenetic stages as such traits represent different ecological niche axes. Particularly, floral traits have been suggested to play an important role in assembling plant communities along environmental gradients as they determine the reproductive success, one of the key functions in plants. Yet, the predictive power of floral traits in community assembly research remains largely unverified empirically.

We analyzed the predictive power of six floral traits of 139 herbaceous species for inferring community assembly process in twenty-one sites located along an elevation gradient in Lesser Himalaya ranging from 2,000 to 4,000 meters above sea level. The floral trait variability along the gradient was analyzed using community-weighted trait mean (CWM) values and functional diversities (FD) calculated for each of the study communities.

The CWM values for onset of flowering and flower display area increased significantly with increasing elevation, whereas specific flower area showed an opposite pattern. In combination with convergence in onset of flowering and specific area (i.e., lower FD values in high elevation sites), these patterns suggest that abiotic filtering and plant-pollinator interactions affected the floral trait composition of the communities studied. Increasing low-temperature stress towards high-elevation sites selected for late-flowering species that produce resource-intensive flowers with larger display areas.

Low pollinator abundancy and activity in high elevation, could also explain why these traits were selected in the study communities. Delayed flowering with increasing elevations might facilitate the phenological overlap of plants and their pollinators, as pollinator activity at higher elevation peaks in the second half of the vegetation period. The dominance of species with low specific flower area and larger display area in high elevation communities were attributed to the increased flower longevity and attraction of pollinators, respectively, to maximize pollination success under pollinator scarcity.

Synthesis. Our study provides empirical support of the recent argument that floral traits contribute considerably to the assembly of plant communities along environmental gradients. Thus, such traits should be included into community assembly research agenda as they represent key growth and survival ecological functions.
Enabling spatiotemporal regulation within biomaterials using DNA reaction-diffusion waveguides
Authors: Dorsey Phillip J. , Scalise Dominic , Schulman Rebecca
Published: March 2022

In multicellular organisms, cells and tissues coordinate biochemical signal propagation across length scales spanning microns to meters. Endowing synthetic materials with similar capacities for coordinated signal propagation could allow these systems to adaptively regulate themselves across space and over time. Here we combine ideas from cell signaling and electronic circuitry to design a biochemical waveguide that transmits information in the form of a concentration of a DNA species on a directed path. The waveguide can be seamlessly integrated into a soft material because there is virtually no difference between the chemical or physical properties of the waveguide and the material it is embedded within. We propose the design of DNA strand displacement reactions to construct the system and, using reaction-diffusion models, identify kinetic and diffusive parameters that enable super-diffusive transport of DNA species via autocatalysis. Finally, to support experimental waveguide implementation, we show how a sink reaction could mitigate the spurious amplification of an autocatalyst within the waveguide, allowing for controlled waveguide triggering. Chemical waveguides could facilitate the design of synthetic biomaterials with distributed sensing machinery integrated throughout their structure and enable coordinated self-regulating programs triggered by changing environmental conditions.
Intraspecific diversification and mitonuclear discordance in native versus introduced areas: co-introduction ofDolicirroplectanum lacustre, a monogenean gill parasite of the invasive Nile perchLates niloticus
Authors: Thys Kelly J. M. , Vanhove Maarten P.M. , Custers Jonas W. J. , Vranken Nathan , Van Steenberge Maarten , Kmentová Nikol
Published: March 2022

The Nile perch (Lates niloticus) is a notorious invasive species. The introductions of Nile perch into several lakes and rivers in the Lake Victoria region led to the impoverishment of the trophic food webs, particularly well documented in Lake Victoria. Along with the introductions of the Nile perch, its parasites were co-introduced.Dolicirroplectanum lacustre(Monogenea, Diplectanidae) is a gill parasite of latid fishes (Latesspp.) inhabiting several major African freshwater systems. We examined the intra-specific diversification ofD. lacustrefromL. niloticusin Lake Albert (native range) and Lake Victoria (introduced range) by assessing morphological and genetic differentiation, and microhabitat preference. We expected reduced morphological and genetic diversity forD. lacustrein Lake Victoria compared to Lake Albert, as a result of the historical introductions.Dolicirroplectanum lacustredisplays high morphological variability within and between African freshwaters. Mitonuclear discordance within the morphotypes ofD. lacustreindicates an incomplete reproductive barrier between the morphotypes. The diversification in the mitochondrial gene portion is directly linked with the morphotypes, while the nuclear gene portions indicate conspecificity. Based on our results, we reported reduced genetic and morphological diversity, potentially being a result of a founder effect in Lake Victoria.
Comparison of Rapid Antigen Tests’ Performance between Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) Variants of SARS-CoV-2: Secondary Analysis from a Serial Home Self-Testing Study
Authors: Soni Apurv , Herbert Carly , Filippaios Andreas , Broach John , Colubri Andres , Fahey Nisha , Woods Kelsey , Nanavati Janvi , Wright Colton , Orwig Taylor , Gilliam Karen , Kheterpal Vik , Suvarna Thejas , Nowak Chris , Schrader Summer , Lin Honghuang , O’Connor Laurel , Pretz Caitlin , Ayturk Didem , Orvek Elizabeth , Flahive Julie , Lazar Peter , Shi Qiming , Achenbach Chad , Murphy Robert , Robinson Matthew , Gibson Laura , Stamegna Pamela , Hafer Nathaniel , Luzuriaga Katherine , Barton Bruce , Heetderks William , Manabe Yukari C. , McManus David
Published: March 2022

Background

There is a need to understand the performance of rapid antigen tests (Ag-RDT) for detection of the Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) SARS-CoV-2 variants.

Methods

Participants without any symptoms were enrolled from October 18, 2021 to January 24, 2022 and performed Ag-RDT and RT-PCR tests every 48 hours for 15 days. This study represents a non-pre-specified analysis in which we sought to determine if sensitivity of Ag-RDT differed in participants with Delta compared to Omicron variant. Participants who were positive on RT-PCR on the first day of the testing period were excluded. Delta and Omicron variants were defined based on sequencing and date of first RT-PCR positive result (RT-PCR+). Comparison of Ag-RDT performance between the variants was based on sensitivity, defined as proportion of participants with Ag-RDT+ results in relation to their first RT-PCR+ result, for different duration of testing with rapid Ag-RDT. Subsample analysis was performed based on the result of participants’ second RT-PCR test within 48 hours of the first RT-PCR+ test.

Results

From the 7,349 participants enrolled in the parent study, 5,506 met the eligibility criteria for this analysis. A total of 153 participants were RT-PCR+ (61 Delta, 92 Omicron); among this group, 36 (23.5%) tested Ag-RDT+ on the same day, and 84 (54.9%) tested Ag-RDT+ within 48 hours as first RT-PCR+. The differences in sensitivity between variants were not statistically significant (same-day: Delta 16.4% [95% CI: 8.2-28.1] vs Omicron 28.2% [95% CI: 19.4-38.6]; and 48-hours: Delta 45.9% [33.1-59.2] vs. Omicron 60.9% [50.1-70.9]). This trend continued among the 86 participants who had consecutive RT-PCR+ result (48-hour sensitivity: Delta 79.3% [60.3-92.1] vs. Omicron: 89.5% [78.5-96.0]). Conversely, the 38 participants who had an isolated RT-PCR+ remained consistently negative on Ag-RDT, regardless of the variant.

Conclusions

The performance of Ag-RDT is not inferior among individuals infected with the SARS-CoV-2 Omicron variant as compared to the Delta variant. The improvement in sensitivity of Ag-RDT noted with serial testing is consistent between Delta and Omicron variant. Performance of Ag-RDT varies based on duration of RT-PCR+ results and more studies are needed to understand the clinical and public health significance of individuals who are RT-PCR+ for less than 48 hours.
GatorTron: A Large Language Model for Clinical Natural Language Processing
Authors: Yang Xi , PourNejatian Nima , Shin Hoo Chang , Smith Kaleb E , Parisien Christopher , Compas Colin , Martin Cheryl , Flores Mona G , Zhang Ying , Magoc Tanja , Harle Christopher A , Lipori Gloria , Mitchell Duane A , Hogan William R , Shenkman Elizabeth A , Bian Jiang , Wu Yonghui
Published: March 2022

Objective

To develop a large pretrained clinical language model from scratch using transformer architecture; systematically examine how transformer models of different sizes could help 5 clinical natural language processing (NLP) tasks at different linguistic levels.

Methods

We created a large corpus with >90 billion words from clinical narratives (>82 billion words), scientific literature (6 billion words), and general English text (2.5 billion words). We developed GatorTron models from scratch using the BERT architecture of different sizes including 345 million, 3.9 billion, and 8.9 billion parameters, compared GatorTron with three existing transformer models in the clinical and biomedical domain on 5 different clinical NLP tasks including clinical concept extraction, relation extraction, semantic textual similarity, natural language inference, and medical question answering, to examine how large transformer models could help clinical NLP at different linguistic levels.

Results and Conclusion

GatorTron scaled up transformer-based clinical language models to a size of 8.9 billion parameters and achieved state-of-the-art performance on 5 clinical NLP tasks of different linguistic levels targeting various healthcare information documented in unstructured electronic health records (EHRs). The proposed GatorTron models performed remarkably better in much complex clinical NLP tasks such as natural language inference (9.6% and 7.5% improvements) and question answering (9.5% and 7.77% improvements) compared with existing smaller clinical transformer models (i.e., BioBERT and ClinicalBERT), demonstrating the potential of large transformer-based clinical models for advanced medical artificial intelligent (AI) applications such as question answering.
Motor Neuron Disease is not clustered or associated with socioeconomic deprivation in Scotland
Authors: Chang Yuan-Ting , Kearns Patrick K.A. , Newton Judith , Larraz Juan , Forbes Deborah , Beswick Emily , Leighton Danielle , Langlands Gavin , Swingler Robert J. , Chandran Siddharthan , Pal Suvankar
Published: March 2022

Background and Objectives

Understanding risk factors and spatial variation of risk may provide insights into the pathological mechanism of motor neuron disease (MND). Socioeconomic status (SES) has been hypothesised as a risk factor, but results from previous studies are inconsistent. No spatial epidemiology studies examining geographic clustering of MND have been performed in Scotland to date. We investigated the effect of SES and geography on MND risk in Scotland using the highly curated and nationally representative Scottish MND Register (CARE-MND) that has over 95% case ascertainment.

Methods

Patients on the Scottish Clinical Audit Research Evaluation for Motor Neurone Disease platform, with date of diagnosis between 01 Jan 2015 and 28 Feb 2021 were included and geocoded with data zones using their residence at diagnosis. Indirectly standardised incidence ratio (SIR) accounting for age and sex was calculated for each health board. Poisson regression was used to examine the effect of SES on MND risk, adjusted for age and sex of population at risk. Geographic clustering was assessed using global Moran’s Index, Bayesian conditional autoregressive models and SaTScan software.

Results

Among 1149 patients included, 1126 (98%) were successfully geocoded. Significantly lower SIR was shown in Highland (0.60, 95% CI 0.44 – 0.80, p<0.001). After adjusting for age and sex in Poisson regression, there was no significant effect of SES on MND risk. Moran’s Index indicated a weak but significant spatial autocorrelation (I=0.017, p=0.008). However, risk maps using Bayesian modelling showed a relatively homogeneous distribution without distinct patterns across Scotland. Similarly, SaTScan did not detect any significant cluster of high or low risks.

Discussion

Our findings support the notion that MND risk is mostly random-distributed and independent of SES in Scotland. Our results are generalizable to other MND populations.
Phantom-based quantification of the spectral accuracy in dual-layer spectral CT for pediatric imaging at 100 kVp
Authors: Meyer Sebastian , Liu Leening P. , Litt Harold I. , Halliburton Sandra S. , Shapira Nadav , Noël Peter B.
Published: March 2022

Objectives

To determine the spectral accuracy in detector-based dual-energy CT (DECT) at 100 kVp and wide (8 cm) collimation width for dose levels and object sizes relevant to pediatric imaging.

Methods

A spectral CT phantom containing tissue-equivalent materials and iodine inserts of varying concentrations was scanned on the latest generation detector-based DECT system. Two 3D-printed extension rings were used to mimic varying pediatric patient sizes. Scans were performed at 100 and 120 kVp, 4 and 8 cm collimation widths, and progressively reduced radiation dose levels, down to 10% of the nominal value for the standard pediatric abdominal protocol. Virtual mono-energetic, iodine density, effective atomic number, and electron density results were quantified and compared to their expected values for all acquisition settings and phantom sizes.

Results

DECT scans at 100 kVp provided highly accurate spectral results; however, a size dependence was observed for iodine quantification. For the medium phantom configuration (15 cm diameter), measurement errors in iodine density, effective atomic number, and electron density (ED) were below 0.3 mg/ml, 0.2 and 1.8 %EDwater, respectively. The average accuracy was slightly different from scans at 120 kVp; however, not statistically significant for all configurations. Collimation width had no substantial impact. Spectral results were accurate and reliable for radiation exposures down to 0.9 mGy CTDIvol.

Conclusions

Detector-based DECT at 100 kVp can provide on-demand or retrospective spectral information with high accuracy even at extremely low doses, thereby making it an attractive solution for pediatric imaging.

Key points

Dual-layer spectral CT at 100 kVp enables high-quality spectral imaging for smaller patients

Larger collimation width does not affect the accuracy of spectral results

Accurate and reliable spectral quantification is achievable at radiation doses down to 0.9 mGy
Vaccine hesitancy strongly correlates with COVID-19 deaths underreporting
Authors: Sobieszek Adam , Lipniacka Miriam , Lipniacki Tomasz
Published: March 2022

Vaccine acceptance is a key factor in achieving high immunization coverage and reducing the death toll of COVID-19 pandemic. Analyzing data from Europe and Americas we demonstrated that vaccine hesitancy strongly correlates with underreporting of COVID-19 deaths and cases. This correlation cannot be explained by the differences in economic indexes: GDP and Gini coefficient (measure of income inequalities). There is no correlation of vaccination percentage and Gini coefficient and the correlation with GDP is decreasing in time. The most striking is the comparison of Eastern European and South American countries; the latter group of countries shows significantly higher vaccination percentage while having a lower or comparable GDP and higher Gini coefficient. The analysis suggests that timely and reliable information about the COVID-19 cases and the associated deaths plays a key role in achieving population-wide vaccine acceptance.
Development and validation of a cardiovascular diseases risk prediction model for Chinese males (CVDMCM)
Authors: Shan Ying , Zhang Yucong , Zhao Yanping , Lu Yueqi , Chen Bangwei , Yang Liuqiao , Tan Cong , Bai Yong , Sang Yu , Liu Juehan , Jian Min , Ruan Lei , Zhang Cuntai , Li Tao
Published: March 2022

Aims

Death due to cardiovascular diseases (CVD) increased significantly in China. One way to reduce CVD is to identify people at risk and provide targeted intervention. We aim to develop and validate a CVD risk prediction model for Chinese males (CVDMCM) to help clinicians identify those at risk of CVD and provide targeted intervention.

Methods and Results

We conducted a retrospective cohort study of 2331 Chinese males without prior CVD to develop and internally validate the CVDMCM. These participants had a baseline physical examination record (2008-2016) and one revisit record by September 2019. With the full cohort, we used single factor cox regression to examine each candidate predictor adjusted for age. 16 sequential prediction models were built on significant predictors. CVDMCM was selected based on the Akaike information criterion, the area under the ROC curve, and the percentage of variation in outcome values explained by the model (R2). This model, the Framingham CVD risk model, and the Wu’s simplified model were all validated by bootstrapping with 1000 repetitions. CVDMCM’s C statistics (0.779, 95% CI: 0.733-0.825), D statistic (4.738, 95% CI: 3.270-6.864), and calibration plot demonstrated that CVDMCM outperformed the other two models.

Conclusions

We developed and internally validated CVDMCM, which predicted 4-year CVD risk for Chinese males with a better performance than Framingham CVD model and Wu’s simplified model. In addition, we developed a web calculator for physicians to conveniently generate CVD risk scores and identify those with a higher risk of CVD. We believe CVDMCM had great potential for clinical usage.