bluuebunny/crossref_metadata_2025 huggingface dataset:
Imbalanced classification for protein subcellular localization with multilabel oversampling
Authors: Rana Priyanka , Sowmya Arcot , Meijering Erik , Song Yang
Published: December 2022

Motivation

Subcellular localization of human proteins is essential to comprehend their functions and roles in physiological processes, which in turn helps in diagnostic and prognostic studies of pathological conditions and impacts clinical decision-making. Since proteins reside at multiple locations at the same time and few subcellular locations host far more proteins than other locations, the computational task for their subcellular localization is to train a multilabel classifier while handling data imbalance. In imbalanced data, minority classes are underrepresented, thus leading to a heavy bias towards the majority classes and the degradation of predictive capability for the minority classes. Furthermore, data imbalance in multilabel settings is an even more complex problem due to the coexistence of majority and minority classes.

Results

Our studies reveal that based on the extent of concurrence of majority and minority classes, oversampling of minority samples through appropriate data augmentation techniques holds promising scope for boosting the classification performance for the minority classes. We measured the magnitude of data imbalance per class and the concurrence of majority and minority classes in the dataset. Based on the obtained values, we identified minority and medium classes, and a new oversampling method is proposed that includes non-linear mixup, geometric and colour transformations for data augmentation and a sampling approach to prepare minibatches. Performance evaluation on the Human Protein Atlas Kaggle challenge dataset shows that the proposed method is capable of achieving better predictions for minority classes than existing methods.

Availability and implementation

Data used in this study are available at https://www.kaggle.com/competitions/human-protein-atlas-image-classification/data. Source code is available at https://github.com/priyarana/Protein-subcellular-localisation-method.

Supplementary information

Supplementary data are available at Bioinformatics online.
PRAWNS: compact pan-genomic features for whole-genome population genomics
Authors: Javkar Kiran , Rand Hugh , Strain Errol , Pop Mihai
Published: December 2022

Motivation

Scientists seeking to understand the genomic basis of bacterial phenotypes, such as antibiotic resistance, today have access to an unprecedented number of complete and nearly complete genomes. Making sense of these data requires computational tools able to perform multiple-genome comparisons efficiently, yet currently available tools cannot scale beyond several tens of genomes.

Results

We describe PRAWNS, an efficient and scalable tool for multiple-genome analysis. PRAWNS defines a concise set of genomic features (metablocks), as well as pairwise relationships between them, which can be used as a basis for large-scale genotype–phenotype association studies. We demonstrate the effectiveness of PRAWNS by identifying genomic regions associated with antibiotic resistance in Acinetobacter baumannii.

Availability and implementation

PRAWNS is implemented in C++ and Python3, licensed under the GPLv3 license, and freely downloadable from GitHub (https://github.com/KiranJavkar/PRAWNS.git).

Supplementary information

Supplementary data are available at Bioinformatics online.
Constrained sense-making in families with parental mental illness and the importance of intra-family communication for positive outcomes
Authors: Yates Scott , Gatsou Lina
Published: December 2022

Recent work in parental mental illness (PMI) has focused attention on mechanisms by which it impacts the lives of family members and is transmitted intergenerationally. This includes arguments for attending to how recovery and experiences of the illness in families are shaped relationally. In this article, we contribute to this area through presenting the results of in-depth qualitative research studying how family communication around PMI shapes families’ experiences of illness and recovery. This comprises thematic analysis of thirty-six semi-structured interviews and eight focus groups with families and multi-agency professionals who worked with them. Findings demonstrate a complex interplay of drivers of lack of communication and of the impacts of this on family relationships and well-being. Notably, families found it difficult to communicate around mental health due to guilt and shame felt by the unwell parent, a belief that concealing the illness will protect children and lack of capacity in families for communication in general. This lack of communication affects how families make sense of one another’s experiences and behaviours and impacts individual coping and family relationships. Fostering positive communication around the illness in social work settings has the potential to improve relationships, reduce perceived burdens of illness and aid recovery.
Fragment Ends of Circulating Microbial DNA as Signatures for Pathogen Detection in Sepsis
Authors: Wang Guangya , Lam W K Jacky , Ling Lowell , Ma Mary-Jane L , Ramakrishnan Saravanan , Chan Don C T , Lee Wing-Shan , Cheng Suk Hang , Chan Rebecca W Y , Yu Stephanie C Y , Tse Irene O L , Wong Wai Tat , Jiang Peiyong , Chiu Rossa W K , Allen Chan K C , Lo Y M Dennis
Published: December 2022

Background

Nuclear-derived cell-free DNA (cfDNA) molecules in blood plasma are nonrandomly fragmented, bearing a wealth of information related to tissues of origin. DNASE1L3 (deoxyribonuclease 1 like 3) is an important player in shaping the fragmentation of nuclear-derived cfDNA molecules, preferentially generating molecules with 5 CC dinucleotide termini (i.e., 5 CC-end motif). However, the fragment end properties of microbial cfDNA and its clinical implication remain to be explored.

Methods

We performed end motif analysis on microbial cfDNA fragments in plasma samples from patients with sepsis. A sequence context-based normalization method was used to minimize the potential biases for end motif analysis.

Results

The end motif profiles of microbial cfDNA appeared to resemble that of nuclear cfDNA (Spearman correlation coefficient: 0.82, P value 0.001). The CC-end motif was the most preferred end motif in microbial cfDNA, suggesting that DNASE1L3 might also play a role in the fragmentation of microbe-derived cfDNA in plasma. Of note, differential end motifs were present between microbial cfDNA originating from infection-causing pathogens (enriched at the CC-end) and contaminating microbial DNA potentially derived from reagents or the environment (nearly random). The use of fragment end signatures allowed differentiation between confirmed pathogens and contaminating microbes, with an area under the receiver operating characteristic curve of 0.99. The performance appeared to be superior to conventional analysis based on microbial cfDNA abundance alone.

Conclusions

The use of fragmentomic features could facilitate the differentiation of underlying contaminating microbes from true pathogens in sepsis. This work demonstrates the potential usefulness of microbial cfDNA fragmentomics in metagenomics analysis.
Males armed with big weapons win fights at limited cost in ant-mimicking jumping spiders
Authors: Yu Guocheng , Wong Boon Hui , Painting Christina J , Li Hongze , Yu Long , Zhang Zengtao , Zhang Shichang , Li Daiqin
Published: December 2022

A core assumption of sexual selection theory is that sexually selected weapons, specialized morphological structures used directly in male contests, can improve an individual’s reproductive success but only if the bearer can overcome associated costs, the negative effects on the bearer’s fitness components. However, recent studies have shown that producing and wielding exaggerated weapons may not necessarily be costly. Rather, some traits can be selected for supporting, or compensating for, the expense of producing and wielding such exaggerated weapons. In the ant-mimicking jumping spider Myrmarachne gisti, exaggerated chelicerae are borne only by adult males and not females, showing sexual dimorphism and steep positive allometry with body size. Here, we determine the potential benefits of bearing exaggerated chelicerae during male contests and explore the potential for costs in terms of prey-capture efficiency and compensation between chelicera size and neighboring trait size. While males with longer chelicerae won most of their male-male contests, we found no significant differences in prey-capture efficiency between males and females regardless of whether prey was winged or flightless. Males’ elongated chelicerae thus do not impede their efficiency at capturing prey. Furthermore, we found that the sizes of all neighboring traits are positively correlated with chelicera size, suggesting that these traits may be under correlational selection. Taken together, our findings suggest that M. gisti males armed with the exaggerated chelicerae that function as weapons win more fights at limited cost for performance in prey capture and compensate for neighboring structures.
Emerging molecular imaging targets and tools for myocardial fibrosis detection
Authors: Barton Anna K , Tzolos Evangelos , Bing Rong , Singh Trisha , Weber Wolfgang , Schwaiger Markus , Varasteh Zohreh , Slart Riemer H J A , Newby David E , Dweck Marc R
Published: December 2022

Myocardial fibrosis is the heart’s common healing response to injury. While initially seeking to optimize the strength of diseased tissue, fibrosis can become maladaptive, producing stiff poorly functioning and pro-arrhythmic myocardium. Different patterns of fibrosis are associated with different myocardial disease states, but the presence and quantity of fibrosis largely confer adverse prognosis. Current imaging techniques can assess the extent and pattern of myocardial scarring, but lack specificity and detect the presence of established fibrosis when the window to modify this process may have ended. For the first time, novel molecular imaging methods, including gallium-68 (68Ga)-fibroblast activation protein inhibitor positron emission tomography (68Ga-FAPI PET), may permit highly specific imaging of fibrosis activity. These approaches may facilitate earlier fibrosis detection, differentiation of active vs. end-stage disease, and assessment of both disease progression and treatment–response thereby improving patient care and clinical outcomes.
Robust nonparametric analysis of dynamic profits, prices and productivity: An application to French meat-processing firms
Authors: Ang Frederic , Kerstens Pieter Jan
Published: December 2022

Appropriately considering adjustment costs, this paper develops a robust nonparametric framework to analyse profits, prices and productivity in a dynamic context. Dynamic profit change is decomposed into a dynamic Bennet price indicator and a dynamic Bennet quantity indicator. The latter is decomposed into explanatory factors. It is shown to be a superlative indicator for the dynamic Luenberger indicator. The application focuses on 1,638 observations of French meat-processing firms for the years 2012–2019. Using m-out-of-n bootstrapped data envelopment analysis, we obtain robust estimates and confidence intervals. The components of dynamic productivity growth fluctuate substantially. However, these fluctuations are often statistically insignificant.
Rational hapten design and establishment of broad-spectrum indirect competitive enzyme-linked immunosorbent assay for benzimidazoles monitoring in milk
Authors: Wang Zile , Zhang Liang , Yang YanHong , Zhang Huixia , Zhang Weichunbai , Zheng Pimiao , Jiang Haiyang
Published: December 2022

Objectives

Benzimidazoles (BZs) are commonly used for the treatment of soil-transmitted helminth infections in veterinary clinics; however, misuse and overdosing of BZs will cause residual problems and have the potential to damage human health through the food chain. Thus, the existence of BZs in foods needs more attention. This study aims to establish a broad-spectrum immunoassay for rapid detection and to simultaneously monitor BZs in milk.

Materials and Methods

Based on structure analysis, a ‘zero epitope loss’ strategy, which introduced a spacer arm into the imino group of the imidazole ring of albendazole, was first adopted for hapten modification to obtain an ultra-sensitive and broad-spectrum antibody. An indirect competitive enzyme-linked immunosorbent assay (icELISA) was established for the detection of 18 BZs in milk sample with a single-step pretreatment. A quantitative structure–activity relationship model was constructed to interpret and predict the recognition.

Results

The antibody could recognize 20 BZs and the half-inhibitory concentrations ranged from 0.054 to 417.58 ng/mL, the limits of detection of icELISA ranged from 0.4 to 89.4 ng/mL, and the mean recovery rates ranged from 76.49% to 120.40%, with a coefficient of variation <20%. Substituent R1 of BZs was considered to be the main influencing factor for recognition, and the comparative molecular field analysis model (q2=0.724, r2=0.998) was finally chosen for further prediction.

Conclusions

The results indicated that the established icELISA could simultaneously identify 18 BZs, with good accuracy and precision, which was suitable for rapid detection of BZs in milk.
Chromosome-Scale Genome Assembly and Annotation of Allotetraploid Annual Bluegrass (Poa annua L.)
Authors: Robbins Matthew D , Bushman B Shaun , Huff David R , Benson Christopher W , Warnke Scott E , Maughan Chase A , Jellen Eric N , Johnson Paul G , Maughan Peter J
Published: December 2022

Poa annua L. is a globally distributed grass with economic and horticultural significance as a weed and as a turfgrass. This dual significance, and its phenotypic plasticity and ecological adaptation, have made P. annua an intriguing plant for genetic and evolutionary studies. Because of the lack of genomic resources and its allotetraploid (2n = 4x = 28) nature, a reference genome sequence would be a valuable asset to better understand the significance and polyploid origin of P. annua. Here we report a genome assembly with scaffolds representing the 14 haploid chromosomes that are 1.78 Gb in length with an N50 of 112 Mb and 96.7% of BUSCO orthologs. Seventy percent of the genome was identified as repetitive elements, 91.0% of which were Copia- or Gypsy-like long-terminal repeats. The genome was annotated with 76,420 genes spanning 13.3% of the 14 chromosomes. The two subgenomes originating from Poa infirma (Knuth) and Poa supina (Schrad) were sufficiently divergent to be distinguishable but syntenic in sequence and annotation with repetitive elements contributing to the expansion of the P. infirma subgenome.
Imaginal disk growth factors are Drosophila chitinase-like proteins with roles in morphogenesis and CO2 response
Authors: Sustar Anne E , Strand Liesl G , Zimmerman Sandra G , Berg Celeste A
Published: December 2022

Chitinase-like proteins (CLPs) are members of the family 18 glycosyl hydrolases, which include chitinases and the enzymatically inactive CLPs. A mutation in the enzyme's catalytic site, conserved in vertebrates and invertebrates, allowed CLPs to evolve independently with functions that do not require chitinase activity. CLPs normally function during inflammatory responses, wound healing, and host defense, but when they persist at excessive levels at sites of chronic inflammation and in tissue-remodeling disorders, they correlate positively with disease progression and poor prognosis. Little is known, however, about their physiological function. Drosophila melanogaster has 6 CLPs, termed Imaginal disk growth factors (Idgfs), encoded by Idgf1, Idgf2, Idgf3, Idgf4, Idgf5, and Idgf6. In this study, we developed tools to facilitate characterization of the physiological roles of the Idgfs by deleting each of the Idgf genes using the CRISPR/Cas9 system and assessing loss-of-function phenotypes. Using null lines, we showed that loss of function for all 6 Idgf proteins significantly lowers viability and fertility. We also showed that Idgfs play roles in epithelial morphogenesis, maintaining proper epithelial architecture and cell shape, regulating E-cadherin and cortical actin, and remarkably, protecting these tissues against CO2 exposure. Defining the normal molecular mechanisms of CLPs is a key to understanding how deviations tip the balance from a physiological to a pathological state.
Effect of 2 vs 3 Doses of COVID-19 Vaccine in Patients With Inflammatory Bowel Disease: A Population-based Propensity Matched Analysis
Authors: Desai Aakash , Deepak Parakkal , Cross Raymond K , Murone Julie , Farraye Francis A , Ungaro Ryan C , Kochhar Gursimran S
Published: December 2022

Aim

There are limited data on the impact of 2 vs 3 doses of COVID-19 vaccine in patients with inflammatory bowel disease (IBD). The primary aim of the study was to assess the efficacy of COVID-19 vaccine based on number of administered doses in patients with IBD.

Methods

We conducted a retrospective cohort study using TriNetX, a multi-institutional database to compare patients with IBD who received 1, 2, or 3 doses of BNT162b2 or mRNA-1273 to unvaccinated IBD patients (1.1.2020-7.26.2022) to assess the risk of COVID-19 after 1:1 propensity score matching. We also evaluated the impact of vaccine on a composite of severe COVID-19 outcomes including hospitalization, intubation, intensive care unit care, acute kidney injury, or mortality.

Results

After propensity score matching, vaccinated patients with 2 (adjusted OR [aOR], 0.8; 95% confidence interval [CI], 0.6-0.9) and 3 doses (aOR, 0.7; 95% CI, 0.5-0.9) were found to have a lower risk of COVID-19 compared with unvaccinated patients. Vaccinated patients with IBD had a lower risk of severe COVID-19 outcomes (aOR, 0.7; 95% CI, 0.6-0.9) compared with unvaccinated patients. There was no difference in the risk of COVID-19 in IBD patients with 2 compared with 3 doses (aOR, 0.97; 95% CI, 0.7-1.3). However, IBD patients with 2 doses were at an increased risk for hospitalization due to COVID-19 (aOR, 1.78; 95% CI, 1.02-3.11) compared with those that received 3 doses.

Conclusion

Vaccinated patients with IBD had a lower risk of severe COVID-19 outcomes compared with unvaccinated patients. A third dose of COVID-19 vaccine compared with 2 doses decreases the risk of hospitalization but not breakthrough infection in patients with IBD.
Effects of fishing on the trophic structure of carnivorous fish assemblages from shallow rocky bottoms of the Mediterranean Sea and the temperate Atlantic Ocean
Authors: Cardona Luis , Reñones Olga , Gouraguine Adam , Saporiti Fabiana , Borrell Asunción , Aguilar Alex , Moranta Joan
Published: December 2022

Here, we assess whether fishery exploitation affects the trophic structure of carnivorous fish. We censused fish and analysed the stable isotope ratios of C and N of species targeted by fishermen in areas open to fishing and marine protected areas (MPAs) in the Mediterranean Sea and the north-eastern Atlantic Ocean. Results demonstrated a major impact of fishing on the biomass and size structure of nektobenthic carnivorous fish. However, those changes did not modify the diversity of the trophic resources used by the assemblage, the pattern of resource partitioning between species, or the degree of trophic redundancy. These results add to recent evidence suggesting that MPAs implemented in fished seascapes may fail to restore the original structure of the food webs that once existed in pre-fished ecosystems because regional decimation and extinction of highly mobile predators prevent recovering the original diversity of predators at local scales, even in no-take areas. If so, more strict local fishing regulations are unlikely to restore the original diversity of high trophic level carnivores and restoration goals should be reframed in terms of an objective that is less unrealistic than restoring the pre-fished condition while still recovering aspects of the historical trophic structure.
Rapidly adapted community health strategies to prevent treatment interruption and improve COVID-19 detection for Syrian refugees and the host population with hypertension and diabetes in Jordan
Authors: Ratnayake Ruwan , Rawashdeh Fatma , AbuAlRub Raeda , Al-Ali Nahla , Fawad Muhammad , Bani Hani Mohammad , Zoubi Saleem , Goyal Ravi , Al-Amire Khaldoun , Mahmoud Refqi , AlMaaitah Rowaida , Parmar Parveen K
Published: December 2022

Background

We evaluated community health volunteer (CHV) strategies to prevent non-communicable disease (NCD) care disruption and promote coronavirus disease 2019 (COVID-19) detection among Syrian refugees and vulnerable Jordanians, as the pandemic started.

Methods

Alongside medication delivery, CHVs called patients monthly to assess stockouts and adherence, provide self-management and psychosocial support, and screen and refer for complications and COVID-19 testing. Cohort analysis was undertaken of stockouts, adherence, complications and suspected COVID-19. Multivariable models of disease control assessed predictors and non-inferiority of the strategy pre-/post-initiation. Cost-efficiency and patient/staff interviews assessed implementation.

Results

Overall, 1119 patients were monitored over 8 mo. The mean monthly proportion of stockouts was 4.9%. The monthly proportion non-adherent (past 5/30 d) remained below 5%; 204 (18.1%) patients had complications, with 63 requiring secondary care. Mean systolic blood pressure and random blood glucose remained stable. For hypertensive disease control, age 41–65 y (OR 0.46, 95% CI 0.2 to 0.78) and with diabetes (OR 0.73, 95% CI 0.54 to 0.98) had decreased odds, and with baseline control had increased odds (OR 3.08, 95% CI 2.31 to 4.13). Cumulative suspected COVID-19 incidence (2.3/1000 population) was suggestive of ongoing transmission. While cost-efficient (108 US${\$}$/patient/year), funding secondary care was challenging.

Conclusions

During multiple crises, CHVs prevented care disruption and reinforced COVID-19 detection.
Classification of proteins inducing liquid–liquid phase separation: sequential, structural and functional characterization
Authors: Ozawa Yuhei , Anbo Hiroto , Ota Motonori , Fukuchi Satoshi
Published: December 2022

Liquid–liquid phase separation (LLPS) within the cell can form biological condensates, which are increasingly recognized to play important roles in various biological processes. Most proteins involved in LLPS are known to be intrinsically disordered proteins containing intrinsically disordered regions (IDRs) with low complexity regions (LCRs). The proteins driving LLPS were selected from databases of LLPS-related proteins and then classified into three classes according to the components in the condensates. Through in silico analyses, we found that proteins in the homo class, those that induce LLPS without partner molecules, have different IDRs and LCRs compared with the reference proteome. In contrast, proteins in the other classes, those that induce LLPS with partner proteins (the hetero class) or nucleic acids (the mixed class), did not show a clear difference to the reference proteome in IDRs and LCRs. The hetero-class proteins contained structural domains to serve protein–protein interactions, and the mixed-class ones had the structural domains associated with nucleic acids. These results suggest that IDRs in the homo-class proteins have unique IDRs, which provide multivalent interaction sites required for LLPS, whereas the hetero- and mixed-class proteins can induce LLPS through the combination of the interaction among LCRs, structural domains and nucleic acids.
Differences in foliar phosphorus fractions, rather than in cell-specific phosphorus allocation, underlie contrasting photosynthetic phosphorus use efficiency among chickpea genotypes
Authors: Wen Zhihui , Pang Jiayin , Wang Xiao , Gille Clément E , De Borda Axel , Hayes Patrick E , Clode Peta L , Ryan Megan H , Siddique Kadambot H M , Shen Jianbo , Lambers Hans
Published: December 2022

Although significant intraspecific variation in photosynthetic phosphorus (P) use efficiency (PPUE) has been shown in numerous species, we still know little about the biochemical basis for differences in PPUE among genotypes within a species. Here, we grew two high PPUE and two low PPUE chickpea (Cicer arietinum) genotypes with low P supply in a glasshouse to compare their photosynthesis-related traits, total foliar P concentration ([P]) and chemical P fractions (i.e. inorganic P (Pi), metabolite P, lipid P, nucleic acid P, and residual P). Foliar cell-specific nutrient concentrations including P were characterized using elemental X-ray microanalysis. Genotypes with high PPUE showed lower total foliar [P] without slower photosynthetic rates. No consistent differences in cellular [P] between the epidermis and mesophyll cells occurred across the four genotypes. In contrast, high PPUE was associated with lower allocation to Pi and metabolite P, with PPUE being negatively correlated with the percentage of these two fractions. Furthermore, a lower allocation to Pi and metabolite P was correlated with a greater allocation to nucleic acid P, but not to lipid P. Collectively, our results suggest that a different allocation to foliar P fractions, rather than preferential P allocation to specific leaf tissues, underlies the contrasting PPUE among chickpea genotypes.
A systematic review of Wikidata in Digital Humanities projects
Authors: Zhao Fudie
Published: December 2022

Wikidata has been widely used in Digital Humanities (DH) projects. However, a focused discussion regarding the current status, potential, and challenges of its application in the field is still lacking. A systematic review was conducted to identify and evaluate how DH projects perceive and utilize Wikidata, as well as its potential and challenges as demonstrated through use. This research concludes that: (1) Wikidata is understood in the DH projects as a content provider, a platform, and a technology stack; (2) it is commonly implemented for annotation and enrichment, metadata curation, knowledge modelling, and Named Entity Recognition (NER); (3) Most projects tend to consume data from Wikidata, whereas there is more potential to utilize it as a platform and a technology stack to publish data on Wikidata or to create an ecosystem of data exchange; and (4) Projects face two types of challenges: technical issues in the implementations and concerns with Wikidata’s data quality. In the discussion, this article contributes to addressing three issues related to coping with the challenges in the specific context of the DH field based on the research findings: the relevance and authority of other available domain sources; domain communities and their practices; and workflow design that coordinates technical and labour resources from projects and Wikidata.
The rapidly spinning intermediate-mass black hole 3XMM J150052.0+015452
Authors: Cao Z , Jonker P G , Wen S , Stone N C , Zabludoff A I
Published: December 2022

A star tidally disrupted by a black hole can form an accretion disc with a super-Eddington mass accretion rate; the X-ray emission produced by the inner disc provides constraints on the black hole mass M• and dimensionless spin parameter a•. Previous studies have suggested that the M• responsible for the tidal disruption event 3XMM J150052.0+015452 (hereafter J150052) is ∼105 M⊙ in the intermediate-mass black hole (IMBH) regime. Fitting multi-epoch XMM–Newton and Chandra X-ray spectra obtained after 2008 during the source’s decade-long decay, with our latest slim accretion disc model, gives $M_\bullet = 2.0^{+1.0}_{-0.3}\times 10^{5}$ M⊙ (at 68 per cent confidence) and a• > 0.97 (an 84.1 per cent confidence lower limit). The spectra obtained between 2008 and 2014 are significantly harder than those after 2014, an evolution that can be well explained by including the effects of inverse Comptonization by a corona on the early-time spectra. The corona is present when the source accretion rate is super-Eddington, while there is no evidence for its effect in data obtained after 2014, when the mass accretion rate is around the Eddington limit. Based on our spectral study, we infer that the corona is optically thick and warm ($kT_\mathrm{ e}=2.3^{+2.7}_{-0.8}$ keV). Our mass and spin measurements of J150052 confirm it as an IMBH and point to a rapid, near-extremal, spin. These M• and a• values rule out both vector bosons and axions of masses ∼10−16 eV.
First detection of the outer edge of an AGN accretion disc: very fast multiband optical variability of NGC 4395 with GTC/HiPERCAM and LT/IO:O
Authors: McHardy I M , Beard M , Breedt E , Knapen J H , Vincentelli F M , Veresvarska M , Dhillon V S , Marsh T R , Littlefair S P , Horne K , Glew R , Goad M R , Kammoun E , Emmanoulopoulos D
Published: December 2022

We present fast (∼200 s sampling) $\it ugriz$ photometry of the low -mass AGN NGC 4395 with the Liverpool Telescope, followed by very fast (3 s sampling) us, gs, rs, is, and zs simultaneous monitoring with HiPERCAM on the 10.4m GTC. These observations provide the fastest ever AGN multiband photometry and very precise lag measurements. Unlike in all other AGN, gs lags us by a large amount, consistent with disc reprocessing but not with reprocessing in the broad-line region (BLR). There is very little increase in lag with wavelength at long wavelengths, indicating an outer edge (Rout) to the reprocessor. We have compared truncated disc reprocessing models to the combined HiPERCAM and previous X-ray/UV lags. For the normally accepted mass of 3.6 × 105M⊙, we obtain reasonable agreement with zero spin, Rout ∼ 1700Rg and the done physically motivated temperature-dependent disc colour-correction factor (f$\rm _{col}$). A smaller mass of 4 × 104M⊙ can only be accommodated if f$\rm _{col}=2.4$, which is probably unrealistically high. Disc self gravity is probably unimportant in this low-mass AGN but an obscuring wind may provide an edge. For the small mass, the dust sublimation radius is similar to Rout so the wind could be dusty. However, for the more likely large mass, the sublimation radius is further out so the optically thick base of a line-driven gaseous wind is more likely. The inner edge of the BLR is close to Rout in both cases. These observations provide the first good evidence for a truncated AGN disc and caution that truncation should be included in reverberation lag modelling.
The H i content of red geyser galaxies
Authors: Frank Emily , Stark David V , Masters Karen , Roy Namrata , Riffel Rogério , Lacerna Ivan , Riffel Rogemar A , Bizyaev Dmitry
Published: December 2022

Red geysers are a specific type of quiescent galaxy, denoted by twin jets emerging from their galactic centres. These bisymmetric jets possibly inject energy and heat into the surrounding material, effectively suppressing star formation by stabilizing cool gas. In order to confirm the presence and evolutionary consequences of these jets, this paper discusses the scaling, stacking, and conversion of 21-cm H i flux data sourced from the H i-MaNGA survey into H i gas-to-stellar mass (G/S) spectra. Our samples were dominated by non-detections, or galaxies with weak H i signals, and consequently by H i upper limits. The stacking technique discussed successfully resolved emission features in both the red geyser G/S spectrum and the control sample G/S spectrum. From these stacked spectra, we find that on average, red geyser galaxies have G/S of 0.086 ± 0.011 (random) + 0.029 (systematic), while non-red geyser galaxies of similar stellar mass have a G/S ratio of 0.039 ± 0.018 (random) + 0.013 (systematic). Therefore, we find no statistically significant evidence that the H i content of red geysers is different from the general quiescent population.
A Phylogenomic Assessment of Processes Underpinning Convergent Evolution in Open-Habitat Chats
Authors: Alaei Kakhki Niloofar , Schweizer Manuel , Lutgen Dave , Bowie Rauri C K , Shirihai Hadoram , Suh Alexander , Schielzeth Holger , Burri Reto
Published: December 2022

Insights into the processes underpinning convergent evolution advance our understanding of the contributions of ancestral, introgressed, and novel genetic variation to phenotypic evolution. Phylogenomic analyses characterizing genome-wide gene tree heterogeneity can provide first clues about the extent of ILS and of introgression and thereby into the potential of these processes or (in their absence) the need to invoke novel mutations to underpin convergent evolution. Here, we were interested in understanding the processes involved in convergent evolution in open-habitat chats (wheatears of the genus Oenanthe and their relatives). To this end, based on whole-genome resequencing data from 50 taxa of 44 species, we established the species tree, characterized gene tree heterogeneity, and investigated the footprints of ILS and introgression within the latter. The species tree corroborates the pattern of abundant convergent evolution, especially in wheatears. The high levels of gene tree heterogeneity in wheatears are explained by ILS alone only for 30% of internal branches. For multiple branches with high gene tree heterogeneity, D-statistics and phylogenetic networks identified footprints of introgression. Finally, long branches without extensive ILS between clades sporting similar phenotypes provide suggestive evidence for the role of novel mutations in the evolution of these phenotypes. Together, our results suggest that convergent evolution in open-habitat chats involved diverse processes and highlight that phenotypic diversification is often complex and best depicted as a network of interacting lineages.
The future of carbon-neutrality science and technology from an industrial transformation perspective: an interview with Hou-Liang Dai
Authors: Huang By Hai-Xia
Published: December 2022

Since China announced that it will strive to achieve its carbon peak by 2030 and carbon neutrality by 2060, it has determined to take steps, which will establish low carbon development and a transition to carbon neutrality, as part of its long-term strategy for sustainable development and prosperity. This will be both a huge challenge and an opportunity. To achieve the dual-carbon goals, the whole society must undergo a broad and profound systemic transformation, involving changes in energy, technology, economy, industry and lifestyle, etc. Carbon-neutrality science and technology should be the foundation of the transformation.

Now, dual-carbon goals have become the focus, not just of scientific and technological circles [1], but of all society. Some Chinese scientists have put forward the concept of green carbon science (GCS) to promote rational and systematic scientific thinking on carbon science and sustainable development [2,3]. Additionally, hundreds of scientists and senior experts have participated in formulating the action plan and guiding the outline of basic research on the dual-carbon strategy and pathways, helping the country to formulate a timetable, roadmap and implementation plan for achieving carbon-peaking and carbon-neutralization goals in industries [4,5]. Among them, Hou-Liang Dai, an academician of the Chinese Academy of Engineering (CAE), took part in a major consulting project of the CAE. He is famous for the development and application of highly efficient and environmentally friendly aromatic hydrocarbon technology and also a leader in high-quality development of the petrochemical industry [6]. He has been working in the petroleum and chemical industry for almost 40 years. Currently, he is the chairman of the China National Petroleum Corporation (CNPC).

NSR spoke to Hou-Liang Dai on the future of carbon-neutrality science and technology.
Can Electronic Clinical Decision Support Systems Improve the Diagnosis of Urinary Tract Infections? A Systematic Review and Meta-Analysis
Authors: Hojat Leila S , Saade Elie A , Hernandez Adrian V , Donskey Curtis J , Deshpande Abhishek
Published: December 2022

Background

Urinary tract infection (UTI) is a commonly misdiagnosed infectious syndrome. Diagnostic stewardship interventions can reduce rates of asymptomatic bacteriuria treatment but are often labor intensive, and thus an automated means of reducing unnecessary urine testing is preferred. In this systematic review and meta-analysis, we sought to identify studies describing interventions utilizing clinical decision support (CDS) to optimize UTI diagnosis and to characterize the effectiveness of these interventions.

Methods

We conducted a comprehensive electronic search and manual reference list review for peer-reviewed articles published before July 2, 2021. Publications describing an intervention intending to enhance UTI diagnosis via CDS were included. The primary outcome was urine culture test rate.

Results

The electronic search identified 5013 studies for screening. After screening and full-text review, 9 studies met criteria for inclusion, and a manual reference list review identified 5 additional studies, yielding a total of 14 studies included in the systematic review. The most common CDS intervention was urinalysis with reflex to urine culture based on prespecified urinalysis parameters. All 9 studies that provided statistical comparisons reported a decreased urine culture rate postintervention, 8 of which were statistically significant. A meta-analysis including 4 studies identified a pooled urine culture incidence rate ratio of 0.56 (95% confidence interval, .52–.60) favoring the postintervention versus preintervention group.

Conclusions

In this systematic review and meta-analysis, CDS appeared to be effective in decreasing urine culture rates. Prospective trials are needed to confirm these findings and to evaluate their impact on antimicrobial prescribing, patient-relevant outcomes, and potential adverse effects.
Bintrafusp Alfa: A Bifunctional Fusion Protein Targeting PD-L1 and TGF-β, in Patients with Pretreated Colorectal Cancer: Results from a Phase I Trial
Authors: Spira Alexander , Wertheim Michael S , Kim Edward J , Tan Benjamin , Lenz Heinz-Josef , Nikolinakos Petros , Rich Patricia L , Jehl Genevieve , Machl Andreas , Ito Rena , Gulley James L , Kopetz Scott
Published: December 2022

Colorectal cancer (CRC) is a heterogeneous and complex disease with limited treatment options. Targeting transforming growth factor β (TGF-β) and programmed death ligand 1 pathways may enhance antitumor efficacy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II (a TGF-β “trap”) fused to a human IgG1 monoclonal antibody blocking programmed cell death ligand 1. We report results from an expansion cohort of a phase I study (NCT02517398) in patients with heavily pretreated advanced CRC treated with bintrafusp alfa. As of May 15, 2020, 32 patients with advanced CRC had received bintrafusp alfa for a median duration of 7.1 weeks. The objective response rate was 3.1% and the disease control rate was 6.3% (1 partial response, 1 stable disease); 2 patients were not evaluable. The safety profile was consistent with previously reported data.
Acute postoperative pain impact trajectories and factors contributing to trajectory membership
Authors: Giordano Nicholas A , Kent Michael L , Kroma Raymond B , Rojas Winifred , Lindl Mary Jo , Lujan Eugenio , Buckenmaier Chester C , Highland Krista B
Published: December 2022

Background

Ongoing postoperative pain assessments are vital to optimizing pain management and attenuating the development of poor health outcomes after surgery. This study aimed to characterize acute multidimensional trajectories of pain impact on physical function, sleep, mood, and stress and to examine clinical characteristics and demographics associated with trajectory membership. Additionally, this study compared levels of pain intensity and prescription opioid use at 2 weeks and 1 month postoperatively across acute symptom trajectories.

Methods

Participants (N = 285) undergoing total knee arthroplasty, total hip arthroplasty, and spinal fusion procedures were recruited for this multisite prospective observational study. Longitudinal, joint k-means clustering was used to identify trajectories based on pain impact on activity, sleep, mood, and stress.

Results

Three distinct pain impact trajectories were observed: Low (33.7%), Improving (35.4%), and Persistently High (30.9%). Participants in the Persistently High impact trajectory reported pain interfering moderately to severely with activity, sleep, mood, and stress. Relative to other trajectories, the Persistently High impact trajectory was associated with greater postoperative pain at 1 month postoperatively. Preoperatively, participants in the Persistently High impact trajectory reported worse Pain Catastrophizing Scale scores and PROMIS Pain Interference, PROMIS Anxiety, and PROMIS Social Isolation scores than did participants presenting with other trajectories. No statistical differences in opioid use were observed across trajectories.

Conclusions

Variation in acute postoperative pain impact on activity, sleep, mood, and stress exists. Given the complex nature of patients’ postoperative pain experiences, understanding how psychosocial presentations acutely change throughout hospitalization could assist in guiding clinicians’ treatment choices and risk assessments.
Development of an in-vitro high-throughput screening system to identify modulators of genitalia development
Authors: Yin Yan , Haller Meade , Li Tian , Ma Liang
Published: December 2022

Sexually dimorphic outgrowth and differentiation of the embryonic genital tubercles (GTs) give rise to the penis in males and the clitoris in females. Defects in androgen production or in response to androgen signaling can lead to various congenital penile anomalies in both mice and humans. Due to lack of a high-throughput screening system, identification of crucial regulators of GT sexual differentiation has been slow. To overcome this research barrier, we isolated embryonic GT mesenchymal (GTme) cells to model genitalia growth and differentiation in vitro. Using either a mechanical or fluorescence-activated cell sorting–assisted purification method, GTme cells were isolated and assayed for their proliferation using a microscopy and image analysis system, on a single cell level over time. Male and female GTme cells inherently exhibit different cellular dynamics, consistent with their in-vivo behaviors. This system allows for the rapid quantitative analyses of numerous drug treatments, and enables the discovery of potential genetic modulators of GT morphogenesis on a large scale. Using this system, we completed a 438-compound library screen and identified 82 kinase inhibitor hits. In mice, in-utero exposure to one such candidate kinase inhibitor, Cediranib, resulted in embryos with severe genitalia defects, especially in males. Gene silencing by RNAi was optimized in this system, laying the foundation for future larger-scale genetic screenings. These findings demonstrate the power of this novel high-throughput system to rapidly and successfully identify modulators of genitalia growth and differentiation, expanding the toolbox for the study of functional genomics and environmental factors.
Biological properties of self-assembled nanofibers of elastin-like block polypeptides for tissue-engineered vascular grafts: platelet inhibition, endothelial cell activation and smooth muscle cell maintenance
Authors: Natsume Kazuki , Nakamura Jin , Sato Kazuhide , Ohtsuki Chikara , Sugawara-Narutaki Ayae
Published: December 2022

Strategic materials design is essential for the development of small-diameter, tissue-engineered vascular grafts. Self-assembled nanofibers of elastin-like polypeptides represent promising vascular graft components as they replicate the organized elastin structure of native blood vessels. Further, the bioactivity of nanofibers can be modified by the addition of functional peptide motifs. In the present study, we describe the development of a novel nanofiber-forming elastin-like polypeptide (ELP) with an arginine–glutamic acid–aspartic acid–valine (REDV) sequence. The biological characteristics of the REDV-modified ELP nanofibers relevant to applications in vascular grafting were compared to ELP without ligands for integrin, ELP with arginine–glycine–aspartic acid (RGD) sequence, collagen and cell culture glass. Among them, REDV-modified ELP nanofibers met the preferred biological properties for vascular graft materials, i.e. (i) inhibition of platelet adhesion and activation, (ii) endothelial cell adhesion and proliferation and (iii) maintenance of smooth muscle cells in a contractile phenotype to prevent cell overgrowth. The results indicate that REDV-modified ELP nanofibers represent promising candidates for the further development of small-diameter vascular grafts.
Model Selection Performance in Phylogenetic Comparative Methods Under Multivariate Ornstein–Uhlenbeck Models of Trait Evolution
Authors: Bartoszek Krzysztof , Fuentes-González Jesualdo , Mitov Venelin , Pienaar Jason , Piwczyński Marcin , Puchałka Radosław , Spalik Krzysztof , Voje Kjetil Lysne
Published: December 2022

The advent of fast computational algorithms for phylogenetic comparative methods allows for considering multiple hypotheses concerning the co-adaptation of traits and also for studying if it is possible to distinguish between such models based on contemporary species measurements. Here we demonstrate how one can perform a study with multiple competing hypotheses using mvSLOUCH by analyzing two data sets, one concerning feeding styles and oral morphology in ungulates, and the other concerning fruit evolution in Ferula (Apiaceae). We also perform simulations to determine if it is possible to distinguish between various adaptive hypotheses. We find that Akaike’s information criterion corrected for small sample size has the ability to distinguish between most pairs of considered models. However, in some cases there seems to be bias towards Brownian motion or simpler Ornstein–Uhlenbeck models. We also find that measurement error and forcing the sign of the diagonal of the drift matrix for an Ornstein–Uhlenbeck process influences identifiability capabilities. It is a cliché that some models, despite being imperfect, are more useful than others. Nonetheless, having a much larger repertoire of models will surely lead to a better understanding of the natural world, as it will allow for dissecting in what ways they are wrong. [Adaptation; AICc; model selection; multivariate Ornstein–Uhlenbeck process; multivariate phylogenetic comparative methods; mvSLOUCH.]
Schistosomiasis mansoni and hydrographical conditions in São Carlos, São Paulo, Brazil
Authors: De Sousa dos Santos Sigrid , Chachá Silvana Gama Florencio , da Rocha Beatriz Correia , Spiller Katia Regina , de Toledo Carlos Fischer , Aníbal Fernanda de Freitas , de Avó Lucimar Retto da Silva , Luporini Rafael Luis , Cereda Junior Abimael , Melanda Edson Augusto
Published: December 2022

Background

In Brazil, schistosomiasis mansoni cases still occur, even in non-endemic areas. This study aimed to evaluate schistosomiasis mansoni cases and to delimit water collections investigated for infested planorbidae in São Carlos, São Paulo, Brazil.

Methods

A cross-sectional descriptive study and spatial analysis of schistosomiasis mansoni cases notified in the city from January 2005 to December 2017 was conducted. The study used geographical information system software to map residential and leisure exposures to water courses and bodies and related them to planorbidae surveys of São Paulo state.

Results

During the study period, 32 cases were notified. The main forms were intestinal and hepatosplenic. Twenty-eight cases were allochthonous, two autochthonous and two indeterminate. Eleven patients (33.3%) had contact with water collections in São Carlos, mainly the 29 and Broa reservoirs. Three of them had contact only with water collections in the region. A third of cases lived in the Água Fria and Água Quente microbasins, highly impacted by the presence of domestic sewage, and the whole region seems to be colonized by Biomphalaria tenagophila.

Conclusions

The resolution of anthropogenic contamination of water bodies is crucial for controlling schistosomiasis mansoni autochthony in São Carlos.