bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale predicting protein functions through heterogeneous feature fusion
Authors: Zheng Rongtao , Huang Zhijian , Deng Lei 
Published: July 2023

Abstract
As the volume of protein sequence and structure data grows rapidly, the functions of the overwhelming majority of proteins cannot be experimentally determined. Automated annotation of protein function at a large scale is becoming increasingly important. Existing computational prediction methods are typically based on expanding the relatively small number of experimentally determined functions to large collections of proteins with various clues, including sequence homology, protein–protein interaction, gene co-expression, etc. Although there has been some progress in protein function prediction in recent years, the development of accurate and reliable solutions still has a long way to go. Here we exploit AlphaFold predicted three-dimensional structural information, together with other non-structural clues, to develop a large-scale approach termed PredGO to annotate Gene Ontology (GO) functions for proteins. We use a pre-trained language model, geometric vector perceptrons and attention mechanisms to extract heterogeneous features of proteins and fuse these features for function prediction. The computational results demonstrate that the proposed method outperforms other state-of-the-art approaches for predicting GO functions of proteins in terms of both coverage and accuracy. The improvement of coverage is because the number of structures predicted by AlphaFold is greatly increased, and on the other hand, PredGO can extensively use non-structural information for functional prediction. Moreover, we show that over 205 000 ($\sim $100%) entries in UniProt for human are annotated by PredGO, over 186 000 ($\sim $90%) of which are based on predicted structure. The webserver and database are available at http://predgo.denglab.org/.
An interpretable block-attention network for identifying regulatory feature interactions
Authors: Prakash Anil , Banerjee Moinak 
Published: July 2023

Abstract
The importance of regulatory features in health and disease is increasing, making it crucial to identify the hallmarks of these features. Self-attention networks (SAN) have given rise to numerous models for the prediction of complex phenomena. But the potential of SANs in biological models was limited because of high memory requirement proportional to input token length and lack of interpretability of self-attention scores. To overcome these constraints, we propose a deep learning model named Interpretable Self-Attention Network for REGulatory interactions (ISANREG) that combines both block self-attention and attention-attribution mechanisms. This model predicts transcription factor-bound motif instances and DNA-mediated TF–TF interactions using self-attention attribution scores derived from the network, overcoming the limitations of previous deep learning models. ISANREG will serve as a framework for other biological models in interpreting the contribution of the input with single-nucleotide resolution.
1LocusSim a mobile-friendly simulator for teaching population genetics
Authors: Carvajal-Rodríguez Antonio 
Published: July 2023

Abstract

Motivation
Biology students often struggle with the fundamental concepts of evolutionary genetics, including genetic drift, mutation and selection. To address this problem, 1LocusSim was developed to simulate the interaction of different factors, such as population size, mutation, selection and dominance, to study their effect on allelic frequency during evolution. With 1LocusSim, students can compare theoretical results with simulation outputs and solve and analyze different problems of population genetics. The 1LocusSim web has a responsive design which means that it has been specifically designed to be used on smartphones.

Results
To demonstrate its use, I review the classical overdominance model of population genetics and highlight a characteristic that is often not explicitly stated. Specifically, it is emphasized that the equilibrium of the model does not depend on the homozygous selection coefficients but rather on the ratio of the selection coefficients. This is already clear from the classical formula but maybe not so much for students. Also it implies that the equilibrium can be expressed solely in terms of the dominance coefficient h. To verify this theoretical prediction, I utilize the simulator and calculate the equilibrium for the well-known case of sickle cell anemia. By utilizing this tool, students can learn at their own pace and convenience, anywhere and anytime.

Availability and implementation
1LocusSim if freely available at https://1LocusSim-biosdev.pythonanywhere.com/. Website implemented under the Bottle micro web-framework for Python, with all major browsers supported.

Supplementary information
Supplementary data are available at Bioinformatics Advances online.
‘There’s No Hope for Any Kind of Decent Life’: A Qualitative Study to Explore the Perspectives of People Experiencing Homelessness with a Recent Non-Fatal Overdose in Scotland
Authors: Farmer Natalia , McPherson Andrew , Thomson Jim , Reilly Frank , Williamson Andrea , Lowrie Richard 
Published: July 2023

Abstract
The past ten years has seen a marked increase in the numbers of people experiencing homelessness globally and an associated public health epidemic of drug-related deaths. Drawing from qualitative interviews as part of a wider pilot randomised controlled trial (RCT) conducted in Glasgow, Scotland with National Health Service pharmacists and third sector homeless outreach caseworkers, insights from those with living experience of both homelessness and a recent non-fatal drug overdose will be presented. Twenty people experiencing homelessness with at least one drug overdose in the past six months were interviewed in person, in a homelessness drop in centre or in emergency accommodation between November 2021 and January 2022. Findings from our study indicate that participants’ drug use and overdose risk were exacerbated during the Covid-19 pandemic due to the pervasive availability of illicit drugs for those placed in emergency accommodation, alongside reduced support and access to health and social care services. Additionally, multi-agency stressors such as a lack of autonomy and dehumanising experiences were reported, leading to a significant sense of powerlessness. Furthermore, the necessity of advocacy-based services as critical aspects of support was identified, with importance placed upon dedicated, homelessness staff and access to safe environments.
Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells
Authors: Xiang Fei , Wang Pei , Gong Hao , Luo Jia , Zhou Xin , Zhan Chenglin , Hu Tianxing , Wang Mengru , Xing Yizhan , Guo Haiying , Luo Gaoxing , Li Yuhong 
Published: July 2023

AbstractBackgroundBurn wound healing is a complex process and the role of Wnt ligands varies in this process. Whether and how Wnt4 functions in burn wound healing is not well understood. In this study, we aim to reveal the effects and potential mechanisms of Wnt4 in burn wound healing.MethodsFirst, the expression of Wnt4 during burn wound healing was determined by immunofluorescence, Western blotting and qPCR. Then, Wnt4 was overexpressed in burn wounds. The healing rate and healing quality were analysed by gross photography and haematoxyline and eosin staining. Collagen secretion was observed by Masson staining. Vessel formation and fibroblast distribution were observed by immunostaining. Next, Wnt4 was knocked down in HaCaT cells. The migration of HaCaT cells was analysed by scratch healing and transwell assays. Next, the expression of β-catenin was detected by Western blotting and immunofluorescence. The binding of Frizzled2 and Wnt4 was detected by coimmunoprecipitation and immunofluorescence. Finally, the molecular changes induced by Wnt4 were analysed by RNA sequencing, immunofluorescence, Western blotting and qPCR in HaCaT cells and burn wound healing tissues.ResultsThe expression of Wnt4 was enhanced in burn wound skin. Overexpression of Wnt4 in burn wound skin increased the thickness of epidermis. Collagen secretion, vessel formation and fibroblast distribution were not significantly impacted by Wnt4 overexpression. When Wnt4 was knocked down in HaCaT cells, the ratio of proliferating cells decreased, the ratio of apoptotic cells increased and the ratio of the healing area in the scratch healing assay to the number of migrated cells in the transwell assay decreased. The nuclear translocation of β-catenin decreased in shRNA of Wnt4 mediated by lentivirus-treated HaCaT cells and increased in Wnt4-overexpressing epidermal cells. RNA-sequencing analysis revealed that cell junction-related signalling pathways were significantly impacted by Wnt4 knockdown. The expression of the cell junction proteins was decreased by the overexpression of Wnt4.ConclusionsWnt4 promoted the migration of epidermal cells. Overexpression of Wnt4 increased the thickness of the burn wound. A potential mechanism for this effect is that Wnt4 binds with Frizzled2 and increases the nuclear translocation of β-catenin, thus activating the canonical Wnt signalling pathway and decreasing the cell junction between epidermal cells.
The locus of recognition memory signals in human cortex depends on the complexity of the memory representations
Authors: Sanders D Merika W , Cowell Rosemary A 
Published: July 2023

Abstract
According to a “Swiss Army Knife” model of the brain, cognitive functions such as episodic memory and face perception map onto distinct neural substrates. In contrast, representational accounts propose that each brain region is best explained not by which specialized function it performs, but by the type of information it represents with its neural firing. In a functional magnetic resonance imaging study, we asked whether the neural signals supporting recognition memory fall mandatorily within the medial temporal lobes (MTL), traditionally thought the seat of declarative memory, or whether these signals shift within cortex according to the content of the memory. Participants studied objects and scenes that were unique conjunctions of pre-defined visual features. Next, we tested recognition memory in a task that required mnemonic discrimination of both simple features and complex conjunctions. Feature memory signals were strongest in posterior visual regions, declining with anterior progression toward the MTL, while conjunction memory signals followed the opposite pattern. Moreover, feature memory signals correlated with feature memory discrimination performance most strongly in posterior visual regions, whereas conjunction memory signals correlated with conjunction memory discrimination most strongly in anterior sites. Thus, recognition memory signals shifted with changes in memory content, in line with representational accounts.
Teaching Whiteness in Shakespeare’s ‘Sonnet 18’
Authors: Stacey Richard 
Published: July 2023

Abstract
This article will outline several strategies which can be used to teach Shakespeare’s poem ‘Sonnet 18’ in the pre-University classroom. Although one of the most famous texts in the canon, and regularly read in non-educational contexts, ‘Sonnet 18’ is rarely discussed in relation to its racial politics and its normalizing treatment of metaphorical whiteness. Being able to detect the operative invisibility of white imagery is a crucial critical skill, as it empowers students to assess the significance of the racialized effects of the poetic evidence placed before them. I touch on the five Assessment Objectives at Key Stage 5 at various stages to meld current critical methodologies with A-Level pedagogical structures. The focus on ‘Sonnet 18’ will also help to sharpen awareness of the coercive properties of canonical texts which are often presented to the reader as ideologically neutral, particularly those on bucolic or ‘English’ themes.
Structure and Function of RhoBTB1 Required for Substrate Specificity and Cullin-3 Ubiquitination
Authors: Kumar Gaurav , Fang Shi , Golosova Daria , Lu Ko-Ting , Brozoski Daniel T , Vazirabad Ibrahim , Sigmund Curt D 
Published: July 2023

Abstract
We identified Rho-related BTB domain containing 1 (RhoBTB1) as a key regulator of phosphodiesterase 5 (PDE5) activity, and through PDE5, a regulator of vascular tone. We identified the binding interface for PDE5 on RhoBTB1 by truncating full-length RhoBTB1 into its component domains. Co-immunoprecipitation analyses revealed that the C-terminal half of RhoBTB1 containing its two BTB domains and the C-terminal domain (B1B2C) is the minimal region required for PDE5 recruitment and subsequent proteasomal degradation via Cullin-3 (CUL3). The C-terminal domain was essential in recruiting PDE5 as constructs lacking this region could not participate in PDE5 binding or proteasomal degradation. We also identified Pro353 and Ser363 as key amino acid residues in the B1B2C region involved in CUL3 binding to RhoBTB1. Mutation of either of these residues exhibited impaired CUL3 binding and PDE5 degradation, although the binding to PDE5 was preserved. Finally, we employed ascorbate peroxidase 2 (APEX2) proximity labeling using a B1B2C–APEX2 fusion protein as bait to capture unknown RhoBTB1 binding partners. Among several B1B2C-binding proteins identified and validated, we focused on SET domain containing 2 (SETD2). SETD2 and RhoBTB1 directly interacted, and the level of SETD2 increased in response to pharmacological inhibition of the proteasome or Cullin complex, CUL3 deletion, and RhoBTB1-inhibition with siRNA. This suggests that SETD2 is regulated by the RhoBTB1–CUL3 axis. Future studies will determine whether SETD2 plays a role in cardiovascular function.
Clinical features of gastric adenoma detected within 3 years after negative screening endoscopy in Korea
Authors: Kim Hyun Young 
Published: July 2023

Abstract

Background
Early detection and management of gastric adenoma are important for preventing gastric cancer. The present study aimed to evaluate the predictors of missed gastric adenoma on screening endoscopy in Korea and identify the risk factors associated with interval precancerous gastric lesions.

Methods
All cases of gastric adenomas diagnosed via screening endoscopy between 2007 and 2019 were reviewed. Among them, those who had undergone endoscopy within 3 years were included in the present study. Missed gastric adenoma was defined as gastric adenoma diagnosed within 3 years after negative screening endoscopy.

Results
In total, 295 cases of gastric adenoma were identified. Of these, 95 (32.2%) were missed gastric adenoma cases (mean age, 60.6 years; average interval between final and index endoscopies, 12.6 months); the remaining 200 (67.8%) were newly detected adenoma cases. Univariate analysis revealed that male sex, endoscopist experience, observation time, and presence of gastric intestinal metaplasia (pathologically proven) were associated with missed gastric adenoma. Multivariate analysis revealed that gastric intestinal metaplasia (odds ratio [OR], 2.736; 95% confidence interval [CI], 1.320–5.667; P = 0.007) and shorter observation time of the index screening endoscopy (B, −0.011; OR, 0.990; 95% CI, 0.986–0.993; P &lt; 0.001) were independent risk factors for missed gastric adenoma. The optimal cut-off for the observation time for detecting gastric adenoma was 3.53 minutes (area under curve, 0.738; 95% CI, 0.677–0.799; P &lt; 0.001).

Conclusions
Gastric intestinal metaplasia is an indication of missed gastric adenoma. Therefore, careful inspection of gastric mucosa with gastric intestinal metaplasia and proper observation time can lower the possibility of missing the gastric adenoma during screening.
Neoproterozoic and Cretaceous crustal structures revealed by a 3-D magnetotelluric investigation of the onshore Espírito Santo Basin and the contiguous Araçuaí Orogen (SE Brazil)
Authors: Oliveira J R D , La Terra E F , Panetto L P , Tupinambá M , Fontes S L 
Published: July 2023

SUMMARY
The study region in southeastern Brazil is composed of two domains: the Cretaceous onshore Espírito Santo Basin and the Neoproterozoic Araçuaí Orogen. In this region, associations among geological evolution, observed structures and geophysical data are limited. Therefore, this study aimed to further investigate this region using magnetotelluric (MT) data obtained from 22 W-E spanning stations over the Espírito Santo State. Because the dimensionality analysis revealed a substantial 3-D characteristic of the data, a 3-D MT inversion using the ModEM code was performed to generate a regional geoelectric model, and potential and well data were used as qualitative support for the interpretation. The resistivity profile obtained from the model revealed a resistive pattern for the Precambrian terrain and a conductive pattern for the sedimentary rocks of the onshore Espírito Santo Basin. The basement of the basin was delimited in the resistivity model, revealing consistency with the basement depths from the well data. Furthermore, three crustal conductors inserted in a resistive Precambrian orogen were identified. These conductors may be related to the recent circulation of saline fluids associated with plume action during the Upper Cretaceous and Cenozoic. However, the structures in which these fluids circulate exhibit different genesis along the resistivity profile. The conductors to the west of the profile may be related to plutons and dykes associated with the NNW Colatina Lineaments generated by the gravitational collapse of the orogen (530–490 Ma). Conversely, the conductor to the east under the Espírito Santo Basin appears to be related to the primary detachment rift fault generated during the Cretaceous breakup of Gondwana.
Mission design aspects for the mass change and geoscience international constellation (MAGIC)
Authors: Heller-Kaikov Betty , Pail Roland , Daras Ilias 
Published: July 2023

SUMMARYThe Mass Change and Geoscience International Constellation (MAGIC) is planned as the first realization of a double-pair low-low satellite-to-satellite (ll-sst) tracking gravity mission consisting of a polar and an inclined satellite pair. Due to the much increased spatial and temporal resolution and multidirectionality of the data to be collected by this mission, new possibilities regarding the resolvability of mass transport processes in space and time are expected. In order to maximize the scientific and societal outcome of this mission, an optimization of both the mission design as well as the methods to process the expected data is fundamental. Using numerical closed-loop simulations, we investigate the impact of several key mission design aspects on the gravity retrieval from a double-pair constellation such as the planned MAGIC mission. Specifically, we show how the choice of the second pair’s inclination poses a trade-off between a reduction of retrieval errors at latitudes covered by data from both pairs and at higher latitudes, thereby requiring a compromise between the latitude-dependent accuracy requirements of different user groups. One of the key mission goals is to provide fast-track gravity products with short latency for operational service applications. Towards the estimation of such short-term gravity fields of a few days, we investigate if coordinating the polar and inclined pairs’ orbits to achieve a stable ground-track coverage is necessary for obtaining a homogeneous accuracy of subsequent gravity solutions. Indeed, combining two freely drifting, uncontrolled orbits significantly degrades short-term gravity fields in time periods in which both pairs show coinciding ground track gaps. Finally, we analyse the relative performance of the two satellite pairs. Double-pair scenarios that are strongly dominated by the inclined pair’s data reveal degraded gravity solutions when co-estimating daily gravity fields as de-aliasing strategy. This effect can be mitigated by choosing a more balanced double-pair configuration, for example by choosing similar orbit heights and instrument noise levels for both satellite pairs. The findings presented in our study will serve to optimize the system design of the upcoming MAGIC constellation.
Characterizing coastal cod vocalization using a towed hydrophone array
Authors: Seri Sai Geetha , Schinault Matthew Edward , Penna Seth Michael , Zhu Chenyang , Sivle Lise Doksæter , de Jong Karen , Handegard Nils Olav , Ratilal Purnima 
Published: July 2023

Abstract
To better understand spawning vocalizations of Norwegian coastal cod (Gadus morhua), a prototype eight-element coherent hydrophone array was deployed in stationary vertical and towed horizontal modes to monitor cod sounds during an experiment in spring 2019. Depth distribution of cod aggregations was monitored concurrently with an ultrasonic echosounder. Cod vocalizations recorded on the hydrophone array are analysed to provide time–frequency characteristics, and source level distribution after correcting for one-way transmission losses from cod locations to the hydrophone array. The recorded cod vocalization frequencies range from ∼20 to 600 Hz with a peak power frequency of ∼60 Hz, average duration of 300 ms, and mean source level of 163.5 ± 7.9 dB re 1 μPa at 1 m. Spatial dependence of received cod vocalization rates is estimated using hydrophone array measurements as the array is towed horizontally from deeper surrounding waters to shallow water inlet areas of the experimental site. The bathymetric-dependent probability of detection regions for cod vocalizations are quantified and are found to be significantly reduced in shallow-water areas of the inlet. We show that the towable hydrophone array deployed from a moving vessel is invaluable because it can survey cod vocalization activity at multiple locations, providing continuous spatial coverage that is complementary to fixed sensor systems that provide continuous temporal coverage at a given location.
Evidence-based appraisal of two guidelines for the diagnosis of suspected, uncomplicated urinary tract infections in primary care: a diagnostic accuracy validation study
Authors: Fanshawe Thomas R , Judge Rebecca K , Mort Sam , Butler Christopher C , Hayward Gail N 
Published: July 2023

Abstract

Objectives
Given the lack of accurate rapid diagnostics for urinary tract infection (UTI) in women, many countries have developed guidelines aiming to support appropriate antibiotic prescribing, but some guidelines have not been validated. We performed a diagnostic accuracy validation study of two guidelines: Public Health England (GW-1263) and Scottish Intercollegiate Guidelines Network (SIGN160).

Methods
We used data from women with symptoms suggestive of uncomplicated UTI from a randomized controlled trial comparing urine collection devices. Symptom information was recorded via baseline questionnaire and primary care assessment. Women provided urine samples for dipstick testing and culture. We calculated the number within each risk category of diagnostic flowcharts who had positive/mixed growth/no significant growth urine culture. Results were presented as positive/negative predictive values, with 95% CIs.

Results
Of women aged under 65 years, 311/509 (61.1%, 95% CI 56.7%–65.3%) classified to the highest risk category (recommended to consider immediate antibiotic prescribing) and 80/199 (40.2%, 95% CI 33.4%–47.4%) classified to the lowest risk category (recommended to reassure that UTI is less likely) by the GW-1263 guideline (n = 810) had positive culture. For the SIGN160 guideline (n = 814), the proportion with positive culture ranged from 60/82 (73.2%, 95% CI 62.1%–82.1%) in those for whom immediate treatment was indicated to 33/76 (43.4%, 95% CI 32.3%–55.3%) in those recommended a self-care/waiting strategy.

Conclusions
Clinicians should be aware of the potential for diagnostic error when using diagnostic guidelines for managing uncomplicated UTI and making antimicrobial prescribing decisions. Infection cannot be excluded on the basis of symptoms and dipstick testing alone.