bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preprint Highlight: Quantitative multiplexed imaging of chromatin ultrastructure with Decode-PAINT
Authors: Takao Dasiuke 
Published: December 2022

Recent innovations have advanced our understanding of how the 3D organization of chromosomes regulates nuclear processes such as transcription. However, further technological innovations are needed to visualize the fine structure of chromatin in cells. The authors developed Decode-PAINT, a chromatin imaging method based on fluorescence in situ DNA hybridization (FISH) and super resolution microscopy. Decode-PAINT enables high-throughput visualization of multiple genomic loci at a resolution close to the nucleosome scale. They used Decode-PAINT to characterize and compare the nanostructures of active and inactive human X chromosomes. By providing a new pipeline that utilizes standard lab equipment, this study makes in situ single-cell structural genomics more accessible and may pave the way for sophisticated spatial multi-omics studies. This preprint has been assigned the following badges: Open Software, New Methods. Read the preprint on bioRxiv ( Sasaki et al., 2022 ): https://doi.org/10.1101/2022.08.01.502089 .
Transcriptional advantage influence odorant receptor gene choice
Authors: Mohanty Sanjay Kumar , Maryam Sidrah , Gautam Vishakha , Mittal Aayushi , Gupta Krishan , Arora Radhika , Bhadra Wrik , Mishra Tripti , Sengupta Debarka , Ahuja Gaurav 
Published: December 2022

Abstract
Odorant receptors (ORs) obey mutual exclusivity and monoallelic mode of expression. Efforts are ongoing to decipher the molecular mechanism that drives the ‘one-neuron-one-receptor’ rule of olfaction. Recently, single-cell profiling of olfactory sensory neurons (OSNs) revealed the expression of multiple ORs in the immature neurons, suggesting that the OR gene choice mechanism is much more complex than previously described by the silence-all-and-activate-one model. These results also led to the genesis of two possible mechanistic models i.e. winner-takes-all and stochastic selection. We developed Reverse Cell Tracking (RCT), a novel computational framework that facilitates OR-guided cellular backtracking by leveraging Uniform Manifold Approximation and Projection embeddings from RNA Velocity Workflow. RCT-based trajectory backtracking, coupled with statistical analysis, revealed the OR gene choice bias for the transcriptionally advanced (highest expressed) OR during neuronal differentiation. Interestingly, the observed selection bias was uniform for all ORs across different spatial zones or their relative expression within the olfactory organ. We validated these findings on independent datasets and further confirmed that the OR gene selection may be regulated by Upf3b. Lastly, our RNA dynamics-based tracking of the differentiation cascade revealed a transition cell state that harbors mixed molecular identities of immature and mature OSNs, and their relative abundance is regulated by Upf3b.
SAM-DTA: a sequence-agnostic model for drug–target binding affinity prediction
Authors: Hu Zhiqiang , Liu Wenfeng , Zhang Chenbin , Huang Jiawen , Zhang Shaoting , Yu Huiqun , Xiong Yi , Liu Hao , Ke Song , Hong Liang 
Published: December 2022

Abstract
Drug–target binding affinity prediction is a fundamental task for drug discovery and has been studied for decades. Most methods follow the canonical paradigm that processes the inputs of the protein (target) and the ligand (drug) separately and then combines them together. In this study we demonstrate, surprisingly, that a model is able to achieve even superior performance without access to any protein-sequence-related information. Instead, a protein is characterized completely by the ligands that it interacts. Specifically, we treat different proteins separately, which are jointly trained in a multi-head manner, so as to learn a robust and universal representation of ligands that is generalizable across proteins. Empirical evidences show that the novel paradigm outperforms its competitive sequence-based counterpart, with the Mean Squared Error (MSE) of 0.4261 versus 0.7612 and the R-Square of 0.7984 versus 0.6570 compared with DeepAffinity. We also investigate the transfer learning scenario where unseen proteins are encountered after the initial training, and the cross-dataset evaluation for prospective studies. The results reveals the robustness of the proposed model in generalizing to unseen proteins as well as in predicting future data. Source codes and data are available at https://github.com/huzqatpku/SAM-DTA.
LncRNA-disease association identification using graph auto-encoder and learning to rank
Authors: Liang Qi , Zhang Wenxiang , Wu Hao , Liu Bin 
Published: December 2022

AbstractDiscovering the relationships between long non-coding RNAs (lncRNAs) and diseases is significant in the treatment, diagnosis and prevention of diseases. However, current identified lncRNA-disease associations are not enough because of the expensive and heavy workload of wet laboratory experiments. Therefore, it is greatly important to develop an efficient computational method for predicting potential lncRNA-disease associations. Previous methods showed that combining the prediction results of the lncRNA-disease associations predicted by different classification methods via Learning to Rank (LTR) algorithm can be effective for predicting potential lncRNA-disease associations. However, when the classification results are incorrect, the ranking results will inevitably be affected. We propose the GraLTR-LDA predictor based on biological knowledge graphs and ranking framework for predicting potential lncRNA-disease associations. Firstly, homogeneous graph and heterogeneous graph are constructed by integrating multi-source biological information. Then, GraLTR-LDA integrates graph auto-encoder and attention mechanism to extract embedded features from the constructed graphs. Finally, GraLTR-LDA incorporates the embedded features into the LTR via feature crossing statistical strategies to predict priority order of diseases associated with query lncRNAs. Experimental results demonstrate that GraLTR-LDA outperforms the other state-of-the-art predictors and can effectively detect potential lncRNA-disease associations. Availability and implementation: Datasets and source codes are available at http://bliulab.net/GraLTR-LDA.
Can a licenced community worker qualify as a professional social worker?—Evidence from China
Authors: Enjian Wang , Mai Sun , Ying Zhang , Boqian Zhang , Wenjing Luan , Yanan Meng , Jiacheng Si 
Published: December 2022

Abstract
China has long suffered from a critical shortage of qualified social workers. To compensate for the inadequacy of formally educated social workers, a number of workers employed in the community neighbourhood committee were granted a social work licence and became registered social workers when they passed licence examinations regardless of whether they had a social work degree. Nevertheless, they are often criticised for a lack of professional competence—they are just registered social workers rather than professional social workers. This study identifies whether licenced community workers have a higher level of professional competence than non-licenced community workers in urban China. Based on a sample of 4,013 participants and the extended regression model, the findings show that the licence promotes the professional competence of community workers, but such promotion is achieved through professional knowledge acquisition rather than professional skills acquisition. Licenced community workers probably perceive stronger professional competence through professional knowledge acquisition, but their professional skills might be inadequate. The findings suggest several implications for the social work licence system.
Late-onset sensory-motor axonal neuropathy, a novelSLC12A6-related phenotype
Authors: Løseth Sissel , Høyer Helle , Le Kim-Mai , Delpire Eric , Kinge Einar , Lande Asgeir , Hilmarsen Hilde Tveitan , Fagerheim Toril , Nilssen Øivind , Braathen Geir Julius 
Published: December 2022

AbstractWe describe five families from different regions in Norway with a late-onset autosomal-dominant hereditary polyneuropathy sharing a heterozygous variant in the SLC12A6 gene. Mutations in the same gene have previously been described in infants with autosomal-recessive hereditary motor and sensory neuropathy with corpus callosum agenesis and mental retardation (Andermann syndrome), and in a few case reports describing dominantly acting de novo mutations, most of them with onset in childhood. The phenotypes in our families demonstrated heterogeneity. Some of our patients only had subtle to moderate symptoms and some individuals even no complaints. None had CNS manifestations. Clinical and neurophysiological evaluations revealed a predominant sensory axonal polyneuropathy with slight to moderate motor components.In all 10 patients the identical SLC12A6 missense variant, NM_001365088.1 c.1655G&gt;A p.(Gly552Asp), was identified. For functional characterization, the mutant potassium chloride cotransporter 3 was modelled in Xenopus oocytes. This revealed a significant reduction in potassium influx for the p.(Gly552Asp) substitution.Our findings further expand the spectrum of SLC12A6 disease, from biallelic hereditary motor and sensory neuropathy with corpus callosum agenesis and mental retardation and monoallelic early-onset hereditary motor and sensory neuropathy caused by de novo mutations, to late-onset autosomal-dominant axonal neuropathy with predominant sensory deficits.
Puerarin improves diabetic wound healing via regulation of macrophage M2 polarization phenotype
Authors: Li Shiyan , Yang Ping , Ding Xiaofeng , Zhang Hao , Ding Youjun , Tan Qian 
Published: December 2022

Abstract

Background
Skin wound healing depends on the progress of different but overlapping stages of healing, including hemostasis, inflammatory, proliferative and remodeling. Failure of these stages to occur in a timely and gradual manner may result in non-healing pathological wounds. Macrophages and neutrophils have been shown to play an essential role in the inflammatory responses of wound tissue, and their active plasticity allows them to modulate tissue damage and repair functions. The ability of macrophages and neutrophils to regulate the occurrence and resolution of inflammatory processes is essential for the treatment of pathological wound healing.

Methods
Mice were categorized into negative control, streptozotocin, streptozotocin + puerarin and puerarin groups. The traditional Chinese medicine extract puerarin was selected to treat different groups of mice with a full-thickness skin defect wound. Cells of the RAW264.7 cell line were stimulated under different puerarin conditions. Then, real time quantitative polymerase chain reaction (RT-qPCR), western blot, immunofluorescence and other assays were carried out to explore the effect of puerarin on wound healing and its molecular mechanism.

Results
Animal experiments found that the wound healing of diabetic mice treated with puerarin was significantly accelerated, and histological analysis found that puerarin treatment markedly decreased the infiltration of macrophages and neutrophils in wound tissue. Through western blot, RT-qPCR and immunofluorescence experiments, it was observed that puerarin treatment remarkably inhibited nuclear factor kinase B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, downregulated the expression of inflammatory cytokines and induced the M2 polarization of macrophages. At the cellular level, we also observed that puerarin improved M2 macrophage polarization and inhibited inflammatory pathway activation in a high-glucose culture.

Conclusion
Puerarin has a significant therapeutic effect on wound healing in diabetic mice. The therapeutic effect is achieved by regulating macrophage polarization through suppressing NF-κB and MAPK signaling cascades.
A Position Statement on Mpox as a Sexually Transmitted Disease
Authors: Allan-Blitz Lao-Tzu , Gandhi Monica , Adamson Paul , Park Ina , Bolan Gail , Klausner Jeffrey D 
Published: December 2022

AbstractThe global outbreak of mpox virus constituted an international public health emergency. Reports have highlighted (1) a temporal association between sexual activity and mpox, (2) an association between specific sexual practices and location of lesion development, (3) a high frequency of sexual practices conferring risk for other sexually transmitted infections among cases of mpox, (4) that mpox virus can be isolated from sexual fluids, (4) that isolated virus is infectious, and (5) a high frequency of anogenital lesions prior to disease dissemination suggesting direct inoculation during sexual activities. Finally, a growing body of evidence suggests that sexual transmission is the predominant mode of transmission for mpox virus. We therefore conclude that mpox is a sexually transmitted disease. Labeling it as such will help focus public health interventions, such as vaccinations, testing, and treatment, as well as facilitate focused awareness and education programs toward behavioral modifications to reduce exposures.
In Situ Metabolomics of Cortisol-Producing Adenomas
Authors: Murakami Masanori , Sun Na , Li Fengxia , Feuchtinger Annette , Gomez-Sanchez Celso , Fassnacht Martin , Reincke Martin , Bancos Irina , Walch Axel , Kroiss Matthias , Beuschlein Felix 
Published: December 2022

Received June 8, 2022; accepted October 11, 2022

Background
Recent advances in omics techniques have allowed detailed genetic characterization of cortisol-producing adrenal adenoma (CPA). In contrast, the pathophysiology of CPAs has not been elucidated in detail on the level of tumor metabolic alterations.

Methods
The current study conducted a comprehensive mass spectrometry imaging (MSI) map of CPAs in relation to clinical phenotypes and immunohistochemical profiles of steroidogenic enzymes. The study cohort comprised 46 patients with adrenal tumors including CPAs (n 35) and nonfunctional adenomas (n 11).

Results
Severity of cortisol hypersecretion was significantly correlated with 29 metabolites (adjusted P 0.05). Adrenal androgens derived from the classic androgen pathway were inversely correlated with both cortisol secretion (rs 0.41, adjusted P 0.035) and CYP11B1 expression (rs 0.77, adjusted P 2.00E-08). The extent of cortisol excess and tumor CYP11B1 expression further correlated with serotonin (rs 0.48 and 0.62, adjusted P 0.008 and 2.41E-05). Tumor size was found to be correlated with abundance of 13 fatty acids (adjusted P 0.05) and negatively associated with 9 polyunsaturated fatty acids including phosphatidic acid 38:8 (rs 0.56, adjusted P 0.009).

Conclusions
MSI reveals novel metabolic links between endocrine function and tumorigenesis, which will further support the understanding of CPA pathophysiology.
Query Operators for Transactional Data: Detecting Similar and Periodic Transactions
Authors: Moreno Arboleda Francisco Javier , Garani Georgia , Bolivar Zapata Carlos Daniel 
Published: December 2022

Abstract
Pattern detection for revealing the patterns of users’ behavior is an important analysis-assisting tool toward the understanding and prediction of their attitudes, manners, activities and habits. In this paper, two novel query operators applied to transactional data are introduced to ease the query processing, strengthening query capabilities and revealing valuable patterns for data analysis and mining. The operators are named as PeriodicTransactions and SimilarTransactions, and as their names imply, they measure periodicity and similarity, respectively, in a set of transactions. The operators are formally defined and the corresponding algorithms are also provided. To show the expediency of the operators, the proposed algorithms are implemented and a set of experiments were conducted with real data from the Ethereum blockchain. The results show the feasibility and usefulness of the proposal for identifying these patterns that help to understand user behavior and reveal a rich interaction between senders and recipients, where periodic and similar transactions occur.
Metabolic rate and critical thermal maximumCTmaxestimates for westslope cutthroat trout,Oncorhynchus clarkii lewisi
Authors: Enders Eva C , Durhack Travis C 
Published: December 2022

AbstractGlobal warming is changing the thermal habitat of cold-water freshwater fishes, which can lead to decreased fitness and survival and cause shifts in species distributions. The Alberta population of westslope cutthroat trout (Oncorhynchus clarkii lewisi) is listed as ‘Threatened’ under the Canadian Species at Risk Act. The major threats to the species are the alteration in habitat and water flow, competition and hybridization with non-native trout species and climate change. Here, we conducted (i) intermittent-flow respirometry experiments with adult native westslope cutthroat trout and non-native rainbow trout (Oncorhynchus mykiss) and (ii) critical thermal maximum experiments (CTmax) with adult westslope cutthroat trout to obtain valuable input data for species distribution models. For both species, standard metabolic rate (SMR) was lower at 10°C compared to 15°C and westslope cutthroat trout had higher SMR than rainbow trout. Although there were inter-specific differences in SMR, forced aerobic scope (using a standardized chase protocol) was different at 10°C, but no significant differences were observed at 15°C because of relative smaller differences in maximum metabolic rate between the species. CTmax of westslope cutthroat trout acclimated to 10°C was 27.0 ± 0.8°C and agitation temperature was 25.2 ± 1.0°C. The results from this study will inform and parametrize cumulative effects assessments and bioenergetics habitat modelling for the recovery planning of the species.
The risk of autism spectrum disorder and intellectual disability but not attention deficit/hyperactivity disorder is increased in individuals with esophageal atresia
Authors: Kassa Ann-Marie , Håkanson Cecilia Arana , Lilja Helene Engstrand 
Published: December 2022

Summary
Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability (ID) in patients with esophageal atresia (EA) is scarce. The aims of this study were to investigate the prevalence and risk of ADHD, ASD and ID in individuals with EA. Data were obtained from four longitudinal population-based registries in Sweden and analyzed using Cox proportional hazards regression. Patients with EA born in Sweden in 1973–2018 were included together with five controls for each individual with the exposure matched on sex, gestational age at birth, birth year and birth county. Individuals with chromosomal aberrations and syndromes were excluded. In total, 735 individuals with EA and 3675 controls were included. Median age at time of the study was 20 years (3–48). ASD was found in 24 (3.9%), ADHD in 34 (5.5%) and ID in 28 (4.6%) individuals with EA. Patients with EA had a 1.66 times higher risk of ASD (95% confidence interval [CI], 1.05–2.64) and a 3.62 times higher risk of ID (95% CI, 2.23–5.89) compared with controls. The risk of ADHD was not significantly increased. ADHD medication had been prescribed to 88.2% of patients with EA and ADHD and to 84.5% of controls with ADHD. Individuals with EA have a higher risk of ASD and ID than individuals without the exposure. These results are important when establishing follow-up programs for children with EA to allow timely detection and consequentially an earlier treatment and support especially before school start.
Long-term Colectomy Rates of Ulcerative Colitis over 40 Years of Different Therapeutic Eras–Results from a Western Hungarian Population-based Inception Cohort Between 1977 and 2020
Authors: Wetwittayakhlang Panu , Gonczi Lorant , Lakatos Laszlo , Kurti Zsuzsanna , Golovics Petra , Pandur Tunde , David Gyula , Erdelyi Zsuzsanna , Szita Istvan , Lakatos Peter L 
Published: December 2022

Abstract

Background and Aims
Few populaion-based studies have investigated the long-term colectomy rates of ulcerative colitis [UC]. We aimed to assess the colectomy rates over 40 years of different therapeutic eras in a prospective population-based inception cohort from Veszprem Province, Western Hungary.

Methods
Patient inclusion lasted between January1, 1977, and December31, 2018. Patient follow-up ended December 31, 2020. Colectomy rates and disease course were examined in three different eras based on the time of UC diagnosis; cohort A [1977–1995], cohort B [1996–2008], and cohort C [2009–2018].

Results
A total of 1370 incident UC patients were included [male 51.2%, median age at diagnosis 37 years]. Median follow-up was 17 years (interquartile range [IQR] 9–24); 87 patients [6.4%] underwent colectomy. The cumulative probability of colectomy in the total population was 2.6% (95% confidence interval [CI] 2.2-3.0), 4.2% [95% CI 3.6-4.8], 7.0% [95% CI 6.2-7.8], and 10.4% [95% CI 9.1-11.7] after 5, 10, 20, and 30 years, respectively. The proportion of extensive colitis at diagnosis increased over time [24.2%/24.3%/34.9% in cohorts A/B/C, respectively, p = 0.001]. Overall exposure to immunomodulators [11.3%/20.9%/34.4% in cohorts A/B/C, respectively, p &lt;0.001], as well as the probability for biologic therapy initiation increased over time (0%/3.3% [95% CI 2.6-4.0]/13.9% [95% CI 12.1-15.7], p &lt;0.001). There were no statistically significant differences in the cumulative probability of colectomies between cohorts A/B/C: 1.7% [95% CI 1.0-2.4], 2.5% [95% CI 1.9-3.1], and 3.7% [95% CI 2.7-4.7] after 5 years; 3.5% [95% CI 2.5-4.5], 4.2% [95% CI 3.4-5.0], and 4.5% [95% CI 3.3-5.7] after 10 years; and 7.5% [95% CI 6.1-8.9] and 6.3% [95% CI 5.2-7.4] in cohorts A/B after 20 years [log-rank = 0.588]. Extensive colitis (hazard ratio [HR] 2.24, 95% CI 1.55-3.23) and continuous active disease activity [HR 6.36, 95% CI 3.46-11.67] were independent predictors for colectomy.

Conclusion
No differences in colectomy rates have been observed in the incident UC patients over 40 years despite increasing use of immunomodulators and biologic therapies.
Helicoverpa zea (Lepidoptera: Noctuidae) In-Season and Overwintering Pupation Response to Soil Type
Authors: Dillard DeShae , Reisig Dominic D , Reay-Jones Francis P F 
Published: December 2022

Abstract
Heliothinae soil pupation is understudied despite the key role this life stage plays in their development. Many Heliothinae are important agricultural pests and understanding the interplay of environment and pupation is important to optimize pest management tactics oriented toward pupae. We studied the impact of three soil types (coarse sand, high organic muck, and fine-textured clay) on Helicoverpa zea (Boddie) in-season and overwintering pupal survivorship, diapause, depth, and weight in at two locations (North and South Carolina). We introduced wild-collected (in-season) and laboratory-reared (over the winter) infestations of H. zea larvae to each of the three soils and later excavated pupae. In-season and over the winter pupal survivorship was lower in fine-textured clay soils than in coarse sand or high organic muck. In addition, pupal depth and weight, in-season and over the winter, varied significantly by soil type. In general, depth was the shallowest, and pupae weight was lower when recovered from fine-textured clay soils. Finally, diapausing characteristics varied significantly by location and year, likely impacted by differing environmental conditions. Our results suggest that fine-textured clay soils negatively impact Heliothinae pupation and may be suppressing populations in areas with these soil types.