bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating convolution and self-attention improves language model of human genome for interpreting non-coding regions at base-resolution
Authors: Yang Meng , Huang Lichao , Huang Haiping , Tang Hui , Zhang Nan , Yang Huanming , Wu Jihong , Mu Feng 
Published: May 2022

AbstractInterpretation of non-coding genome remains an unsolved challenge in human genetics due to impracticality of exhaustively annotating biochemically active elements in all conditions. Deep learning based computational approaches emerge recently to help interpret non-coding regions. Here, we present LOGO (Language of Genome), a self-attention based contextualized pre-trained language model containing only two self-attention layers with 1 million parameters as a substantially light architecture that applies self-supervision techniques to learn bidirectional representations of the unlabelled human reference genome. LOGO is then fine-tuned for sequence labelling task, and further extended to variant prioritization task via a special input encoding scheme of alternative alleles followed by adding a convolutional module. Experiments show that LOGO achieves 15% absolute improvement for promoter identification and up to 4.5% absolute improvement for enhancer-promoter interaction prediction. LOGO exhibits state-of-the-art multi-task predictive power on thousands of chromatin features with only 3% parameterization benchmarking against the fully supervised model, DeepSEA and 1% parameterization against a recent BERT-based DNA language model. For allelic-effect prediction, locality introduced by one dimensional convolution shows improved sensitivity and specificity for prioritizing non-coding variants associated with human diseases. In addition, we apply LOGO to interpret type 2 diabetes (T2D) GWAS signals and infer underlying regulatory mechanisms. We make a conceptual analogy between natural language and human genome and demonstrate LOGO is an accurate, fast, scalable, and robust framework to interpret non-coding regions for global sequence labeling as well as for variant prioritization at base-resolution.
The topoisomerase 3 zinc finger domain cooperates with the RMI1 scaffold to promote stable association of the BTR complex to recombination intermediates in the Caenorhabditis elegans germline
Authors: Dello Stritto Maria Rosaria , Vojtassakova Nina , Velkova Maria , Hamminger Patricia , Ulm Patricia , Jantsch Verena 
Published: May 2022

Abstract
Homologous recombination is the predominant DNA repair pathway used in the gonad. Of the excess DNA double-strand breaks formed in meiosis, only a subset matures into crossovers, with the remainder repaired as non-crossovers. The conserved BTR complex (comprising Bloom helicase, topoisomerase 3 and RMI1/2 scaffold proteins) acts at multiple steps during recombination to dismantle joint DNA molecules, thereby mediating the non-crossover outcome and chromosome integrity. Furthermore, the complex displays a role at the crossover site that is less well understood. Besides catalytic and TOPRIM domains, topoisomerase 3 enzymes contain a variable number of carboxy terminal zinc finger (ZnF) domains. Here, we studied the Caenorhabditis elegans mutant, in which the single ZnF domain is deleted. In contrast to the gene disruption allele, the top-3-ZnF mutant is viable, with no replication defects; the allele appears to be a hypomorph. The TOP-3-ZnF protein is recruited into foci but the mutant has increased numbers of crossovers along its chromosomes, with minor defects in repressing heterologous recombination, and a marked delay in the maturation/processing of recombination intermediates after loading of the RAD-51 recombinase. The ZnF domain cooperates with the RMI1 homolog RMH-2 to stabilize association of the BTR complex with recombination intermediates and to prevent recombination between heterologous DNA sequences.
Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats
Authors: D’Souza Michael H , Mrozowich Tyler , Badmalia Maulik D , Geeraert Mitchell , Frederickson Angela , Henrickson Amy , Demeler Borries , Wolfinger Michael T , Patel Trushar R 
Published: May 2022

AbstractHuman Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on the RNA tertiary structure. Previous studies have determined the two-dimensional secondary structures of the sense and antisense human LincRNA-p21 AluSx1 IRs using SHAPE. However, there were no insights into its three-dimensional structure. Therefore, we in vitro transcribed the sense and antisense regions of LincRNA-p21 AluSx1 Inverted Repeats (IRs) and performed analytical ultracentrifugation, size exclusion chromatography, light scattering, and small angle X-ray scattering (SAXS) studies. Based on these studies, we determined low-resolution, three-dimensional structures of sense and antisense LincRNA-p21. By adapting previously known two-dimensional information, we calculated their sense and antisense high-resolution models and determined that they agree with the low-resolution structures determined using SAXS. Thus, our integrated approach provides insights into the structure of LincRNA-p21 Alu IRs. Our study also offers a viable pipeline for combining the secondary structure information with biophysical and computational studies to obtain high-resolution atomistic models for long noncoding RNAs.
RaacFold: a webserver for 3D visualization and analysis of protein structure by using reduced amino acid alphabets
Authors: Zheng Lei , Liu Dongyang , Li Yuan Alex , Yang Siqi , Liang Yuchao , Xing Yongqiang , Zuo Yongchun 
Published: May 2022

Abstract
Protein structure exhibits greater complexity and diversity than DNA structure, and usually affects the interpretation of the function, interactions and biological annotations. Reduced amino acid alphabets (Raaa) exhibit a powerful ability to decrease protein complexity and identify functional conserved regions, which motivated us to create RaacFold. The RaacFold provides 687 reduced amino acid clusters (Raac) based on 58 reduction methods and offers three analysis tools: Protein Analysis, Align Analysis, and Multi Analysis. The Protein Analysis and Align Analysis provide reduced representations of sequence-structure according to physicochemical similarities and computational biology strategies. With the simplified representations, the protein structure can be viewed more concise and clearer to capture biological insight than the unreduced structure. Thus, the design of artificial protein will be more convenient, and redundant interference is avoided. In addition, Multi Analysis allows users to explore biophysical variation and conservation in the evolution of protein structure and function. This supplies important information for the identification and exploration of the nonhomologous functions of paralogs. Simultaneously, RaacFold provides powerful 2D and 3D rendering performance with advanced parameters for sequences, structures, and related annotations. RaacFold is freely available at http://bioinfor.imu.edu.cn/raacfold.
Identification and characterization of a prokaryotic 6-4 photolyase from Synechococcus elongatus with a deazariboflavin antenna chromophore
Authors: Chen Simeng , Liu Chenxi , Zhou Chenchen , Wei Zhihui , Li Yuting , Xiong Lei , Yan Liang , Lv Jun , Shen Liang , Xu Lei 
Published: May 2022

Abstract
Synechococcus elongatus, formerly known as Anacystis nidulans, is a representative species of cyanobacteria. It is also a model organism for the study of photoreactivation, which can be fully photoreactivated even after receiving high UV doses. However, for a long time, only one photolyase was found in S. elongatus that is only able to photorepair UV induced cyclobutane pyrimidine dimers (CPDs) in DNA. Here, we characterize another photolyase in S. elongatus, which belongs to iron-sulfur bacterial cryptochromes and photolyases (FeS-BCP), a subtype of prokaryotic 6–4 photolyases. This photolyase was named SePhrB that could efficiently photorepair 6–4 photoproducts in DNA. Chemical analyses revealed that SePhrB contains a catalytic FAD cofactor and an iron-sulfur cluster. All of previously reported FeS-BCPs contain 6,7-dimethyl-8-ribityllumazine (DMRL) as their antenna chromophores. Here, we first demonstrated that SePhrB possesses 7,8-didemethyl-8-hydroxy-5-deazariboflavin (8-HDF) as an antenna chromophore. Nevertheless, SePhrB could be photoreduced without external electron donors. After being photoreduced, the reduced FAD cofactor in SePhrB was extremely stable against air oxidation. These results suggest that FeS-BCPs are more diverse than expected which deserve further investigation.
Metal-organic frameworks as effective sensors and scavengers for toxic environmental pollutants
Authors: Karmakar Avishek , Velasco Ever , Li Jing 
Published: May 2022

Abstract
Metal-organic frameworks (MOFs) constructed from a rich library of organic struts and metal ions/clusters represent promising candidates for a wide range of applications. The unique structure, porous nature, easy tunability and processability of these materials make them an outstanding class of materials for tackling serious global problems relating to energy and environment. Among them, environmental pollution is one aspect that has increased at an alarming rate in the past decade or so. With rapid urbanization and industrialization, toxic environmental pollutants are constantly released and accumulated leading to serious contamination in water bodies and thereby having adverse effects on human health. Recent studies have shown that many toxic pollutants, as listed by the World Health Organization and the US Environmental Protection Agency, can be selectively detected, captured, sequestered and removed by MOFs from air and aquatic systems. Most of these sensing/capture processes in MOFs are quantifiable and effective for even a trace amount of the targeted chemical species. The functional sites (ligands and metals) play a critical role in such recognition processes and offer an extensive scope of structural tunability for guest (pollutants, toxic entities) recognition. Whereas on the one hand, the underlying mechanisms governing such sensing and capture are important, it is also crucial to identify MOFs that are best suited for commercial applications for the future. In this review article, we provide an overview of the most recent progress in the sensing, capture and removal of various common toxic pollutants, including neutral and ionic, inorganic and organic species, with brief discussions on the mechanism and efficacy of selected MOFs.
A Fatal Fungal Infection: Cryptococcus gattii (VGI) Meningitis in Texas
Authors: Nielsen Marisa C , Peterson Joshua M , Shine Billie , Hornak J Patrik , Esechie Aimalohi , Bhatt Sandeep , Desai Kinjal , Dabi Alok , Felicella Michelle M , Ren Ping 
Published: May 2022

Abstract
Cryptococcus gattii is an underrecognized cause of meningitis, especially in nonendemic regions. This report details C gattii disease progression from admission to autopsy in an otherwise healthy 40-year-old male in Texas. It brings awareness to an often unsuspected organism that can cause severe infection requiring early recognition and treatment in immunocompetent individuals.
A Bundle of the Top 10 OPAT Publications in 2021
Authors: Rivera Christina G , Beieler Alison M , Childs-Kean Lindsey M , Cortés-Penfield Nicolás , Idusuyi Ann-Marie , Keller Sara C , Rajapakse Nipunie S , Ryan Keenan L , Yoke Leah H , Mahoney Monica V 
Published: May 2022

Abstract
As outpatient parenteral antimicrobial therapy (OPAT) becomes more common, it may be difficult to stay current with recent related publications. A group of multidisciplinary OPAT clinicians reviewed and ranked all OPAT publications published in 2021. This article provides a high-level summary of the OPAT manuscripts that were voted the “top 10” publications of 2021.
The Many Values of Night Soil in Wartime China
Authors: Barnes Nicole Elizabeth 
Published: May 2022

Abstract
In March 1940, leaders of the Chongqing night-soil trade union sent a petition to the governor of China’s Sichuan province to contest health officials’ attempts to seize the night-soil industry. Cleanliness in Chongqing, the national capital during the War of Resistance against Japan (1937–45), held profound significance for China’s hygienic modernity, but Nationalist authorities failed to ensure it. On their part, the petitioners failed to recognize the centrality of odour in health officials’ agenda. These joint failures left the wartime capital mired in muck. This article employs microhistorical analysis of the 1940 petition to highlight a significant shift in olfactory sensibility. Comparison with a similar instance in nearby Hankou eleven years later, when Communist cadres succeeded in breaking the local night-soil gang, elucidates key distinctions between the Nationalist and Communist states. The conclusion considers what might be possible if we imagine using night soil to fertilize soils not as an anti-modern practice but as a sustainable means of processing waste and caring for our planet. To regain a portion of night soil’s many values, we must conquer the obstacles of disease transmission and disgust. The former is a technical problem for which solutions already exist; the latter is a formidable social problem.
The ongoing need for rates: can physiology and omics come together to co-design the measurements needed to understand complex ocean biogeochemistry?
Authors: Strzepek Robert F , Nunn Brook L , Bach Lennart T , Berges John A , Young Erica B , Boyd Philip W 
Published: May 2022

Abstract
The necessity to understand the influence of global ocean change on biota has exposed wide-ranging gaps in our knowledge of the fundamental principles that underpin marine life. Concurrently, physiological research has stagnated, in part driven by the advent and rapid evolution of molecular biological techniques, such that they now influence all lines of enquiry in biological oceanography. This dominance has led to an implicit assumption that physiology is outmoded, and advocacy that ecological and biogeochemical models can be directly informed by omics. However, the main modeling currencies are biological rates and biogeochemical fluxes. Here, we ask: how do we translate the wealth of information on physiological potential from omics-based studies to quantifiable physiological rates and, ultimately, to biogeochemical fluxes? Based on the trajectory of the state-of-the-art in biomedical sciences, along with case-studies from ocean sciences, we conclude that it is unlikely that omics can provide such rates in the coming decade. Thus, while physiological rates will continue to be central to providing projections of global change biology, we must revisit the metrics we rely upon. We advocate for the co-design of a new generation of rate measurements that better link the benefits of omics and physiology.
ABERRANT PANICLE ORGANIZATION2 controls multiple steps in panicle formation through common direct-target genes
Authors: Miao Yiling , Xun Qian , Taji Teruaki , Tanaka Keisuke , Yasuno Naoko , Ding Chengqiang , Kyozuka Junko 
Published: May 2022

Abstract
At the transition from vegetative to reproductive growth in rice (Oryza sativa), a developmental program change occurs, resulting in panicle (rice inflorescence) formation. The initial event of the transition is the change of the shoot apical meristem to an inflorescence meristem (IM), accompanied by a rapid increase in the meristem size. Suppression of leaf growth also occurs, resulting in the formation of bracts. The IM generates branch meristems (BMs), indeterminate meristems that reiteratively generate next-order meristems. All meristems eventually acquire a determinate spikelet meristem identity and terminate after producing a floret. ABERRANT PANICLE ORGANIZATION2 (APO2) is the rice ortholog of Arabidopsis (Arabidopsis thaliana) LEAFY (LFY), a plant-specific transcription factor (TF). APO2 is a positive regulator of panicle branch formation. Here, we show that APO2 is also required to increase the meristem size of the IM and suppress bract outgrowth. We identified genes directly and indirectly regulated by APO2 and identified APO2-binding sites. These analyses showed that APO2 directly controls known regulators of panicle development, including SQUAMOSA PROMOTER BINDING PROTEIN LIKE14 and NECK LEAF1. Furthermore, we revealed that a set of genes act as downstream regulators of APO2 in controlling meristem cell proliferation during reproductive transition, bract suppression, and panicle branch formation. Our findings indicate that APO2 acts as a master regulator of rice panicle development by regulating multiple steps in the reproductive transition through directly controlling a set of genes.
SAfety and Feasibility of EArly Resistance Training After Median Sternotomy: The SAFE-ARMS Study
Authors: Pengelly Jacqueline , Boggett Stuart , Bryant Adam , Royse Colin , Royse Alistair , Williams Gavin , El-Ansary Doa 
Published: May 2022

Abstract

Objective
The purpose of this study was to determine the safety and feasibility of subacute upper limb resistance exercise on sternal micromotion and pain and the reliability of sternal ultrasound assessment following cardiac surgery via median sternotomy.

Methods
This experimental study used a pretest–posttest design to investigate the effects of upper limb resistance exercise on the sternum in patients following their first cardiac surgery via median sternotomy. Six bilateral upper limb machine-based exercises were commenced at a base resistance of 20 lb (9 kg) and progressed for each participant. Sternal micromotion was assessed using ultrasound at the mid and lower sternum at 2, 8, and 14 weeks postsurgery. Intrarater and interrater reliability was calculated using intraclass correlation coefficients (ICCs). Participant-reported pain was recorded at rest and with each exercise using a visual analogue scale.

Results
Sixteen adults (n = 15 males; 71.3 [SD = 6.2] years of age) consented to participate. Twelve participants completed the study, 2 withdrew prior to the 8-week assessment, and 2 assessments were not completed at 14 weeks due to assessor unavailability. The highest median micromotion at the sternal edges was observed during the bicep curl (median = 1.33 mm; range = −0.8 to 2.0 mm) in the lateral direction and the shoulder pulldown (median = 0.65 mm; range = −0.8 to 1.6 mm) in the anterior–posterior direction. Furthermore, participants reported no increase in pain when performing any of the 6 upper limb exercises. Interrater reliability was moderate to good for both lateral–posterior (ICC = 0.73; 95% CI = 0.58 to 0.83) and anterior–posterior micromotion (ICC = 0.83; 95% CI = 0.73 to 0.89) of the sternal edges.

Conclusion
Bilateral upper limb resistance exercises performed on cam-based machines do not result in sternal micromotion exceeding 2.0 mm or an increase in participant-reported pain.

Impact
Upper limb resistance training commenced as early as 2 weeks following cardiac surgery via median sternotomy and performed within the safe limits of pain and sternal micromotion appears to be safe and may accelerate postoperative recovery rather than muscular deconditioning.
Abdominal Massage in Functional Chronic Constipation: A Randomized Placebo-Controlled Trial
Authors: Doğan İrem Gül , Gürşen Ceren , Akbayrak Türkan , Balaban Yasemin Hatice , Vahabov Cavanşir , Üzelpasacı Esra , Özgül Serap 
Published: May 2022

Abstract

Objective
The aim of this study was to investigate the effects of abdominal massage on the severity of constipation, bowel function, and quality of life (QoL) in patients with functional chronic constipation in a randomized placebo-controlled design.

Methods
Seventy-four patients diagnosed with functional constipation according to the Rome IV diagnostic criteria were included. Patients were randomly assigned to the intervention group (abdominal massage plus lifestyle advice) or the control group (placebo therapeutic ultrasound plus lifestyle advice). Abdominal massage or placebo ultrasound was applied for 4 weeks. The primary outcome measure was the Constipation Severity Instrument score. Bowel diary data and the Patient Assessment of Constipation Quality of Life Questionnaire score were used as secondary outcome measures. Differences in outcome measures within and between groups were analyzed by repeated-measures analysis of variance.

Results
Although constipation severity, bowel function indicators (defecation frequency and duration and stool consistency), and QoL were found to improve significantly over time in both groups, improvements in both primary and secondary outcomes were much more significant in the abdominal massage group. In addition, group × time interaction effects were found to be significant for constipation severity, bowel function findings, and QoL. There were approximately 70% and 28% reductions in constipation severity, 56% and 38% improvement rates in QoL, and 70% and 43% increases in defecation frequency in the intervention and placebo groups, respectively.

Conclusion
Abdominal massage should be one of the first-line conservative approaches in the management of functional chronic constipation. Further randomized placebo-controlled studies with long-term follow-up are needed.

Impact
For functional constipation, which is a common gastrointestinal problem, abdominal massage should be considered as an option in first-line therapy because of its effect beyond the placebo effect.

Lay Summary
If you have functional constipation, your physical therapist may be able to provide abdominal massage to help reduce your symptoms.
Clarissa’s Insomnia
Authors: Fanning Christopher 
Published: May 2022

Abstract
This essay focuses on the attention to sleep and sleeplessness in Samuel Richardson’s epistolary novel, Clarissa (1747–1748). It places Clarissa’s insomnia in the context of a historical change in cultural attitudes toward sleep in the eighteenth century by which the understanding of sleep shifts from a symbolic and moral one to a medical and physiological one. Clarissa is on the cusp of this change. While characters within Clarissa are aware of the different symbolic meanings of sleep—both the heroine and the villain, Lovelace, interpret and represent their behaviour in the light of traditional understandings of sleep and insomnia—the novel itself evinces a medicalized knowledge of sleep, made clear in its careful documentation of Clarissa’s sleep patterns. Both symbolic and medical understandings of insomnia bear upon the questions of agency and volition that have been of interest to recent critics of the novel in addition to elaborating Richardson’s major contribution to the development of psychological realism in fiction.