bluuebunny/crossref_metadata_2025_split huggingface dataset:
In the twilight zone of protein sequence homology: do protein language models learn protein structure?
Authors: Kabir Anowarul , Moldwin Asher , Bromberg Yana , Shehu Amarda 
Published: August 2024

Abstract

Motivation
Protein language models based on the transformer architecture are increasingly improving performance on protein prediction tasks, including secondary structure, subcellular localization, and more. Despite being trained only on protein sequences, protein language models appear to implicitly learn protein structure. This paper investigates whether sequence representations learned by protein language models encode structural information and to what extent.

Results
We address this by evaluating protein language models on remote homology prediction, where identifying remote homologs from sequence information alone requires structural knowledge, especially in the “twilight zone” of very low sequence identity. Through rigorous testing at progressively lower sequence identities, we profile the performance of protein language models ranging from millions to billions of parameters in a zero-shot setting. Our findings indicate that while transformer-based protein language models outperform traditional sequence alignment methods, they still struggle in the twilight zone. This suggests that current protein language models have not sufficiently learned protein structure to address remote homology prediction when sequence signals are weak.

Availability and implementation
We believe this opens the way for further research both on remote homology prediction and on the broader goal of learning sequence- and structure-rich representations of protein molecules. All code, data, and models are made publicly available.
Improving protein function prediction by learning and integrating representations of protein sequences and function labels
Authors: Boadu Frimpong , Cheng Jianlin 
Published: August 2024

Abstract

Motivation
As fewer than 1% of proteins have protein function information determined experimentally, computationally predicting the function of proteins is critical for obtaining functional information for most proteins and has been a major challenge in protein bioinformatics. Despite the significant progress made in protein function prediction by the community in the last decade, the general accuracy of protein function prediction is still not high, particularly for rare function terms associated with few proteins in the protein function annotation database such as the UniProt.

Results
We introduce TransFew, a new transformer model, to learn the representations of both protein sequences and function labels [Gene Ontology (GO) terms] to predict the function of proteins. TransFew leverages a large pre-trained protein language model (ESM2-t48) to learn function-relevant representations of proteins from raw protein sequences and uses a biological natural language model (BioBert) and a graph convolutional neural network-based autoencoder to generate semantic representations of GO terms from their textual definition and hierarchical relationships, which are combined together to predict protein function via the cross-attention. Integrating the protein sequence and label representations not only enhances overall function prediction accuracy, but delivers a robust performance of predicting rare function terms with limited annotations by facilitating annotation transfer between GO terms.

Availability and implementation
https://github.com/BioinfoMachineLearning/TransFew.
splicekit: an integrative toolkit for splicing analysis from short-read RNA-seq
Authors: Rot Gregor , Wehling Arne , Schmucki Roland , Berntenis Nikolaos , Zhang Jitao David , Ebeling Martin 
Published: August 2024

Abstract

Motivation
Analysis of alternative splicing using short-read RNA-seq data is a complex process that involves several steps: alignment of reads to the reference genome, identification of alternatively spliced features, motif discovery, analysis of RNA-protein binding near donor and acceptor splice sites, and exploratory data visualization. To the best of our knowledge, there is currently no integrative open-source software dedicated to this task.

Results
Here, we introduce splicekit, a Python package that provides and integrates a set of existing and novel splicing analysis tools for conducting splicing analysis.

Availability and implementation
The software splicekit is open-source and available at Github (https://github.com/bedapub/splicekit) and via the Python Package Index.
Spaln3: improvement in speed and accuracy of genome mapping and spliced alignment of protein query sequences
Authors: Gotoh Osamu 
Published: August 2024

Abstract

Motivation
Spaln is the earliest practical tool for self-sufficient genome mapping and spliced alignment of protein query sequences onto a mammalian-sized eukaryotic genomic sequence. However, its computational speed has become inadequate for the analysis of rapidly growing genomic and transcript sequence data.

Results
The dynamic programming calculation of Spaln has been sped up in two ways: (i) the introduction of the multi-intermediate unidirectional Hirschberg method and (ii) SIMD-based vectorization. The new version, Spaln3, is ∼7 times faster than the latest Spaln version 2, and its gene prediction accuracy is consistently higher than that of Miniprot.

Availability and implementation
https://github.com/ogotoh/spaln.
The structure of the environment influences the patterns and genetics of local adaptation
Authors: Booker Tom R 
Published: August 2024

Abstract
Environmental heterogeneity can lead to spatially varying selection, which can, in turn, lead to local adaptation. Population genetic models have shown that the pattern of environmental variation in space can strongly influence the evolution of local adaptation. In particular, when environmental variation is highly autocorrelated in space local adaptation will more readily evolve. However, there have been few attempts to test this prediction empirically or characterize the consequences it would have for the genetic architecture underlying local adaptation. In this study, I analyze a large-scale provenance trial conducted on lodgepole pine and find suggestive evidence that spatial autocorrelation in environmental variation is related to the strength of local adaptation that has evolved in that species. Motivated by those results, I use simulations to model local adaptation to different spatial patterns of environmental variation. The simulations confirm that local adaptation is expected to increase with the degree of spatial autocorrelation in the selective environment, but also show that highly heterogeneous environments are more likely to exhibit high variation in local adaptation, a result not previously described. I find that the spatial pattern of environmental variation influences the genetic architectures underlying local adaptation. In highly autocorrelated environments, the genetic architecture of local adaptation tends to be composed of high-frequency alleles with small phenotypic effects. In weakly autocorrelated environments, locally adaptive alleles may have larger phenotypic effects but are present at lower frequencies across species’ ranges and experience more evolutionary turnover. Overall, this work emphasizes the profound importance that the spatial pattern of selection can have on the evolution of local adaptation and how spatial autocorrelation should be considered when formulating hypotheses in ecological and genetic studies.
Anisogamy and the Darwin–Bateman paradigm
Authors: Janicke Tim 
Published: August 2024

Abstract
The Darwin–Bateman paradigm advanced as the central concept to explain the evolutionary origin of sex differences. However, debates regarding its theoretical underpinnings persist, particularly with respect to the role of anisogamy in sexual selection. The theoretical work presented by Lehtonen and Parker suggests that the initial split in gamete production rate drives sex differences in sexual selection but that any further variation in the degree of anisogamy is not expected to alter the strength of sexual selection in males and females. Here, I discuss the historical background of a recently emerged controversy and present empirical data that corroborate the theoretical predictions. Lehtonen and Parker’s contribution refines our understanding of the Darwin–Bateman paradigm by providing a broad theory for large-scale patterns of sex differences that can be observed in nature. Further understanding of how demographic and environmental factors influence sexual selection is essential to predict the vast diversity of sex differences across the tree of life, beyond the primordial impact of anisogamy.
Carbon metabolism of a novel isolate from Lacticaseibacillus rhamnosus Probio-M9 derived through space mutant
Authors: Sun Yue , Su Xin , Zhao Lixia , Sun Tiansong , Liu Wenjun 
Published: August 2024

Abstract

Aims
Carbon source is a necessary nutrient for bacterial strain growth. In industrial production, the cost of using different carbon sources varies greatly. Moreover, the complex environment in space may cause metabolic a series of changes in the strain, and this method has been successfully applied in some basic research. To date, space mutagenesis is still limited number of studies, particularly in carbon metabolism of probiotics.

Methods and results
HG-R7970-41 was isolated from bacterium suspension (Probio-M9) after space flight, which can produce capsular polysaccharide after space mutagenesis. Phenotype Microarray (PM) was used to evaluated the metabolism of HG-R7970-41 in 190 single carbon sources. RNA sequencing and total protein identification of two strains revealed their different carbon metabolism mechanisms. PM results demonstrated the metabolism of 10 carbon sources were different between Probio-M9 and HG-R7970-41. Transcriptomic and proteomic analyses revealed that this change in carbon metabolism of HG-R7970-41 mainly related to changes in phosphorylation and the glycolysis pathway. Based on the metabolic mechanism of different carbon sources and related gene cluster analysis, we found that the final metabolic activities of HG-R7970-41 and Probio-M9 were mainly regulated by PTS-specific membrane embedded permease, carbohydrate kinase and two rate-limiting enzymes (phosphofructokinase and pyruvate kinase) in the glycolysis pathway. The expanded culture test also confirmed that HG-R7970-41 had different metabolic characteristics from original strain.

Conclusions
These results suggested that space environment could change carbon metabolism of Probio-M9. The new isolate (HG-R7970-41) showed a different carbon metabolism pattern from the original strain mainly by the regulation of two rate-limiting enzymes.
Evaluation of YouTube as a Health Education Resource for Skin Graft Procedures
Authors: Torres Grant B , Brondeel Kimberley C , Sledge Trey R , Nus Bradley M , Kamma Sai A , Wu Kylie , Branski Ludwik K 
Published: August 2024

Abstract
Recent studies indicate that YouTube has become a primary source of healthcare information for patients. Videos about Skin Graft Procedures (SGP) on YouTube have accumulated millions of views, yet there lacks a publication investigating the educational quality of this content. With current literature revealing misleading healthcare information found on YouTube, this study aims to evaluate the educational quality of videos related to SGP. YouTube was searched for various terms such as “Skin Graft Procedures” and “Skin Graft Surgery.” One hundred and five videos were assessed, with 21 excluded. Four independent reviewers rated the material with the Global Quality Scale (GQS) (5 = highest quality, 1 = lowest quality) to judge educational value. Viewership, source, modality, and date of upload were also collected from each video and compiled for further analysis. The average GQS was 2.60 amongst all videos, with videos led by physicians recording significantly higher scores than those not led by physicians (P &lt; .01). In comparing educational modalities, physician-led presentations provided the highest educational value, whereas live surgeries and consumer-friendly content contained low educational quality (P &lt; .01). Assessing videos split into cohorts based on viewership noted a significantly higher GQS in videos with lower view counts (P &lt; .05). Skin graft videos on YouTube largely provide low-quality information. Videos performed by physicians, particularly physician-led presentations, significantly improved the educational quality of skin graft content. Physicians must involve themselves in enhancing the quality of online content to better guide patients in navigating treatment options and making healthcare decisions.
Reviving the Lieb–Schultz–Mattis theorem in open quantum systems
Authors: Zhou Yi-Neng , Li Xingyu , Zhai Hui , Li Chengshu , Gu Yingfei 
Published: August 2024

ABSTRACT
In closed systems, the celebrated Lieb–Schultz–Mattis (LSM) theorem states that a one-dimensional locally interacting half-integer spin chain with translation and spin rotation symmetries cannot have a non-degenerate gapped ground state. However, the applicability of this theorem is diminished when the system interacts with a bath and loses its energy conservation. In this letter, we propose that the LSM theorem can be revived in the entanglement Hamiltonian when the coupling to the bath renders the system short-range correlated. Specifically, we argue that the entanglement spectrum cannot have a non-degenerate minimum, isolated by a gap from other states. We further support the results with numerical examples where a spin-$1/2$ system is coupled to another spin-$3/2$ chain serving as the bath. Compared with the original LSM theorem that primarily addresses UV–IR correspondence, our findings reveal that the UV data and topological constraints also play a pivotal role in shaping the entanglement in open quantum many-body systems.
Biomimetic ROS-responsive hyaluronic acid nanoparticles loaded with methotrexate for targeted anti-atherosclerosis
Authors: Li Bingyi , He Mei , Xu Zichen , Zhang Qianting , Zhang Liyuan , Zhao Shuang , Cao Yu , Mou Nianlian , Wang Yi , Wang Guixue 
Published: August 2024

Abstract
Atherosclerosis (AS), an inflammatory disease characterized by lipid accumulation, has a high global incidence and mortality rate. Recently, nanotherapeutic approaches that target pathological sites and improve drug bioavailability and biocompatibility hold great promise for AS treatment. In this study, a biomimetic ROS-responsive hyaluronic acid–based nanomaterial was prepared for targeted anti-AS. Specifically, a safe ROS-responsive carrier based on hyaluronic acid (HSP) was prepared to load methotrexate (MTX), a drug known for its ability to enhance lipid excretion, resulting in the formation of MTX-loaded nanoparticles (MTXNPs). Furthermore, the macrophage membrane was coated on the surface of MTXNPs to obtain MM/MTXNPs. Both MTXNPs and MM/MTXNPs exhibited ROS responsiveness and demonstrated excellent biocompatibility. In vitro experiments revealed that MM/MTXNPs could evade macrophage phagocytosis and exhibited high uptake rates by inflamed endothelial cells. MM/MTXNPs also reduced lipid accumulation in foam cells. In vivo experiments showed that MM/MTXNPs exhibited superior accumulation at AS plaque sites, facilitated by the surface membrane layer containing integrin α4β1 and CD47, resulting in an enhanced therapeutic effect in inhibiting plaque development compared to free MTX and MTXNPs. Therefore, HSP represents a promising nanocarrier to load hydrophobic MTX, enabling effective and biocompatible enhancement of AS treatment.
Factors influencing the prognosis of patients with cardiogenic shock treated with extracorporeal membrane oxygenation: A protocol for systematic review and meta-analysis
Authors: Hang Ming-Ming , Shen Mei-Rong , Chen Tie-Long , Wang Yu 
Published: August 2024

Background:
Cardiogenic shock is a clinical syndrome caused by primary heart disease that results in decreased cardiac output and insufficient systemic perfusion. A study was conducted to determine what factors affect survival in patients with cardiogenic shock treated with extracorporeal membrane oxygenation (ECMO).

Methods:
A systematic search was conducted across various databases, including CKNI, VIP, Wan Fang, CBM, Embase, PubMed, Cochrane Library, and Web of Science databases, to gather factors linked to the prognosis of patients with cardiogenic shock who underwent ECMO treatment. The search period for each database was set to conclude on April 30, 2024.

Results:
The findings suggest that, in comparison to the death group, the lactic acid levels of the survival group after treatment were significantly lower (95% confidence interval [CI]: −0.79, −0.58). In addition, the creatinine levels of the survival group after treatment were also significantly lower than those of the death group (95% CI: −0.39, −0.14). Furthermore, the troponin levels in the survival group after treatment were lower than those in the death group (95% CI: −0.32, 0.04), and the total bilirubin levels in the survival group after treatment were also lower than those in the death group (95% CI: −0.62, −0.23).

Conclusions:
According to the study, total bilirubin, creatinine, and lactic acid levels were lower in the survival group than in the death group when ECMO was used to treat cardiogenic patients, suggesting a better prognosis for patients with cardiogenic shock. Therefore, total bilirubin, creatinine, and lactic acid could be influential factors in the prognosis of survival in patients with cardiogenic shock.
The clinical efficacy of combined ESA and Roxadustat treatment for renal anemia in hemodialysis patients with secondary hyperparathyroidism: A case series
Authors: Zhong Jing-jing , Wang Ming-li , Zheng Gao-feng , Li Ming-peng , Chen De-zheng 
Published: August 2024

Rationale:
Pharmacological mechanism of Roxadustat in the treatment of renal anemia.

Patient concerns:
To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism.

Diagnoses:
A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022.

Interventions:
The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed.

Outcomes:
The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = −3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = −2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients.

Lessons subsections:
The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients.
Uterine tumors mimicking ovarian sex cord tumors with rhabdoid differentiation: a clinicopathologic study of 4 cases: A case series analysis
Authors: Li Hongling , Xie Le , Zhang Jinhui , Xu Yuanyuan , Wu Xingyan , Chen Zengwei , Mao Rongjun 
Published: August 2024

Rationale:
Uterine tumors resembling ovarian sex cord tumors (UTROSCT) with rhabdoid features are uncommon mesenchymal neoplasms exhibiting diverse histological patterns, including significant rhabdoid morphology. A thorough comprehension of their clinicopathologic features is crucial for precise diagnosis and effective management.

Patient concerns:
This study presents 4 cases of UTROSCT with rhabdoid features, diagnosed in patients aged 31 to 58. Varied recurrence patterns were observed, including similar recurrent lesions to the primary tumors with subsequent mortality, initial invasion and lymph node metastasis, and presence of only primary tumor.

Diagnoses:
Histopathological examination revealed diverse morphological patterns, prominently featuring rhabdoid differentiation. Immunohistochemical analysis showed expression of hormone receptors, sex cord, smooth muscle, and epithelial markers, notably WT1, CD56, and CD99. Molecular analysis identified ESR1-NCOA2 fusions and ESR1 and NCOA2/3 rearrangements, indicating a potential association between these genetic alterations and extensive rhabdoid differentiation.

Interventions:
Various treatments were administered post-recurrence, including chemotherapy and targeted therapies. However, poor clinical outcomes were observed in all cases.

Outcomes:
Despite aggressive treatments, including chemotherapy and targeted therapies, poor clinical outcomes were observed, highlighting the aggressive nature of UTROSCT with significant rhabdoid differentiation.

Lessons:
This case series emphasizes the importance of detailed pathological reporting, comprehensive molecular testing, and thorough tumor staging in UTROSCT cases with rhabdoid features. Enhanced understanding of the clinicopathologic characteristics of UTROSCT with rhabdoid differentiation is crucial for accurate diagnosis, prognostication, and management strategies.
Pilon fracture with central articular surface collapse treated by posterior tibial fenestration indirect reduction and compression technique: Two cases report
Authors: Sang Chaohui , Zeng Langqing , Zhong Huafeng , Wang Qiang , Zeng Lulu 
Published: August 2024

Rationale:
Central collapsed fracture blocks traditionally require either an anteromedial or anterolateral approach for reduction. However, existing techniques face challenges such as soft tissue damage and compromised tibial strength, especially in pilon fractures with central articular surface collapse and an intact anterior cortex, as classified under 43B2.3 in the 2018 Orthopaedic Trauma Association/Association for the Study of Internal Fixation Fracture and Dislocation Classification Compendium.

Patient concerns:
We address the management of pilon fractures with central articular surface collapse, focusing on 2 cases where conventional reduction techniques posed a risk to soft tissues and tibial integrity.

Diagnoses:
The patients presented with pilon fractures characterized by a central articular surface collapse and an intact anterior cortex, aligning with the 43B2.3 classification.

Interventions:
A novel approach was employed, utilizing posterior tibial fenestration and indirect reduction with compression techniques. This method leveraged the talus as a template for precise articular surface realignment.

Outcomes:
Both cases demonstrated excellent reduction of the distal tibial articular surface and achieved favorable functional recovery of the ankle, evidenced by high American Orthopedic Foot and Ankle Society Ankle Hindfoot Scale scores during the 3-year follow-up.

Lessons:
The posterior tibial fenestration technique offers significant advantages for distal tibial pilon fracture reduction. It allows for precise articular realignment, facilitates bone grafting, and minimizes soft tissue and cortical bone disruption. This method is particularly effective for pilon fractures with an intact anterolateral cortex and central articular collapse, providing a valuable surgical alternative.