bluuebunny/crossref_metadata_2025 huggingface dataset:
The New Mythology of the Body and the Transformation of the Therapeutic Space
Authors: Astărăstoae Vasile , Rogozea Liliana M. , Aron Ioan , Botezat Doru
Published: September 2023

Background:

The history of medicine has flowed in the wake of knowledge and social perceptions about the body and corporeality. There is no idea of health without reference to the notion of body (although “health” can have other meanings, figuratively). Considering the same history, the body was the subject of numerous segregations and categorizations due to which it was and is a “social object” and a “political object.” In turn, the spatial and cultural framework was the environment and determinant of the medicine development which is not only a science but also an inter-human interactive practice.

Areas of Uncertainty:

In this article, we will analyze the current social (re)construction of the notions of body and space by referring to the technological and structural changes that are manifested in medicine and society and their ethical implications.

Data Sources:

A review of the specialized literature was performed in June-July 2023, using keywords like human enhancement, therapeutic enhancement, transhumanist medicine, ethics from PubMed, Scopus, Web of Science, and Google Scholar, and official documents issued at the international level (World Health Organization, European Commission).

Ethics and Therapeutic Advances:

This literature review suggests that few practical solutions to human enhancement, both curative and preventive, whether cognitive or physical, have been approached entirely from an ethical point of view. The historical evolution of the concept of human enhancement has led to debates between “transhumanists” and “bioconservatives” depending on how they relate to the improvement of the human condition without or with reticence interventions to improve human capabilities being related to various interventions, from pharmacological, surgical ones to those in the field of genetics, nanomedicine, or cybernetics. In addition to the technical aspects, which are often the major concern of researchers and those applying new technologies, there are also ethical and legislative aspects, to better understand the impact that the dynamics and diffusion of these processes have on the evolution of the human species.

Conclusions:

In interference with these technologies, the body is exposed to possibilities of change and evolution with colossal (expected) social impact that can change norms and values that have been stable for centuries. Social space and place are also proving to be “processes in the making'” for which we need to detect what developments are possible or have already imposed themselves as a trend in the social and medical world.
Current management of cervicofacial nontuberculous mycobacterial infections in the pediatric population
Authors: Shah Keshav V. , Peraza Lazaro R. , Wiedermann Joshua P.
Published: September 2023

Purpose of review

The purpose of this review is to analyze and consolidate recently published literature to provide updated guidelines on the diagnosis and management of nontuberculous mycobacterial lymphadenitis (NTM LAD) in the pediatric population and to suggest areas of further research.

Recent findings

Diagnosis of NTM LAD relies on a detailed clinical history, physical examination, laboratory tests, and imaging techniques. Treatment strategies vary widely, with a shift towards complete surgical excision being observed due to its higher cure rate, improved aesthetic outcomes, and lower recurrence rates. However, patient-specific factors must be considered. The role of genetic factors, such as Mendelian susceptibility to mycobacterial disease (MSMD), is being increasingly recognized and could lead to targeted therapies.

Despite strides in the understanding and management of NTM LAD, substantial gaps remain in key areas such as the role of diagnostic imaging, optimal treatment parameters, postoperative care, and surveillance strategies. In this article, we explain our approach to NTM using the most relevant evidence-based medicine while offering directions for future work.
The development of a pediatric skull base team: how, where and why?
Authors: Lee Joseph , Leonard Jeffrey , Walz Patrick
Published: September 2023

Purpose of review

The purpose of this review is to describe the development of pediatric skull base surgical techniques and illustrate the advantages of pediatric endonasal skull base surgery (ESBS) when applied in appropriate settings. Additionally, this manuscript endeavors to define the pediatric skull base team components, highlight circumstances amenable to the development of a pediatric skull base surgery team, and describe the relative advantages of independent pediatric teams versus incorporation with adult skull base practices.

Recent findings

Multiple series published within the last decade have described the application of ESBS to the pediatric population, demonstrating adoption of these interventions in many academic centers. Most series include relatively small numbers of patients, highlighting the relative infrequency of anterior skull base pathology in the pediatric patient. Given the relatively low volume and high technical demands of this skillset, general guidelines for the timing, suggested training, and volume necessary to support a pediatric skull base team are offered.

The interest in pediatric ESBS continues to expand though case volumes may limit maintenance of skills in lower volume centers. The development of a dedicated pediatric skull base team in areas where sufficient volume exists facilitates concentration of expertise and interdisciplinary relationships necessary to provide the highest level of care. Collaborating with adult skull base teams can enhance the pediatric team experience, increasing exposure to complex surgical planning and radiologic nuances. However, a pediatric-focused skull base team can tailor treatment to meet the specific psychosocial and developmental needs of children.
Large-data contextualizations of social determinant associations in pediatric head and neck cancers
Authors: Fei-Zhang David J. , Chelius Daniel C. , Sheyn Anthony M. , Rastatter Jeff C.
Published: September 2023

Purpose of review

Prior investigations in social determinants of health (SDoH) and their impact on pediatric head and neck cancers are limited by the narrow scope of cancer types and SDoH being studied while lacking inquiry on the interrelational contribution of varied SDoH in real-world contexts. The purpose of this review is to discuss the current research tackling these shortcomings of SDoH-based studies in head and neck cancer and to discuss means of applying these findings in prospective initiatives and implementations.

Recent findings

Through leveraging contemporary, large-data analyses measuring diverse social vulnerabilities, several studies have identified comprehensive delineations of which social disparities contribute the largest quantifiable impact on the care of head and neck cancer patients. Progressing from prior SDoH-based research of the decade, these studies contextualize the effect of social vulnerabilities and have laid the foundations to begin addressing these issues in the complex, modern-day environment of interrelated

social factors.

Social determinants of health markedly affect pediatric head and neck cancer care and prognosis in complex and surprising ways. Modern-day tools and analyses derived from large-data techniques have unveiled the quantifiable underpinnings of how SDoH impact these pathologies.
Effect of Virtual Simulation on Nurse Residents’ Prioritization and Delegation Skills
Authors: Klenke-Borgmann Laura , Setter Robyn , Stubenrauch Cate , Black Caroline
Published: September 2023

Data indicate a widening academic–practice gap. Utilizing a single-group pre–post interventional design, the purpose of this project was to determine if repeated participation in Sentinel U Patient Management and Delegation virtual simulations influenced new graduate nurses’ prioritization and delegation. Increased confidence in ability to complete patient care assignments on time and transferability of learning outcomes to practice were identified. There may be value in nurses receiving virtual simulations within their residency program to close the academic–practice gap.
Supporting Rural Community Emergency Planning, Response, and Recovery
Authors: Kappel Rachel , Chavez Alva , Melnick Meghan , Siegfried Alexa L.
Published: September 2023

When rural communities are faced with an emergency or disaster, their capacity to support the response is often exceeded. The NORC Walsh Center for Rural Health Analysis and the Rural Health Information Hub (RHIhub) developed the Rural Emergency Preparedness and Response Toolkit (the Toolkit) to support rural communities with disaster planning, response, and recovery. The Toolkit provides information drawn from literature, subject matter experts, and case studies and shares key considerations for emergency preparedness. This article highlights the development of and key insights from the Toolkit, including preparedness frameworks, population considerations, plan and assessment examples, and funding support. Investing in emergency preparedness is vital for rural communities and this Toolkit offers strategies and best practices for each phase of a disaster.
A Clinical Data Warehouse Analysis of Risk Factors for Inpatient Falls in a Tertiary Hospital: A Case-Control Study
Authors: Kwon Eunok , Chang Sun Ju , Kwon Mikyung
Published: September 2023

Objectives

The aims of the study are to identify fall risk factors and to establish automatic risk assessments based on clinical data from electronic medical records of hospitalized patients.

Methods

In this retrospective case-control study, we reviewed the electronic medical records of 1454 patients (292 and 1162 patients in the fall and nonfall groups, respectively) who were hospitalized at a 1800-bed tertiary hospital in South Korea between January 1, 2017, and December 31, 2017. Patients’ age, sex, and clinical department were matched, and all laboratory reports, clinical flow sheets, and nursing initial assessment records of case from the Clinical Data Warehouse system were analyzed. The collated patient records data were analyzed using SAS (version 9.4) and logistic regression.

Results

Overall, 65 risk factors, including low body mass index, low blood pressure, low albumin levels, high fasting blood sugar level, low red blood cell counts, and high potassium levels, that significantly increased the incidence of falls were identified. Falls were also associated with 21 items from the clinical flow sheet and nursing initial assessment, including frequent bowel movements, 24-hour urine tests, imaging tests, biopsy, pain, intravenous tubes, unclear consciousness, and taking medication.

Conclusions

Fall risk factors identified via the Clinical Data Warehouse can be used to build an automated detection system to detect fall risk in electronic medical records, enabling nurses to assess the fall risk in addition to using the fall scale.
Prevalence of Psychiatric Disorders in Aesthetic Surgery
Authors: Marron Mendes Vanessa , Diluiso Giuseppe , Jidjouc Kamdem Catherine , Goulliart Stephen , Schettino Michela , Dziubek Melvin , Di Fiore Christella , Ortiz Carrillo Socorro , Delhaye Marie
Published: September 2023

Purpose

Our study aimed to characterize and objectify the prevalence of psychiatric disorders and the use of psychotropic drugs in patients interested in undergoing aesthetic surgery. The psychiatric profile of this population is particularly interesting and is related to self-perception and the general concept of beauty.

Methods

We conducted an observational, retrospective, and bicenter study of 2092 patients seen in plastic surgery departments. Data on general characteristics, pathology, psychiatric history (PH), use of psychotropic drugs, addictions, surgical requests, and surgical complications were recorded and analyzed.

Results

Based on our inclusion criteria, we selected 524 patients. The prevalence of psychiatric disorders was 32.25%. The prevalence of depressive disorders (19.27%), anxiety disorders (8.21%), and sleep-wake cycle disorders (7.06%) should be noted. Comparing the population with psychiatric history (PH+) and without psychiatric history (PH−), significant differences were found in patient ethnicity, addictions (tobacco, 37.50% vs 15.00%; drugs, 3.26% vs 0.59%), and comorbidities. In the 66.86% (n = 113) of PH+ patients, the plastic surgeon did not record the presence of psychiatric disorders in the medical record.

Discussion

This study offers a broad view of the prevalence and characteristics of psychiatric disorders and the use of psychotropic drugs among patients who want to undergo aesthetic surgery. The prevalence of psychiatric problems in the study population is higher than in the general population (32.25% vs 15.02%).

Conclusions

Our results suggest that plastic surgeons should be properly trained to manage these patients. A multidisciplinary approach involving plastic surgeons, psychiatrists, and psychologists is advocated.
Reclassification of Streptomyces griseostramineus as a synonym of Streptomyces griseomycini based on a polyphasic taxonomic approach
Authors: Wang Yinfeng , Long PeiLan , Fu Li , Xiao Yan , Wang Nengqiang , Gao Jian
Published: September 2023

In the present work, the taxonomic relationship between

Streptomyces griseomycini

and

Streptomyces griseostramineus

was reevaluated by a comprehensive comparison of phenotypic, chemotaxonomic and genomic characteristics, as well as phylogeny. Phylogenetic analysis based on 16S rRNA gene sequences and whole-genome sequences indicated that

Streptomyces griseostramineus

JCM 4385T was clustered together with

Streptomyces griseomycini

JCM 4382T, suggesting they were closely related to each other. However, the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between their genomes were 99.7 and 97.5 %, respectively, much larger than the recommended threshold values of 96.7 % ANI and 70 % dDDH for

Streptomyces

species delineation. In addition, the morphological, cultural, physio-biochemical and chemotaxonomic features of these two species further demonstrated that they belonged to the same genome species. Based on the above data and the principle of priority in nomenclature, it is proposed that

S. griseostramineus

(Preobrazhenskaya et al. 1957) Pridham et al. 1958 (Approved Lists 1980) is a later heterotypic synonym of

S. griseomycini

(Preobrazhenskaya et al. 1957) Pridham et al. 1958 (Approved Lists 1980).
De novo drug designing coupled with brute force screening and structure guided lead optimization gives highly specific inhibitor of METTL3: a potential cure for Acute Myeloid Leukaemia
Authors: Ganguly Manisha , Gupta Radhika , Roychowdhury Amlan , Hazra Ditipriya
Published: September 2023

Expression of METTL3, a SAM dependent methyltransferase, which deposits m6A on mRNA is linked to poor prognosis in Acute Myeloid Leukaemia and other type of cancers. Down regulation of this epitranscriptomic regulator has been found to inhibit cancer progression. Silencing the methyltransferase activity of METTL3 is a lucrative strategy to design anticancer drugs. In this study 3600 commercially available molecules were screened against METTL3 using brute force screening approach. However, none of these compounds take advantage of the unique Y-shaped binding cavity of the protein, raising the need for de novo drug designing strategies. As such, 125 branched, Y-shaped molecules were designed by “stitching” together the chemical fragments of the best inhibitors that interact strongly with the METTL3 binding pocket. This results in molecules that have the three-dimensional structure and functional groups which enable it to fit in the METTL3 cavity like fingers in a glove, having unprecedented selectivity and binding affinities. The designed compounds were further refined based on Lipinski’s rule, docking score and synthetic accessibility. The molecules faring well in these criteria were simulated for 100ns to check the stability of the protein inhibitor complex followed by binding free energy calculation.
Benchmarking Cross-Docking Strategies for Structure-Informed Machine Learning in Kinase Drug Discovery
Authors: Schaller David , Christ Clara D. , Chodera John D. , Volkamer Andrea
Published: September 2023

In recent years machine learning has transformed many aspects of the drug discovery process including small molecule design for which the prediction of the bioactivity is an integral part. Leveraging structural information about the interactions between a small molecule and its protein target has great potential for downstream machine learning scoring approaches, but is fundamentally limited by the accuracy with which protein:ligand complex structures can be predicted in a reliable and automated fashion.

With the goal of finding practical approaches to generating useful kinase:inhibitor complex geometries for downstream machine learning scoring approaches, we present a kinase-centric docking benchmark assessing the performance of different classes of docking and pose selection strategies to assess how well experimentally observed binding modes are recapitulated in a realistic crossdocking scenario. The assembled benchmark data set focuses on the well-studied protein kinase family and comprises a subset of 589 protein structures co-crystallized with 423 ATP-competitive ligands. We find that the docking methods biased by the co-crystallized ligand—utilizing shape overlap with or without maximum common substructure matching—are more successful in recovering binding poses than standard physics-based docking alone. Also, docking into multiple structures significantly increases the chance to generate a low RMSD docking pose. Docking utilizing an approach that combines all three methods (Posit) into structures with the most similar co-crystallized ligands according to shape and electrostatics proofed to be the most efficient way to reproduce binding poses achieving a success rate of 66.9 % across all included systems.

The studied docking and pose selection strategies—which utilize the OpenEye Toolkit—were implemented into pipelines of theKinoML frameworkallowing automated and reliable protein:ligand complex generation for future downstream machine learning tasks. Although focused on protein kinases, we believe the general findings can also be transferred to other protein families.
Enabling Model-based Design for closed-loop applications in neuroengineering
Authors: Florio M. Di , Bornat Y. , Caré M. , Cota V. R. , Buccelli S. , Chiappalone M.
Published: September 2023

This study addresses the inherent difficulties in the creation of neuroengineering devices for closed-loop stimulation, a task typically characterized by intricate and technically demanding processes. Beneath the substantial hardware advancements in neurotechnology, there is often rather complex low-level code that poses challenges in terms of development, documentation, and long-term maintenance. To overcome these obstacles, we adopted an alternative strategy centered on Model-based Design (MBD) as a means to simplify the creation of closed-loop systems and reduce the entry barriers. MBD offers distinct advantages by streamlining the development workflow and facilitating the implementation of intricate systems. In this study, we applied MBD techniques to implement a spike detection algorithm on a Field-Programmable Gate Array (FPGA) using commercially available hardware that combines neural probe electronics with programmable FPGA-based hardware. The entire process of data handling and data processing was designed within the Simulink® environment, with subsequent generation of HDL code tailored to the FPGA hardware. The validation of our approach was conducted through in vivo experiments involving six animals. We have made all project code files open-source, thereby providing free access to fellow scientists interested in the development of closed-loop systems.
Comparison of the three-dimensional chromatin structures of adolescent and adult peripheral blood B cells: implications for the study of pediatric autoimmune diseases
Authors: Jiang Kaiyu , Fu Yao , Kelly Jennifer A. , Gaffney Patrick M. , Holmes Lucy C. , Jarvis James N.
Published: September 2023

Background/Purpose

Knowledge of the 3D genome is essential to elucidate genetic mechanisms driving autoimmune diseases. The 3D genome is distinct for each cell type, and it is uncertain whether cell lines faithfully recapitulate the 3D architecture of primary human cells or whether developmental aspects of the pediatric immune system require use of pediatric samples. We undertook a systematic analysis of B cells and B cell lines to compare 3D genomic features encompassing risk loci for juvenile idiopathic arthritis (JIA), systemic lupus (SLE), and type 1 diabetes (T1D).

Methods

We isolated B cells from healthy individuals, ages 9-17. HiChIP was performed using CTCF antibody, and CTCF peaks were identified. CTCF loops within the pediatric were compared to three datasets: 1) self-called CTCF consensus peaks called within the pediatric samples, 2) ENCODE’s publicly available GM12878 CTCF ChIP-seq peaks, and 3) ENCODE’s primary B cell CTCF ChIP-seq peaks from two adult females. Differential looping was assessed within the pediatric samples and each of the three peak datasets.

Results

The number of consensus peaks called in the pediatric samples was similar to that identified in ENCODE’s GM12878 and primary B cell datasets. We observed <1% of loops that demonstrated significantly differential looping between peaks called within the pediatric samples themselves and when called using ENCODE GM12878 peaks. Significant looping differences were even less when comparing loops of the pediatric called peaks to those of the ENCODE primary B cell peaks. When querying loops found in juvenile idiopathic arthritis, type 1 diabetes, or systemic lupus erythematosus risk haplotypes, we observed significant differences in only 2.2%, 1.0%, and 1.3% loops, respectively, when comparing peaks called within the pediatric samples and ENCODE GM12878 dataset. The differences were even less apparent when comparing loops called with the pediatric vs ENCODE adult primary B cell peak datasets.The 3D chromatin architecture in B cells is similar across pediatric, adult, and EBVtransformed cell lines. This conservation of 3D structure includes regions encompassing autoimmune risk haplotypes.

Conclusion

Thus, even for pediatric autoimmune diseases, publicly available adult B cell and cell line datasets may be sufficient for assessing effects exerted in the 3D genomic space.
SnapATAC2: a fast, scalable and versatile tool for analysis of single-cell omics data
Authors: Zhang Kai , Zemke Nathan R , Armand Ethan J , Ren Bing
Published: September 2023

Single-cell omics technologies have ushered in a new era for the study of dynamic gene regulation in complex tissues during development and disease pathogenesis. A major computational challenge in analyzing these datasets is to project the large-scale and high dimensional data into low-dimensional space while retaining the relative relationships between cells in order to decompose the cellular heterogeneity and reconstruct cell-type-specific gene regulatory programs. Conventional dimensionality reduction methods suffer from computational inefficiency, difficulty to capture the full spectrum of cellular heterogeneity, or inability to apply across diverse molecular modalities. Here, we report a fast and nonlinear dimensionality reduction algorithm that not only more accurately captures the heterogeneities of single-cell omics data, but also features runtime and memory usage that is computational efficient and linearly proportional to cell numbers. We implement this algorithm in a Python package named SnapATAC2, and demonstrate its superior performance, remarkable scalability and general adaptability using an array of single-cell omics data types, including single-cell ATAC-seq, single-cell RNA-seq, single-cell Hi-C, and single-cell multiomics datasets.
Shrinking in the dark: Parallel endosymbiont genome erosions are associated with repeated host transitions to an underground life
Authors: Beasley-Hall Perry G. , Kinjo Yukihiro , Rose Harley A. , Walker James , Foster Charles S. P. , Kovacs Toby G. L. , Bourguignon Thomas , Ho Simon Y. W. , Lo Nathan
Published: September 2023

Microbial symbioses have had profound impacts on the evolution of animals. Conversely, changes in host biology may impact the evolutionary trajectory of symbionts themselves.Blattabacterium cuenotiis present in almost all cockroach species and enables hosts to subsist on a nutrient-poor diet. To investigate if host biology has impactedBlattabacteriumat the genomic level, we sequenced and analysed 25 genomes from Australian soil-burrowing cockroaches (Blaberidae: Panesthiinae) which have undergone at least seven independent subterranean transitions from above-ground, wood-feeding ancestors. We find at least three independent instances of genome erosion have occurred inBlattabacteriumstrains exclusive to Australian soil-burrowing cockroaches. Such shrinkages have involved the repeated inactivation of genes involved in amino acid biosynthesis and nitrogen recycling, the core role of Blattabacterium in the host-symbiont relationship. The most drastic of these erosions have occurred in hosts thought to have transitioned underground the earliest relative to other lineages. AsBlattabacteriumis unable to fulfil its core function in such host groups, our findings suggest soil-burrowing cockroaches must acquire these nutrients from novel sources. Our study represents one of the first cases, to our knowledge, of parallel host adaptations leading to concomitant parallelism in their mutualistic symbionts, further underscoring the intimate relationship between these two partners.
PlexinD1 deficiency in CD11c+ dendritic cells exacerbates airway hyperresponsiveness and enhances IgE and mucus production in allergic asthma
Authors: Shan Lianyu , Matloubi Mojdeh , Okwor Ifeoma , Kung Sam , Almiski Mohamed Sadek , Basu Sujata , Halayko Andrew , Koussih Latifa , Gounni Abdelilah S.
Published: September 2023

Dendritic cells (DC) play a crucial role in regulating allergic asthma. We have demonstrated that the absence of semaphorin3E (Sema3E) exacerbates asthma features in acute and chronic asthma models. However, the role of plexinD1 in these events, especially in DC is unknown. Therefore, we investigated the role of plexinD1 in CD11c+ DC in the HDM model of asthma. CD11c+ DC-specific plexinD1 knockout mice and wild-type mice were subjected to HDM acute allergen protocol. Airway hyperresponsiveness (AHR) parameters were measured using the FlexiVent ventilator. Lung tissue and bronchoalveolar lavage fluid (BALF) were processed by flow cytometry. Cytokines and antibodies were measured using mesoscale and ELISA. Collagen deposition and mucus production were visualized by histological staining, and associated genes were investigated using Real-time PCR. We showed that DC-specific plexinD1 knockout mice exhibited exacerbated airway hyperresponsiveness, including increased airway resistance and tissue elastance. These mice displayed enhanced levels of mucus production and collagen gene expression compared to wild-type mice. These events were accompanied by enhanced recruitment of conventional DCs, specifically CD11b+ cDC2, into the lungs and higher levels of total and HDM-specific serum IgE inCD11cPLXND1KOcompared to wild-type counterparts. Mechanistically, a significantly higher level of IgE in the co-culture of B-DCs isolated fromCD11cPLXND1KOmice compared to DCs isolated from wild-type mice. Overall, our data reveals that the Sema3E-plexinD1 signalling pathway in CD11c+ DC is critical in modulating asthma features.

Graphical Abstract
Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology
Authors: Philip Drake T. , Goins Nigel M. , Catanzaro Nicholas J. , Misumi Ichiro , Whitmire Jason K. , Atkins Hannah M. , Lazear Helen M.
Published: September 2023

Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (Ifnlr1-/-), both the IFN-λ and the IFN-αβ receptor (Ifnar1-/-Ifnlr1-/-), or IFN-λ cytokines (Ifnl2/3-/-) and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions, independent of a direct effect on viral load. Using conditional knockout mice, we found that IFN-λ signaling in both keratinocytes and neutrophils was necessary to control HSV-1 skin lesion severity, and that IFN-λ signaling in keratinocytes suppressed CXCL9-mediated neutrophil recruitment to the skin. Furthermore, depleting neutrophils or blocking CXCL9 protected against severe HSV-1 skin lesions inIfnlr1-/-mice. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection, and suggest potential applications for IFN-λ in treating viral skin infections.

Graphical Abstract
Cell2Sentence: Teaching Large Language Models the Language of Biology
Authors: Levine Daniel , Rizvi Syed Asad , Lévy Sacha , Pallikkavaliyaveetil Nazreen , Zhang David , Chen Xingyu , Ghadermarzi Sina , Wu Ruiming , Zheng Zihe , Vrkic Ivan , Zhong Anna , Raskin Daphne , Han Insu , de Oliveira Fonseca Antonio Henrique , Caro Josue Ortega , Karbasi Amin , Dhodapkar Rahul M. , van Dijk David
Published: September 2023

We introduce Cell2Sentence (C2S), a novel method to directly adapt large language models to a biological context, specifically single-cell transcriptomics. By transforming gene expression data into “cell sentences,” C2S bridges the gap between natural language processing and biology. We demonstrate cell sentences enable the fine-tuning of language models for diverse tasks in biology, including cell generation, complex cell-type annotation, and direct data-driven text generation. Our experiments reveal that GPT-2, when fine-tuned with C2S, can generate biologically valid cells based on cell type inputs, and accurately predict cell types from cell sentences. This illustrates that language models, through C2S fine-tuning, can acquire a significant understanding of single-cell biology while maintaining robust text generation capabilities. C2S offers a flexible, accessible framework to integrate natural language processing with transcriptomics, utilizing existing models and libraries for a wide range of biological applications.
An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies
Authors: Wang Yiquan , Lv Huibin , Lei Ruipeng , Yeung Yuen-Hei , Shen Ivana R. , Choi Danbi , Teo Qi Wen , Tan Timothy J.C. , Gopal Akshita B. , Chen Xin , Graham Claire S. , Wu Nicholas C.
Published: September 2023

Despite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and inaccessibility of datasets for model training. In this study, we curated a dataset of >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features between antibodies to HA head and stem domains. We then leveraged this dataset to develop a lightweight memory B cell language model (mBLM) for sequence-based antibody specificity prediction. Model explainability analysis showed that mBLM captured key sequence motifs of HA stem antibodies. Additionally, by applying mBLM to HA antibodies with unknown epitopes, we discovered and experimentally validated many HA stem antibodies. Overall, this study not only advances our molecular understanding of antibody response to influenza virus, but also provides an invaluable resource for applying deep learning to antibody research.
Sperm length evolution in relation to body mass is shaped by multiple trade-offs in tetrapods
Authors: Koçillari L. , Cattelan S. , Rasotto M.B. , Seno F. , Maritan A. , Pilastro A.
Published: September 2023

Sperm size is highly variable across species and is influenced by various factors including fertilization mode, female reproductive traits and sperm competition. Despite considerable efforts, many questions about sperm size variation remain open. Variation in body size may affect sperm size evolution through its influence on these factors, but the extent to which sperm size variation is linked to body mass remains elusive. In this study, we use the general theory of Pareto Optimality to investigate the relationship between sperm size and body mass across tetrapods. We find that tetrapods fall within a triangular-shaped Pareto front in the trait space of body mass and sperm length suggesting that the evolution of sperm size in relation to body size is shaped by trade-offs. We then explore the three main factors predicted to influence sperm size evolution, namely sperm competition, clutch size and genome size. Our results demonstrate that body mass optimally shapes sperm size evolution in tetrapods mainly through its association with sperm competition and clutch size. Finally, we show that the triangular-shaped Pareto front is maintained when tested separately within mammals, birds, endothermic species and internal fertilizers, suggesting that similar evolutionary trade-offs characterize the evolution of sperm size in relation to body size within taxonomic/phylogenetic and functional subgroups of tetrapods. This study provides insights into the evolutionary mechanisms driving interspecific sperm size variation and highlights the importance of considering multiple trade-offs in optimizing reproductive traits.
ORM-mediated regulation of sphingolipid biosynthesis is essential for nodule formation inAeschynomene evenia
Authors: Nouwen Nico , Pervent Marjorie , El M’Chirgui Franck , Tellier Frédérique , Rios Maëlle , Araújo Natasha Horta , Klopp Christophe , Gressent Frédéric , Arrighi Jean-François
Published: September 2023

Legumes are able to establish symbiotic interactions with nitrogen-fixing rhizobia that are accomodated in root-derived organs, the nodules. Rhizobia recognition triggers a plant symbiotic signalling pathway activating two coordinated processes: infection and nodule organogenesis. How these are orchestrated in legumes species utilizing intercellular infection and lateral root-base nodulation remain elusive. Here, we show thatAeschynomene eveniaOROSOMUCOID PROTEIN 1 (AeORM1), a key regulator of sphingolipid biosynthesis, is required for nodule formation in this legume species. UsingA. evenia orm1mutants, we demonstrate that alterations in AeORM1 function result in numerous early aborted nodules, exhibiting defense-like reactions, and shortened lateral roots. Consistantly,AeORM1was expressed during lateral root initiation and elongation, including at lateral root bases where nodule primordia form in the presence of symbiotic bradyrhizobia. Sphingolipidomics revealed that mutations inAeORM1leaded to sphingolipid overaccumulation in roots, in particular the very-long-chain-fatty-acid (VLCFA)-containing ceramids relative to the wild-type plants. Taken together, our findings reveal that AeORM1-regulated sphingolipid homeostasis is essential for rhizobial infection and nodule organogenesis, and indicate a shared requirement for nodule formation and lateral root development inA. evenia.
Prioritizing ecological connectivity among protected areas in Colombia using a functional approach for birds
Authors: Linero Triana Daniela , Correa-Ayram Camilo Andrés , Velásquez-Tibatá Jorge
Published: September 2023

Ecological connectivity among protected areas (PAs) is essential to improve biodiversity conservation and management effectiveness in the long term under global change. Developing strategic plans and identifying spatial priorities are practical actions for establishing and strengthening interconnected networks of PAs. In Colombia, this planning is fundamental to conserve its extraordinary bird diversity in the face of multiple threats, including climate change and deforestation. We develop a connectivity model focused on multiple bird species to identify critical sites to preserve the ecological connections among PAs in Colombia. Based on land cover data and expert knowledge, we created movement resistance surfaces and modeled Least-Cost Corridors among terrestrial PAs for 26 forest-dependent species. We also used circuit and least-cost models to locate conservation priorities and restoration opportunities, estimating the potential gain in connectivity with the Equivalent Connected Area (ECA) index. We found 581,531 km2belonging to corridors among PAs for all focal species. Priority sites for movement within corridors covered 212,551 km2and were predominantly located across Andean and Amazonian forests. Restoration opportunities covered 79,203 km2and were concentrated in agricultural lands of the Andes and Caribbean regions. Restoring these areas could increase the national forest cover by 7% and connectivity by 14%. Our results provide a national-level assessment of functional connectivity priorities to maintain and improve the interconnections among PAs. This assessment could guide efforts related to conservation, restoration, and implementation of management tools that facilitate the movement of native species across transformed lands. These actions are crucial to meet the targets outlined in the post-2020 global biodiversity framework to achieve well-connected systems of PAs during this decade and until 2050.
A scaling law for epithelial tissue rheology
Authors: Cheikh M. I. , Rodriguez N. , Doubrovinski K.
Published: September 2023

Epithelial morphogenesis is a process through which simple cellular sheets are shaped into complex tissues and organs in a developing animal. From a physics perspective, understanding any shape change requires knowing the active forces driving its dynamics, as well as the material properties, i.e. the rheology, of the material that is undergoing the deformation. Despite a long-standing effort, rheological properties of embryonic tissues have remained elusive. Here, we develop a minimal theory providing a comprehensive explanation of rheological measurements characterizing the mechanics of epithelia in the early fly embryo. Our theory explains a key experimental observation: when subjected to concentrated pulling force, the embryonic epithelium of the fruit flyDrosophila melanogasterdeforms following a power law with an exponent of 1/2. All dimensional parameters of our theory are constrained by direct measurements and have allowed us to estimate the spring constant of an individual cellular edge. We show that stress relaxation (attributable to actin turnover), stretching elasticity of individual cellular edges, and the floppy topology of the cellular network are the sole physical properties governing tissue rheology on the developmentally relevant time scale of 1-10 minutes.
Development and implementation of an integrated preclinical atherosclerosis database
Authors: Xiang Rachel , Wang Yihua , Shuey Megan M. , Carvajal Brigett , Wells Quinn S. , Beckman Joshua A. , Jaffe Iris Z.
Published: September 2023

Background

Basic scientists have used preclinical animal models to explore mechanisms driving human diseases for decades, resulting in thousands of publications, each supporting causative inferences. Despite substantial advances in the mechanistic construct of disease, there has been limited translation from individual studies to advances in clinical care. An integrated approach to these individual studies has the potential to improve translational success.

Methods

Using atherosclerosis as a test case, we extracted data from the two most common mouse models of atherosclerosis (ApoE and LDLR knockout). We restricted analyses to manuscripts published in two well-established journals,Arteriosclerosis, Thrombosis, and Vascular BiologyandCirculation, as of query in 2021. Predefined variables including experimental conditions, intervention and outcomes were extracted from each publication to produce a preclinical atherosclerosis database.

Results

Extracted data include animal sex, diet, intervention type and distinct plaque pathologies (size, inflammation, lipid content). Procedures are provided to standardize data extraction, attribute interventions to specific genes and transform the database for use with available transcriptomics software. The database integrates hundreds of genes, each directly tested in vivo for causation in a murine atherosclerosis model. The database is provided to allow the research community to perform integrated analyses that reflect the global impact of decades of atherosclerosis investigation.

Conclusions

Future database uses include interrogation of sub-datasets associated with distinct plaque pathologies, cell-type or sex. We provide the methods and software needed to apply this approach to the extensive repository of peer-reviewed data utilizing preclinical models to interrogate mechanisms of diverse human diseases.
Triacylglycerol stability limits futile cycles and inhibition of carbon capture in oil-accumulating leaves
Authors: Johnson Brandon S. , Allen Doug K. , Bates Philip D.
Published: September 2023

Engineering plant vegetative tissue to accumulate triacylglycerols (TAG, e.g., oil) can increase the amount of oil harvested per acre to levels that exceed current oilseed crops. EngineeredNicotiana tabacum(tobacco) lines that accumulate 15% to 30% oil of leaf dry weight resulted in starkly different metabolic phenotypes. In-depth analysis of the leaf lipid accumulation and14CO2metabolic tracing mechanistically described metabolic adaptations to the leaf oil engineering. An oil-for-membrane lipid tradeoff in the 15% oil line (referred to as HO) was surprisingly not further exacerbated when lipid production was enhanced to 30% (LEC2 line). The HO line exhibited a futile cycle that limited TAG yield through exchange with starch, altered carbon flux into various metabolite pools and end products, and suggested overlapping pathways of the glyoxylate cycle and photorespiration that limited CO2assimilation by 50%. In contrast, inclusion of the LEC2 transcription factor in tobacco improved TAG stability, alleviated the TAG-to-starch futile cycle, and recovered CO2assimilation and plant growth comparable to wild type but with much higher lipid levels in the leaves. Thus, the unstable production of storage reserves and futile cycling limit vegetative oil engineering approaches. The capacity to overcome futile cycles and maintain enhanced stable TAG levels in LEC2 demonstrated the importance of considering unanticipated metabolic adaptations while engineering vegetative oil crops.
ERF and WRKY transcription factors regulateIDAand abscission timing in Arabidopsis
Authors: Galindo-Trigo Sergio , Bågman Anne-Maarit , Ishida Takashi , Sawa Shinichiro , Brady Siobhán M. , Butenko Melinka A.
Published: September 2023

Plants shed organs like leaves, petals or fruits through the process of abscission. Monitoring cues like age, resource availability, biotic and abiotic stresses allows plants to abscise organs in a timely manner. How these signals are integrated in the molecular pathways that drive abscission is largely unknown. TheINFLORESCENCE DEFICIENT IN ABSCISSION(IDA) gene is one of the main drivers of floral organ abscission in Arabidopsis and is known to transcriptionally respond to most abscission-regulating cues. Interrogating theIDApromoterin silicoandin vitrowe identified transcription factors that can potentially modulateIDAexpression. We functionally characterized the importance of ERF and WRKY binding sites forIDAexpression during floral organ abscission, with WRKYs being of special relevance to mediateIDAupregulation in response to biotic stress in tissues destined for separation. We further characterized WRKY57 as a positive regulator ofIDAandIDA-likegene expression in abscission zones. Our findings highlight the promise of promoter element-targeted approaches to modulate the responsiveness of the IDA signaling pathway to harness controlled abscission timing for improved crop productivity.

Highlight

ERF and WRKY transcription factors distinctly contribute to the regulation ofIDAexpression and thereby abscission timing. WRKY57 modulates abscission via redundant IDA/IDA-like peptides.
Preferences of people living with HIV for features of tuberculosis preventive treatment regimens – a discrete choice experiment
Authors: Aschmann Hélène E. , Musinguzi Allan , Kadota Jillian L. , Namale Catherine , Kakeeto Juliet , Nakimuli Jane , Akello Lydia , Welishe Fred , Nakitende Anne , Berger Christopher , Dowdy David W. , Cattamanchi Adithya , Semitala Fred C. , Kerkhoff Andrew D.
Published: September 2023

Background

Tuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens.

Methods

We conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. In nine random choice tasks, participants chose between two hypothetical TPT regimens with different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects). We analyzed preferences using hierarchical Bayesian estimation, latent class analysis, and willingness-to-trade simulations.

Results

Of 400 PLHIV, 392 (median age 44, 72% female, 91% TPT-experienced) had high quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6 – 33.2), followed by frequency (20.5% [95% CI 19.7 – 21.3]), duration (19.5% [95% CI 18.6 – 20.5]), and need for ART dosage adjustment (18.2% [95% CI 17.2 – 19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N=222; 57%); another was averse to ART dosage adjustment (N=107; 27%); and the last prioritized short and tolerable regimens (N=63; 16%). All groups highly valued fewer pills per dose. Participants were willing to accept a regimen of 2.8 months’ additional duration [95% CI: 2.4 – 3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4 – 4.8] months for weekly rather than daily dosing, and 2.2 [95% CI 1.3 – 3.0] months to avoid ART dosage adjustment.

Conclusions

To align with preferences of PLHIV, decision-makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing, and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.