bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Bimodal to Unimodal: The Transformed Incidence of Osteosarcoma in the United States
Authors: Kar Emma , Ammanamanchi Amrit , Yousif Miranda , Geetha Saroja Devi , Schwartz Kendall , Mishra Arya , Ling Jiali , Nonyelu Kristie Nneoma , Kannadath Bijun Sai 
Published: September 2023

ABSTRACTBackgroundOsteosarcoma is the most common primary bone malignancy. It has classically been described as having a bimodal incidence by age, with the first peak in the second decade of life and the second peak after 65 years of age. We sought to identify whether the bimodal incidence distribution still exists for osteosarcoma using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) and the National Inpatient Sample (NIS) (Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality) databases.MethodsIncidence rates of osteosarcoma between 1975-2020 were analyzed by age, year of occurrence, sex, race, and primary tumor site using the SEER program data. The age of maximum incidence in patients 40 years of age and older was analyzed by calendar year to observe for a consistent second peak. Fisher’s Exact test was also conducted with the SEER data to assess if there was a significant association between the occurrence of osteosarcoma in patients 35-64 years old and those 65+ years old. Incidence of tumors of the long bones of the lower limbs using ICD-9 and 10 diagnosis codes from the NIS discharge database 2012-2019 were also analyzed for comparison.ResultsA total of 1,779 cases of osteosarcoma were reported in the SEER database from 1975-2020. Across the 46 calendar year span, a consistent first peak appeared in the second decade of life alternating between the 10-14 and 15-19 age groups. In the 40+ cohort, the age of the highest incidence varied widely each calendar year: being found in age groups 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, & 85+ years old (5, 3, 5, 1, 2, 1, 2, 1, & 1 times respectively). For 25 years of the 46-year span, the max was shared by more than one age group. Overall, no single age group from the 40+ age group held a consistent maximum from 1975-2020.Using the NIS program and similar methodology, we analyzed 86,100 discharges of lower limb long bone tumors from 2012-2019 as a reference. The NIS data exhibited nearly identical patterns, with a unimodal incidence in adolescence and no obvious second peak.ConclusionOur analysis shows that the incidence of osteosarcoma is no longer bimodally distributed. This may be due to the increased use of bisphosphonates in recent years for the effective management of Paget’s disease, leading to a decline in late-age bone tumors. Our findings suggest the need to update our understanding of the epidemiology of osteosarcoma, as it should be considered more as a disease of adolescence with only sporadic incidence later on in older age.
Associating with kin selects against disease tolerance
Authors: Walsman Jason Cosens , Lambe Madalyn , Stephenson Jessica F 
Published: September 2023

AbstractBehavioural and physiological immunity are key to slowing epidemic spread. Here, we explore the evolutionary and epidemic consequences of their different costs for the evolution of tolerance vs. resistance: behavioural resistance affects social cohesion, with associated group-level costs, while physiological resistance costs should accrue to the individual. Further, the transmission-reduction benefits of resistance accrue differently to susceptible hosts and those already infected; infected hosts only benefit indirectly, by reducing transmission to kin. We therefore model the coevolution of transmission-reducing defences expressed in susceptible hosts with those expressed in infected hosts, as a function of kin association, and analyse the effect on population-level outcomes. Using parameter values for guppies,Poecilia reticulata, and their gyrodactylid parasites, we find that: 1) either susceptible or infected hosts should invest heavily in preventing infection, but not both; 2) kin association drives investment in physiological resistance more strongly than in behavioural resistance; 3) even weak levels of kin association can favour altruistic infected hosts that invest heavily in resistance (vs. selfish tolerance), eliminating the disease. Overall, our finding that weak kin association affects the coevolution of infected and susceptible investment in both behavioural and physiological immunity suggests that kin selection may affect disease dynamics across systems.
The immunoglobulin A isotype of the Arabian camel (Camelus dromedarius) preserves the dualistic structure of unconventional single-domain and canonical heavy chains
Authors: Conca Walter , Salih Soad , Al-Rabiah Rana , Parhar Ranjit , Abd-Elnaeim Mahmoud , Al-Hindas Hussein , Tinson Alexander , Collison Kate , Kishore Uday , Al-Mohanna Futwan 
Published: September 2023

AbstractEvolutionary processes of adaptive immunity inCamelidaeand some cartilaginous fishes resulted in the concurrent expression of classic heavy-light chain heterotetrameric antibodies together with unconventional heavy chain-only homodimeric antibodies of the IgG class. Heavy chain-only IgG bears a single variable domain and lacks the constant heavy (CH) γ1 domain required for the covalent pairing with the light chain. It has so far not been reported whether this distinctive feature of IgG is also observed in the IgA isotype. Therefore, gene-specific primers were used to generate a library of IgA heavy chain cDNA derived from RNA extracted from the third eyelid of the dromedary where isolated lymphoid follicles and plasma cells abound at inductive and effector sites, respectively. Majority of the cDNA clones revealed the hallmarks of heavy chain-only antibodies,i.e.camelid-specific amino acid substitutions in framework region 1 and 2, broad length distribution of complementarity determining region 3, and the absence of the CHα1 domain. In a few clones, however, the cDNA of canonical IgA heavy chain was amplified which included the CHα1 domain, analogous to CHγ1 domain in dromedary IgG1 subclass. Moreover, we noticed a short, proline-rich hinge, similar to that in human IgA2, and, at the N-terminal end of the CHα3 domain, a unique, camelid-specific pentapeptide consisting of serine, glutamic acid, aspartic acid, alanine or threonine, and isoleucine, of undetermined function, designated as the inter-α region. Immunoblots using rabbit anti-camel IgA antibodies raised against CHα2 and CHα3 domains as well as the inter-α region revealed the expression of a ∼52 kDa and a ∼60 kDa IgA species, corresponding to unconventional and canonical IgA heavy chain, respectively, in tissue extracts of the third eyelid,trachea, small and large intestine. In contrast, the leporine anti-CHα1 antibody detected canonical, but not unconventional IgA heavy chain, in all the examined tissues, milk, and serum, in addition to another hitherto unexplored species of ∼45 kDa in milk and serum. Immunohistology using anti-CHα domain antibodies confirmed the expression of both variants of IgA heavy chains in plasma cells in the third eyelid’s lacrimal gland, and in thelamina propriaofconjunctiva, bronchial and intestinalmucosa. We conclude that in the dromedary, the IgA isotype has expanded the immunoglobulin repertoire by co-expressing single-domain unconventional as well as canonical IgA heavy chains, comparable to the IgG class, thus underscoring the crucial role of heavy chain-only antibodies in immune defense not only in circulation but also at the mucosal frontiers.
Abca4 inhibition in a cone-rich rodent leads to Stargardt Disease type 1-like retinal degeneration
Authors: Sassone Fabiana , Roux Michel J. , Ciocca Dominique , Rossolillo Paola , Birling Marie-Christine , Sparrow Janet R. , Hicks David 
Published: September 2023

AbstractMutations in the geneABCA4coding for photoreceptor-specificATP-bindingcassette subfamilyAmember4, are responsible for the most common form of inherited macular degeneration known as Stargardt Disease type 1 (STGD1). STGD1 typically declares early in life and leads to severe visual handicap.Abca4gene deletion mouse models of STGD1 show increased accumulation of lipofuscin, a hallmark of the disease, but unlike the human disease show mostly no photoreceptor degeneration or functional decline (an albinoAbca4-/-mouse exhibits photoreceptor degeneration although functional parameters were not studied). Reasoning that the small cone population of mice (<3%) might compromise more faithful modelling of human maculopathies, we performed subretinal injections of CRISPR/Cas9-Abca4 recombinant Adeno-Associated Virus constructs into young Fat Sand Rats (Psammomys obesus), a diurnal rodent containing >30% cones. Sanger sequencing of the CRISPR-targeted sequence showed clear edition of theAbca4gene. At 2 months post- injection, non-invasive fundus imaging showed widespread photoreceptor loss, confirmed by optical coherence tomography. Functional recording by scotopic and photopic single flash, and photopic flicker electroretinography, showed significant decline in photopic (cone) but not scotopic (rod) light responses. Post-mortem real-time PCR, immunohistochemistry and western blotting showed significant decrease of cone-specific (MW cone opsin) but not rod- specific (rhodopsin) markers. Transmission electron microscopy showed large numbers of lipid inclusions in treated but not control retinal pigmented epithelium. Finally, ultrahigh performance liquid chromatographic analysis of wholeP. obesuseyes showed the presence ofall-transretinal-dimer, also seen inAbca4-/-mice but not normal rod-rich mouse or rat eyes. In conclusion, this animal model of STGD1 more accurately reflects human STGD1 and should be valuable for characterizing pathogenic pathways and exploring treatment options.
Deep learning enables accurate soft tissue deformation estimationin vivo
Authors: Huff Reece D. , Houghton Frederick , Earl Conner C. , Ghajar-Rahimi Elnaz , Dogra Ishan , Yu Denny , Harris-Adamson Carisa , Goergen Craig J. , O’Connell Grace D. 
Published: September 2023

ABSTRACTImage-based deformation estimation is an important tool used in a variety of engineering problems, including crack propagation, fracture, and fatigue failure. These tools have been instrumental in biomechanics research where measuringin vitroandin vivotissue deformations help evaluate tissue health and disease progression. However, accurately measuring tissue deformationin vivois particularly challenging due to limited image signal-to-noise ratio. Therefore, we created a novel deep-learning approach for measuring deformation from a sequence ofin vivoimages calledStrainNet. Utilizing a training dataset that incorporates image artifacts,StrainNetwas designed to maximize performance in challengingin vivosettings. Artificially generated image sequences of human flexor tendons undergoing known deformations were used to compareStrainNetagainst two conventional image-based strain measurement techniques.StrainNetoutperformed the traditional techniques by nearly 90%. High-frequency ultrasound imaging was then used to acquire images of the flexor tendons engaged during contraction. OnlyStrainNetwas able to track tissue deformations under thein vivotest conditions. Findings revealed strong correlations between tendon deformation and contraction effort, highlighting the potential forStrainNetto be a valuable tool for assessing preventative care, rehabilitation strategies, or disease progression. Additionally, by using real-world data to train our model,StrainNetwas able to generalize and reveal important relationships between the effort exerted by the participant and tendon mechanics. Overall,StrainNetdemonstrated the effectiveness of using deep learning for image-based strain analysisin vivo.
An experimental approach towards untangling the role of nature versus nurture in shaping the microbiome of social insects
Authors: Cohen Tali Magory , Bodner Levona , Turjeman Sondra , Sharon Efrat , Cohen Alisa , Bouchebti Sofia , Tikhonov Evgeny , Koren Omry , Levin Eran 
Published: September 2023

AbstractThe gut microbiota is intimately related to host wellbeing, in terms of physiology, immune function, and even social interactions. The strength of this relationship is dynamic, but the extent to which the microbiome is shaped by the identity of the host (nature) or its environment (nurture) remains largely unknown. Here we aimed to identify factors shaping the microbiomes of nursing workers and larvae of two Vespidae species, using a cross-species experimental design to control for effects of environment, host identity and their interactions. We found that the microbiome composition of adults depended principally on the environment. Conversely, larval microbiome composition differed more between host species, regardless of treatment. We also found distinct microbiota profiles between the two species, across life stages and independently. These findings further elucidate the complexity of the host-microbiome relationship shaped by the environment while retaining symbionts that benefit the host. These results suggest that holobiont evolution may have promoted the rise of social behavior in animals.
Antibody Humanization via Protein Language Model and Neighbor Retrieval
Authors: Zou Honggang , Yuan Rongqing , Lai Boqiao , Dou Yang , Wei Li , Xu Jinbo 
Published: September 2023

AbstractAntibody (Ab), also known as immunoglobulin (Ig), is an essential macromolecule involved in human immune response and plays an increasingly vital role in drug discovery. However, the development of antibody drugs heavily relies on humanization of murine antibodies, which often necessitates multiple rounds of sequence optimizations through laborious experimental processes. In recent years, the remarkable capabilities of machine learning have revolutionized the field of natural sciences and have also demonstrated promising applications in the field of antibody humanization. Here, we present Protein-LAnguage-model-knN (PLAN), a machine learning model leveraging protein language model and information retrieval for improving humanization of antibodies. Further, we proposeDE, a computed value shows a positive correlation with antigen-binding affinity. Ourin silicoexperimental results demonstrate that 1) the PLAN-humanized sequences’ average humanness score reaches 0.592, improving over the best existing method by 44.7%; 2) a 63% overlap between the PLAN-proposed mutations and the mutations validated through wet lab experiments, which is 16.7% higher than the best existing result; 3) comparable antigen-binding affinity afterDEguided back mutation.
Blood transfusion in care of patients with Visceral Leishmaniasis: a review of practices in therapeutic efficacy studies
Authors: Dahal Prabin , Singh-Phulgenda Sauman , Wilson James , Cota Glaucia , Ritmeijer Koert , Musa Ahmed , Alves Fabiana , Stepniewska Kasia , Guerin Philippe J 
Published: September 2023

AbstractAnaemia is a common presentation feature in patients with visceral leishmaniasis (VL). Blood transfusion remains an important aspect of patient management in VL. However, triggers considered for making decisions on transfusion are poorly understood. This review is based on the Infectious Diseases Data Observatory (IDDO) VL clinical trials library, a database of all published efficacy studies since 1980 and has indexed 160 published trials (1980–2021). Description of blood transfusion was reported in 16 (10.1%) trials (n=3,459 patients). Transfusion was initiated solely based on haemoglobin (Hb) measurement in 9 studies, using a combination of Hb and other health conditions (epistaxis, poor health, or clinical instability) in 3 studies, and the criteria was unclear in 4 studies; Hb threshold ranged from 3-8 g/dL. Overall, the number of patients receiving transfusion was explicitly reported in 10 trials (n=2,421 patients enrolled). Of these, 217 patients underwent transfusion; 58 before treatment initiation and 46 during treatment or the follow-up phase, and the time of transfusion was unclear in 113. The median proportion of patients who received a transfusion in a study was 8.0% [Interquartile range (IQR): 4.7% to 47.2%; range: 0-100%; n=10 studies]. This review describes the variation in current clinical practice and is an important initial step in policy/guideline development, where both the patient’s haemoglobin concentration and clinical status must be considered.
Framingham risk score prediction at 12 months in the STANDFIRM randomised control trial
Authors: Phan Thanh G , Srikanth Velandai K , Cadilhac Dominique A , Nelson Mark , Kim Joosup , Olaiya Muideen T , Fitzgerald Sharyn M , Bladin Christopher , Gerraty Richard , Ma Henry , Thrift Amanda G 
Published: September 2023

BackgroundThe Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STANDFIRM, ACTRN12608000166370) trial was designed to test the effectiveness of chronic disease care management for modifying the Framingham risk score (FRS) among patients with stroke or transient ischemic attack. The primary outcome of change in FRS between baseline and 12 months was not met. We aimed to determine characteristics of participants at baseline that predict reduction in FRS at 12 months and whether future FRS is predetermined at the time of randomizationMethodData included 35 variables encompassing demographics, risk factors, psychological, social and education status, and laboratory tests. Five supervised machine learning (ML) methods were used: random forest (RF), extreme gradient boosting (XGBoost), support vector regression (SVR), multilayer perceptron artificial neural network (MLP) and K-nearest neighbor (KNN). We split data for training (80%, n=406) and testing (20%, n=102).ResultsTraining and test data were evenly matched for age, sex, baseline and 12-month FRS. Following tuning of the five ML methods, the optimal model for predicting FRS at 12 months was SVR (R2=0.763, root mean squared error or RMSE=8.52). The five most important variables for SVR were: baseline FRS, age, male sex, sodium/potassium excretion and proteinuria. All ML methods were poor at determining change in FRS at 12 months (R2<0.161).ConclusionOur findings suggest that change in FRS as an endpoint in trials may have limited value as it is largely determined at baseline. In this cohort, Support Vector Regression was the optimal method to predict future but not change in FRS.
Preliminary study of transcranial Doppler observation of cerebral herniation in acute internal carotid artery occlusion
Authors: Chen Jin , Su Jun , Chang Hong , Bai Peng 
Published: September 2023

AbstractBackground and PurposeThe purpose of this study was to attempt early detection of the risk of cerebral herniation after acute internal carotid artery occlusion (AICAO) using transcranial Doppler.MethodsTwenty-four patients were enrolled within 6 hours of symptom onset. All patients underwent transcranial Doppler (TCD), head computed tomography (CT), magnetic resonance angiography (MRA) or computed tomography angiography (CTA). The National Institutes of Health Stroke Scale (NIHSS) score and the Alberta Stroke Program Early CT Score (ASPECTS) were performed in emergency department and 24 hours after the onset of acute ischemic stroke (AIS) (designated as NIHSS1 and ASPECTS1, respectively). TCD to determine collateral circulation was performed immediately after patient admission.ResultsSex, risk factors, hemisphere, intravenous recombinant tissue plasminogen activator (rt-PA), and time from onset of symptoms to initiation treatment showed no difference between patients with or without cerebral herniation. The age of the group with cerebral hernia was significantly younger than that of the group without cerebral hernia (P=0.000). Assessment of the anterior communicating artery (ACoA) by TCD was in high agreement with assessment by MRA or CTA (kappa=0.625, P=0.002). Correlation analysis showed that the likelihood of a cerebral herniation event was positively correlated with absence of a communicating artery (rn=0.660, P=0.002) and negatively correlated with ACoA (rn=0.513, P=0.003) and ASPECTS1 (rs=0.528, P=0.008), but was not correlated with NIHSS score, NIHSS1 score, △NIHSS (NIHSS1-NIHSS), admission awareness, and stroke volume (P > 0.05).ConclusionsTCD assessment of collateral status could more rapidly indicate the risk of cerebral herniation. Lack of collateral flow may predict the occurrence of cerebral hernia. Compensation of ACoA may indicate a lower risk of cerebral hernia.
De novo genome assembly and annotation of the saw-scaled viperEchis carinatus, a medically important venomous snake in the Indian Subcontinent
Authors: Blotra Avni , Sharma Anukrati , Sowpati Divya Tej , Vasudevan Karthikeyan 
Published: September 2023

ABSTRACTEchis carinatusis a widely distributed venomous snake in the Indian subcontinent. It is one of the “Big Four” snake species responsible for mortality and severe health complications caused by envenomations. Given the significance of the species for human health, we assembled and annotated the whole genome ofE. carinatus. Using long reads for assembly and short reads for correction, we achieved a highly contiguous 1.57Gb assembly, with a contig N50 of 17.1 Mb and scaffold N50 of 23.5 Mb. We could map 96.58% of our reads back to the assembled genome, and Benchmarking Universal Single-Copy Orthologs (BUSCO) score of 97.4%, indicates near completeness. 48.59% of the genome had repeat elements. The predominant types of repeats include retrotransposons (LINEs, SINEs and LTR elements), DNA transposons and satellite DNA (SSRs). Additionally, we conducted a gene prediction analysis, identifying a total of 26,711 protein-coding genes. These genes included alternatively spliced products, leading to the prediction of 31,106 proteins, 77.6% of which were successfully annotated usingBlastpandInterProScan. Out of the total predicted gene set, we identified 119 toxin-coding genes, crucial for venom toxin production in the species. The acquisition of toxin sequence-based information resulted in a valuable dataset of genes that are involved in venom production inE. carinatus. This dataset advances our understanding of the biological processes underlying venom production and lays the foundation for the development of new antivenom formulations.
GametesOmics: A Comprehensive Multi-Omics Database for Exploring the Gametogenesis in Humans and Mice
Authors: An Jianting , Wang Jing , Kong Siming , Song Shi , Chen Wei , Yuan Peng , He Qilong , Chen Yidong , Li Ye , Yang Yi , Wang Wei , Li Rong , Yan Liying , Yan Zhiqiang , Qiao Jie 
Published: September 2023

AbstractGametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we developed GametesOmics, a comprehensive database that integrated the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, includingSearchandAdvanced Searchfor querying the expression and epigenetic modification of each gene;Analysis ToolswithDifferentially Expressed Gene (DEG) analysisfor identifying DEGs,Correlation analysisfor demonstrating the genetic and epigenetic changes,Visualizationfor displaying single-cell cluster and screening marker genes as well as master transcription factors (TFs), andMethylViewfor studying the genomic distribution of epigenetic modifications. GametesOmics also providesGenome BrowserandOrthologsfor tracking and comparing gene expression, DNA methylations, as well as chromatin accessibilities between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed athttp://gametesomics.cn/.