bluuebunny/crossref_metadata_2025 huggingface dataset:
Uniform cerebral organoid culture on a pillar plate by simple and reproducible spheroid transfer from an ultralow attachment well plate
Authors: Acharya Prabha , Joshi Pranav , Shrestha Sunil , Choi Na Young , Jeong Sehoon , Lee Moo-Yeal
Published: January 2024

Human induced pluripotent stem cell (iPSC)-derived brain organoids have potential to recapitulate the earliest stages of brain development, serving as an effective in vitro model for studying both normal brain development and disorders. However, current brain organoid culture methods face several challenges, including low throughput, high variability in organoid generation, and time-consuming, multiple transfer and encapsulation of cells in hydrogels throughout the culture. These limitations hinder the widespread application of brain organoids including high-throughput assessment of compounds in clinical and industrial lab settings. In this study, we demonstrate a straightforward approach of generating multiple cerebral organoids from iPSCs on a pillar plate platform, eliminating the need for labor-intensive, multiple transfer and encapsulation steps to ensure the reproducible generation of cerebral organoids. We formed embryoid bodies in an ultra-low attachment 384-well plate and subsequently transferred them to the pillar plate containing Matrigel, using a straightforward sandwiching and inverting method. Each pillar on the pillar plate contains a single spheroid, and the success rate of spheroid transfer was in a range of 95%–100%. Using this approach, we robustly generated cerebral organoids on the pillar plate and demonstrated an intra-batch coefficient of variation below 9%–19% based on ATP-based cell viability and compound treatment. Notably, our spheroid transfer method in combination with the pillar plate allows miniaturized culture of cerebral organoids, alleviates the issue of organoid variability, and has potential to significantly enhance assay throughput by allowing in situ organoid assessment as compared to conventional organoid culture in 6-/24-well plates, petri dishes, and spinner flasks.
Investigating the impact of infill patterns on shape memory effect in material extrusion
Authors: Choi Jiwoo , Waheed Usman , Myant Connor
Published: January 2024

Extensive research has been conducted on Shape Memory Polymers (SMPs) for their potential application in additive manufacturing. The Shape Memory Effect (SME), a key attribute of SMPs, enables 3D-printed objects to alter their shape in response to external stimuli. Several methods for programming SMEs have been explored, such as modifying printing parameters like infill patterns or density. However, incorporating SMPs as substitutes for conventional functional components has been challenging due to grafting difficulties and the limited reliability of SMEs. In this research, the influence of internal structures on SMEs is examined by comparing the full shape recovery period. This investigation has revealed the impact of different infill structures on SMEs and uncovered a complex shape recovery pattern termed multi-phased SME. This occurs when straight infill structures are nearly parallel along the length of a cuboid specimen that has been programmed to form a 90° curve. This finding enhances the creation of complex shape recovery behaviours by simply modifying printing parameters and is applicable to a variety of SMPs.
Electronic transport properties of spin-crossover polymer plus polyaniline composites with Fe3O4 nanoparticles
Authors: Mishra Esha , Chin WaiKiat , McElveen Kayleigh A , Ekanayaka Thilini K , Zaz M Zaid , Viswan Gauthami , Zielinski Ruthi , N’Diaye Alpha T , Shapiro David , Lai Rebecca Y , Streubel Robert , Dowben Peter A
Published: January 2024

Adding Fe3O4 nanoparticles to composites of [Fe(Htrz)2(trz)](BF4) spin-crossover polymer and polyaniline (PANI) drives a phase separation of both and restores the molecular structure and cooperative effects of the spin-crossover polymer without compromising the increased conductivity gained through the addition of PANI. We observe an increased on-off ratio for the DC conductivity owing to an enlarged off state resistivity and a 20 times larger AC conductivity of the on state compared with DC values. The Fe3O4 nanoparticles, primarily confined to the [Fe(Htrz)2(trz)](BF4) phase, are ferromagnetically coupled to the local moment of the spin-crossover molecule suggesting the existence of an exchange interaction between both components.
An effective hybrid particle swarm—artificial neural network optimization for predicting green bio-fiber mechanical characteristics and optimizing biomaterial performance
Authors: Nawafleh Nashat , Al-Oqla Faris M
Published: January 2024

Natural fiber-reinforced composites are currently utilized in several applications due to worldwide environmental and cost concerns. However, these composites have production challenges such as poor reinforcement-matrix adhesion, that sophisticates the prediction of their mechanical properties. This study presents a novel, robust hybrid particle swarm—artificial neural network optimization (PSO-ANN) methodology to assess and create accurate predictions of the green bio-fibers to optimize and improve the mechanical features of biomaterials for green bio-products instead of performing tedious experimental works. As the mechanical qualities of green bio-fibers might differ from one fiber to another due to several interacted parameters, high complexity in predicting the bio-fiber capabilities exists. Therefore, this work utilizes suitable methods with a non-linear activation function to predict the mechanical characteristics of natural fibers that allow the researchers to improve the choices of natural fibers for biomaterials on the basis of cellulose content, the microfibrillar angle, and the diameter of natural fibers, decreasing the duration of the process required to characterize materials experimentally. The reliability of the introduced PSO-ANN model was verified by the investigations of the fiber’s tensile stress and Young’s modulus. Results showed that the presented model is capable of consistently and accurately monitoring the mechanical performance to a large degree, in comparison with experimental results. This in fact would facilitate and simplify the process of selecting the best natural fiber composites, which speeds up the experimental characterization phase and improves energy efficiency in the process of converting energy into monetary income, which would have ramifications for both economies and ecosystems. The anticipated method would also boost scientific evaluation of green fibers, confirming their role as a replacement material for green product fulfillment in future eco-friendly manufacturing.
Printability disparities in heterogeneous material combinations via laser directed energy deposition: a comparative study
Authors: Ning Jinsheng , Zhu Lida , Wang Shuhao , Yang Zhichao , Xu Peihua , Xue Pengsheng , Lu Hao , Yu Miao , Zhao Yunhang , Li Jiachen , Bose Susmita , Bandyopadhyay Amit
Published: January 2024

Additive manufacturing provides achievability for the fabrication of bimetallic and multi-material structures; however, the material compatibility and bondability directly affect the parts’ formability and final quality. It is essential to understand the underlying printability of different material combinations based on an adapted process. Here, the printability disparities of two common and attractive material combinations (nickel- and iron-based alloys) are evaluated at the macro and micro levels via laser directed energy deposition (DED). The deposition processes were captured using in situ high-speed imaging, and the dissimilarities in melt pool features and track morphology were quantitatively investigated within specific process windows. Moreover, the microstructure diversity of the tracks and blocks processed with varied material pairs was comparatively elaborated and, complemented with the informative multi-physics modeling, the presented non-uniformity in mechanical properties (microhardness) among the heterogeneous material pairs was rationalized. The differences in melt flow induced by the unlike thermophysical properties of the material pairs and the resulting element intermixing and localized re-alloying during solidification dominate the presented dissimilarity in printability among the material combinations. This work provides an in-depth understanding of the phenomenological differences in the deposition of dissimilar materials and aims to guide more reliable DED forming of bimetallic parts.
High fatty acid accumulation and coloration molecular mechanism of the elm mushroom (Pleurotus citrinopileatus)
Authors: Bao Xuemei , Ke Danmin , Wang Wei , Ye Fahui , Zeng Jiangyi , Zong Yuan
Published: January 2024

Pleurotus citrinopileatus is a low-cholesterol, protein-rich, and high-nutrient food. The molecular mechanisms of the compounds and coloration have not been reported. Metabolome and transcriptome were used to clarify the molecular mechanisms of key compounds biosynthesis. K-means analysis identified 19 compounds in P. citrinopileatus, mainly lipids and alkaloids in class 8. In addition, 84 lipids were higher and that the different compounds were mainly enriched in linoleic acid metabolism. A total of 14 compounds detected in the linoleic acid metabolism pathway were significantly up-regulated, while 3 sterol regulatory element binding protein (SREBP) transcription factors were screened. Tryptophan metabolism and riboflavin biosynthesis pathway analysis indicated that 3 Unigenes had tryptophan decarboxylase similar elements, which belonged to tyrosine decarboxylase 1. Moreover, CL15618.Contig5_All had high homology with MFS. In conclusion, the expression of 3 SREBP, the synthesis of isobavachalcone D, and the regulation of riboflavin transport by MCH5 were the reasons for fatty acid accumulation and yellow cap formation in the P. citrinopileatus.
Joint deep autoencoder and subgraph augmentation for inferring microbial responses to drugs
Authors: Zhou Zhecheng , Zhuo Linlin , Fu Xiangzheng , Zou Quan
Published: January 2024

Exploring microbial stress responses to drugs is crucial for the advancement of new therapeutic methods. While current artificial intelligence methodologies have expedited our understanding of potential microbial responses to drugs, the models are constrained by the imprecise representation of microbes and drugs. To this end, we combine deep autoencoder and subgraph augmentation technology for the first time to propose a model called JDASA-MRD, which can identify the potential indistinguishable responses of microbes to drugs. In the JDASA-MRD model, we begin by feeding the established similarity matrices of microbe and drug into the deep autoencoder, enabling to extract robust initial features of both microbes and drugs. Subsequently, we employ the MinHash and HyperLogLog algorithms to account intersections and cardinality data between microbe and drug subgraphs, thus deeply extracting the multi-hop neighborhood information of nodes. Finally, by integrating the initial node features with subgraph topological information, we leverage graph neural network technology to predict the microbes’ responses to drugs, offering a more effective solution to the ’over-smoothing’ challenge. Comparative analyses on multiple public datasets confirm that the JDASA-MRD model’s performance surpasses that of current state-of-the-art models. This research aims to offer a more profound insight into the adaptability of microbes to drugs and to furnish pivotal guidance for drug treatment strategies. Our data and code are publicly available at: https://github.com/ZZCrazy00/JDASA-MRD.
Joint regression analysis of multiple traits based on genetic relationships
Authors: Buchardt Ann-Sophie , Zhou Xiang , Ekstrøm Claus Thorn
Published: January 2024

Motivation

Polygenic scores (PGSs) are widely available and employed in genomic data analyses for predicting and understanding genetic architectures. Existing approaches either require information on SNP level, do not infer clusters of traits sharing genetic characteristic, or do not have any immediate predictive properties.

Results

Here, we present geneJAM, which is a novel clustering and estimation method using PGSs for inferring a genetic relationship among multiple, simultaneously measured and potentially correlated traits in a multivariate GWAS.

Using graphical lasso, we estimate a sparse covariance matrix of the PGSs and obtain clusters of traits sharing genetic characteristics. We use the clusters to specify the structure of the error covariance matrix of a generalized least squares (GLS) model and use the feasible GLS estimator for estimating a linear regression model with a certain unknown degree of correlation between the residuals.

The method suits many biology studies well with traits embedded in some genetic functioning groups and facilitates development of the PGS research. We compare the method with fully parametric techniques on simulated data and illustrate the utility of the methods by examining a heterogeneous stock mouse data set from the Wellcome Trust Centre for Human Genetics. We demonstrate that the method successfully identifies clusters of traits and increases precision, power, and computational efficiency.

Availability and implementation

GeneJAM is implemented in R and available at: https://github.com/abuchardt/geneJAM.
RPEMHC: improved prediction of MHC–peptide binding affinity by a deep learning approach based on residue–residue pair encoding
Authors: Wang Xuejiao , Wu Tingfang , Jiang Yelu , Chen Taoning , Pan Deng , Jin Zhi , Xie Jingxin , Quan Lijun , Lyu Qiang
Published: January 2024

Motivation

Binding of peptides to major histocompatibility complex (MHC) molecules plays a crucial role in triggering T cell recognition mechanisms essential for immune response. Accurate prediction of MHC–peptide binding is vital for the development of cancer therapeutic vaccines. While recent deep learning-based methods have achieved significant performance in predicting MHC–peptide binding affinity, most of them separately encode MHC molecules and peptides as inputs, potentially overlooking critical interaction information between the two.

Results

In this work, we propose RPEMHC, a new deep learning approach based on residue–residue pair encoding to predict the binding affinity between peptides and MHC, which encode an MHC molecule and a peptide as a residue–residue pair map. We evaluate the performance of RPEMHC on various MHC-II-related datasets for MHC–peptide binding prediction, demonstrating that RPEMHC achieves better or comparable performance against other state-of-the-art baselines. Moreover, we further construct experiments on MHC-I-related datasets, and experimental results demonstrate that our method can work on both two MHC classes. These extensive validations have manifested that RPEMHC is an effective tool for studying MHC–peptide interactions and can potentially facilitate the vaccine development.

Availability

The source code of the method along with trained models is freely available at https://github.com/lennylv/RPEMHC.
Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children
Authors: Cox Charles S , Notrica David M , Juranek Jenifer , Miller Jeffrey H , Triolo Fabio , Kosmach Steven , Savitz Sean I , Adelson P David , Pedroza Claudia , Olson Scott D , Scott Michael C , Kumar Akshita , Aertker Benjamin M , Caplan Henry W , Jackson Margaret L , Gill Brijesh S , Hetz Robert A , Lavoie Michael S , Ewing-Cobbs Linda
Published: January 2024

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood–brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes.

We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5–17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups.

Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of −20 600, 95% confidence interval (CI): −35 868 to −5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (−431 streamlines placebo versus −37 streamlines BMMNC; mean difference of −394, 95% CI: −803 to 15; P = 0.055), but this did not reach statistical significance due to high variability.

We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.
Sex disparities in the utilization of nurse-assisted peritoneal dialysis: a mediation analysis using data from the REIN registry
Authors: Danneville Isabelle , Beaumier Mathilde , Boyer Annabel , Chatelet Valérie , Monnet Elisabeth , Edet Stéphane , Lanot Antoine , Bechade Clémence , Lobbedez Thierry
Published: January 2024

Background

This study was carried out to evaluate the association between patient sex and the proportion of nurse-assisted peritoneal dialysis (PD) at dialysis initiation and to explore whether sex disparities in nurse-assisted PD utilization was explained by predialysis care and/or by social deprivation using mediation analysis.

Methods

This was a retrospective study using data from the Renal Epidemiology and Information Network (REIN) registry linked to the French National Healthcare Database (SNDS) of incident patients between 1 January 2017 and 30 June 2018. A regression logistic was used for statistical analysis. A mediation analysis explored the direct effect of sex on nurse-assisted PD proportion and the indirect effect through the European Deprivation Index (EDI), and the number of general practitioner (GP) and nephrologist visits before dialysis initiation.

Results

Among 1706 patients on PD, there were 637 women (37.3%) and 1069 men (62.7%). Nurse-assisted PD proportion was 332/610 (54.4%) for women vs 464/1036 (44.8%) for men. In the multivariable analysis women were more likely to be treated by nurse-assisted PD {odds ratio (OR) 1.92 [95% confidence interval (CI) 1.46–2.52]}. Nurse-assisted PD was associated with the median number of GP visits [OR 1.44 (95% CI 1.11–1.86)] and with the median number of nephrologist visits [OR 0.59 (95% CI 0.46–0.76)]. The mediation analysis showed a direct effect of sex on nurse-assisted PD [OR 1.90 (95% CI 1.80–2.01)] and an indirect effect through the median number of GP visits [OR 1.05 (95% CI 1.04–1.06], the median number of nephrologist visits [OR 1.02 (95% CI 1.02–1.03)] and quintile 5 of the EDI [OR 1.03 (95% CI 1.02–1.03)].

Conclusion

Women were more frequently treated by nurse-assisted PD than men. Differences between women and men in predialysis care and social deprivation could explain the greater utilization of nurse-assisted PD among women.
Chronic Lymphocytic Leukemia IGHV Somatic Hypermutation Detection by Targeted Capture Next-Generation Sequencing
Authors: Grants Jennifer M , May Christina , Bridgers Josh , Huang Shujun , Gillis Sierra , Meissner Barbara , Boyle Merrill , Ben-Neriah Susana , Hung Stacy , Duns Gerben , Hilton Laura , Gerrie Alina S , Marra Marco , Kridel Robert , Sabatini Peter J B , Steidl Christian , Scott David W , Karsan Aly
Published: January 2024

Background

Somatic hypermutation (SHM) status of the immunoglobulin heavy variable (IGHV) gene plays a crucial role in determining the prognosis and treatment of patients with chronic lymphocytic leukemia (CLL). A common approach for determining SHM status is multiplex polymerase chain reaction and Sanger sequencing of the immunoglobin heavy locus; however, this technique is low throughput, is vulnerable to failure, and does not allow multiplexing with other diagnostic assays.

Methods

Here we designed and validated a DNA targeted capture approach to detect immunoglobulin heavy variable somatic hypermutation (IGHV SHM) status as a submodule of a larger next-generation sequencing (NGS) panel that also includes probes for ATM, BIRC3, CHD2, KLHL6, MYD88, NOTCH1, NOTCH2, POT1, SF3B1, TP53, and XPO1. The assay takes as input FASTQ files and outputs a report containing IGHV SHM status and V allele usage following European Research Initiative on CLL guidelines.

Results

We validated the approach on 35 CLL patient samples, 34 of which were characterized using Sanger sequencing. The NGS panel identified the IGHV SHM status of 34 of 35 CLL patients. We showed 100% sensitivity and specificity among the 33 CLL samples with both NGS and Sanger sequencing calls. Furthermore, we demonstrated that this panel can be combined with additional targeted capture panels to detect prognostically important CLL single nucleotide variants, insertions/deletions, and copy number variants (TP53 copy number loss).

Conclusions

A targeted capture approach to IGHV SHM detection can be integrated into broader sequencing panels, allowing broad CLL prognostication in a single molecular assay.
Screening in Multiple Myeloma and Its Precursors: Are We There Yet?
Authors: Rögnvaldsson Sæmundur , Thorsteinsdóttir Sigrún , Kristinsson Sigurður Yngvi
Published: January 2024

Background

Multiple myeloma (MM) is a hematological malignancy that develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma. Recent evidence shows that by initiating treatment at an asymptomatic stage, outcomes in MM can be significantly improved. However, a vast majority of MM patients are diagnosed after the development of symptomatic end-organ damage and cannot reap the benefits of early treatment. The precursors of MM are easily detected by serum protein electrophoresis and free light chain assay of the serum, raising the question of whether population-based screening could detect MM at an asymptomatic stage and significantly expand the availability of early treatment in MM. Screening is a hallmark of care in many malignancies, and there are accepted criteria for when screening is appropriate.

Content

Here we review the available relevant evidence for the introduction of screening and discuss whether screening for MM and its precursors fulfills these criteria. We also highlight gaps in our current knowledge, most notably a lack of data on the benefits and harms of screening and the lack of a defined target population. There are ongoing studies that may fill these critical gaps in the literature, but their results are still pending.

Screening could lead to a paradigm shift in the care of patients with MM, but critical scientific questions need to be answered before screening of healthy individuals can be recommended. In short, we should not screen for MM and its precursors—yet.
Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer
Authors: León-Letelier Ricardo A , Dou Rongzhang , Vykoukal Jody , Yip-Schneider Michele T , Maitra Anirban , Irajizad Ehsan , Wu Ranran , Dennison Jennifer B , Do Kim-An , Zhang Jianjun , Schmidt C Max , Hanash Samir , Fahrmann Johannes F
Published: January 2024

Background

Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response.

Content

The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, as well as having potential for design of interception strategies. In this review, we first highlight the relevance of the microbiome for progression of precancerous lesions in the pancreas and, using liquid chromatography–mass spectrometry, provide supporting evidence that microbe-derived metabolites manifest in pancreatic cystic fluid and are associated with malignant progression of intraductal papillary mucinous neoplasm(s). We secondly summarize the biomarker potential of microbe-derived metabolite signatures for (a) identifying individuals at high risk of developing or harboring PDAC and (b) predicting response to treatment and disease outcomes.

The microbiome-derived metabolome holds considerable promise for risk assessment and prognostication of PDAC.
The effect of abatacept on T-cell activation is not long-lived in vivo
Authors: da Rosa Larissa C , Scales Hannah E , Benson Robert A , Brewer James M , McInnes Iain B , Garside Paul
Published: January 2024

Abatacept, a co-stimulatory blocker comprising the extracellular portion of human CTLA-4 linked to the Fc region of IgG1, is approved for the treatment of rheumatoid arthritis. By impairing the interaction between CD28 on T cells and CD80/CD86 on APCs, its mechanisms of action include the suppression of follicular T helper cells (preventing the breach of self-tolerance in B cells), inhibition of cell cycle progression holding T cells in a state described as ‘induced naïve’ and reduction in DC conditioning. However, less is known about how long these inhibitory effects might last, which is a critical question for therapeutic use in patients. Herein, employing a murine model of OVA-induced DTH, we demonstrate that the effect of abatacept is short-lived in vivo and that the inhibitory effects diminish markedly when treatment is ceased.
A rare case report of Erdheim–Chester disease with pericardial effusion, conduction abnormalities, and atrial infiltration
Authors: Yassine Charaf , Colletti Giuseppe , Ciprian Acasandrei , George Mairesse
Published: January 2024

Background

Erdheim–Chester disease (ECD) is a rare multisystem disorder that primarily affects adults. It is characterized by the excessive production and accumulation of histiocytes, a type of white blood cell, within multiple tissues and organs, including the cardiovascular system. The infiltration of histiocytes can cause a range of cardiovascular symptoms, including pericardial effusion, myocardial infiltration, and heart failure, among others. Despite the potential severity of these cardiovascular manifestations, ECD is often misdiagnosed or underdiagnosed, leading to delays in appropriate treatment and poor outcomes for patients. As such, there is a pressing need for increased awareness and understanding of ECD’s cardiovascular manifestations among clinicians and researchers. This article aims to highlight the importance of considering ECD as a potential underlying cause of cardiovascular complaints and to encourage further investigation into this uncommon but potentially life-threatening condition.

Case summary

A 63-year-old man presented as outpatient complaining of dyspnoea on exertion during the last 3 weeks (New York Heart Association functional class III). He had also experienced a left shoulder and bilateral knee pain over the last 6 months. The patient was found to have a massive pericardial effusion associated with ECD. While pericardial effusions can have various causes, including infection, cancer, and autoimmune disorders, ECD is one potential cause of this condition. Therefore, it is important for clinicians to consider ECD in the differential diagnosis of patients presenting with unexplained pericardial effusions, particularly in the context of other systemic symptoms suggestive of ECD. We discuss about this specific aetiology and the clinical management of this uncommon condition.

Discussion

Erdheim–Chester disease, a non-Langerhans cell histiocytosis, is a rare multisystem disorder. Diagnosis is challenging and should be suspected in the presence of a pericardial effusion with conduction abnormalities with indicators of a multisystem disease.
Effects of biocontrol Bacillus sp. strain D5 on the pathogenic Fusarium oxysporum R1 at the microscopic and molecular level in Crocus sativus L. (saffron) corm
Authors: Bhagat Nancy , Vakhlu Jyoti
Published: January 2024

Corm rot of saffron caused by Fusarium oxysporum is a major threat to saffron cultivation the world over. To minimize the ill effects of chemical fungicides, attention has been shifted to the use of biocontrol agents for disease management in a sustainable way. In saffron, various biocontrol agents against corm rot disease have been reported and characterized but no study has been done so far to understand their interaction at the molecular level. The present study was conducted to unravel the mechanism of action of an already characterized native biocontrol agent i.e. Bacillus sp. strain D5 (Bar D5) against F. oxsporum R1 (Fox R1) in the saffron corm. The growth inhibition of Fox R1 was observed in vitro and in planta (saffron corm) by real time imaging. Bacillus sp. strain D5 reduced Fox R1 load in infected corms by 50% as quantified by q-PCR and the colony-forming unit method. Comparative transcriptome analysis revealed upregulation and downregulation of various Fox R1 genes in presence of Bar D5. The genes related to carbon metabolism, cell wall and membrane synthesis, and growth of Fox R1 were significantly downregulated in Bar D5-primed and Fox R1-inoculated corms as compared to only Fox R1-inoculated corms.
Archaeal virus entry and egress
Authors: Kuiper Bastiaan P , Schöntag Anna M C , Oksanen Hanna M , Daum Bertram , Quax Tessa E F
Published: January 2024

Archaeal viruses display a high degree of structural and genomic diversity. Few details are known about the mechanisms by which these viruses enter and exit their host cells. Research on archaeal viruses has lately made significant progress due to advances in genetic tools and imaging techniques, such as cryo-electron tomography (cryo-ET). In recent years, a steady output of newly identified archaeal viral receptors and egress mechanisms has offered the first insight into how archaeal viruses interact with the archaeal cell envelope. As more details about archaeal viral entry and egress are unravelled, patterns are starting to emerge. This helps to better understand the interactions between viruses and the archaeal cell envelope and how these compare to infection strategies of viruses in other domains of life. Here, we provide an overview of recent developments in the field of archaeal viral entry and egress, shedding light onto the most elusive part of the virosphere.
Chromatin accessibility and epigenetic deoxyribose nucleic acid (DNA) modifications in chronic kidney disease (CKD) osteoblasts: a study of bone and osteoblasts from pediatric patients with CKD
Authors: Martin Aline , Kawaguchi Riki , Wang Qing , Salusky Isidro B , Pereira Renata C , Wesseling-Perry Katherine
Published: January 2024

Maturation defects are intrinsic features of osteoblast lineage cells in CKD patients. These defects persist ex vivo, suggesting that CKD induces epigenetic changes in bone cells. To gain insights into which signaling pathways contribute to CKD-mediated, epigenetically driven, impairments in osteoblast maturation, we characterized RNA expression and DNA methylation patterns by RNA-Seq and MethylationEpic in primary osteoblasts from nine adolescent and young adult dialysis patients with end-stage kidney disease and three healthy references. ATAC-Seq was also performed on a subset of osteoblasts. Bone matrix protein expression was extracted from the iliac crest and evaluated by proteomics. Gene set enrichment analysis was used to establish signaling pathways consistently altered in chromatin accessibility, DNA methylation, and RNA expression patterns. Single genes were suppressed in primary osteoblasts using shRNA and mineralization characterized in vitro. The effect of nuclear factor of activated T cells (NFAT) signaling suppression was also assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) incorporation. We found that signaling pathways critical for osteoblast differentiation were strongly downregulated in CKD osteoblasts. Gene set enrichment analysis identified highly significant methylation changes, differential chromatin accessibility, and altered RNA expression in NFAT signaling targets. NFAT inhibition reduced osteoblast proliferation. Combined analysis of osteoblast RNA expression and whole bone matrix composition identified 13 potential ligand-receptor pairs. In summary, epigenetic changes in CKD osteoblasts associate with altered expression of multiple osteoblast genes and signaling pathways. An increase in NFAT signaling may play a role in impaired CKD osteoblast maturation. Epigenetic changes also associate with an altered bone matrix, which may contribute to bone fragility. Further studies are necessary to elucidate the pathways affected by these genetic alterations since elucidating these pathways will be vital to correcting the underlying biology of bone disease in the CKD population.
Pten knockout in mouse preosteoblasts leads to changes in bone turnover and strength
Authors: Lorenz Judith , Richter Sandy , Kirstein Anna S , Kolbig Florentien , Nebe Michèle , Schulze Marco , Kiess Wieland , Spitzbarth Ingo , Klöting Nora , Le Duc Diana , Baschant Ulrike , Garten Antje
Published: January 2024

Bone development and remodeling are controlled by the phosphoinositide-3-kinase (Pi3k) signaling pathway. We investigated the effects of downregulation of phosphatase and tensin homolog (Pten), a negative regulator of Pi3k signaling, in a mouse model of Pten deficiency in preosteoblasts. We aimed to identify mechanisms that are involved in the regulation of bone turnover and are linked to bone disorders.

Femora, tibiae, and bone marrow stromal cells (BMSCs) isolated from mice with a conditional deletion of Pten (Pten cKO) in Osterix/Sp7-expressing osteoprogenitor cells were compared to Cre-negative controls. Bone phenotyping was performed by μCT measurements, bone histomorphometry, quantification of bone turnover markers CTX and procollagen type 1 N propeptide (P1NP), and three-point bending test. Proliferation of BMSCs was measured by counting nuclei and Ki-67–stained cells. In vitro, osteogenic differentiation capacity was determined by ALP staining, as well as by detecting gene expression of osteogenic markers.

BMSCs from Pten cKO mice were functionally different from control BMSCs. Osteogenic markers were increased in BMSCs derived from Pten cKO mice, while Pten protein expression was lower and Akt phosphorylation was increased. We detected a higher trabecular bone volume and an altered cortical bone morphology in Pten cKO bones with a progressive decrease in bone and tissue mineral density. Pten cKO bones displayed fewer osteoclasts and more osteoblasts (P = .00095) per trabecular bone surface and a higher trabecular bone formation rate. Biomechanical analysis revealed a significantly higher bone strength (P = .00012 for males) and elasticity of Pten cKO femora. On the cellular level, both proliferation and osteogenic differentiation capacity of Pten cKO BMSCs were significantly increased compared to controls.

Our findings suggest that Pten knockout in osteoprogenitor cells increases bone stability and elasticity by increasing trabecular bone mass and leads to increased proliferation and osteogenic differentiation of BMSCs.
Advanced glycation end products are not associated with bone mineral density, trabecular bone score, and bone turnover markers in adults with and without type 1 diabetes: a cross-sectional study
Authors: Coll Julie-Catherine , Turcotte Anne-Frédérique , Leslie William D , Michou Laëtitia , Weisnagel Stanley John , Mac-Way Fabrice , Albert Caroline , Berger Claudie , Morin Suzanne N , Rabasa-Lhoret Rémi , Gagnon Claudia
Published: January 2024

It is unclear if AGEs are involved in the bone fragility of type 1 diabetes (T1D). We evaluated whether skin AGEs by skin autofluorescence and serum AGEs (pentosidine, carboxymethyl-lysine [CML]) are independently associated with BMD by DXA (lumbar spine, hip, distal radius), trabecular bone score (TBS), serum bone turnover markers (BTMs: CTX; P1NP; osteocalcin), and sclerostin in participants with and without T1D. Linear regression models were used, with interaction terms to test effect modification by T1D status. In participants with T1D, correlations between skin and serum AGEs as well as between AGEs and 3-year HbA1C were evaluated using Spearman’s correlations. Data are mean ± SD or median (interquartile range). We included individuals who participated in a cross-sectional study and had BMD and TBS assessment (106 T1D/65 controls, 53.2% women, age 43 ± 15 yr, BMI 26.6 ± 5.5 kg/m2). Participants with T1D had diabetes for 27.6 ± 12.3 yr, a mean 3-yr HbA1C of 7.5 ± 0.9% and skin AGEs of 2.15 ± 0.54 arbitrary units. A subgroup of 65 T1D/57 controls had BTMs and sclerostin measurements, and those with T1D also had serum pentosidine (16.8[8.2–32.0] ng/mL) and CML [48.0 ± 16.8] ng/mL) measured. Femoral neck BMD, TBS, and BTMs were lower, while sclerostin levels were similar in participants with T1D vs controls. T1D status did not modify the associations between AGEs and bone outcomes. Skin AGEs were significantly associated with total hip and femoral neck BMD, TBS, BTMs, and sclerostin before, but not after, adjustment for confounders. Serum AGEs were not associated with any bone outcome. There were no significant correlations between skin and serum AGEs or between AGEs and 3-yr HbA1C. In conclusion, skin and serum AGEs are not independently associated with BMD, TBS, BTMs, and sclerostin in participants with relatively well-controlled T1D and participants without diabetes.
A study on ship hull form transformation using convolutional autoencoder
Authors: Seo Jeongbeom , Kim Dayeon , Lee Inwon
Published: January 2024

The optimal ship hull form in contemporary design practice primarily consists of three parts: hull form modification, performance prediction, and optimization. Hull form modification is a crucial step to affect optimization efficiency because the baseline hull form is varied to search for performance improvements. The conventional hull form modification methods mainly rely on human decisions and intervention. As a direct expression of the three-dimensional hull form, the lines are not appropriate for machine learning techniques. This is because they do not explicitly express a meaningful performance metric despite their relatively large data dimension. To solve this problem and develop a novel machine-based hull form design technique, an autoencoder, which is a dimensional reduction technique based on an artificial neural network, was created in this study. Specifically, a convolutional autoencoder was designed; firstly, a convolutional neural network (CNN) preprocessor was used to effectively train the offsets, which are the half-width coordinate values on the hull surface, to extract feature maps. Secondly, the stacked encoder compressed the feature maps into an optimal lower dimensional-latent vector. Finally, a transposed convolution layer restored the dimension of the lines. In this study, 21 250 hull forms belonging to three different ship types of containership, LNG carrier, and tanker, were used as training data. To describe the hull form in more detail, each was divided into several zones, which were then input into the CNN preprocessor separately. After the training, a low-dimensional manifold consisting of the components of the latent vector was derived to represent the distinctive hull form features of the three ship types considered. The autoencoder technique was then combined with another novel approach of the surrogate model to form an objective function neural network. Further combination with the deterministic particle swarm optimization method led to a successful hull form optimization example. In summary, the present convolutional autoencoder has demonstrated its significance within the machine learning-based design process for ship hull forms.
Exploring Racial Disparities in the 1918 Influenza Pandemic: A Case Study of Durham, North Carolina
Authors: Bryant Mallory , Baker Jeffrey
Published: January 2024

The paradox of excess mortality among White Americans during the 1918 influenza pandemic has long puzzled historians and scientists. Recent scholarship has suggested that this disparity was not true for the country as a whole, but rather regional variation was observed. The factors influencing these disparities remain speculative. A case study was conducted of Durham, North Carolina, a city known nationally for the achievements of its Black middle class, to further explore these themes relying on numerous sources including newspapers and death certificates. Though Durham’s overall mortality was lower than many places in North Carolina, the White mortality rate greatly exceeded that of the Black population. Previously described theories, including Alfred Crosby’s exposure hypothesis and segregation, were explored. The most notable difference between Durham’s pandemic narrative and other comparable towns was the robust healthcare response, which was made possible by the excellence of the Black nursing force from Lincoln Hospital. Nursing care was the best treatment available for the 1918 influenza, but most of the nation experienced severe nursing shortages due to the war effort. This study thus provides an example of how the Black health community has proven an active agent in countering the structural forces driving racial disparities.
Study on the fastening property of precision locknut under simulated dynamic impact loading with consideration of interference factors
Authors: Chang Huey-Ling , Chen Chih-Ming , Lee Chun-Ying , Huang Zi-Xuan
Published: January 2024

Screw thread fastening system is the category of mechanical connection utilizing both wedge and friction actions to transfer clamping force and torque. This fastening system shows the advantages of simple in structure and ease in application. However, its shortcomings include the performance limitation by dimension and precision, stress concentration induced by the notch geometry, loosening in dynamical service, susceptible to atmospheric condition, etc. Therefore, the possible interference on the anti-loosening property of the locknut by noise factors of the ambient temperature, operator characteristics, and type of torque wrench used was investigated using Taguchi method in this study beside the main control factors of type of locknut, fit clearance, and type of lubrication grease. The goal was to evaluate the anti-loosening property of the locknut, i.e. the anti-loosening ratio and axial force ratio, in a more realistic manner. The connection joint of the locknut was subjected to cyclic transverse impact and the anti-loosening property was measured after a specified number of cycles. The loading effect on the surface roughness of thread surface was examined and discussed after the test. It was found that the factor of locknut type dominated the influence over the lubrication grease and fit clearance factors. Through the analysis, the design with optimal combination of the control factors improved the axial force ratio and anti-loosening ratio by 7.8% and 47.9%, respectively.
Combined approach in the treatment of comminuted lateral Hoffa fracture: a case report
Authors: Nastov Nebojsha , Bekteshi Labinot , Nikolovski Andrej
Published: January 2024

Coronal-plane intra-articular fractures of the femoral condyle (Hoffa fractures) are rare, and difficult to diagnose and treat. They mostly result as a consequence of high-energy trauma and are combined with concomitant fractures (patellar, tibia shaft) and/or soft-tissue damage. A plain X-ray can miss the diagnosis initially and therefore computerized tomography scan is recommended, which can also help in the preoperative planning. The vast majority of these fractures are unicondylar (mostly lateral condyle fractured). The approach for their treatment can be anterior or posterior. In cases of fracture comminution, much more mutilant approaches with osteotomy have been described. A combined two-stage approach can be used to obtain anatomical reduction and fixation of all the fragments. We present a case of a 46-year-old male patient with comminuted lateral Hoffa fracture treated with a combined approach (extended posterior approach to the proximal tibia and lateral parapatellar) in a time interval of one month.
Severe right ventricular infarction due to iatrogenic aortocoronary dissection successfully treated by surgical repair and extracorporeal membrane oxygenation
Authors: Ono Shunya , Kawamoto Shuhei , Fukushima Toshiya , Shimozawa Motoharu , Tateishi Retsu , Haba Fumiya , Nakahara Yoshinori , Kanemura Takeyuki
Published: January 2024

Iatrogenic aortocoronary dissection (IACD) is a rare but potentially fatal complication of percutaneous coronary intervention or coronary angiography (CAG). In particular, if the condition of the patient is complicated by cardiogenic shock and right ventricular (RV) dysfunction, the mortality rate is high. Herein, we report the case of an 85-year-old woman with IACD who underwent elective CAG of the right coronary artery complicated with cardiogenic shock due to RV infarction. After prompt surgical repair and postoperative extracorporeal membrane oxygenation, the postoperative course was uneventful and the patient was discharged to a rehabilitation facility.
Berry shrivel in grapevine: a review considering multiple approaches
Authors: Griesser Michaela , Savoi Stefania , Bondada Bhaskar , Forneck Astrid , Keller Markus
Published: January 2024

Grapevine berry shrivel, a ripening disorder, causes significant economic losses in the worldwide wine and table grape industries. An early interruption in ripening leads to this disorder, resulting in shriveling and reduced sugar accumulation affecting yield and fruit quality. Loss of sink strength associated with berry mesocarp cell death is an early symptom of this disorder; however, potential internal or external triggers are yet to be explored. No pathogens have been identified that might cause the ripening syndrome. Understanding the underlying causes and mechanisms contributing to berry shrivel is crucial for developing effective mitigation strategies and finding solutions for other ripening disorders associated with climacteric and non-climacteric fruits. This review discusses alterations in the fruit ripening mechanism induced by berry shrivel disorder, focusing primarily on sugar transport and metabolism, cell wall modification and cell death, and changes in the phytohormone profile. The essential open questions are highlighted and analyzed, thus identifying the critical knowledge gaps and key challenges for future research.