bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automation and innovation in home hemodialysis machines
Authors: Shamy Osama El , Sloand James A. 
Published: October 2024

Purpose of review
In this review, we discuss the timeline of innovation and technologic development in home hemodialysis (HHD) in the United States and the legislative approvals that accompanied them.

Recent findings
The most recently FDA-approved home hemodialysis devices provide features that include on-demand and batch dialysate generation, access disconnect for venous needle dislodgement, touchscreen interface with visual and auditory prompts and animations, drop-in sterilized cartridges with prestrung tubing, hot water disinfection of tubing allowing extended-use, dialysate flow rates as high as 500 ml/min, as well as remote treatment monitoring capabilities. Furthermore, wearable/portable dialysis devices are currently under development to simplify dialysis delivery to patients with end-stage kidney disease.

Summary
Home hemodialysis devices providing longitudinal hemodialysis across different clinical settings, virtual reality headsets for more personalized training, automated patient support, as well as wearable device development and innovations give hope for a future where home hemodialysis is more accessible and seamless.
The Key to Successful Social Interactions
Authors: Brien Ashley R. , Hutchins Tiffany L. 
Published: October 2024

Autobiographical memory (ABM) is memory for past personal experiences and is foundational to the development of many cognitive processes. As such, ABM and social learning are developmentally intertwined and functionally dependent, and impairments in each are well-documented in autism. Evidence suggests that elaborative reminiscing (ER) causally and positively impacts neurotypical children’s ABM and social learning. The purpose of this study was to evaluate the effectiveness of a new caregiver-mediated ABM intervention that adapts the principles of ER in ways that align with best practices for supporting social learning in autistic children. Participants were 26 caregiver-child dyads; all children (ages 6–15 years) had a diagnosis of autism. We hypothesized that: (1) caregivers would demonstrate improvements in ER across three phases of study (pre-treatment, post-treatment, and follow-up) and (2) children would demonstrate improvements in supported and unsupported ABM and social learning. Results indicated that caregivers demonstrated increased elaborativeness at post-intervention, and that this was maintained at follow-up. Additionally, children demonstrated improvements in supported memory and some measures of social learning at post-intervention, and this was maintained at follow-up. Children also showed improvements in unsupported memory at post-intervention; however, this was not maintained. Results suggest that caregivers of autistic children can be trained to use ER, and that ER is associated with the development of supported memory in autistic children across a wide range of ages. Clinical applications include supporting social learning and connection in autism using ER.
SPP1+ tumor-associated macrophages induce radioresistance of nasopharyngeal carcinoma through crosstalk with the tumor microenvironment
Authors: Zhang Wenda , Lin Lili , Haoxuan Ying , Li Nan , Zhou Xinyi , Yang Qi , Hu Shulu , Cai Jiayi , Lin Anqi , Quan Cheng , Liu Zaoqu , Zhang Jian , Luo Peng , Wei Ting 
Published: October 2024

AbstractThe function and phenotype of tumor-associated macrophages (TAMs) influence the efficacy of radiotherapy. However, the effect of different subsets of TAMs on the radioresistance in nasopharyngeal carcinoma (NPC) still needs to be further explored. This study utilized single-cell RNA sequencing (scRNA-seq) to analyze 120,579 cells obtained from 15 NPC samples. Cell annotation, cell‒cell communication analysis, and functional annotation were used to investigate the impact of TAMs on the effectiveness of radiotherapy in NPC patients. Additionally, we employed RNA-seq data and clinical information from many patients, including 24 NPC samples from Zhujiang Hospital, 3,934 samples from patients with a history of radiotherapy, for further validation. We identified a hub TAM subpopulation, SPP1+ TAMs, that induced radioresistance in NPC based on single-cell RNA sequencing (scRNA-seq) data. We combined many public datasets to confirm their prognostic value in radiotherapy patients. We found that SPP1+ TAMs had stronger protumorigenic and immunosuppressive effects in the postradiotherapy recurrent tumor (PRRT) group. SPI1 transcription factor efficiently regulates the expression level of SPP1 in macrophages. In addition, we validated the underlying mechanisms by molecular docking, multiplex immunofluorescence and cellular experiments. In conclusions, by forming an immunosuppressive microenvironment and promoting tumor cell proliferation, SPP1+ TAMs leading to radioresistance and poor clinical prognosis in NPC patients. Targeting SPP1+ TAMs could provide new insights into improving the efficacy of radiotherapy in NPC patients.
Dietary Fiber Modulates Macrophage Activity in a Microfluidic Model of Colonocyte-Microbiota Interactions in Colorectal Cancer
Authors: Penarete-Acosta Daniel , Mittal Mohet , Chakraborty Sanjukta , Han Arum , Jayaraman Arul 
Published: October 2024

AbstractDietary fiber has been consistently associated with a decreased risk of colorectal cancer (CRC) development. While the apoptotic effect of dietary fiber microbial fermentation products on tumor colonocytes is well established, the role of these products on other components of the tumor microenvironment remains unexplored. Tumor associated macrophages play a critical role in tumor development in the colon; however, the effect of dietary fiber fermentation by microbiota on macrophage-colonocyte interaction in colorectal cancer has been difficult to dissect due to a lack of complexin vitromodels of CRC containing both immune cells and microbiota. Recently, we developed a microfluidic model that facilitates the coculture of CRC spheroids with complex microbial communities. Here, we expand our model to include macrophages and employ it to study the impact of dietary fiber on macrophage-colonocyte interaction. We optimized monocyte differentiation parametersin vitroand demonstrated the capacity of our model to recapitulate changes in microbiota composition and metabolic output associated with dietary fiber administrationin vivo. Combinatorial coculture of colonocytes with microbiota and macrophages revealed that alterations in microbial production of SCFA derived from dietary fiber fermentation correlated with enhanced colonocyte death, possibly mediated by an increase in transcription of tumor pro-apoptotic signals by macrophages. Our work highlights the capacity of complexin vitrosystems to study the role of microbial metabolism of dietary molecules on CRC colonocyte viability and macrophage activity.
Dopamine controls the Sensitivity to Manganese induced Dopaminergic neurotoxicity inCaenorhabditis elegans
Authors: Raj Vishnu , Thekkuveettil Anoopkumar 
Published: October 2024

AbstractManganism, a disease with characteristic degeneration of dopamine neurons, has distinct aetiology and clinical manifestations, striking similarities with Parkinson’s Disease (PD). Environmental exposure to manganese (Mn) is one of the risk factors for the occurrence of PD. The definitive role of dopamine (DA) in Mn mediated neurodegeneration, and its developmental impact has not been well studied. To understand the pathways involved in Mn-induced neurotoxicity, we usedC. elegansas the model system. Our results showed that adult worms treated with 50 and 100 mM MnCl2significantly increased DA neurodegeneration. L1 larvae spared without neurodegeneration when treated with MnCl2alone showed a significant increase in neurodegeneration (>50%) when MnCl2exposure was given after DA pretreatment. However, both adult and larval exposure to MnCl2demonstrated significant toxicity by reducing the survival rate. In adult worms, 100 mM MnCl2treatment after DA pretreatment further elevated the percentage of neurodegeneration. The Mn or DA alone exposed adult worms showed recovery of neuronal dopamine function within 24 hours, although exogenous DA and Mn treated worms showed prolonged behavioural defects.Cat-2mutants, without DA, were resistant to Mn mediated neurodegeneration. In contrast,Cat-2overexpressing strain displayed severe neurodegeneration at lower concentrations of MnCl2(50 mM). Our results on biochemical, behavioural and genetic assays proved endogenous/exogenous DA level controls the sensitivity to Mn induced dopaminergic neurotoxicity.
FoldMark: Protecting Protein Generative Models with Watermarking
Authors: Zhang Zaixi , Jin Ruofan , Fu Kaidi , Cong Le , Zitnik Marinka , Wang Mengdi 
Published: October 2024

ABSTRACTProtein structure is key to understanding protein function and is essential for progress in bioengineering, drug discovery, and molecular biology. Recently, with the incorporation of generative AI, the power and accuracy of computational protein structure prediction/design have been improved significantly. However, ethical concerns such as copyright protection and harmful content generation (biosecurity) pose challenges to the wide implementation of protein generative models. Here, we investigate whether it is possible to embed watermarks into protein generative models and their outputs for copyright authentication and the tracking of generated structures. As a proof of concept, we propose a two-stage method FoldMark as a generalized watermarking strategy for protein generative models. FoldMark first pretrain watermark encoder and decoder, which can minorly adjust protein structures to embed user-specific information and faithfully recover the information from the encoded structure. In the second step, protein generative models are fine-tuned with Low-Rank Adaptation modules with watermark as condition to preserve generation quality while learning to generate watermarked structures with high recovery rates. Extensive experiments are conducted on open-source protein structure prediction models (e.g., ESMFold and MultiFlow) and de novo structure design models (e.g., FrameDiff and FoldFlow) and we demonstrate that our method is effective across all these generative models. Meanwhile, our watermarking framework only exerts a negligible impact on the original protein structure quality and is robust under potential post-processing and adaptive attacks.
Activating p53Y220Cwith a Mutant-Specific Small Molecule
Authors: Zhu Xijun , Byun Woong Sub , Pieńkowska Dominika Ewa , Nguyen Kha The , Gerhartz Jan , Geng Qixiang , Qiu Tian , Zhong Jianing , Jiang Zixuan , Wang Mengxiong , Sarott Roman C. , Hinshaw Stephen M. , Zhang Tinghu , Attardi Laura D. , Nowak Radosław P. , Gray Nathanael S. 
Published: October 2024

AbstractTP53is the most commonly mutated gene in cancer, but it remains recalcitrant to clinically meaningful therapeutic reactivation. We present here the discovery and characterization of a small molecule chemical inducer of proximity that activates mutant p53. We named this compoundTRanscriptionalActivator ofp53 (TRAP-1) due to its ability to engage mutant p53 and BRD4 in a ternary complex, which potently activates mutant p53 and triggers robust p53 target gene transcription. Treatment of p53Y220Cexpressing pancreatic cell lines withTRAP-1results in rapid upregulation of p21 and other p53 target genes and inhibits the growth of p53Y220C-expressing cell lines. Negative control compounds that are unable to form a ternary complex do not have these effects, demonstrating the necessity of chemically induced proximity for the observed pharmacology. This approach to activating mutant p53 highlights how chemically induced proximity can be used to restore the functions of tumor suppressor proteins that have been inactivated by mutation in cancer.
A tumor-secreted protein utilizes glucagon release to cause host wasting
Authors: Ding Guangming , Li Yingge , Cheng Chen , Tan Kai , Deng Yifei , Pang Huiwen , Wang Zhongyuan , Dang Peixuan , Wu Xing , Rushworth Elisabeth , Yuan Yufeng , Yang Zhiyong , Song Wei 
Published: October 2024

AbstractTumor-host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional wasting of individual peripheral organs by tumors, whether and how tumors utilize critical host catabolic hormone(s) to simultaneously induce systemic host wasting, however, is largely unknown. Using the conserved yki3SA-tumor model inDrosophila, we discovered that tumors increase the production of adipokinetic hormone (Akh), a glucagon-like catabolic hormone, to cause systemic host wasting, including muscle dysfunction, lipid loss, hyperglycemia, and ovary atrophy. We next integrated RNAi screening and Gal4-LexA dual expression system to identify that yki3SA-gut tumors secrete Pvf1 to remotely activate its receptor Pvr in Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved the Pvf1-Pvr axis that triggers Mmp2-dependent ECM remodeling of APCs and enhances innervation from the excitatory cholinergic neurons. Interestingly, we also confirmed the similar mechanisms governing tumor-induced glucagon release and organ wasting in mammals. Blockade of either glucagon or PDGFR (homolog of Pvr) action efficiently ameliorated organ wasting in the presence of malignant tumors. Therefore, our results demonstrate that tumors remotely promote neural-associated Akh/glucagon production via Pvf1-Pvr axis to cause systemic host wasting.
Point mutations of the mitochondrial chaperone TRAP1 affect its functions and pro-neoplastic activity
Authors: Laquatra Claudio , Magro Alessia , Guarra Federica , Lambrughi Matteo , Fracasso Giulio , Bacchin Melissa , Ferrone Lavinia , La Spina Martina , Moroni Elisabetta , Papaleo Elena , Colombo Giorgio , Rasola Andrea 
Published: October 2024

AbstractThe mitochondrial chaperone TRAP1 is a key regulator of cellular homeostasis and its activity has important implications in neurodegeneration, ischemia and cancer. Recent evidence has indicated that TRAP1 mutations are involved in several disorders, even though the structural basis for the impact of point mutations on TRAP1 functions has never been studied. By exploiting a modular structure-based framework and molecular dynamics simulations, we investigated the effect of five TRAP1 mutations on its structure and stability. Each mutation differentially impacts long-range interactions, intra and inter-protomer dynamics and ATPase activity. Changes in these parameters influence TRAP1 functions, as revealed by their effects on the activity of the TRAP1 interactor succinate dehydrogenase (SDH). In keeping with this, TRAP1 point mutations affect the growth and migration of aggressive sarcoma cells, and alter sensitivity to a selective TRAP1 inhibitor. Our work provides new insights on the structure-activity relationship of TRAP1, identifying crucial amino acid residues that regulate TRAP1 proteostatic functions and pro-neoplastic activity.
Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypesin vitro
Authors: Podlesny-Drabiniok Anna , Romero-Molina Carmen , Patel Tulsi , See Wen Yi , Liu Yiyuan , Marcora Edoardo , Goate Alison M. 
Published: October 2024

AbstractMyeloid cells including brain-resident (microglia) and peripheral macrophages play a crucial role in various pathological conditions, including neurodegenerative disorders like Alzheimer’s disease (AD). They respond to disruption of tissue homeostasis associated with disease conditions by acquiring various transcriptional and functional states. Experimental investigation of these states is hampered by the lack of tools that enable accessible and robust reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypesin vitro. In this study, we investigated the ability of a cytokine mix, including interleukin-4 (IL4), colony stimulating factor 1 (CSF1/MCSF), interleukin 34 (IL34) and transforming growth factor beta (TGFβ), to induce reprogramming of cultured human THP-1 macrophages. Our results indicate this treatment led to significant transcriptomic changes, driving THP-1 macrophages towards a transcriptional state reminiscent of disease-associated microglia (DAM) and lipid-associated macrophages (LAM) collectively referred to as DLAM. Transcriptome profiling revealed gene expression changes related to oxidative phosphorylation, lysosome function, and lipid metabolism. Single-cell RNA sequencing revealed an increased proportion of DLAM clusters in cytokine mix-treated THP-1 macrophages. Functional assays demonstrated alterations in cell motility, phagocytosis, lysosomal activity, and metabolic and energetic profiles. Our findings provide insights into the cytokine-mediated reprogramming of macrophages towards disease-relevant states, highlighting their role in neurodegenerative diseases and potential for therapeutic development.
Effect of thermoneutral housing on MASLD severity, hepatic gene expression, and BAT activation during β3-adrenergic stimulation in mice
Authors: Pauline Martin Céline Marie , Polizzi Arnaud , Alquier-Bacquié Valérie , Huillet Marine , Rives Clémence , Dauriat Charlène , Bruse Justine , Melin Valentine , Naylies Claire , Lippi Yannick , Lasserre Frédéric , Wan JingHong , Flores-Flores Rémy , Bertrand-Michel Justine , Blas-Y-Estrada Florence , Rousseau-Bacquié Elodie , Levade Thierry , Rémignon Hervé , Langin Dominique , Mouisel Etienne , Lotersztajn Sophie , Chassaing Benoit , Gamet-Payrastre Laurence , Guillou Hervé , Ellero-Simatos Sandrine , Fougerat Anne , Loiseau Nicolas 
Published: October 2024

SummaryMetabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. No medication is approved for MASLD treatment, and relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis, and evaluate therapeutic approaches. Here we demonstrated that compared to standard temperature housing, thermoneutral housing aggravated western diet (WD)-induced obesity, diabetes, and steatosis in male mice, which was associated with increased hepatic expression of inflammation- and fibrosis-related genes. Accordingly, compared to standard-housed mice, thermoneutral-housed WD-fed mice developed more severe hepatic inflammation and fibrosis. The liver is the central metabolic organ in whole-body metabolic homeostasis. We used thermoneutrally housed mice with WD-induced MASLD to examine the effect of MASLD during β3- adrenergic stimulation, and found that diet-induced MASLD was associated with defective inter- organ metabolic cross-talk, leading to impaired brown adipose tissue activation.HighlightsThermoneutral housing promotes WD-induced obesity and MASLD in miceThermoneutral housing fosters WD-induced change in gene expressionThermoneutral housing fosters hepatic inflammation and fibrosisMASLD is associated with defective BAT response to β3-adrenergic stimulation
SPONGE: Simple Prior Omics Network GEnerator
Authors: Hovan Ladislav , Kuijjer Marieke L. 
Published: October 2024

AbstractGene regulatory networks modelled from experimental data can be improved through the use of prior biological knowledge on e.g. transcription factor binding. There are several tools that utilise this information. However, the prior networks used with them are often not updated and may fail to reflect the most up-to-date information. Here we present SPONGE, a Python module designed to access information across biological databases, chiefly JASPAR and STRING, to model two types of networks—a prior gene regulatory network mapping transcription factors to genes based on their predicted binding sites, and a prior protein-protein interaction network mapping potential interactions between transcription factors. SPONGE is mainly designed to work with the PANDA algorithm and the corresponding NetZoo family of tools. However, the networks are provided in an easily adaptable format for other tools. SPONGE was designed with ease of use in mind, and it provides sensible default values for all of its parameters while giving the users freedom to fine-tune them. The code for the Python module and the documentation can be found inour GitHub repository.
Serum and Tear Autoantibodies from NOD and NOR Mice as Potential Diagnostic Indicators of Local and Systemic Inflammation in Sjögren’s Disease
Authors: Kakan Shruti Singh , Abdelhamid Sara , Ju Yaping , MacKay J Andrew , Edman Maria C. , Raman Indu , Zhu Chengsong , Raj Prithvi , Hamm-Alvarez Sarah F 
Published: October 2024

AbstractBackgroundSjögren’s Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition.MethodsThe presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male NOD and male NOR mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Data were analyzed by R package Limma.ResultsAnalysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models.ConclusionNOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies.