bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review on the pathogenesis theory of cancerous toxin from the viewpoint of system theory
Authors: Guo Tianhao , Zhou Hongguang , Chen Fangping , Gu Yutian , Li Liu , Cheng Haibo 
Published: September 2024

Abstract
In recent years, traditional Chinese medicine (TCM) has made great progress in the prevention and treatment of cancer. It has gradually revealed its characteristics and advantages in clinical practice, including alleviating clinical symptoms, prolonging survival time, decreasing the adverse effects of chemotherapy, and improving living quality. However, clinical TCM treatment of cancer lacks systematic theoretical guidance, because ancient TCM has not formed a recognized theoretical system of cognitive cancer, and there still are different opinions on the pathogenesis of cancer. Due to the complexity of cancer, the essence of cancer pathogenesis has not been described accurately by using common pathogenic factors, such as pathogenic wind, cold, dampness, summer heat, dryness, and fire. Ancient and modern TCM physicians have a similar understanding that the occurrence of cancer is related to toxin. In the 1990s, the thought of cancerous toxin was first proposed by Prof Zhou Zhongying, a TCM master based on more than 60 years of clinical practice, who used “pandemic Qi (Li-Qi) is a specific pathogenic factor of epidemic disease” in Wenyi Lun (Treatise on Pestilence) for references. The pathogenesis theory of cancerous toxin was gradually established under the guidance of the thought of cancerous toxin. It holds that the cancerous toxin, a special pathogenic factor of cancer, is the key pathogenesis of the occurrence of malignant tumors. According to the pathogenesis theory of cancerous toxin, the basic pathogenesis of malignant tumors is the accumulation of pathogenic factors and cancerous toxin, and the deficiency of the vital Qi (Zheng-Qi). Therefore, the treatment principle involves eliminating pathogenic factors, resolving cancerous toxin, and supporting the vital Qi. The anticancer detoxification methods and the classification of Chinese medicinal herbs with anticancer detoxification effects were put forward. System theory has much in common with the concepts in the theory system of TCM, such as the universal relation theory, asking for a concrete analysis of concrete conditions, the humanism thought, and so on. This article aims to describe, review, and analyze the pathogenesis theory of cancerous toxin based on system theory for clinical practices.
Comparison of thoracic epidural catheter and continuous peripheral infusion for management of traumatic rib fracture pain
Authors: Beyene Robel T. , Wallace Marshall W. , Statzer Nicholas , Hamblin Susan E. , Woo Edward , Nelson Scott D. , Allen Brian F.S. , McEvoy Matthew D. , Riffert Derek A. , Wesoloski Amber N. , Ye Fei , Irlmeier Rebecca , Fiorentino Michele , Dennis Bradley M. 
Published: September 2024

BACKGROUND
Thoracic epidural catheters (TECs) are useful adjuncts to multimodal pain regimens in traumatic rib fractures. However, TEC placement is limited by contraindications, patient risk profile, and provider availability. Continuous peripheral infusion of ketamine and/or lidocaine is an alternative that has a modest risk profile and few contraindications. We hypothesized that patients with multiple traumatic rib fractures receiving TECs would have better pain control, in terms of daily morphine milligram equivalents (MMEs) and mean pain scores (MPSs) when compared with continuous peripheral infusions of ketamine and/or lidocaine.

METHODS
We retrospectively analyzed traumatic rib fracture admissions to a level 1 trauma center between January 2018 and December 2020. We evaluated two treatment groups: TEC only and continuous infusion only (drip only). A linear mixed-effects model evaluated the association of MME with treatment group. An interaction term of treatment group by time (days 1–7) was included to allow estimating potential time-dependent treatment effect on MME. A zero-inflated Poisson mixed-effects model evaluated the association of treatment with MPS. Both models adjusted for confounders.

RESULTS
A total of 1,647 patients were included. After multivariable analysis, a significant, time-varying dose-response relationship between treatment group and MME was found, indicating an opioid-sparing effect favoring the TEC-only group. The opioid-sparing benefit for TEC-only therapy was most prominent at day 3 (27.4 vs 36.5 MME) and day 4 (27.3 vs 36.2 MME) (p < 0.01). The drip-only group had 1.21 times greater MPS than patients with TEC only (p < 0.001).

CONCLUSION
Drip-only analgesia is associated with higher daily MME use and MPS, compared with TEC only. The maximal benefit of TEC therapy appears to be on days 3 and 4. Prospective, randomized comparison between groups is necessary to evaluate the magnitude of the treatment effect.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Real-time attending trauma surgeon assessment of direct-to-operating room trauma resuscitations: Results from a prospective observational study
Authors: Lee Heewon , Dilday Joshua , Johnson Amelia , Kuchler Andrea , Rott Michael , Cole Frederick , Barbosa Ronald , Long William , Martin Matthew J. 
Published: September 2024

BACKGROUND
Direct-to-operating room (DOR) resuscitation expedites interventions for trauma patients. Perceived benefit from the surgeon's perspective is not well known. This study assesses the integration of a real-time surgeon assessment tool into a DOR protocol.

METHODS
Surgeon assessment tool results from a prospective study of DOR cases were analyzed. Analysis assessed patient factors and surgeon perception for appropriateness and benefit of DOR. Multivariate analysis identified independent factors associated with perceived DOR benefit.

RESULTS
A total of 104 trauma patients underwent DOR resuscitation; 84% were perceived as appropriate triage, and 48% as beneficial. Patients with Injury Severity Score of >15 (50% vs. 28%), systolic blood pressure of <90 mm Hg (24% vs. 9%), and severe abdominal injury (28% vs. 9%) had higher perceived DOR benefits (all p < 0.05). Patients deemed to benefit from DOR underwent more emergent interventions or truncal surgery (44% vs. 92%, p < 0.01). No difference in benefit was seen based on age, sex, Glasgow Coma Scale score of <9, or injury mechanism. Forty-four percent had perceived benefit from DOR resuscitation despite requiring imaging after initial evaluation. Patients with perceived benefit had a higher rate of unplanned return to the operating room (16% vs. 2%, p < 0.05), but no differences in complication rates, Glasgow Outcome Score, or mortality. Injury Severity Score of >15 was the only independently associated variable with a perceived benefit on surgeon assessment tool (odds ratio, 3.5; p < 0.05).

CONCLUSION
The majority of DOR resuscitations were deemed as appropriately triaged, and approximately half had a perceived benefit. Benefit was associated with higher injury severity and the need for urgent interventions but was not predicted by injury mechanism or other triage variables.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Nutrient starvation activates ECM remodeling gene enhancers associated with inflammatory bowel disease risk in fibroblasts
Authors: Secchia Stefano , Beilinson Vera , Chen Xiaoting , Yang Zi F. , Wayman Joseph A. , Dhaliwal Jasbir , Jurickova Ingrid , Angerman Elizabeth , Denson Lee A. , Miraldi Emily R. , Weirauch Matthew T. , Ikegami Kohta 
Published: September 2024

ABSTRACTNutrient deprivation induces a reversible cell cycle arrest state termed quiescence, which often accompanies transcriptional silencing and chromatin compaction. Paradoxically, nutrient deprivation is associated with activated fibroblast states in pathological microenvironments in which fibroblasts drive extracellular matrix (ECM) remodeling to alter tissue environments. The relationship between nutrient deprivation and fibroblast activation remains unclear. Here, we report that serum deprivation extensively activates transcription of ECM remodeling genes in cultured fibroblasts, despite the induction of quiescence. Starvation-induced transcriptional activation accompanied large-scale histone acetylation of putative distal enhancers, but not promoters. The starvation-activated putative enhancers were enriched for non-coding genetic risk variants associated with inflammatory bowel disease (IBD), suggesting that the starvation-activated gene regulatory network may contribute to fibroblast activation in IBD. Indeed, the starvation-activated genePLAU, encoding uPA serine protease for plasminogen and ECM, was upregulated in inflammatory fibroblasts in the intestines of IBD patients. Furthermore, the starvation-activated putative enhancer atPLAU, which harbors an IBD risk variant, gained chromatin accessibility in IBD patient fibroblasts. This study implicates nutrient deprivation in transcriptional activation of ECM remodeling genes in fibroblasts and suggests nutrient deprivation as a potential mechanism for pathological fibroblast activation in IBD.HIGHLIGHTS- Serum starvation transcriptionally activates ECM remodeling genes in fibroblasts.- Fibroblast starvation activates putative distal enhancers associated with ECM remodeling genes.- Starvation-activated putative enhancers are enriched for inflammatory bowel disease (IBD) risk variants.-PLAUenhancer and expression are activated in IBD intestinal fibroblasts, as in starved fibroblasts.
Non-canonical IL-22 receptor signaling remodels the mucosal barrier during fungal immunosurveillance
Authors: Millet Nicolas , Sekar Jinendiran , Solis Norma V. , Millet Antoine , Aggor Felix E.Y. , Wildeman Asia , Lionakis Michail S. , Gaffen Sarah L. , Jendzjowsky Nicholas , Filler Scott G. , Swidergall Marc 
Published: September 2024

AbstractMucosal barrier integrity is vital for homeostasis with commensal organisms while preventing pathogen invasion. We unexpectedly found that fungal-induced immunosurveillance enhances resistance to fungal outgrowth and tissue invasion by remodeling the oral mucosal epithelial barrier in mouse models of adult and neonatalCandida albicanscolonization. Epithelial subset expansion and tissue remodeling were dependent on interleukin-22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) signaling, through a non-canonical receptor complex composed of glycoprotein 130 (gp130) coupled with IL-22RA1 and IL-10RB. Immunosurveillance-induced epithelial remodeling was restricted to the oral mucosa, whereas barrier architecture was reset once fungal-specific immunity developed. Collectively, these findings identify fungal-induced transient mucosal remodeling as a critical determinant of resistance to mucosal fungal infection during early stages of microbial colonization.
Phylogeny-based selection of representative variants with Navargator: Proof of principle using humoral cross-reactivity data from two immunization studies
Authors: Curran David M. , Ng Dixon , Parkinson John , Moraes Trevor F. , Gray-Owen Scott D. , Fegan Jamie E. 
Published: September 2024

AbstractBackgroundThe accessibility to the immune system of bacterial surface proteins makes them attractive targets for subunit vaccines. However, this same property also means they tend to exhibit high sequence variability. Achieving broad cross-protection usually necessitates that antigens from multiple isolates are included, but the choice of sequence variant is a non-trivial problem. Visual inspection of phylogenetic trees is the norm, but this is subjective and can be greatly influenced by the choice of viewing software. This has real-world implications, as groups have shown that the selection of non-optimal antigens likely led to lower cross-protection in the commercially available vaccines againstNeisseria meningitidisserogroup B.Aim / MethodsTo address this problem, we have developed Navargator, bioinformatics software that takes a phylogenetic tree as input and identifies the variants that are the most similar to the greatest number of other sequences. The underlying premise is that cross-reactivity will be correlated with phylogenetic distances extracted from the tree; this was validated by several rodent immunization studies with the proteins transferrin-binding protein B and factor H binding protein fromN. meningitidisandN. gonorrhoeae, measuring antibody-based cross-reactivity between an antigen panel using a custom high-throughput ELISA.ResultsNavargator has been made freely available both as an online tool and as source code for local installation. We implemented several different clustering methods, with exact algorithms for smaller datasets, and heuristics suitable for large trees of thousands of sequences. Our immunization studies have shown that this approach is sound, and that cross-reactivity is predicted well by phylogenetic distances in a sigmoidal manner.ConclusionsThe complexity of vaccine development rises sharply with each additional antigen included, so using the minimal number required is an important consideration. Navargator attempts to facilitate this in a systematic and generalizable manner. The user can run the analysis by selecting their desired number of representatives, or they can provide any form of cross-reactivity data and have the program identify a minimum reactivity threshold via correlation with the phylogenetic tree. The program will then identify the smallest number of representatives required to satisfy this threshold.
genomesizeR: An R package for genome size prediction
Authors: Mercier Celine , Elleouet Joane , Garrett Loretta , Wakelin Steve A 
Published: September 2024

SummaryThe genome size of organisms present in an environment can provide many insights into evolutionary and ecological processes at play in that environment. The genomic revolution has enabled a rapid expansion of our knowledge of genomes in many living organisms, and most of that knowledge is classified and readily available in the databases of the National Center for Biotechnology Information (NCBI). ThegenomesizeRtool leverages the wealth of taxonomic and genomic information present in NCBI databases to infer the genome size of Archeae, Bacteria, or Eukaryote organisms identified at any taxonomic level. This R package uses statistical modelling on data from the most up-to-date NCBI databases and provides three statistical methods for genome size prediction of a given taxon, or group of taxa. A straightforward ‘weighted mean’ method identifies the closest taxa with available genome size information in the taxonomic tree, and averages their genome sizes using weights based on taxonomic distance. A frequentist random effect model uses nested genus and family information to output genome size estimates. Finally a third option provides predictions from a distributional Bayesian multilevel model which uses taxonomic information from genus all the way to superkingdom, therefore providing estimates and uncertainty bounds even for under-represented taxa.All three methods use:A list of queries; a query being a taxon or a list of several taxa. The package was designed to make it easy to use with data coming from environmental DNA experiments, but works with any table of taxa.A reference database containing all the known genome sizes, built from the NCBI databases, with associated taxa, provided in an archive to download.A taxonomic tree structure as built by the NCBI, provided in the same archive.genomesizeRretrieves the taxonomic classification of input queries, estimates the genome size of each query, and provides 95% confidence intervals for each estimate.
Mutations inPSEN1predispose inflammation in an astrocyte model of familial Alzheimer’s disease through disrupted regulated intramembrane proteolysis
Authors: Ziff Oliver J. , Jolly Sarah , Casey Jackie M. , Granat Lucy , Samra Satinder , Seto-Salvia Nuria , Alatza Argyro , Phadke Leela , Galet Benjamin , Ravassard Philippe , Potier Marie-Claude , Fox Nick C. , Hardy John , Salih Dervis , Whiting Paul , Ducotterd Fiona , Patani Rickie , Wray Selina , Arber Charles 
Published: September 2024

AbstractMutations inPSEN1cause familial Alzheimer’s disease with almost complete penetrance. Age at onset is highly variable between differentPSEN1mutations and even within families with the same mutation. Current research into late onset Alzheimer’s disease implicates inflammation in both disease onset and progression. PSEN1 is the catalytic subunit of γ-secretase, responsible for regulated intramembrane proteolysis of numerous substrates that include cytokine receptors. For this reason, we tested the hypothesis that mutations inPSEN1impact inflammatory responses in astrocytes, thereby contributing to disease progression.Here, using iPSC-astrocytes, we show that PSEN1 is upregulated in response to inflammatory stimuli, and this upregulation is disrupted by pathologicalPSEN1mutations. Using transcriptomic analyses, we demonstrate thatPSEN1mutant astrocytes have an augmented inflammatory profile in their basal state, concomitant with an upregulation of genes coding for regulated intramembrane proteolytic and robust activation of JAK-STAT signalling. Using JAK-STAT2 as an example signalling pathway, we show altered phosphorylation cascades inPSEN1mutant astrocytes, reinforcing the notion of altered cytokine signalling cascades. Finally, we use small molecule modulators of γ-secretase to confirm a role for PSEN1/γ-secretase in regulating the astrocytic response to inflammatory stimuli.Together, these data suggest that mutations inPSEN1enhance cytokine signalling via impaired regulated intramembrane proteolysis, thereby predisposing astrocytic inflammatory profiles. These findings support a two-hit contribution ofPSEN1mutations to fAD pathogenesis, not only impacting APP and Aβ processing but also altering the cellular response to inflammation.
Burst firing optimizes invariant coding of natural communication signals by electrosensory neural populations
Authors: Metzen Michael G. , Akhshi Amin , Bashivan Pouya , Khadra Anmar , Chacron Maurice J. 
Published: September 2024

AbstractAccurate perception of objects within the environment independent of context is essential for an organism’s survival. While neurons that respond in an invariant manner to identity-preserving transformations of objects are thought to provide a neural correlate of context-independent perception, how these emerge in the brain remains poorly understood. Here we demonstrate that burst firing in neural populations can give rise to an invariant representation of highly heterogeneous natural communication stimuli. Multi-unit recordings from central sensory neural populations showed that considering burst spike trains led to invariant representations at the population but not the single neuron level. Computational modeling further revealed that optimal invariance is achieved for levels of burst firing seen experimentally. Taken together, our results demonstrate a novel function for burst firing towards establishing invariant representations of sensory input in neural populations.
Inferring cell differentiation maps from lineage tracing data
Authors: Sashittal Palash , Zhang Richard Y. , Law Benjamin K. , Strzalkowski Alexander , Schmidt Henri , Bolondi Adriano , Chan Michelle M. , Raphael Benjamin J. 
Published: September 2024

AbstractDuring development, mulitpotent cells differentiate through a hierarchy of increasingly restricted progenitor cell types until they realize specialized cell types. A cell differentiation map describes this hierarchy, and inferring these maps is an active area of research spanning traditional single marker lineage studies to data-driven trajectory inference methods on single-cell RNA-seq data. Recent high-throughput lineage tracing technologies profile lineages and cell types at scale, but current methods to infer cell differentiation maps from these data rely on simple models with restrictive assumptions about the developmental process. We introduce a mathematical framework for cell differentiation maps based on the concept of potency, and develop an algorithm,Carta, that infers an optimal cell differentiation map from single-cell lineage tracing data. The key insight inCartais to balance the trade-off between the complexity of the cell differentiation map and the number of unobserved cell type transitions on the lineage tree. We show thatCartamore accurately infers cell differentiation maps on both simulated and real data compared to existing methods. In models of mammalian trunk development and mouse hematopoiesis,Cartaidentifies important features of development that are not revealed by other methods including convergent differentiation of specialized cell types, progenitor differentiation dynamics, and the refinement of routes of differentiation via new intermediate progenitors.Code availabilityCartasoftware is available athttps://github.com/raphael-group/CARTA
CNValidatron, automated validation of CNV calls using computer vision
Authors: Montalbano Simone , Walters G. Bragi , Jonsson Gudbjorn F. , Gådin Jesper R. , Werge Thomas , Stefansson Hreinn , Stefánsson Kári , Ingason Andrés 
Published: September 2024

AbstractMotivationFor more than a decade, running PennCNV on SNP array data has been the gold standard for detecting Copy Number Variants (CNVs, deletions and duplications). It is generally assumed that PennCNV has high sensitivity but poor specificity, leading to a large portion of CNV calls being false positives. Researchers often rely on manual inspection of the raw data to validate CNV calls. However, this approach is not feasible for more than a handful of loci in large collections.ResultsHere we present an R package implementing a convolutional neural network capable of automating CNV validation with an accuracy comparable to a trained human analyst. We also present an in-depth analysis into PennCNV false positive and false negative rates. Finally, we propose an algorithm to simplify the analysis of genome-wide CNV calls computing CNV regions.Availability and implementationThe code is available on GitHubhttps://github.com/SinomeM/CNValidatron_fl.
Expansion of functional human salivary acinar cell spheroids with reversible thermo-ionically crosslinked 3D hydrogels
Authors: Munguia-Lopez Jose G. , Pillai Sangeeth , Zhang Yuli , Gantz Amatzia , Camasao Dimitria B. , Nazhat Showan N. , Kinsella Joseph M. , Tran Simon D. 
Published: September 2024

AbstractXerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome, with no permanent cure existing for this debilitating condition. To this end,in vitroplatforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: 1) alginate-gelatin (AG), 2) collagen-containing AG (AGC), and 3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (∼11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids for downstream applications.