bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revolution in sepsis: a symptoms-based to a systems-based approach?
Authors: Dobson Geoffrey P. , Letson Hayley L. , Morris Jodie L. 
Published: May 2024

AbstractSevere infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy and multiple organ dysfunction. Males appear to have a higher risk of mortality than females. Currently, there are few or no effective drug therapies to protect the brain, maintain the blood brain barrier, resolve excessive inflammation and reduce secondary injury in other vital organs. We propose a major reason for lack of progress is a consequence of the treat-as-you-go, single-nodal target approach, rather than a more integrated, systems-based approach. A new revolution is required to better understand how the body responds to an infection, identify new markers to detect its progression and discover new system-acting drugs to treat it. In this review, we present a brief history of sepsis followed by its pathophysiology from a systems’ perspective and future opportunities. We argue that targeting the body’s early immune-driven CNS-response may improve patient outcomes. If the barrage of PAMPs and DAMPs can be reduced early, we propose the multiple CNS-organ circuits (or axes) will be preserved and secondary injury will be reduced. We have been developing a systems-based, small-volume, fluid therapy comprising adenosine, lidocaine and magnesium (ALM) to treat sepsis and endotoxemia. Our early studies indicate that ALM therapy shifts the CNS from sympathetic to parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces inflammation, corrects coagulopathy, and maintains tissue O2supply. Future research will investigate the potential translation to humans.
Glutathione-depleting Liposome Adjuvant for Augmenting the Efficacy of a Glutathione Covalent Inhibitor Oridonin for Acute Myeloid Leukemia Therapy
Authors: Liu Yi , Wang Xiaoning , Feng Hui , Li Xinyan , Yang Runyu , Zhang Mengyao , Du Yue , Liu Ruimin , Luo Minna , Li Zhiyi , Liu Bo , Wang Jincheng , Wang Wenjuan , An Feifei , Niu Fan , He Pengcheng 
Published: May 2024

Abstract
Background
Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH.

Methods
We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug’s water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes’ surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug’s impact on AML targets.

Results
We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells.

Conclusion
The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.
Effect of robot-assisted gait training on improving cardiopulmonary function in stroke patients: a meta-analysis
Authors: Chen Xiao , Yin Lu , Hou Yangbo , Wang Jie , Li Yongyi , Yan Juntao , Tao Jiming , Ma Shujie 
Published: May 2024

Abstract
Objective
Understanding the characteristics related to cardiorespiratory fitness after stroke can provide reference values for patients in clinical rehabilitation exercise. This meta- analysis aimed to investigate the effect of robot-assisted gait training in improving cardiorespiratory fitness in post-stroke patients, compared to conventional rehabilitation training.

Methods
PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, CBM, CNKI and Wanfang databases were searched until March 18th, 2024. Randomized controlled trials (RCTs) comparing the effectiveness of robot-assisted gait training versus control group were included. The main outcome variable was peak oxygen uptake. 6-minute walking test, peak heart rate, peak inspiratory expiratory ratio as our secondary indicators. RevMan 5.3 software was used for statistical analysis.

Results
A total of 17 articles were included, involving 689 subjects. The results showed a significant effect for robot-assisted gait training to improve VO2peak (MD = 1.85; 95% CI: -0.13 to 3.57; p = 0.04) and 6WMT (MD = 19.26; 95% CI: 10.43 to 28.08; p < 0.0001). However, no significant difference favouring robot-assisted gait training were found in HRpeak (MD = 3.56; 95% CI: -1.90 to 9.02; p = 0.20) and RERpeak (MD = -0.01; 95% CI: -0.04 to 0.01; p = 0.34).

Conclusion
These results showed that robot-assisted gait training may have a beneficial effect in improving VO2peak and 6WMT, with a moderate recommendation level according to the GRADE guidelines.
Effect of umbilical cord blood-mononuclear cells on knee osteoarthritis in rabbits
Authors: Fu Yuhang , Zhang Chi , Yang Yong , Zhou Baisui , Yang Meng , Zhu Guoshuai , Zhu Yonglin 
Published: May 2024

Abstract
Background
To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.

Methods
A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1β levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR.

Results
The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1β in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs.

Conclusion
Injections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.
The novel SMYD3 inhibitor EM127 impairs DNA repair response to chemotherapy-induced DNA damage and reverses cancer chemoresistance
Authors: Sanese Paola , De Marco Katia , Lepore Signorile Martina , La Rocca Francesca , Forte Giovanna , Latrofa Marialaura , Fasano Candida , Disciglio Vittoria , Di Nicola Elisabetta , Pantaleo Antonino , Bianco Giusy , Spilotro Vito , Ferroni Claudia , Tubertini Matilde , Labarile Nicoletta , De Marinis Lucia , Armentano Raffaele , Gigante Gianluigi , Lantone Valerio , Lantone Giuliano , Naldi Marina , Bartolini Manuela , Varchi Greta , Del Rio Alberto , Grossi Valentina , Simone Cristiano 
Published: May 2024

Abstract
Background
SMYD3 has been found implicated in cancer progression. Its overexpression correlates with cancer growth and invasion, especially in gastrointestinal tumors. SMYD3 transactivates multiple oncogenic mechanisms, favoring cancer development. Moreover, it was recently shown that SMYD3 is required for DNA restoration by promoting homologous recombination (HR) repair.

Methods
In cellulo and in vivo models were employed to investigate the role of SMYD3 in cancer chemoresistance. Analyses of SMYD3-KO cells, drug-resistant cancer cell lines, patients’ residual gastric or rectal tumors that were resected after neoadjuvant therapy and mice models were performed. In addition, the novel SMYD3 covalent inhibitor EM127 was used to evaluate the impact of manipulating SMYD3 activity on the sensitization of cancer cell lines, tumorspheres and cancer murine models to chemotherapeutics (CHTs).

Results
Here we report that SMYD3 mediates cancer cell sensitivity to CHTs. Indeed, cancer cells lacking SMYD3 functions showed increased responsiveness to CHTs, while restoring its expression promoted chemoresistance. Specifically, SMYD3 is essential for the repair of CHT-induced double-strand breaks as it methylates the upstream sensor ATM and allows HR cascade propagation through CHK2 and p53 phosphorylation, thereby promoting cancer cell survival. SMYD3 inhibition with the novel compound EM127 showed a synergistic effect with CHTs in colorectal, gastric, and breast cancer cells, tumorspheres, and preclinical colorectal cancer models.

Conclusions
Overall, our results show that targeting SMYD3 may be an effective therapeutic strategy to overcome chemoresistance.
Identifying uncertainty in physical–chemical property estimation with IFSQSAR
Authors: Brown Trevor N. , Sangion Alessandro , Arnot Jon A. 
Published: May 2024

AbstractThis study describes the development and evaluation of six new models for predicting physical–chemical (PC) properties that are highly relevant for chemical hazard, exposure, and risk estimation: solubility (in water SW and octanol SO), vapor pressure (VP), and the octanol–water (KOW), octanol–air (KOA), and air–water (KAW) partition ratios. The models are implemented in the Iterative Fragment Selection Quantitative Structure–Activity Relationship (IFSQSAR) python package, Version 1.1.0. These models are implemented as Poly-Parameter Linear Free Energy Relationship (PPLFER) equations which combine experimentally calibrated system parameters and solute descriptors predicted with QSPRs. Two other ancillary models have been developed and implemented, a QSPR for Molar Volume (MV) and a classifier for the physical state of chemicals at room temperature. The IFSQSAR methods for characterizing applicability domain (AD) and calculating uncertainty estimates expressed as 95% prediction intervals (PI) for predicted properties are described and tested on 9,000 measured partition ratios and 4,000 VP and SW values. The measured data are external to IFSQSAR training and validation datasets and are used to assess the predictivity of the models for “novel chemicals” in an unbiased manner. The 95% PI intervals calculated from validation datasets for partition ratios needed to be scaled by a factor of 1.25 to capture 95% of the external data. Predictions for VP and SW are more uncertain, primarily due to the challenges in differentiating their physical state (i.e., liquids or solids) at room temperature. The prediction accuracy of the models for log KOW, log KAW and log KOA of novel, data-poor chemicals is estimated to be in the range of 0.7 to 1.4 root mean squared error of prediction (RMSEP), with RMSEP in the range 1.7–1.8 for log VP and log SW. Scientific contributionNew partitioning models integrate empirical PPLFER equations and QSARs, allowing for seamless integration of experimental data and model predictions. This work tests the real predictivity of the models for novel chemicals which are not in the model training or external validation datasets.
Graphical Abstract
Multilayer 3D seismic attribute analysis and fault framework modeling of shallow extensional fault systems in the Delaware Basin
Authors: Petkovsek Chesney 
Published: May 2024

Shallow extensional fault systems within the southern Delaware Basin have gained the interest of Permian operators since published works noted them in 2019. These shallow extensional fault systems, referred to as “lineaments” by operators, are seismogenic hazards, pose significant hazards to drilling operations, and are associated with elevated water-oil ratios and H2S concentrations. Previous work using seismic attribute analysis has resulted in the successful mapping of extensional fault systems at the Ochoan/Guadalupian interface, whereas fault geometry, origin, and depth of penetration have remained elusive. First- and second-order ant tracking of the variance cube is rendered on multiple seismic horizons throughout an 856 km2 (approximately 330 mi2) depth-migrated 3D seismic reflection volume to expand the interpretation of the deformation zone at depth and guide a robust 3D fault model that forms the framework for the predictive model. A total of 60 previously undocumented features are identified in southwestern Reeves County — 56 penetrate the Ochoan/Guadalupian interface, 60 penetrate the middle Guadalupian, 29 penetrate the early Guadalupian, and 21 penetrate the early Leonardian. Structural modeling returns an average strike orientation of 318° north-northwest–south-southeast and an average dip of 84°. Spatial and temporal analysis of the model constrains the timing of extension to the Cenozoic. In contrast to previous studies, the improved depth of investigation of the 3D fault model allows for the correlation of documented drilling hazards with offset wastewater disposal wells along shared lineaments. Communication is indicated by H2S risking flags from mass spectrometry data along the vertical and horizontal sections of producing and injecting wells. Drilling data validates the seismic characterization and prediction of the 3D faulted architecture within the largest contiguous study of shallow extensional fault systems within the Delaware Basin and establishes a repeatable workflow for mitigating the negative impacts of shallow lineament geohazards on drilling operations and production profiles.
International Variations in Surgical Quality of Care in Men With Prostate Cancer: Results From the TrueNTH Global Registry
Authors: Sibert Nora Tabea , Garin Olatz , Ferrer Montserrat , Connor Sarah E. , Graham Ian D. , Litwin Mark S. , Millar Jeremy , Moore Caroline M. , Nguyen Anissa V. , Paich Kellie , Kowalski Christoph 
Published: May 2024

PURPOSE Functional problems such as incontinence and sexual dysfunction after radical prostatectomy (RP) are important outcomes to evaluate surgical quality in prostate cancer (PC) care. Differences in survival after RP between countries are known, but differences in functional outcomes after RP between providers from different countries are not well described. METHODS Data from a multinational database of patients with PC (nonmetastatic, treated by RP) who answered the EPIC-26 questionnaire at baseline (before RP, T0) and 1 year after RP (T1) were used, linking survey data to clinical information. Casemix-adjusted incontinence and sexual function scores (T1) were calculated for each country and provider on the basis of regression models and then compared using minimally important differences (MIDs). RESULTS A total of 21,922 patients treated by 151 providers from 10 countries were included. For the EPIC-26 incontinence domain, the median adjusted T1 score of countries was 76, with one country performing more than one MID (for incontinence: 6) worse than the median. Eighteen percent of the variance ( R2) of incontinence scores was explained by the country of the providers. The median adjusted T1 score of sexual function was 33 with no country performing perceivably worse than the median (more than one MID worse), and 34% ( R2) of the variance of the providers' scores could be explained by country. CONCLUSION To our knowledge, this is the first comparison of functional outcomes 1 year after surgical treatment of patients with PC between different countries. Country is a relevant predictor for providers' incontinence and sexual function scores. Although the results are limited because of small samples from some countries, they should be used to enhance cross-country initiatives on quality improvement in PC care.
Contours of a Historical Materialist Theory of Transsexuality
Authors: Llaveria Caselles Eric 
Published: May 2024

Abstract
This article proposes to engage with the etiological question haunting the transsexual subject as a sociogenic project of identifying and analyzing relevant problematizations of transsexuality. The article elaborates on the social contexts of the biomedical, sociological, and genealogical problematizations of transsexuality, critically assessing their onto-epistemic stances and political fields. Building on the limitations of these three problematizations, the article projects a fourth problematization drawing from Marxist-feminist approaches. To this end, it engages critically with four different conceptualizations of transsexuality in current trans Marxist debates and establishes the conditions for a distinct historical materialist problematization. Finally, the article puts forward a definition of transsexuality as a technology of containment of the possibility of gender mobility and ambiguity within the Western biopolitical generative dispositive in its functional relation to the capitalist mode of production. The containment works through the displacement of a structural conflict of social reproduction specific to the Western modern/colonial gender order to the interiority of the trans subject, ultimately foreclosing the possibility of the democratization of relations of procreation. Gender intransigence is proposed as an epistemic and political category for historical materialist problematization of transsexuality which can provide an alternative to the hegemonic framework of gender identity.
Shadows of the Empire/A New Hope
Authors: Fulloon JD 
Published: May 2024

Abstract
Online news outlets have published a fair amount of journalism concerning Isabel Fall's 2020 science fiction short story, “I Sexually Identify as an Attack Helicopter,” later retitled “Helicopter Story.” Yet the highly polarized reception the story received has made up the bulk of the discourse. This is a tragic oversight, as the most interesting thing about “Helicopter Story” is not the online reaction to its original title but how the content of the story itself serves as an illustration of a dialectical history of gender in the United States. In Fall's story, gender is partially demystified by acknowledging the eradication of Indigenous cross-gender practices, racially imbricated plasticity, and the fusion of state and medical power that determines and shapes gender. Even so, some mystification remains. Gender is a reified social relation whose origins are an attempt to install binary biological sex. However, this reification does not result in the reinstallation of gender as ineluctable truth. Rather, it provides the opportunity for the expression of utopian desire, as theorized in the queer Marxism of Kevin Floyd or the dialectical literary criticism of Fredric Jameson, both of whom draw heavily from Frankfurt School theorist Herbert Marcuse when proposing that the only way out of reification is through. A proposed subgenre of science fiction, “speculative gender fiction,” is a literary form uniquely suited for exploring both the reification of gender and the utopian desire to escape from it.
Becoming Spectral
Authors: Montgomery Westley 
Published: May 2024

Abstract
Often defined by its characteristic and heavy use of autotuned vocals, the microgenre hyper-pop is perhaps just as recognizable for the ubiquitous transness of its most important artists. Reading trans hyper-pop performers Blackwinterwells, laura les, and quinn's uses of the figure of the “bedsheet ghost,” this article explores trans artists’ responses to late capitalism's regimes of alienation as a means of desubjectivization through strategies of becoming spectral—resisting commodification through a spectral orientation toward their sonic corporeality.
Archipelagic Thinking and Mozambican Women's Multivalent Articulations: Paulina Chiziane'sThe First Wife
Authors: Lim R. J. 
Published: May 2024

AbstractArchipelagic thinking today has ventured beyond its shores of merely dialoguing with island narratives and their related territorialities. Perusing this in contemporary times calls for a flexible definition of this, via conversations that engage textual heterogeneity. The article examines contemporary notions of archipelagic thought together with the women-centric Afro-Luso writing of Mozambican author Paulina Chiziane. It analyzes Chiziane's novel The First Wife or Niketche, with its intrinsically archipelagic-centric female articulations, through its multivalent prisms of island-configured thought that counters the petrified continental rhetoric pervading in her society. Chiziane's nonconforming viewpoints offer distinction from colonial and postindependence rhetoric that has attempted to hegemonize Mozambique's diverse regional social and cultural outlooks. The article contends that through ruminating on its Indian Ocean imaginaries, the divergent impetuses of women-centric language in Chiziane's Afro-Luso writings arise, revealing its polyphonic cadences and traits. The movements of island thought lend cogency to unraveling Chiziane's writing through its interpersonal yet paradoxically collective approach, which underscores the multivalence of Mozambican women's distinctive voices.