Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's disease.

BACKGROUND: Crohn's disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry. METHODS: We profiled single cells from diverse patients with Crohn's disease with perianal fistula from colorectal mucosa and fistulous tracts. Immunofluorescence was performed to validate predicted cell-cell interactions. Unstimulated monocytes were chronically cultured in diverse cohorts. A subset was analyzed by single-nucleus RNA + ATAC sequencing. FINDINGS: Fistulous tract cells from complete proctectomies demonstrated enrichment of myeloid cells compared to paired rectal tissues. Ligand-receptor analysis highlights myeloid-stromal cross-talk and cellular senescence, with cellular co-localization validated by immunofluorescence. Chitinase-3 like-protein-1 (CHI3L1) is a top upregulated gene in stromal cells from fistulae expressing both destructive and fibrotic gene signatures. Monocyte cultures from patients of African ancestry and controls demonstrated differences in CHI3L1 and oncostatin M (OSM) expression upon differentiation compared to individuals of European ancestry. Activating protein-1 footprints are present in ATAC-seq peaks in stress response genes, including CHI3L1 and OSM; genome-wide chromatin accessibility including JUN footprints was observed, consistent with reported mechanisms of inflammatory memory. Regulon analyses confirm known cell-specific transcription factor regulation and implicate novel ones in fibroblast subsets. All pseudo-bulked clusters demonstrate enrichment of genetic loci, establishing multicellular contributions. In the most significant African American Crohn's genetic locus, upstream of prostaglandin E receptor 4, lymphoid-predominant ATAC-seq peaks were observed, with predicted RORC footprints. CONCLUSIONS: Population differences in myeloid-stromal cross-talk implicate fibrotic and destructive fibroblasts, senescence, epigenetic memory, and cell-specific enhancers in perianal fistula pathogenesis. The transcriptomic and epigenetic data provided here may guide optimization of promising mesenchymal stem cell therapies for perianal fistula. FUNDING: This work was supported by grants U01DK062422, U24DK062429, and R01DK123758.

A 30-nation investigation of lay heritability beliefs.

Lay beliefs about human trait heritability are consequential for cooperation and social cohesion, yet there has been no global characterisation of these beliefs. Participants from 30 countries (N = 6128) reported heritability beliefs for intelligence, personality, body weight and criminality, and transnational factors that could influence these beliefs were explored using public nation-level data. Globally, mean lay beliefs differ from published heritability (h2) estimated by twin studies, with a worldwide majority overestimating the heritability of personality and intelligence, and underestimating body weight and criminality. Criminality was seen as substantially less attributable to genes than other traits. People from countries with high infant mortality tended to ascribe greater heritability for most traits, relative to people from low infant mortality countries. This study provides the first systematic foray into worldwide lay heritability beliefs. Future research must incorporate diverse global perspectives to further contextualise and extend upon these findings.

What impact have the IOC medical consensus statements made on athlete health? A survey of medical commissions from National Olympic/Paralympic Committees and International Sports Federations.

Background: The International Olympic Committee (IOC) Medical and Scientific Commission has supported collating and sharing evidence globally by developing sports medicine consensus statements ('Statements''). Publishing the Statements requires substantial resources that must be balanced by use and impact on policy and practice. This study aimed to gain a better understanding of awareness and uptake of the Statements globally through a survey of the National Olympic Committees (NOC), National Paralympic Committees (NPC) and International Federations (IF). Method: A cross-sectional survey of medical commission representatives from NOCs/NPCs/IFs. A structured questionnaire was distributed through the IOC head office, informed by prior research. Questions comprised a mix of closed and open-text responses with results presented descriptively by organisation type and total. Results: 55 responses were included: 29 (52%) from NOC/NPC representatives (response rate 14%) and 26 (47%) from IF representatives (response rate 63%). All Statements had been used by at least one respondent, with the Statement addressing concussion ranked highest (used by 33/55). The main barriers to use were financial limitations (n=21), club/sport culture and behaviours (n=19) and lack of understanding from coaches/team sport personnel (n=19). Participants believed the Statements were a successful strategy for improving athlete health (n=39/51 agree or strongly agree). Conclusion: There was clear support for the continued development of sports medicine guidance, including in the format of these Statements. To ensure Statements lead to demonstrable health benefits for athletes, input from athletes, coaches and supporting staff is needed, as well as clearer identification of the purpose and audience of each topic developed.

National strategies for knowledge translation in health policy-making: A scoping review of grey literature.

BACKGROUND AND OBJECTIVES: Without strategic actions in its support, the translation of scientific research evidence into health policy is often absent or delayed. This review systematically maps and assesses national-level strategic documents in the field of knowledge translation (KT) for health policy, and develops a practical template that can support Evidence-informed Policy Network (EVIPNet) Europe countries in producing national strategies for evidence-informed policy-making. METHODS: Websites of organizations with strategic responsibilities in KT were electronically searched, on the basis of pre-defined criteria, in July-August 2017, and an updated search was carried out in April-June 2021. We included national strategies or elements of national strategies that dealt with KT activities, as well as similar strategies of individual institutions with a national policy focus. Two reviewers screened the strategies for inclusion. Data were analysed using qualitative content analysis. RESULTS: A total of 65 unique documents were identified, of which 17 were eligible and analysed for their structure and content. Of the 17, 1 document was a national health KT action plan and 6 documents were institution-level KT strategies. The remaining 10 strategies, which were also included were 2 national health strategies, 5 national health research strategies and 3 national KT strategies (not specific to the field of health alone). In all, 13 structural elements and 7 major themes of health policy KT strategies were identified from the included documents. CONCLUSION: KT in health policy, as emerged from the national strategies that our mapping identified, is based on the production and accessibility of policy-relevant research, its packaging for policy-making and the activities related to knowledge exchange. KT strategies may play different roles in the complex and context-specific process of policy-making. Our findings show that the main ideas of health-specific evidence-informed policy literature appear in these strategies, but their effectiveness depends on the way stakeholders use them. Specific knowledge-brokering institutions and organizational capacity, advocacy about the use of evidence, and close collaboration and co-decision-making with key stakeholders are essential in furthering the policy uptake of research results.

From bench to policy: a critical analysis of models for evidence-informed policymaking in healthcare.

Background: The use of research evidence in policy making is a complex and challenging process that has a long history in various fields, especially in healthcare. Different terms and concepts have been used to describe the relationship between research and policy, but they often lack clarity and consensus. To address this gap, several strategies and models have been proposed to facilitate evidence informed policy making and to identify the key factors and mechanisms involved. This study aims to critically review the existing models of evidence informed policy making (EIPM) in healthcare and to assess their strengths and limitations. Method: A systematic search and review conducted to identify and critically assess EIPM models in healthcare. We searched PubMed, Web of Science and Scopus databases as major electronic databases and applied predefined inclusion criteria to select the models. We also checked the citations of the included models to find other scholars' perspectives. Each model was described and critiqued each model in detail and discussed their features and limitations. Result: Nine models of EIPM in healthcare were identified. While models had some strengths in comprehension, flexibility and theoretical foundations, analysis also identified limitations including: presupposing rational policymaking; lacking alternatives for time-sensitive situations; not capturing policy complexity; neglecting unintended effects; limited context considerations; inadequate complexity concepts; limited collaboration guidance; and unspecified evidence adaptations. Conclusion: The reviewed models provide useful frameworks for EIPM but need further improvement to address their limitations. Concepts from sociology of knowledge, change theory and complexity science can enrich the models. Future EIPM models should better account for the complexity of research-policy relationships and provide tailored strategies based on the policy context.

Attenuating ribosome load improves protein output from mRNA by limiting translation-dependent mRNA decay.

Developing an effective mRNA therapeutic often requires maximizing protein output per delivered mRNA molecule. We previously found that coding sequence (CDS) design can substantially affect protein output, with mRNA variants containing more optimal codons and higher secondary structure yielding the highest protein outputs due to their slow rates of mRNA decay. Here, we demonstrate that CDS-dependent differences in translation initiation and elongation rates lead to differences in translation- and deadenylation-dependent mRNA decay rates, thus explaining the effect of CDS on mRNA half-life. Surprisingly, the most stable and highest-expressing mRNAs in our test set have modest initiation/elongation rates and ribosome loads, leading to minimal translation-dependent mRNA decay. These findings are of potential interest for optimization of protein output from therapeutic mRNAs, which may be achieved by attenuating rather than maximizing ribosome load.

UPF1 regulates mRNA stability by sensing poorly translated coding sequences.

Post-transcriptional mRNA regulation shapes gene expression, yet how cis-elements and mRNA translation interface to regulate mRNA stability is poorly understood. We find that the strength of translation initiation, upstream open reading frame (uORF) content, codon optimality, AU-rich elements, microRNA binding sites, and open reading frame (ORF) length function combinatorially to regulate mRNA stability. Machine-learning analysis identifies ORF length as the most important conserved feature regulating mRNA decay. We find that Upf1 binds poorly translated and untranslated ORFs, which are associated with a higher decay rate, including mRNAs with uORFs and those with exposed ORFs after stop codons. Our study emphasizes Upf1's converging role in surveilling mRNAs with exposed ORFs that are poorly translated, such as mRNAs with long ORFs, ORF-like 3' UTRs, and mRNAs containing uORFs. We propose that Upf1 regulation of poorly/untranslated ORFs provides a unifying mechanism of surveillance in regulating mRNA stability and homeostasis in an exon-junction complex (EJC)-independent nonsense-mediated decay (NMD) pathway that we term ORF-mediated decay (OMD).

Mistranslating the genetic code with leucine in yeast and mammalian cells.

Translation fidelity relies on accurate aminoacylation of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases (AARSs). AARSs specific for alanine (Ala), leucine (Leu), serine, and pyrrolysine do not recognize the anticodon bases. Single nucleotide anticodon variants in their cognate tRNAs can lead to mistranslation. Human genomes include both rare and more common mistranslating tRNA variants. We investigated three rare human tRNALeu variants that mis-incorporate Leu at phenylalanine or tryptophan codons. Expression of each tRNALeu anticodon variant in neuroblastoma cells caused defects in fluorescent protein production without significantly increased cytotoxicity under normal conditions or in the context of proteasome inhibition. Using tRNA sequencing and mass spectrometry we confirmed that each tRNALeu variant was expressed and generated mistranslation with Leu. To probe the flexibility of the entire genetic code towards Leu mis-incorporation, we created 64 yeast strains to express all possible tRNALeu anticodon variants in a doxycycline-inducible system. While some variants showed mild or no growth defects, many anticodon variants, enriched with G/C at positions 35 and 36, including those replacing Leu for proline, arginine, alanine, or glycine, caused dramatic reductions in growth. Differential phenotypic defects were observed for tRNALeu mutants with synonymous anticodons and for different tRNALeu isoacceptors with the same anticodon. A comparison to tRNAAla anticodon variants demonstrates that Ala mis-incorporation is more tolerable than Leu at nearly every codon. The data show that the nature of the amino acid substitution, the tRNA gene, and the anticodon are each important factors that influence the ability of cells to tolerate mistranslating tRNAs.

Translation and Validation of the Sinus and Nasal Quality of Life Surgery Survey in Serbian.

Objective: The aim of this study was to translate the Sinus and Nasal Quality of Life Surgery Survey into the Serbian language to evaluate the test-retest reliability and validity. Study Design: The study included 49 consecutive patients between 12 and 18 years old with rhinologic symptoms. Patients were given a paper survey to complete along with a link to complete the online survey within the same day. Setting: The study was conducted at the University Children's Hospital Clinic for Pulmonology and Allergology between January 2023 and March 2023. Methods: Responses between the paper and online survey were compared and regression analysis was performed to evaluate the relationship. Internal reliability and test-retest reliability were assessed using Cronbach's α coefficient and intraclass correlation coefficient. All data were collected and analyzed using SPSS 29.0. Results: Pearson correlation coefficient between the paper and online survey was very high and statistically significant (r = 0.999; P < .001). Each item had a high correlation (0.993-1.000), where the lowest correlation coefficient was obtained from question 2 (0.993). Average scores in each item differed slightly for only item 2 (mean difference = -0.041), but not to the level of statistical significance. Bland-Altman plot indicated no proportional bias between the 2 versions. Linear regression analysis suggested a high level of agreement between the 2 versions (slope = 1.00, R 2 = 0.999). Conclusion: The survey is a useful questionnaire to evaluate the quality of life in patients with rhinologic symptoms. The high correlation between the paper and online survey shows the reliability of the questionnaire regardless of administration modality.

Electron FLASH radiotherapy in vivo studies. A systematic review.

FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an equivalent tumor response. Although not completely understood, this radiobiological phenomenon has been proved in several animal models with a spectrum of all kinds of particles currently used in contemporary radiotherapy, especially electrons. However, all the research teams have performed FLASH preclinical studies using industrial linear accelerator or LINAC commonly employed in conventional radiotherapy and modified for the delivery of ultra-high-dose-rate (UHDRs). Unfortunately, the delivering and measuring of UHDR beams have been proved not to be completely reliable with such devices. Concerns arise regarding the accuracy of beam monitoring and dosimetry systems. Additionally, this LINAC totally lacks an integrated and dedicated Treatment Planning System (TPS) able to evaluate the internal dose distribution in the case of in vivo experiments. Finally, these devices cannot modify dose-time parameters of the beam relevant to the flash effect, such as average dose rate; dose per pulse; and instantaneous dose rate. This aspect also precludes the exploration of the quantitative relationship with biological phenomena. The dependence on these parameters need to be further investigated. A promising advancement is represented by a new generation of electron LINAC that has successfully overcome some of these technological challenges. In this review, we aim to provide a comprehensive summary of the existing literature on in vivo experiments using electron FLASH radiotherapy and explore the promising clinical perspectives associated with this technology.

The MYCN 5' UTR as a therapeutic target in neuroblastoma.

Tumor MYCN amplification is seen in high-risk neuroblastoma, yet direct targeting of this oncogenic transcription factor has been challenging. Here, we take advantage of the dependence of MYCN-amplified neuroblastoma cells on increased protein synthesis to inhibit the activity of eukaryotic translation initiation factor 4A1 (eIF4A1) using an amidino-rocaglate, CMLD012824. Consistent with the role of this RNA helicase in resolving structural barriers in 5' untranslated regions (UTRs), CMLD012824 increased eIF4A1 affinity for polypurine-rich 5' UTRs, including that of the MYCN and associated transcripts with critical roles in cell proliferation. CMLD012824-mediated clamping of eIF4A1 spanned the full lengths of mRNAs, while translational inhibition was mediated through 5' UTR binding in a cap-dependent and -independent manner. Finally, CMLD012824 led to growth inhibition in MYCN-amplified neuroblastoma models without generalized toxicity. Our studies highlight the key role of eIF4A1 in MYCN-amplified neuroblastoma and demonstrate the therapeutic potential of disrupting its function.

L2NLF: a novel linear-to-nonlinear framework for multi-modal medical image registration.

In recent years, deep learning has ushered in significant development in medical image registration, and the method of non-rigid registration using deep neural networks to generate a deformation field has higher accuracy. However, unlike monomodal medical image registration, multimodal medical image registration is a more complex and challenging task. This paper proposes a new linear-to-nonlinear framework (L2NLF) for multimodal medical image registration. The first linear stage is essentially image conversion, which can reduce the difference between two images without changing the authenticity of medical images, thus transforming multimodal registration into monomodal registration. The second nonlinear stage is essentially unsupervised deformable registration based on the deep neural network. In this paper, a brand-new registration network, CrossMorph, is designed, a deep neural network similar to the U-net structure. As the backbone of the encoder, the volume CrossFormer block can better extract local and global information. Booster promotes the reduction of more deep features and shallow features. The qualitative and quantitative experimental results on T1 and T2 data of 240 patients' brains show that L2NLF can achieve excellent registration effect in the image conversion part with very low computation, and it will not change the authenticity of the converted image at all. Compared with the current state-of-the-art registration method, CrossMorph can effectively reduce average surface distance, improve dice score, and improve the deformation field's smoothness. The proposed methods have potential value in clinical application.

Dengue virus pathogenesis and host molecular machineries.

Dengue viruses (DENV) are positive-stranded RNA viruses belonging to the Flaviviridae family. DENV is the causative agent of dengue, the most rapidly spreading viral disease transmitted by mosquitoes. Each year, millions of people contract the virus through bites from infected female mosquitoes of the Aedes species. In the majority of individuals, the infection is asymptomatic, and the immune system successfully manages to control virus replication within a few days. Symptomatic individuals may present with a mild fever (Dengue fever or DF) that may or may not progress to a more critical disease termed Dengue hemorrhagic fever (DHF) or the fatal Dengue shock syndrome (DSS). In the absence of a universally accepted prophylactic vaccine or therapeutic drug, treatment is mostly restricted to supportive measures. Similar to many other viruses that induce acute illness, DENV has developed several ways to modulate host metabolism to create an environment conducive to genome replication and the dissemination of viral progeny. To search for new therapeutic options, understanding the underlying host-virus regulatory system involved in various biological processes of the viral life cycle is essential. This review aims to summarize the complex interaction between DENV and the host cellular machinery, comprising regulatory mechanisms at various molecular levels such as epigenetic modulation of the host genome, transcription of host genes, translation of viral and host mRNAs, post-transcriptional regulation of the host transcriptome, post-translational regulation of viral proteins, and pathways involved in protein degradation.

"Expression of concern": publication bias for positive preclinical cardioprotection studies.

The present analysis reports on the robustness of preclinical cardioprotection studies with infarct size as endpoint which were published in Basic Research in Cardiology, Cardiovascular Research, and Circulation Research between January 2013 and December 2023. Only 26 out of 269 papers with technically robust analysis of infarct size by triphenyltetrazolium chloride staining, magnetic resonance imaging or single photon emission tomography applied a prospective power analysis. A retrospective power calculation revealed that only 75% of the reported data sets with statistically significant positive results from all these studies had a statistical power of ≥ 0.9, and an additional 9% had a statistical power ≥ 0.8. The remaining 16% of all significant positive data sets did not even reach the 0.8 threshold. Only 13% of all analyzed data sets were neutral. We conclude that neutral studies are underreported and there is indeed a significant lack of robustness in many of the published preclinical cardioprotection studies which may contribute to the difficulties of translating cardioprotection to patient benefit.

The Arabic psychosocial impact of assistive devices scale: Development, translation, and evaluation.

This paper describes the development, translation, and early evaluation of the Arabic Psychosocial Impact of Assistive Devices Scale (AR-PIADS), an outcome measure instrument for the subjective impact of Assistive Technology on a person with a disabilities' quality of life. Developing the AR = PIADS instrument involved forward and backward translation by two independent teams of bilingual, Arabic-English speakers (n = 5) and a quality and usability review by a panel of people with disabilities (n = 18). The emergent version was evaluated with a group of experienced Arabic-speaking Assistive Technology users (n = 67) for its psychometric properties. Initial results demonstrate a favorable comparison for 16 of the 26 questionnaire items with scores recorded for the original, English language version. Internal consistency, measured using Cronbach's alpha, yielded a range of 0.97-0.99 for AR-PIADS while the new instrument's reliability was assessed using an intraclass correlation coefficient resulting in scores within the range of 0.86-0.97 for the overall instrument. Despite these positive results however, the translation process did highlight a number of challenges with language and cultural interpretation of the translated instrument. This suggests that further work is warranted to explore its utility in service provision.

An update on stem cell therapy for stroke patients: Where are we now?

With a foundation built upon initial work from the 1980s demonstrating graft viability in cerebral ischemia, stem cell transplantation has shown immense promise in promoting survival, enhancing neuroprotection and inducing neuroregeneration, while mitigating both histological and behavioral deficits that frequently accompany ischemic stroke. These findings have led to a number of clinical trials that have thoroughly supported a strong safety profile for stem cell therapy in patients but have generated variable efficacy. As preclinical evidence continues to expand through the investigation of new cell lines and optimization of stem cell delivery, it remains critical for translational models to adhere to the protocols established through basic scientific research. With the recent shift in approach towards utilization of stem cells as a conjunctive therapy alongside standard thrombolytic treatments, key issues including timing, route of administration, and stem cell type must each be appropriately translated from the laboratory in order to resolve the question of stem cell efficacy for cerebral ischemia that ultimately will enhance therapeutics for stroke patients towards improving quality of life.

Beyond surface modification strategies to control infections associated with implanted biomaterials and devices - Addressing the opportunities offered by nanotechnology.

Biomaterial-associated infection (BAI) is considered a unique infection due to the presence of a biomaterial yielding frustrated immune-cells, ineffective in clearing local micro-organisms. The involvement of surface-adherent/surface-adapted micro-organisms in BAI, logically points to biomaterial surface-modifications for BAI-control. Biomaterial surface-modification is most suitable for prevention before adhering bacteria have grown into a mature biofilm, while BAI-treatment is virtually impossible through surface-modification. Hundreds of different surface-modifications have been proposed for BAI-control but few have passed clinical trials due to the statistical near-impossibility of benefit-demonstration. Yet, no biomaterial surface-modification forwarded, is clinically embraced. Collectively, this leads us to conclude that surface-modification is a dead-end road. Accepting that BAI is, like most human infections, due to surface-adherent biofilms (though not always to a foreign material), and regarding BAI as a common infection, opens a more-generally-applicable and therewith easier-to-validate road. Pre-clinical models have shown that stimuli-responsive nano-antimicrobials and antibiotic-loaded nanocarriers exhibit prolonged blood-circulation times and can respond to a biofilm's micro-environment to penetrate and accumulate within biofilms, prompt ROS-generation and synergistic killing with antibiotics of antibiotic-resistant pathogens without inducing further antimicrobial-resistance. Moreover, they can boost frustrated immune-cells around a biomaterial reducing the importance of this unique BAI-feature. Time to start exploring the nano-road for BAI-control.

Porcine epidemic diarrhea virus E protein induces formation of stress granules and attenuates protein translation through activation of the PERK/eIF2α signaling pathway.

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) has been characterized as an important structural protein that plays critical roles in the interplay with its host to affect the virus life cycle. Stress granules (SGs) are host translationally silent ribonucleoproteins, which are mainly induced by the phosphorylation of eIF2α in the PERK/eIF2α signaling pathway. Our previous study found that PEDV E protein caused endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins' translation. However, the link and the underlying mechanism by which PEDV induces SGs formation and suppresses host translation remain elusive. In this study, our results showed that PEDV E protein significantly elevated the expression of GRP78, CANX, and phosphorylation of PERK and eIF2α, indicating that the PERK/eIF2α branch of ERS was activated. PEDV E protein localized to the ER and aggregated into puncta to reconstruct ER structure, and further induced SGs formation, which has been caused through upregulating the G3BP1 expression level. In addition, a significant global translational stall and endogenous protein translation attenuation were detected in the presence of E protein overexpression, but the global mRNA transcriptional level remained unchanged, suggesting that the shutoff of protein translation was associated with the translation, not with the transcription process. Collectively, this study demonstrates that PERK/eIF2α activation is required for SGs formation and protein translation stall. This study is beneficial for us to better understand the mechanism by which PEDV E suppresses host protein synthesis, and provides us a new insight into the host translation regulation during virus infection.

Role of Rmd9p in 3'-end processing of mitochondrial 15S rRNA in Saccharomyces cerevisiae.

Ribosome biogenesis, involving processing/assembly of rRNAs and r-proteins is a vital process. In Saccharomyces cerevisiae mitochondria, ribosomal small subunit comprises 15S rRNA (15S). While the 15S 5'-end processing uses Ccm1p and Pet127p, the mechanisms of the 3'-end processing remain unclear. We reveal involvement of Rmd9p in safeguarding/processing 15S 3'-end. Rmd9p deficiency results in a cleavage at a position 183 nucleotides upstream of 15S 3'-end, and in the loss of the 3'-minor domain. Rmd9p binds to the sequences in the 3'-end region of 15S, and a genetic interaction between rmd9 and dss1 indicates that Rmd9p regulates/limits mtEXO activity during the 3'-end spacer processing.

A measure centrality index for systematic empirical comparison of consciousness theories.

Consciousness science is marred by disparate constructs and methodologies, making it challenging to systematically compare theories. This foundational crisis casts doubts on the scientific character of the field itself. Addressing it, we propose a framework for systematically comparing consciousness theories by introducing a novel inter-theory classification interface, the Measure Centrality Index (MCI). Recognizing its gradient distribution, the MCI assesses the degree of importance a specific empirical measure has for a given consciousness theory. We apply the MCI to probe how the empirical measures of the Global Neuronal Workspace Theory (GNW), Integrated Information Theory (IIT), and Temporospatial Theory of Consciousness (TTC) would fare within the context of the other two. We demonstrate that direct comparison of IIT, GNW, and TTC is meaningful and valid for some measures like Lempel-Ziv Complexity (LZC), Autocorrelation Window (ACW), and possibly Mutual Information (MI). In contrast, it is problematic for others like the anatomical and physiological neural correlates of consciousness (NCC) due to their MCI-based differential weightings within the structure of the theories. In sum, we introduce and provide proof-of-principle of a novel systematic method for direct inter-theory empirical comparisons, thereby addressing isolated evolution of theories and confirmatory bias issues in the state-of-the-art neuroscience of consciousness.