bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
Authors: Grabowski Matthew M. , Watson Dionysios C. , Chung Kunho , Lee Juyeun , Bayik Defne , Lauko Adam , Alban Tyler , Melenhorst Jan Joseph , Chan Timothy , Lathia Justin D. , Ahluwalia Manmeet S. , Mohammadi Alireza M.
Published: March 2023

Glioblastoma (GBM) treatment includes maximal safe resection of the core and MRI contrast-enhancing (CE) tumor. Complete resection of the infiltrative non-contrast-enhancing (NCE) tumor rim is rarely achieved. We established a safe, semi-automated workflow for spatially-registered sampling of MRI-defined GBM regions in 19 patients with downstream analysis and biobanking, enabling studies of NCE, wherefrom recurrence/progression typically occurs. Immunophenotyping revealed underrepresentation of myeloid cell subsets and CD8+ T cells in the NCE. While NCE T cells phenotypically and functionally resembled those in matching CE tumor, subsets of activated (CD69hi) effector memory CD8+ T cells were overrepresented. Contrarily, CD25hiTregs and other subsets were underrepresented. Overall, our study demonstrated that MRI-guided, spatially-registered, intraoperative immunosampling is feasible as part of routine GBM surgery. Further elucidation of the shared and spatially distinct microenvironmental biology of GBM will enable development of therapeutic approaches targeting the NCE infiltrative tumor to decrease GBM recurrence.
Usability and acceptability of oral fluid- and blood-based hepatitis C virus self-testing among the general population and men who have sex with men in Malaysia
Authors: Chan Huan-Keat , Sem Xiaohui , Ivanova Elena , Pannir Selvam Sheela Bai A/P , Salleh Narul Aida , Mohamad Gani Abdul Hafiz Bin , Fajardo Emmanuel , Shilton Sonjelle , Abu Hassan Muhammad Radzi
Published: March 2023

Hepatitis C self-testing (HCVST) is emerging as an additional strategy that could help to expand access to HCV testing. We conducted a study to assess the usability and acceptability of two types of HCVST, oral fluid- and blood-based, among the general population and men who have sex with men (MSM) in Malaysia.

An observational study was conducted in three primary care centres in Malaysia. Participants who were layman users performed the oral fluid- and blood-based HCVST sequentially. Usability was assessed by calculating the rate of errors observed, the rate of difficulties faced by participants as well as inter-reader (self-test interpreted by self-tester vs interpreted by trained user) and inter-operator concordances (self-test vs test performed by trained user). The acceptability of HCV self-testing was assessed using an interviewer-administered semi-structured questionnaire. Participants were also required to read contrived test results which included “positive”, “negative”, and “invalid”.

There was a total of 200 participants (100 general population, 100 MSM; mean age 33.6 ± 14.0 years). We found a high acceptability of oral fluid- and blood-based HCVST across both general population and MSM. User errors, related to timekeeping and reading within stipulated time, were common. However, the majority of the participants were still able to obtain and interpret results correctly, including that of contrived results. The high acceptability of HCVST among the participants did not appreciably change after they had experienced both tests, with 97.0% of all participants indicating they would be willing to use HCVST again and 98.5% of them indicating they would recommend it to people they knew. There was no significant difference between the general population and MSM in these aspects.

Our study demonstrates that both oral fluid- and blood-based HCVST are highly acceptable among both the general population and MSM. Both populations also showed comparable ability to conduct the tests and interpret the results. Overall, this study suggests that HCVST could be introduced as an addition to existing HCV testing services in Malaysia. Further studies are needed to establish the optimal positioning of self-testing alongside facility-based testing to expand access to HCV diagnosis in the country.
S100A9 induces neuroinflammation and aggravates early brain injury after subarachnoid hemorrhage by activating the TLR4/MYD88/NF-κB pathway
Authors: Wang Guijun , Huang Kesheng , Zhang Zhan , Guo Yujia , Tian Qi , Liu Chengli , Li Zhijie , Yu Zhui , Li Mingchang
Published: March 2023

Background

Subarachnoid hemorrhage (SAH) is a stroke subtype with an extremely high mortality rate, and its severity is closely related to the short-term prognosis of patients with SAH. The S100 calcium-binding protein A9 (S100A9) has been shown to be associated with some neurological diseases, and this study aimed to investigate the relationship between S100A9 and neuroinflammation, as well as its mechanism in SAH.

Methods

An enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of S100A9 in clinical cerebrospinal fluid samples. Furthermore, an in vivo mouse SAH model was established using intravascular perforation; S100A9 knockout mice were used for the in vivo experiments. S100A9 recombinant protein was administered via lateral ventricular injection 1 h before SAH model induction. SAH grade, neurological function score, and brain water content were measured after a specific time. BV2 and HT22 cells and co-culture models were treated with heme chloride to establish an in vitro model of SAH. Paquinimod was used to explore the potential neuroprotective mechanisms of S100A9 inhibition. Western blotting and immunofluorescence staining were used to explore microglial activation, inflammatory responses, and its related protein pathways.

Results

The expression of S100A9 protein in the cerebrospinal fluid of patients with SAH increased and was related to the short-term prognosis of patients with SAH; S100A9 was highly expressed in the microglia. S100A9 knockout significantly improved neurological function scores, reduced brain edema, and reduced neuronal apoptosis. S100A9 inhibition with Paquinimod restrained neuronal apoptosis, while administration of recombinant S100A9 aggravated neuroinflammation, activated the TLR4 receptor, promoted NF-κB nuclear transcription, and ultimately aggravated nerve injury.

Conclusion

S100A9 protein expression increased after SAH, which induced neuroinflammation and promote neuronal apoptosis by activating the TLR4/MYD88/ NF-κB pathway, ultimately aggravating nerve injury after SAH.
Is the Juice Worth the Squeeze? Overall Survival gain per unit treatment time as a metric of clinical benefit of systemic treatment in incurable cancers
Authors: Joseph Nuradh , Bamunuarachchi Vodathi , Peiris Vimukthini , Wijeskera Sidath , Rajapakse Daminda , Gunasekera Sanjeeva
Published: March 2023

Introduction

Novel systemic therapeutic options such as enzyme inhibitors and monoclonal antibodies have transformed the practice of medical oncology in the recent past. However, survival gains remain modest in most cases. Quantifying the magnitude of benefit against financial and non-financial toxicity of treatment is pivotal in deciding treatment. We describe a novel metric which can be used to assess effectiveness novel therapeutics for incurable cancers.

Methods

The median overall survival was divided by the median duration of treatment to obtain the overall survival gain per treatment time which was the primary end-point of the study. This parameter was compared with the European Society of Medical Oncology Magnitude of clinical benefit scale (ESMO-MCBS) score. Spearman’s rank correlation coefficient was used to test the association between the novel metric and the ESMO-MCBS scores.

Results

Data were available for 30 drugs across 60 indications. The median overall survival per unit treatment time ranged from 0.68 (range 0.2-0.51). Only 18/60 indications had a ratio greater than 1 while 13/60 indications had a ratio less than 0.5. The median treatment duration was not mentioned in 11 indications and median progression free survival was substituted for the analysis. The ESMO-MCBS score was available for 49 of the indications. The Spearman’s rank correlation coefficient was 0.44575 and showed a statistically significant association between survival gain per unit treatment time and the ESMO-MCBS score (p = 0.00133).

Conclusions

Along with other metrics, the ratio of survival gain over treatment duration is a useful parameter to assess effectiveness of novel therapeutics in the palliative setting.
A hippocampus-accumbens code guides goal-directed appetitive behavior
Authors: Barnstedt Oliver , Mocellin Petra , Remy Stefan
Published: March 2023

Neurons in dorsal hippocampus (dHPC) encode a rich repertoire of task-relevant environmental features, while downstream regions such as the nucleus accumbens (NAc) translate this information into task-adaptive behaviors. Yet, the contents of this information stream and their acute role in behavior remain largely unknown. Here, we usedin vivodual-color two-photon imaging to simultaneously record from both large numbers of hippocampal neurons and an identified subpopulation of NAc-projecting neurons during goal-directed navigation towards a hidden reward zone. We found that NAc-projecting neurons contain enriched spatial information and enhanced representations of non-spatial task-relevant behaviors such as deceleration and appetitive licking, both of which could be elicited by optogenetic activation of dHPC terminals in NAc. A generalized linear model revealed enhanced conjunctive coding in NAc-projecting dHPC neurons, improving the identification of the reward zone. We propose that dHPC routes specific reward-related spatial and behavioral state information to guide NAc action selection.
Sanglifehrin A mitigates multi-organ fibrosis in vivo by inducing secretion of the collagen chaperone cyclophilin B
Authors: Flaxman Hope A. , Chrysovergi Maria-Anna , Han Hongwei , Kabir Farah , Lister Rachael T. , Chang Chia-Fu , Black Katharine E. , Lagares David , Woo Christina M.
Published: March 2023

Pathological deposition and crosslinking of collagen type I by activated myofibroblasts drives progressive tissue fibrosis. Therapies that inhibit collagen synthesis by myofibroblasts have clinical potential as anti-fibrotic agents. Lysine hydroxylation by the prolyl-3-hydroxylase complex, comprised of cartilage associated protein, prolyl 3-hydroxylase 1, and cyclophilin B, is essential for collagen type I crosslinking and formation of stable fibers. Here, we identify the collagen chaperone cyclophilin B as a major cellular target of the macrocyclic natural product sanglifehrin A (SfA) using photo-affinity labeling and chemical proteomics. Our studies reveal a unique mechanism of action in which SfA binding to cyclophilin B in the endoplasmic reticulum (ER) induces the secretion of cyclophilin B to the extracellular space, preventing TGF-β1–activated myofibroblasts from synthesizing collagen type Iin vitrowithout inhibiting collagen type I mRNA transcription or inducing ER stress. In addition, SfA prevents collagen type I secretion without affecting myofibroblast contractility or TGF-β1 signaling.In vivo,we provide chemical, molecular, functional, and translational evidence that SfA mitigates the development of lung and skin fibrosis in mouse models by inducing cyclophilin B secretion, thereby inhibiting collagen synthesis from fibrotic fibroblastsin vivo. Consistent with these findings in preclinical models, SfA reduces collagen type I secretion from fibrotic human lung fibroblasts and precision cut lung slices from patients with idiopathic pulmonary fibrosis, a fatal fibrotic lung disease with limited therapeutic options. Our results identify the primary liganded target of SfA in cells, the collagen chaperone cyclophilin B, as a new mechanistic target for the treatment of organ fibrosis.
ZC3H11A interacts with PABPN1 and alters polyadenylation of viral transcripts
Authors: Kases Katharina , Schubert Erik , Hajikhezri Zamaneh , Larsson Mårten , Andersson Leif , Akusjärvi Göran , Punga Tanel , Younis Shady
Published: March 2023

Nuclear mRNA metabolism is regulated by multiple proteins, which either directly bind to RNA or form multi-protein complexes. The RNA-binding protein ZC3H11A is involved in nuclear mRNA export, and NF-κB signaling and is essential during mouse embryo development. Furthermore, previous studies have shown that ZC3H11A is important for nuclear-replicating viruses. However, detailed biochemical characterization of the ZC3H11A protein has been lacking. In this study, we established the ZC3H11A protein interactome in human and mouse cells. We demonstrate that the nuclear poly(A)-binding protein PABPN1 interacts specifically with the ZC3H11A protein and controls ZC3H11A localization into nuclear speckles. We report that ZC3H11A specifically interacts with the human adenovirus type 5 (HAdV-5) capsid mRNA in a PABPN1-dependent manner. Notably, ZC3H11A uses the same zinc finger motifs to interact with PABPN1 and mRNA, with a single zinc finger motif responsible for these functions. Further, we demonstrate that the lack of ZC3H11A alters the polyadenylation of HAdV-5 capsid mRNA. Taken together, our results suggest that the ZC3H11A protein acts as a novel regulator of polyadenylation of nuclear mRNA.
Ophiobolin A Covalently Targets Complex IV Leading to Mitochondrial Metabolic Collapse in Cancer Cells
Authors: Gowans Flor A. , Thach Danny Q. , Wang Yangzhi , Altamirano Poblano Belen E. , Dovala Dustin , Tallarico John A. , McKenna Jeffrey M. , Schirle Markus , Maimone Thomas J. , Nomura Daniel K.
Published: March 2023

Ophiobolin A (OPA) is a sesterterpenoid fungal natural product with broad anti-cancer activity. While OPA possesses multiple electrophilic moieties that can covalently react with nucleophilic amino acids on proteins, the proteome-wide targets and mechanism of OPA remain poorly understood in many contexts. In this study, we used covalent chemoproteomic platforms to map the proteome-wide reactivity of OPA in a highly sensitive lung cancer cell line. Among several proteins that OPA engaged, we focused on two targets—cysteine C53 of HIG2DA and lysine K72 of COX5A—that are part of complex IV of the electron transport chain and contributed significantly to the anti-proliferative activity. OPA activated mitochondrial respiration in a HIG2DA and COX5A-dependent manner, led to an initial spike in mitochondrial ATP, but then compromised mitochondrial membrane potential leading to ATP depletion. We have used chemoproteomic strategies to discover a unique anti-cancer mechanism of OPA through activation of complex IV leading to compromised mitochondrial energetics and rapid cell death.
Plasma NT1-tau and Aβ42correlate with age and cognitive function in two large Down syndrome cohorts
Authors: Stern Andrew M. , Van Pelt Kathryn L. , Liu Lei , Anderson Amirah K. , Ostaszewski Beth , Mapstone Mark , O’Bryant Sid , Petersen Melissa E. , Christian Bradley T. , Handen Benjamin L. , Selkoe Dennis J. , Schmitt Frederick , Head Elizabeth ,   the Alzheimer’s Biomarker Consortium – Down Syndrome (ABC-DS) investigators
Published: March 2023

Structured Abstract

Introduction

People with Down syndrome (DS) often develop Alzheimer disease (AD). Here we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive impairment.

Methods

Plasma NT1-tau, Aβ37, Aβ40, and Aβ42levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort.

Results

Linear mixed models for NT1-tau, Aβ42,and Aβ37:42were significant for age, there was no main effect of time in the discovery cohort. In cross-sectional models, NT1-tau and Aβ42increased with age. NT1-tau predicted DLD scores. The discovery cohort linear model for NT1-tau predicted NT1-tau levels in the validation cohort.

Discussion

NT1-tau correlates with age and worse cognition in DS. Further validation of NT1-tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.
Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that bind a conserved membrane proximal epitope of the spike
Authors: De Cae Sieglinde , Van Molle Inge , van Schie Loes , Shoemaker Sophie R. , Deckers Julie , Debeuf Nincy , Lameire Sahine , Nerinckx Wim , Roose Kenny , Fijalkowska Daria , Devos Simon , Desmet Anne-Sophie , Zavala Marchan Jackeline Cecilia , Venneman Toon , Sedeyn Koen , Ballegeer Marlies , Vanheerswynghels Manon , De Wolf Caroline , Demol Hans , Vanhaverbeke Pieter , Ghassabeh Gholamreza Hassanzadeh , Lonigro Chiara , Bockstal Viki , Rinaldi Manuela , Abdelnabi Rana , Neyts Johan , Marqusee Susan , Lambrecht Bart N. , Callewaert Nico , Remaut Han , Saelens Xavier , Schepens Bert
Published: March 2023

Currently circulating SARS-CoV-2 variants have gained complete or significant resistance to all SARS-CoV-2-neutralizing antibodies that have been used in the clinic. Such antibodies can prevent severe disease in SARS-CoV-2 exposed patients for whom vaccines may not provide optimal protection. Here, we describe single-domain antibodies (VHHs), also known as nanobodies, that can broadly neutralize SARS-CoV-2 with unusually high potency. Structural analysis revealed their binding to a unique, highly conserved, membrane proximal, quaternary epitope in the S2 subunit of the spike. Furthermore, a VHH-human IgG1 Fc fusion, efficiently expressed in Chinese hamster ovary cells as a stable antibody construct, protected hamsters against SARS-CoV-2 replication in a therapeutic setting when administered systemically at low dose. This VHH-based antibody represents a new candidate anti-COVID-19 biologic that targets the Achilles heel of the viral spike.
Numerical investigation of active flow control using zero-net-mass-flux jets around a high-lift morphing cambered wing-flap system
Authors: Truong Hung , Marouf Abderahmane , Gehri Alain , Vos Jan , Braza Marianna , Hoarau Yannick
Published: March 2023

Purpose

This study aims to investigate the physical mechanisms of the use of active flow control (AFC) for a high-lift wing-flap configuration.

Design/methodology/approach

By means of high-fidelity numerical simulations, the flow dynamics around a high-lift wing-flap system at high Reynolds number (Re/c = 4.6 million) is studied. Adapted turbulence models based on the URANS approach are used to capture the flow separation and the subsequent development of coherent structures. The present study focuses on the use of AFC using a synthetic jet known as zero-net-mass-flux (ZNMF) using the blowing–suction approach. Different parameters (geometry, frequency and velocity) of a ZNMF placed at the cambered flap’s chord are optimized to obtain the most efficient parameter settings to suppress the flow separation.

Findings

A synthetic jet with the optimal shape and orientation enforces the flow reattachment on the wing-flap surface. This leads to an improvement of the aerodynamic performance of the system. The wake thickness was reduced by 30%, and an increase of 17.6% in lift-to-drag ratio was obtained. Concerning the ZNMF location, they should be installed upstream of the separation point to achieve the best performance.

Originality/value

The effectiveness of ZNMF devices integrated on a high-lift wing-flap configuration was studied in real flight conditions at high Reynolds number. A detailed analysis of the wake dynamics explains how AFC forces the reattachment of the boundary layer and attenuates the predominant wake instabilities up to −20 dB.
Relationship clusters and performance of conflict management strategies in cross-organisational projects teams
Authors: Kwofie Titus Ebenezer , Ellis Florence Akyaa , Addy Michael Nii , Amos-Abanyie Samuel , Aigbavboa Clinton , Afram Samuel Owusu
Published: March 2023

Purpose

The link between relationship typologies and effectiveness of conflict resolution approaches remains to be tested despite its significance in conflict management in construction project delivery. By using the four relationships attributes based on the group attachment theory, the purpose of the study was to explore the cluster of relationships among project teams and organisations and the performance of conflict management strategies across these clusters in the Ghanaian construction industry.

Design/methodology/approach

Using a deductive questionnaire survey in the Ghanaian construction industry, a total of 137 responses were gathered and analyzed using cluster analysis, mean scores and ANOVA to reveal the relationship clusters and performance of conflict management strategies across these clusters.

Findings

The results revealed eight relationship clusters that exist among project teams and organisations with distinct influence of roles & tasks function, cognition, emotions and behavior attributes across the relationship clusters. In the aspect of the effectiveness of conflict management strategies, it was noted that the performance of these strategies were significantly different across the groups. For instance, integrating as a conflict management strategy was deemed to be effective in resolving conflict in unitary, adversarial, pluralist, mutuality, collaborative and partnering relationship clusters. In the case of coopetitive and coercive relationships, the performance of integrating as a conflict management strategy was less effective. This study thus has empirically proved that, different relationship clusters of teams and organizations exist within the Ghanaian construction industry, and that they perform different roles & tasks functions, cognition, emotions and behavioural attributes in their formation. Additionally, the performance effectiveness of conflict management strategies differed across the relationship clusters.

Originality/value

By aligning the relationship attributes to the dynamics of relationship clusters experienced in project teams and organisations, relationship quality, suitability and effectiveness of conflict management strategies can be optimized. The findings can inform project teams and stakeholders to develop fit-for-purpose relationship attributes among teams and organisations to enhance team effectiveness, relationship quality and conflict management in the industry.
Relational quality in public–private partnerships: understanding social relationships in contract-based exchanges
Authors: Warsen Rianne
Published: March 2023

Purpose

The purpose of this paper is to conduct a systematic literature review of studies addressing relational quality in public–private partnerships (PPPs). The ambition of this study is twofold: first, to present more clarity regarding the definition of the concept. Second, to develop a framework that explains the antecedents, characteristics and outcomes of relational quality in PPPs.

Design/methodology/approach

A systematic literature review of 99 academic articles, which were analyzed and coded on the definition, characteristics, antecedents and outcomes of relational quality.

Findings

The study shows that trust, communication, commitment, openness and reciprocity are considered core aspects of the concept. The analysis further identifies important antecedents (e.g. shared values, leadership) and outcomes (performance, innovation) of relational quality in PPPs. The findings result in the development of a framework on relational quality in PPPs to be used for further research.

Research limitations/implications

The findings indicate that relational quality is valuable for the functioning of PPPs, but the current focus of this review excludes studies addressing relational quality in other types of collaboration and public–private exchange. The lessons from these research fields might further improve people’s understanding of relational quality.

Practical implications

Practitioners should pay attention to relational quality in long-term PPPs. Among others, (process) management activities might contribute to relational quality as it stimulates communication and openness.

Originality/value

The presented framework explaining antecedents, characteristics and outcomes of relational quality allows for more structured use of this concept in future research.
Anomaly detection in the course evaluation process: a learning analytics–based approach
Authors: Vaidya Anagha , Sharma Sarika
Published: March 2023

Purpose

Course evaluations are formative and are used to evaluate learnings of the students for a course. Anomalies in the evaluation process can lead to a faulty educational outcome. Learning analytics and educational data mining provide a set of techniques that can be conveniently applied to extensive data collected as part of the evaluation process to ensure remedial actions. This study aims to conduct an experimental research to detect anomalies in the evaluation methods.

Design/methodology/approach

Experimental research is conducted with scientific approach and design. The researchers categorized anomaly into three categories, namely, an anomaly in criteria assessment, subject anomaly and anomaly in subject marks allocation. The different anomaly detection algorithms are used to educate data through the software R, and the results are summarized in the tables.

Findings

The data points occurring in all algorithms are finally detected as an anomaly. The anomaly identifies the data points that deviate from the data set’s normal behavior. The subject which is consistently identified as anomalous by the different techniques is marked as an anomaly in evaluation. After identification, one can drill down to more details into the title of anomalies in the evaluation criteria.

Originality/value

This paper proposes an analytical model for the course evaluation process and demonstrates the use of actionable analytics to detect anomalies in the evaluation process.
On the dynamic relationship between transaction volume and returns: evidence from the cryptocurrency market
Authors: Ghabri Yosra , Gana Marjène Rabah
Published: March 2023

Purpose

Using vector autoregressive modelling (VAR) and Granger causality tests, this paper attempts to empirically investigate the dynamic relationship between return and volume of transactions of two main cryptocurrencies: Bitcoin and Ethereum.

Design/methodology/approach

Based on a generalized autoregressive conditional heteroskedasticity (GARCH) model with a transaction volume parameter in the conditional volatility equation.

Findings

The results provide empirical evidence of a positive contemporaneous relationship between the variation in transaction volume and the daily return of Bitcoin and Ethereum. The results also show that the conditional volatility of the returns is affected by the past volatility, which implies weak-form inefficiency for both Bitcoin and Ethereum markets. The results of the VAR model, testing Granger causality, indicate that the volume of transactions Granger-Causes Bitcoin and Ethereum returns. Furthermore, the findings show a Granger causal relation from returns to volume.

Originality/value

This result suggests that cryptocurrency returns can predict transaction volumes and vice versa.
Automation, the growth of online information and digital formats: the story of libraries
Authors: Frederick Donna Ellen
Published: March 2023

Purpose

The purpose of this paper is to examine the impact of technological change, the data deluge, social change and policy change on the materials in their collection, the services they offer and how service is provided.

Design/methodology/approach

The author examines over four decades of personal experience as a library user and library worker to discover the progression of library resources, reference practices and the storage of information from analogue to digital.

Findings

Since the 1970s, there has been a gradual shift away from analogue technologies towards digital ones. One exception is that of the low-tech analogue book which, while it is not as central as it once was, remains important for most library collections. The change was and is driven by internal and external pressures and can be impeded by factors such as financial and skill limitations or decision makers who do not support changes.

Originality/value

While the Data Deluge Column has many instalments that examine problems created by the growing mass of data and information and the progression to technological change, this instalment puts all of that into a human or lived perspective.
Review article: Mechanisms underlying the effectiveness of exclusive enteral nutrition in Crohn's disease
Authors: Melton Sarah L. , Taylor Kirstin M. , Gibson Peter R. , Halmos Emma P.
Published: March 2023

Background

Exclusive enteral nutrition (EEN) induces remission and mucosal healing in patients with Crohn's disease, but the mechanism of action remains unknown.

Aim

To outline current understanding of the mechanisms of action of EEN.

Methods

From a comprehensive literature search, published data were critically examined in a narrative review.

Results

Multiple potential mechanisms of action have been identified. EEN optimises nutritional status. Differences in gut microbiota in terms of overall diversity and taxonomic community structure are observed between responders and non‐responders to EEN. Therapy with EEN alters microbial metabolites (including faecal short‐chain fatty acids, amino acids, branched‐chain amino acids and sulphide) and faecal pH. Epithelial effects and restoration of barrier function, as well as changes in mucosal cytokine profiles and T‐cell subsets are observed in responders to EEN. The impact of inclusion or exclusion of specific dietary components may be of importance, but putative detrimental components are found in many formulas. A major challenge in interpreting these findings is that they often contradict or change in opposite directions to what is considered ‘beneficial’. It is difficult to differentiate between the observations following EEN being driven by EEN per se and those associated with resolving inflammation.

Conclusions

The mechanisms of action of EEN are likely to involve a complex interplay between host mucosal immune response and luminal environment, but the identity of key factors remains poorly understood. A better definition of pathogenic factors may aid in developing more targeted dietary treatment and provide insights into the pathogenesis of Crohn's disease.
L'agrandissement de la communauté Uashat mak Mani‐utenam : regard sur une collaboration dans la durée entre une université et une communauté innue
Authors: Gouin Élisa
Published: March 2023

Cet article présente une étude de cas ayant pour but de cerner les facteurs de succès et les effets d'une collaboration entre des étudiants en architecture et une communauté autochtone. Cet exercice, qui s'inscrit dans le contexte d'une relation collaborative de plusieurs années, a été effectué dans le cadre d'un atelier en design urbain mené par l'École d'architecture de l'Université Laval et la communauté innue de Uashat mak Mani‐utenam, voisine de la ville de Sept‐Îles, au Québec. L'agrandissement de la communauté et l'aménagement de zones résidentielles étaient au cœur de la démarche de collaboration. L'analyse de l'évolution des différentes versions des plans d'aménagement, à la lumière de critères d'aménagement innus, met en exergue les apports positifs de l'atelier, notamment en ce qui concerne le programme communautaire et le symbolisme tectonique. Néanmoins, le statu quo est maintenu relativement à l'implantation et au respect des éléments naturels. Les témoignages d'acteurs clefs impliqués dans le projet illustre le caractère authentique du partenariat de recherche entre le groupe de recherche « Habitats et cultures » et la communauté. La qualité de la relation entre les chercheurs et les partenaires innus, la durée du partenariat dans le temps et la valorisation des savoirs culturels innus ont favorisé le succès du partenariat.
Introduction to the special section on Biology of Termites
Authors: Xing Lian‐Xi , Beukeboom Leo W.
Published: March 2023

As descendants of social cockroaches, termites have an intriguing biology that makes them highly suitable study subjects in a wide variety of fields, such as eusocial evolution, ageing mechanisms, wood decomposition, ecosystem engineering, and pest management. This special section presents four studies ranging from the role of chemical compounds in foraging behaviour and food digestion to genetics and physiology of reproduction. Taken together, these studies offer new insights and ample suggestions for future work on these fascinating insects.
Current anthropogenic warming threatens shallow Lake ecosystems on the Tibetan plateau: A palaeolimnological study covering the past 1,600 years in Genggahai Lake
Authors: Li Yuan , Zhao Hui , Sun Mingjie , Zhao Yongtao , Jeppesen Erik
Published: March 2023

The Tibetan Plateau has ∼1,200 lakes larger than 1 km2 with a total area of ~46,000 km2. The annual mean air temperature of the Tibetan Plateau has increased 2.5°C over the past 60 years. Lakes in this region are extremely responsive to climate changes as a result of their low biodiversity and simple food webs. However, it is unclear whether the current anthropogenic warming will benefit or threaten the aquatic ecosystems in this region.

We assessed patterns of change associated with climate change in a shallow, freshwater lake (Genggahai Lake) on the NE Tibetan Plateau over the past ~1,600 years based on diverse aquatic fossils (macrophytes, molluscs, cladocerans and diatoms), total organic carbon (TOC) and total nitrogen (TN) of a sediment core.

The abundances of macrophytes, molluscs and cladocerans, and the concentrations of TOC and TN in the sediments were high during the Mediaeval Warm Period (MWP, ~940–1,410 CE) but low during the Dark Ages Cold Period (DACP, ~390–940 CE) and the Little Ice Age (LIA, ~1,410–1970 CE), suggesting that modest natural warming was associated with the biomass of macrophytes and consumers in the food web. By contrast, low abundance of macrophytes and high abundance of planktonic diatoms were recorded in the sediments during the Current Warm Period (CWP, ~1970–2020 CE). Current anthropogenic warming has resulted in significantly higher temperatures than during the MWP, associated with the development of planktonic algae rather than macrophytes.

Our findings show that the current anthropogenic warming, coupled with increased atmospheric nitrogen deposition and activated nutrients from thawed permafrost, is associated with phytoplankton dominance in lakes on the Tibetan Plateau, and may lead to significant reductions in ecosystem services provided by the lakes.
Cerebrospinal fluid virology in people with HIV
Authors: Henderson Merle , Pepper Nuala , Bawa Manraj , Muir David , Everitt Alex , Mackie Nicola E. , Winston Alan
Published: March 2023

Objective

Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors.

Method

This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV‐1) and 2 (HSV‐2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV‐6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling.

Results

CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non‐integrase strand transfer inhibitor‐based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV‐6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T‐cell count (p < 0.05 for all).

Conclusion

In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.
Liberté syndicale et négociation collective dans l'économie des plateformes: de la mobilisation des travailleurs à l'approche axée sur les droits de l'homme
Authors: STYLOGIANNIS Charalampos
Published: March 2023

L'étude porte sur l'exercice de la liberté syndicale et du droit de négociation collective dans l'économie des plateformes. Après avoir commenté plusieurs exemples de mobilisation collective des travailleurs des plateformes dans le monde, l'auteur plaide pour l'adoption d'une approche axée sur les droits de l'homme de ces deux garanties, que divers instruments internationaux consacrent, et que de nombreux tribunaux nationaux et internationaux ont utilisées pour justifier leurs décisions. C'est pour lui la seule façon de protéger tous les travailleurs, indépendamment de leur situation au regard de l'emploi, dans un monde du travail en mutation.
Resistin G–A haplotype at SNP‐420/‐358 is associated with the latent sarcopenic obesity index in the toon genome study
Authors: Ikeda Yosuke , Kawamura Ryoichi , Takata Yasunori , Tabara Yasuharu , Maruyama Koutatsu , Takakado Misaki , Hadate Toshimi , Ohashi Jun , Saito Isao , Ogawa Yoshihiro , Osawa Haruhiko
Published: March 2023

Aim/Introduction

Resistin, which induces insulin resistance, is mainly expressed in monocytes/macrophages in humans. We reported previously that serum resistin was highest in the G–A haplotype defined by resistin single nucleotide polymorphisms (SNPs) at −420 (rs1862513) and − 358 (rs3219175). As sarcopenic obesity is associated with insulin resistance, we aimed to examine whether serum resistin and its haplotypes were associated with sarcopenic obesity at a latent stage.

Materials and Methods

We cross‐sectionally analyzed 567 community‐dwelling Japanese participants attending annual medical check‐ups in which the sarcopenic obesity index was evaluated. The age‐ and gender‐matched normal glucose tolerance subjects with G–A homozygotes and those with C–G homozygotes were examined via RNA‐sequencing and pathway analysis (each n = 3), and RT‐PCR (each n = 8).

Results

In multivariate logistic regression analyses, the fourth quartile (Q4) of serum resistin and G–A homozygotes were both associated with the latent sarcopenic obesity index defined by a visceral fat area of ≥ 100 cm2 and grip strength Q1 after adjustment for age and gender, with or without other confounding factors. RNA sequencing and pathway analysis showed that tumor necrosis factor (TNF) was involved in the top five pathways in the whole blood cells of G–A homozygotes compared with C–G homozygotes. RT‐PCR revealed that TNF mRNA was higher in G–A homozygotes than in C–G homozygotes.

Conclusions

The G–A haplotype was associated with the latent sarcopenic obesity index defined by grip strength in the Japanese cohort, could be mediated by TNF‐α.
The impact of psoriasis biologic therapy on HIV viral load and CD4+ cell counts in HIV‐positive individuals: A real‐world cohort study
Authors: Xu Jennifer , Gill Kyra , Flora Akshay , Kozera Emily , Frew John W.
Published: March 2023

Background

Psoriasis is a chronic immune‐mediated inflammatory disorder that also occurs in the setting of human immunodeficiency virus (HIV). Biological therapy has transformed the treatment landscape for psoriasis; however, individuals with HIV are excluded from clinical trials. The impact of biological therapy on blood parameters in HIV is unclear and is only observed in small case series.

Objective

The aim of this study was to assess the effect of biological therapy in psoriasis vulgaris in individuals with well‐controlled HIV on CD4+ cell counts, CD4+ proportion and HIV viral load over 12 months.

Methods

This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV‐positive individuals with psoriasis treated with biological therapy, compared with 144 age‐, gender‐ and HAART‐matched individuals without psoriasis seen between 2010 and 2022. Outcomes of interest included HIV viral load, CD4+ cell count and incidence of infections.

Results

No statistically significant difference was seen in baseline HIV viral load and CD4+ count between individuals with and without psoriasis. No significant change in CD4+ count or HIV viral load was seen over the 12‐month period of analysis in the HIV cohort without psoriasis. The HIV cohort treated with biological therapy for psoriasis also did not demonstrate any significant change in HIV viral load and CD4+ counts over the 12‐month period examined. Stratification by type of biological therapy used did not identify any significant changes in these parameters. Rates of infections and adverse events were also not significantly different between cohorts. It is possible that minor blips seen in the biologics cohort may be a risk factor for future virological failure, and future prospective longitudinal studies are required.

Conclusions

In individuals with well‐controlled HIV, the use of biological therapy for psoriasis does not significantly impact HIV viral load, CD4+ cell count, CD4+ proportion and rates of infection over the first 12 months of therapy.
Prospective comparative trial comparing O‐RADS, IOTA ADNEX model, and RMI score for preoperative evaluation of adnexal masses for prediction of ovarian cancer
Authors: Poonyakanok Vitcha , Tanmahasamut Prasong , Jaishuen Atthapon
Published: March 2023

Introduction

Preoperative assessment of ovarian tumors to distinguish between benign and malignant is important. At this time, many diagnostic models were available and the popularity of the risk of malignancy index (RMI) in Thailand is still high. The IOTA Assessment of Different NEoplasias in adneXa (ADNEX) model and the Ovarian‐Adnexal Reporting and Data System (O‐RADS) model were both new models with good performance.

Objectives

The purpose of this study was to compare O‐RADS, RMI, and ADNEX models.

Design

This diagnostic study was performed using data from the prospective study.

Methods

Data from 357 patients from a previous study were included and calculated using the RMI‐2 formula then applied to the O‐RADS system and the IOTA ADNEX model. The diagnostic significance of the results was evaluated by receiver operating characteristic (ROC) analysis and pairwise comparison between models was made.

Results

The area under the receiver operating characteristic curve (AUC) to distinguish an adnexal mass as a benign or malignant tumor was 0.975 (95% CI, 0.953–0.988) for the IOTA ADNEX model; 0.974 (95% CI, 0.960–0.988) for O‐RADS; 0.909 for RMI‐2 (95% CI, 0.865–0.952). There were no differences in pairwise AUC comparisons between the IOTA ADNEX and O‐RADS models, and both were better than those of RMI‐2.

Conclusions

The IOTA ADEX and O‐RADS models are excellent tools for distinguishing the adnexal mass in the preoperative assessment and were better than RMI‐2. The use of one of these models is recommended.
A novel machine learning‐based web application for field identification of infectious and inflammatory disorders of the central nervous system in cattle
Authors: Ferrini Sara , Rollo Cesare , Bellino Claudio , Borriello Giuliano , Cagnotti Giulia , Corona Cristiano , Di Muro Giorgia , Giacobini Mario , Iulini Barbara , D'Angelo Antonio
Published: March 2023

Background

Central nervous system (CNS) infections in cattle are a major cause of economic loss and mortality. Machine learning (ML) techniques are gaining widespread application in solving predictive tasks in both human and veterinary medicine.

Objectives

Our primary aim was to develop and compare ML models that could predict the likelihood of a CNS disorder of infectious or inflammatory origin in neurologically‐impaired cattle. Our secondary aim was to create a user‐friendly web application based on the ML model for the diagnosis of infection and inflammation of the CNS.

Animals

Ninety‐eight cattle with CNS infection and 86 with CNS disorders of other origin.

Methods

Retrospective observational study. Six different ML methods (logistic regression [LR]; support vector machine [SVM]; random forest [RF]; multilayer perceptron [MLP]; K‐nearest neighbors [KNN]; gradient boosting [GB]) were compared for their ability to predict whether an infectious or inflammatory disease was present based on demographics, neurological examination findings, and cerebrospinal fluid (CSF) analysis.

Results

All 6 methods had high prediction accuracy (≥80%). The accuracy of the LR model was significantly higher (0.843 ± 0.005; receiver operating characteristic [ROC] curve ) than the other models and was selected for implementation in a web application.

Conclusion and Clinical Importance

Our findings support the use of ML algorithms as promising tools for veterinarians to improve diagnosis. The open‐access web application may aid clinicians in achieving correct diagnosis of infectious and inflammatory neurological disorders in livestock, with the added benefit of promoting appropriate use of antimicrobials.
Space Arms Control or Space Behavior Control? The Competition between American and Chinese Ideas of an International Space Order
Authors: Qisong He
Published: March 2023

The weaponization and battlefieldization of outer space is becoming increasingly evident. China and the United States have obvious differences in their proposals for maintaining space security. China advocates a legally binding international treaty according to international law to limit outer space armament based on multilateralism with the framework of the United Nations at its core. The United States advocates establishing voluntary rule‐based agreements within the allied system as rules for the international community to constrain space behavior. The contest between China and the United States over how to maintain space security is in actuality a competition between the two countries over what type of international space order to establish. In the foreseeable future, the outcome of the competition between the two countries could be that an international space order based on US rules prevails, partially absorbing China's rules.