bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework
Authors: Wang Xuan , Haeussler Katrin , Spellman Anne , Phillips Leslie E. , Ramiller Allison , Bausch-Jurken Mary T. , Sharma Pawana , Krivelyova Anna , Vats Sonam , Van de Velde Nicolas
Published: September 2023

Introduction

Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response after vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) vs BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework.

Methods

The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were symptomatic, laboratory-confirmed SARS-CoV-2 infection, SARS-CoV-2 infection, severe SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Evidence was evaluated using the GRADE framework.

Results

Overall, 17 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.75–0.97]; P=0.0151; I2 = 67.7%), severe SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.77–0.93]; P=0.0009; I2 = 0%), COVID-19–associated hospitalization (RR, 0.88 [95% CI, 0.79–0.97]; P<0.0001; I2 = 0%), and COVID-19–associated mortality (RR, 0.63 [95% CI, 0.44–0.90]; P=0.0119; I2 = 0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials. Based on nonrandomized studies, evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies.

Conclusion

This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.
RETRACTED: Baricitinib protects mice from sepsis-induced cardiac dysfunction and multiple-organ failure
Authors: Verra Chiara , Mohammad Shireen , Alves Gustavo Ferreira , Porchietto Elisa , Coldewey Sina Maren , Collino Massimo , Thiemermann Christoph
Published: September 2023

Sepsis is one of the major complications of surgery resulting in high morbidity and mortality, but there are no specific therapies for sepsis-induced organ dysfunction. Data obtained under Gene Expression Omnibus accession GSE131761 were re-analyzed and showed an increased gene expression of Janus Kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3) in the whole blood of post-operative septic patients. Based on these results, we hypothesized that JAK/STAT activation may contribute to the pathophysiology of septic shock and, hence, investigated the effects of baricitinib (JAK1/JAK2 inhibitor) on sepsis-induced cardiac dysfunction and multiple-organ failure (MOF). In a mouse model of post-trauma sepsis induced by midline laparotomy and cecal ligation and puncture (CLP), 10-week-old male (n=32) and female (n=32) C57BL/6 mice received baricitinib (1mg/kg; i.p.) or vehicle at 1h or 3h post-surgery. Cardiac function was assessed at 24h post-CLP by echocardiography in vivo, and the degree of MOF was analyzed by determination of biomarkers in the serum. The potential mechanism underlying both the cardiac dysfunction and the effect of baricitinib was analyzed by western blot analysis in the heart. Trauma and subsequent sepsis significantly depressed the cardiac function and induced multiple-organ failure, associated with an increase in the activation of JAK2/STAT3, NLRP3 inflammasome and NF- κβ pathways in the heart of both male and female animals. These pathways were inhibited by the administration of baricitinib post the onset of sepsis. Moreover, treatment with baricitinib at 1h or 3h post-CLP protected mice from sepsis-induced cardiac injury and multiple-organ failure. Thus, baricitinib may be repurposed for trauma-associated sepsis.
Complement inhibition can decrease the haemostatic response in a microvascular bleeding model at multiple levels
Authors: Golomingi Murielle , Kohler Jessie , Lamers Christina , Pouw Richard B. , Ricklin Daniel , Dobó József , Gál Péter , Pál Gábor , Kiss Bence , Dopler Arthur , Schmidt Christoph Q. , Hardy Elaissa Trybus , Lam Wilbur , Schroeder Verena
Published: September 2023

Background

Haemostasis is a crucial process by which the body stops bleeding. It is achieved by the formation of a platelet plug, which is strengthened by formation of a fibrin mesh mediated by the coagulation cascade. In proinflammatory and prothrombotic conditions, multiple interactions of the complement system and the coagulation cascade are known to aggravate thromboinflammatory processes and increase the risk of arterial and venous thrombosis. Whether those interactions also play a relevant role during the physiological process of haemostasis is not yet completely understood. The aim of this study was to investigate the potential role of complement components and activation during the haemostatic response to mechanical vessel injury.

Methods

We used a microvascular bleeding model that simulates a blood vessel, featuring human endothelial cells, perfusion with fresh human whole blood, and an inducible mechanical injury to the vessel. We studied the effects of complement inhibitors against components of the lectin (MASP-1, MASP-2), classical (C1s), alternative (FD) and common pathways (C3, C5), as well as a novel triple fusion inhibitor of all three complement pathways (TriFu). Effects on clot formation were analysed by recording of fibrin deposition and the platelet activation marker CD62P at the injury site in real time using a confocal microscope.

Results

With the inhibitors targeting MASP-2 or C1s, no significant reduction of fibrin formation was observed, while platelet activation was significantly reduced in the presence of the FD inhibitor. Both common pathway inhibitors targeting C3 or C5, respectively, were associated with a substantial reduction of fibrin formation, and platelet activation was also reduced in the presence of the C3 inhibitor. Triple inhibition of all three activation pathways at the C3-convertase level by TriFu reduced both fibrin formation and platelet activation. When several complement inhibitors were directly compared in two individual donors, TriFu and the inhibitors of MASP-1 and C3 had the strongest effects on clot formation.

Conclusion

The observed impact of complement inhibition on reducing fibrin clot formation and platelet activation suggests a role of the complement system in haemostasis, with modulators of complement initiation, amplification or effector functions showing distinct profiles. While the interactions between complement and coagulation might have evolved to support haemostasis and protect against bleeding in case of vessel injury, they can turn harmful in pathological conditions when aggravating thromboinflammation and promoting thrombosis.
Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus
Authors: Tsai Yi-Giien , Liao Pei-Fen , Hsiao Kai-Hung , Wu Hung-Ming , Lin Ching-Yuang , Yang Kuender D.
Published: September 2023

Systemic lupus erythematosus (SLE) is a heterogeneous multisystem inflammatory disease with wide variability in clinical manifestations. Natural arising CD4+ regulatory T cells (Tregs) play a critical role in maintaining peripheral tolerance by suppressing inflammation and preventing autoimmune responses in SLE. Additionally, CD8+ regulatory T cells, type 1 regulatory T cells (Tr1), and B regulatory cells also have a less well-defined role in the pathogenesis of SLE. Elucidation of the roles of various Treg subsets dedicated to immune homeostasis will provide a novel therapeutic approach that governs immune tolerance for the remission of active lupus. Diminished interleukin (IL)-2 production is associated with a depleted Treg cell population, and its reversibility by IL-2 therapy provides important reasons for the treatment of lupus. This review focuses on the pathogenesis and new therapeutics of human Treg subsets and low-dose IL-2 therapy in clinical benefits with SLE.
Correlations between gut microbiota and lichen planus: a two-sample Mendelian randomization study
Authors: Yan Ming , Ouyang Yu-Long , Xiao Li-Yuan , Ao Man , Gosau Martin , Friedrich Reinhard E. , Smeets Ralf , Fu Ling-Ling , Feng Hong-chao , Burg Simon
Published: September 2023

Purpose

Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method.

Methods

Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP.

Results

According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP.

Conclusion

The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.
The CX3CL1-CX3CR1 chemokine axis can contribute to tumor immune evasion and blockade with a novel CX3CR1 monoclonal antibody enhances response to anti-PD-1 immunotherapy
Authors: Chaudhri Apoorvi , Bu Xia , Wang Yunfei , Gomez Michael , Torchia James A. , Hua Ping , Hung Shao-Hsi , Davies Michael A. , Lizee Gregory A. , Andrian Ulrich von , Hwu Patrick , Freeman Gordon J.
Published: September 2023

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration. We generated a novel monoclonal antibody against mouse CX3CR1 that binds to CX3CR1 and blocks the CX3CL1-CX3CR1 interaction. We next explored the immune evasion strategies implemented by the CX3CL1-CX3CR1 axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of soluble mediators to attract myeloid populations, and 4) generation of tumor-inflammasome. The CX3CR1 monoclonal antibody reduces migration of tumor cells and decreases secretion of immune suppressive soluble mediators by tumor cells. In combination with anti-PD-1 immunotherapy, this CX3CR1 monoclonal antibody enhances survival in an immunocompetent mouse colon carcinoma model through a decrease in tumor-promoting myeloid populations. Thus, this axis is involved in the mechanisms of resistance to anti-PD-1 immunotherapy and the combination therapy can overcome a portion of the resistance mechanisms to anti-PD-1.
Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer
Authors: Zeller Tobias , Münnich Ira A. , Windisch Roland , Hilger Patricia , Schewe Denis M. , Humpe Andreas , Kellner Christian
Published: September 2023

Immune checkpoint blockade is a compelling approach in tumor immunotherapy. Blocking inhibitory pathways in T cells has demonstrated clinical efficacy in different types of cancer and may hold potential to also stimulate innate immune responses. A novel emerging potential target for immune checkpoint therapy is leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1). LILRB1 belongs to the superfamily of leukocyte immunoglobulin-like receptors and exerts inhibitory functions. The receptor is expressed by a variety of immune cells including macrophages as well as certain cytotoxic lymphocytes and contributes to the regulation of different immune responses by interaction with classical as well as non-classical human leukocyte antigen (HLA) class I molecules. LILRB1 has gained increasing attention as it has been demonstrated to function as a phagocytosis checkpoint on macrophages by recognizing HLA class I, which represents a ‘Don’t Eat Me!’ signal that impairs phagocytic uptake of cancer cells, similar to CD47. The specific blockade of the HLA class I:LILRB1 axis may provide an option to promote phagocytosis by macrophages and also to enhance cytotoxic functions of T cells and natural killer (NK) cells. Currently, LILRB1 specific antibodies are in different stages of pre-clinical and clinical development. In this review, we introduce LILRB1 and highlight the features that make this immune checkpoint a promising target for cancer immunotherapy.
Zα domain proteins mediate the immune response
Authors: Zhong Yuhan , Zhong Xiao , Qiao Liangjun , Wu Hong , Liu Chang , Zhang Ting
Published: September 2023

The Zα domain has a compact α/β architecture containing a three-helix bundle flanked on one side by a twisted antiparallel β sheet. This domain displays a specific affinity for double-stranded nucleic acids that adopt a left-handed helical conformation. Currently, only three Zα-domain proteins have been identified in eukaryotes, specifically ADAR1, ZBP1, and PKZ. ADAR1 is a double-stranded RNA (dsRNA) binding protein that catalyzes the conversion of adenosine residues to inosine, resulting in changes in RNA structure, function, and expression. In addition to its editing function, ADAR1 has been shown to play a role in antiviral defense, gene regulation, and cellular differentiation. Dysregulation of ADAR1 expression and activity has been associated with various disease states, including cancer, autoimmune disorders, and neurological disorders. As a sensing molecule, ZBP1 exhibits the ability to recognize nucleic acids with a left-handed conformation. ZBP1 harbors a RIP homotypic interaction motif (RHIM), composed of a highly charged surface region and a leucine-rich hydrophobic core, enabling the formation of homotypic interactions between proteins with similar structure. Upon activation, ZBP1 initiates a downstream signaling cascade leading to programmed cell death, a process mediated by RIPK3 via the RHIM motif. PKZ was identified in fish, and contains two Zα domains at the N-terminus. PKZ is essential for normal growth and development and may contribute to the regulation of immune system function in fish. Interestingly, some pathogenic microorganisms also encode Zα domain proteins, such as, Vaccinia virus and Cyprinid Herpesvirus. Zα domain proteins derived from pathogenic microorganisms have been demonstrated to be pivotal contributors in impeding the host immune response and promoting virus replication and spread. This review focuses on the mammalian Zα domain proteins: ADAR1 and ZBP1, and thoroughly elucidates their functions in the immune response.
Mitochondrial PGAM5−Drp1 signaling regulates the metabolic reprogramming of macrophages and regulates the induction of inflammatory responses
Authors: Bang Bo-Ram , Miki Haruka , Kang Young Jun
Published: September 2023

Macrophages play a critical role in the regulation of inflammation and tissue homeostasis. In addition to their vital functions for cell survival and physiology, mitochondria play a crucial role in innate immunity as a platform for the induction of inflammatory responses by regulating cell signaling and dynamics. Dynamin-related protein 1 (Drp1) plays a role in the induction of inflammatory responses and the subsequent development of various diseases. PGAM5 (phosphoglycerate mutase member 5) is a mitochondrial outer membrane phosphatase that dephosphorylates its substrate, Drp1. Previous studies showed that PGAM5 regulates the phosphorylation of Drp1 for the activation of NKT cells and T cells. However, it is not clear how PGAM5 regulates Drp1 activity for the induction of inflammation in macrophages. Here, we demonstrate that PGAM5 activity regulates the dephosphorylation of Drp1 in macrophages, leading to the induction of proinflammatory responses in macrophages. In TLR signaling, PGAM5 regulates the expression and production of inflammatory cytokines by regulating the activation of downstream signaling pathways, including the NF-κB and MAPK pathways. Upon LPS stimulation, PGAM5 interacts with Drp1 to form a complex, leading to the production of mtROS. Furthermore, PGAM5-Drp1 signaling promotes the polarization of macrophages toward a proinflammatory phenotype. Our study further demonstrates that PGAM5-Drp1 signaling promotes metabolic reprogramming by upregulating glycolysis and mitochondrial metabolism in macrophages. Altogether, PGAM5 signaling is a linker between alterations in Drp1-mediated mitochondrial dynamics and inflammatory responses in macrophages and may be a target for the treatment of inflammatory diseases.
p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection
Authors: Suwandi Abdulhadi , Menon Manoj B. , Kotlyarov Alexey , Grassl Guntram A. , Gaestel Matthias
Published: September 2023

Autophagy plays an important role in recognizing and protecting cells from invading intracellular pathogens such as Salmonella. In this work, we investigated the role of p38MAPK/MK2 in modulating the host cell susceptibility to Salmonella infection. Inhibition of p38MAPK or MK2 led to a significant increase of bacterial counts in Salmonella infected mouse embryonic fibroblasts (MEFs), as well as in MK2-deficient (Mk2-/-) cells. Furthermore, western blot analysis showed that Mk2-/- cells have lower level of LC3 lipidation, which is the indicator of general autophagy compared to Mk2-rescued cells. In Mk2-/- cells, we also observed lower activated TANK-binding kinase-1 phosphorylation on Ser172 and p62/SQTM1-Ser403 phosphorylation, which are important to promote the translocation of p62 to ubiquitinated microbes and required for efficient autophagy of bacteria. Furthermore, immunofluorescence analysis revealed reduced colocalization of Salmonella with LC3 and p62 in MEFs. Inhibition of autophagy with bafilomycin A1 showed increased bacterial counts in treated cells compared to control cell. Overall, these results indicate that p38MAPK/MK2-mediated protein phosphorylation modulates the host cell susceptibility to Salmonella infection by affecting the autophagy pathways.
Multi-omics segregate different transcriptomic impacts of anti-IL-17A blockade on type 17 T-cells and regulatory immune cells in psoriasis skin
Authors: Kim Jaehwan , Lee Jongmi , Li Xuan , Kunjravia Norma , Rambhia Darshna , Cueto Inna , Kim Katherine , Chaparala Vasuma , Ko Younhee , Garcet Sandra , Zhou Wei , Cao Junyue , Krueger James G.
Published: September 2023

Durable psoriasis improvement has been reported in a subset of psoriasis patients after treatment withdrawal of biologics blocking IL-23/Type 17 T-cell (T17) autoimmune axis. However, it is not well understood if systemic blockade of the IL-23/T17 axis promotes immune tolerance in psoriasis skin. The purpose of the study was to find translational evidence that systemic IL-17A blockade promotes regulatory transcriptome modification in human psoriasis skin immune cell subsets. We analyzed human psoriasis lesional skin 6 mm punch biopsy tissues before and after systemic IL-17A blockade using the muti-genomics approach integrating immune cell-enriched scRNA-seq (n = 18), microarray (n = 61), and immunohistochemistry (n = 61) with repository normal control skin immune cell-enriched scRNA-seq (n = 10) and microarray (n = 8) data. For the T17 axis transcriptome, systemic IL-17A blockade depleted 100% of IL17A+ T-cells and 95% of IL17F+ T-cells in psoriasis skin. The expression of IL23A in DC subsets was also downregulated by IL-17A blockade. The expression of IL-17-driven inflammatory mediators (IL36G, S100A8, DEFB4A, and DEFB4B) in suprabasal keratinocytes was correlated with psoriasis severity and was downregulated by IL-17A blockade. For the regulatory DC transcriptome, the proportion of regulatory semimature DCs expressing regulatory DC markers of BDCA-3 (THBD) and DCIR (CLEC4A) was increased in posttreatment psoriasis lesional skin compared to pretreatment psoriasis lesional skin. In addition, IL-17A blockade induced higher expression of CD1C and CD14, which are markers of CD1c+ CD14+ dendritic cell (DC) subset that suppresses antigen-specific T-cell responses, in posttreatment regulatory semimature DCs compared to pretreatment regulatory semimature DCs. In conclusion, systemic IL-17A inhibition not only blocks the entire IL-23/T17 cell axis but also promotes regulatory gene expression in regulatory DCs in human psoriasis skin.
Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses
Authors: Uzcategui Nestor L. , Güçer Sena , Richter Cris , Speidel Annika , Zirdum Elizabeta , Duszenko Michael , Garaschuk Olga , Figarella Katherine
Published: September 2023

Introduction

Invasion of the central nervous system (CNS) is the most serious consequence of Trypanosoma brucei infection, which causes sleeping sickness. Recent experimental data have revealed some more insights into the disease during the meningoencephalitic stage. However, detailed cellular processes befalling the CNS during the disease are poorly understood.

Methods

To further address this issue, we implanted a cranial window on the cortex of B6.129P2(Cg)-Cx3cr1tm1Litt/J mice, infected them with Trypanosoma brucei expressing RFP via intraperitoneal injection, and monitored microglial cells and parasites longitudinally over 30 days using in vivo 2-photon imaging. We correlated the observed changes with histological analyses to evaluate the recruitment of peripheral immune cells.

Results and discussion

We uncovered an early involvement of microglia that precedes invasion of the CNS by the parasite. We accomplished a detailed characterization of the progressive sequence of events that correlates with microglial morphological changes and microgliosis. Our findings unveiled a heterogeneous microglial response in places of initial homeostatic disruption near brain barriers and pointed out an exceptional capability of microglia to hamper parasite proliferation inside the brain. We also found early signs of inflammation in the meninges, which synchronize with the microglial response. Moreover, we observed a massive infiltration of peripheral immune cells into the parenchyma as a signature in the final disease stage. Overall, our study provides new insights into the host-pathogen immune interactions in the meningeal and parenchymal compartments of the neocortex.
The gasdermins: a pore-forming protein family expressed in the epidermis
Authors: Slaufova Marta , Karakaya Tugay , Di Filippo Michela , Hennig Paulina , Beer Hans-Dietmar
Published: September 2023

Gasdermins comprise a family of pore-forming proteins, which play critical roles in (auto)inflammatory diseases and cancer. They are expressed as self-inhibited precursor proteins consisting of an aminoterminal cytotoxic effector domain (NT-GSDM) and a carboxyterminal inhibitor domain (GSDM-CT) separated by an unstructured linker region. Proteolytic processing in the linker region liberates NT-GSDM, which translocates to membranes, forms oligomers, and induces membrane permeabilization, which can disturb the cellular equilibrium that can lead to cell death. Gasdermin activation and pore formation are associated with inflammation, particularly when induced by the inflammatory protease caspase-1 upon inflammasome activation. These gasdermin pores allow the release of the pro-inflammatory cytokines interleukin(IL)-1β and IL-18 and induce a lytic type of cell death, termed pyroptosis that supports inflammation, immunity, and tissue repair. However, even at the cellular level, the consequences of gasdermin activation are diverse and range from induction of programmed cell death - pyroptosis or apoptosis - to poorly characterized protective mechanisms. The specific effects of gasdermin activation can vary between species, cell types, the membrane that is being permeabilized (plasma membrane, mitochondrial membrane, etc.), and the overall biological state of the local tissue/cells. In epithelia, gasdermins seem to play crucial roles. Keratinocytes represent the main cell type of the epidermis, which is the outermost skin layer with an essential barrier function. Compared to other tissues, keratinocytes express all members of the gasdermin family, in part in a differentiation-specific manner. That raises questions regarding the specific roles of individual GSDM family members in the skin, the mechanisms and consequences of their activation, and the potential crosstalk between them. In this review, we summarize the current knowledge about gasdermins with a focus on keratinocytes and the skin and discuss the possible roles of the different family members in immunity and disease.
Camera-based automated monitoring of flying insects (Camfi). I. Field and computational methods
Authors: Wallace Jesse Rudolf Amenuvegbe , Reber Therese Maria Joanna , Dreyer David , Beaton Brendan , Zeil Jochen , Warrant Eric
Published: September 2023

The ability to measure flying insect activity and abundance is important for ecologists, conservationists and agronomists alike. However, existing methods are laborious and produce data with low temporal resolution (e.g. trapping and direct observation), or are expensive, technically complex, and require vehicle access to field sites (e.g. radar and lidar entomology). We propose a method called “Camfi” for long-term non-invasive population monitoring and high-throughput behavioural observation of low-flying insects using images and videos obtained from wildlife cameras, which are inexpensive and simple to operate. To facilitate very large monitoring programs, we have developed and implemented a tool for automatic detection and annotation of flying insect targets in still images or video clips based on the popular Mask R-CNN framework. This tool can be trained to detect and annotate insects in a few hours, taking advantage of transfer learning. Our method will prove invaluable for ongoing efforts to understand the behaviour and ecology of declining insect populations and could also be applied to agronomy. The method is particularly suited to studies of low-flying insects in remote areas, and is suitable for very large-scale monitoring programs, or programs with relatively low budgets.
Identifying a machine-learning structural descriptor linked to the creep behavior of Kob-Andersen glasses
Authors: Wu Mingyue , Ruiz Pestana Luis
Published: September 2023

A wide variety of materials, ranging from metals to concrete, experience, typically at high-temperatures or over long time scales, permanent deformations when subjected to sustained loads below their yield stress—a phenomenon known as creep. While theories grounded on defects such as vacancies, dislocations, or grain boundaries can explain creep in crystalline materials, our understanding of creep in disordered solids remains incomplete due to the lack of analogous structural descriptors. In this study, we use molecular dynamics to simulate the creep response of a Kob-Andersen glass model system under constant, uniaxial, compressive stress at finite temperature. We leverage that data to derive, using a machine-learning classification model, a structural descriptor termed looseness, L, which is based on simple and interpretable local structural features and can predict imminent plastic rearrangements within the glass. We show that the average looseness of the system evolves logarithmically with time, mirroring the time dependence of the creep strain and demonstrating the ability of our model to bridge local, short-term particle dynamics with the long-term macroscopic creep response. A detailed feature importance analysis reveals the particular significance of short-range structural heterogeneity in the prediction. We also scrutinize the spatial and temporal correlations of looseness, which mirror the lack of long-range order in glasses and their dynamic heterogeneity. Our research underscores the substantial predictive potential of machine-learning-derived structural indicators in systems experiencing concurrent stress and thermal excitations, paving the way for future work to elucidate the interplay between thermal and mechanical activation of structural defects in disordered solids.
Application of the Team Emergency Assessment Measure Scale in undergraduate medical students and interprofessional clinical teams: validity evidence of a Spanish version applied in Chile
Authors: Armijo-Rivera Soledad , Ferrada-Rivera Sandra , Aliaga-Toledo Marcela , Pérez Leonardo A.
Published: September 2023

Background

Teamwork is one of the competencies necessary for physicians to work effectively in health systems and is a competency that can be developed with simulation in professionals and medicine students. The Team Emergency Assessment Measurement (TEAM) was created to evaluate the non-technical performance of team members during resuscitation events in real teams. The TEAM scale includes items to assess leadership, teamwork, situational awareness, and task management. An objective evaluation tool in Spanish is valuable for training health professionals at all undergraduate and continuing education levels. This study aimed to generate evidence of the validity of the Team Emergency Assessment Measure (TEAM) in Spanish to measure the performance of medical students and adult, pediatric, and obstetric emergency clinical teams in simulated emergencies as a self-assessment tool.

Methods

To develop the Spanish version of the instrument, a forward and backward translation process was followed by independent translators, native and fluent in English and Spanish, and a review by a panel of Chilean experts comprising three trained simulation instructors to verify semantics and cultural equivalence. High-fidelity simulations with debriefing were conducted with 5th-year medical students, in which students and instructors applied the Spanish version of the TEAM scale. In the second stage, adult, pediatric, and obstetric emergency management simulations were conducted using the TEAM scale for real clinical teams as a self-assessment tool.

Findings

By applying the overall TEAM scale to medicine students and clinical teams, Cronbach's alpha was 0.921. For medical students' self-assessment, we obtained Cronbach's alpha of 0.869. No significant differences were found between the overall scores and the scores by dimensions evaluated by instructors and students (p > 0.05). In the case of clinical team training, Cronbach's alpha was 0.755 for adult emergency teams, 0.797 for pediatric emergency teams, and 0.853 for obstetric emergency teams.

Conclusion

The validated instrument is adequate for evaluating teamwork in medical student simulations by instructors and peers and for self-assessment in adult, pediatric, and obstetric emergency clinical teams.
Functional proteins in breast milk and their correlation with the development of the infant gut microbiota: a study of mother-infant pairs
Authors: Xi Menglu , Liang Dong , Yan Yalu , Duan Sufang , Leng Houxi , Yang Haibing , Shi Xiaojin , Na Xiaona , Yang Yucheng , Yang Celi , Szeto Ignatius Man-Yau , Zhao Ai
Published: September 2023

Introduction

Proteins in breast milk play an important role in the growth and development of infants. This study aims to explore the correlation between functional proteins in breast milk and the infant gut microbiota.

Methods

Twenty-three mothers and their infants were enrolled and breast milk samples and infant fecal samples were collected. Breast milk protein content was determined by UPLC-MS/MS, and 16S rRNA sequencing was employed to analyze the gut microbiota of infant.

Results

The results indicated that the secretory immunoglobulin A (sIgA) content in breast milk was positively correlated with the abundance of Veillonella parvula. The κ-casein content was positively correlated with the abundance of Clostridium butyricum. The osteopontin (OPN) and lactalbumin contents were positively correlated with the abundance of Parabacteroides distasonis at 42 days. Functional pathway analysis showed that the OPN and κ-casein contents in breast milk were significantly correlated with amino acid, pyruvate, propionic acid, linoleic acid, and alpha-linolenic acid metabolic pathways in early life.

Discussion

The results of this study suggest that specific proteins in breast milk can influence the abundance of certain gut microbes in infants, playing an important role in early immune and metabolic development.
Archaeome structure and function of the intestinal tract in healthy and H1N1 infected swine
Authors: Meene Alexander , Gierse Laurin , Schwaiger Theresa , Karte Claudia , Schröder Charlotte , Höper Dirk , Wang Haitao , Groß Verena , Wünsche Christine , Mücke Pierre , Kreikemeyer Bernd , Beer Martin , Becher Dörte , Mettenleiter Thomas C. , Riedel Katharina , Urich Tim
Published: September 2023

Background

Methanogenic archaea represent a less investigated and likely underestimated part of the intestinal tract microbiome in swine.

Aims/Methods

This study aims to elucidate the archaeome structure and function in the porcine intestinal tract of healthy and H1N1 infected swine. We performed multi-omics analysis consisting of 16S rRNA gene profiling, metatranscriptomics and metaproteomics.

Results and discussion

We observed a significant increase from 0.48 to 4.50% of archaea in the intestinal tract microbiome along the ileum and colon, dominated by genera Methanobrevibacter and Methanosphaera. Furthermore, in feces of naïve and H1N1 infected swine, we observed significant but minor differences in the occurrence of archaeal phylotypes over the course of an infection experiment. Metatranscriptomic analysis of archaeal mRNAs revealed the major methanogenesis pathways of Methanobrevibacter and Methanosphaera to be hydrogenotrophic and methyl-reducing, respectively. Metaproteomics of archaeal peptides indicated some effects of the H1N1 infection on central metabolism of the gut archaea.

Conclusions/Take home message

Finally, this study provides the first multi-omics analysis and high-resolution insights into the structure and function of the porcine intestinal tract archaeome during a non-lethal Influenza A virus infection of the respiratory tract, demonstrating significant alterations in archaeal community composition and central metabolic functions.
Biosurfactant: an emerging tool for the petroleum industries
Authors: Sharma Neha , Lavania Meeta , Lal Banwari
Published: September 2023

The petroleum sector is essential to supplying the world’s energy demand, but it also involves numerous environmental problems, such as soil pollution and oil spills. The review explores biosurfactants’ potential as a new tool for the petroleum sector. Comparing biosurfactants to their chemical equivalents reveals several advantages. They are ecologically sustainable solutions since they are renewable, nontoxic, and biodegradable. Biosurfactants are used in a variety of ways in the petroleum sector. They can improve the mobilization and extraction of trapped hydrocarbons during oil recovery procedures. By encouraging the dispersion and solubilization of hydrocarbons, biosurfactants also assist in the cleanup of oil spills and polluted locations by accelerating their breakdown by local microorganisms. The review gives insights into alternative methods for the petroleum industry that are more viable and cost-effective.
The oxidative stress response of Streptococcus pneumoniae: its contribution to both extracellular and intracellular survival
Authors: Hernandez-Morfa Mirelys , Olivero Nadia B. , Zappia Victoria E. , Piñas German E. , Reinoso-Vizcaino Nicolas M. , Cian Melina B. , Nuñez-Fernandez Mariana , Cortes Paulo R. , Echenique Jose
Published: September 2023

Streptococcus pneumoniae is a gram-positive, aerotolerant bacterium that naturally colonizes the human nasopharynx, but also causes invasive infections and is a major cause of morbidity and mortality worldwide. This pathogen produces high levels of H2O2 to eliminate other microorganisms that belong to the microbiota of the respiratory tract. However, it also induces an oxidative stress response to survive under this stressful condition. Furthermore, this self-defense mechanism is advantageous in tolerating oxidative stress imposed by the host’s immune response. This review provides a comprehensive overview of the strategies employed by the pneumococcus to survive oxidative stress. These strategies encompass the utilization of H2O2 scavengers and thioredoxins, the adaptive response to antimicrobial host oxidants, the regulation of manganese and iron homeostasis, and the intricate regulatory networks that control the stress response. Here, we have also summarized less explored aspects such as the involvement of reparation systems and polyamine metabolism. A particular emphasis is put on the role of the oxidative stress response during the transient intracellular life of Streptococcus pneumoniae, including coinfection with influenza A and the induction of antibiotic persistence in host cells.
Elevated white blood cell counts in ischemic stroke patients are associated with increased mortality and new vascular events
Authors: Vo Thao Phuong , Kristiansen Marie Hvelplund , Hasselbalch Hans Carl , Wienecke Troels
Published: September 2023

Background and purpose

High levels of white blood cells (WBC) in ischemic stroke have been shown to increase the risk of new vascular events and mortality in short and intermediate follow-up studies, but long-term effects remain unknown. We studied whether elevated levels of WBC in ischemic stroke patients are associated with new vascular events and mortality in a 10-year follow-up period.

Methods

We included ischemic stroke patients hospitalized between 2011 and 2012, categorizing their WBC counts within 48 h of stroke onset as high or normal (3.5–8.8 × 109 mmol/L; >8.8 × 109 mmol/L). Using Aahlen Johansen and Cox proportional hazard models with competing risk, we analyzed the association between WBC levels and new vascular events. Kaplan–Meier and standard Cox proportional hazard models were used to assess the risk of all-cause mortality.

Results

Among 395 patients (median age 69, [IQR: 63, 78], female patients 38,0%), 38.5% had elevated WBC at admission. During the 10-year follow-up, 113 vascular events occurred, with 46% in patients with elevated WBC and 54% in patients with normal WBC. After adjusting for relevant factors, elevated WBC levels were independently associated with increased risk of new vascular events (HR: 1.61, CI: 1.09–2.39 p < 0.05) and death (HR: 1.55, CI: 1.15–2.09, p < 0.05).

Conclusion

Elevated WBC levels in ischemic stroke patients are linked to a higher risk of new vascular events and mortality. Thus, ischemic stroke patients with elevated WBC without clinical infection need special attention to investigate possible underlying conditions to prevent future vascular events and reduce mortality. The interpretation of our results is limited by the absence of adjustment to premorbid functional status, stroke severity, and stroke treatment.
ALBSNN: ultra-low latency adaptive local binary spiking neural network with accuracy loss estimator
Authors: Pei Yijian , Xu Changqing , Wu Zili , Liu Yi , Yang Yintang
Published: September 2023

Spiking neural network (SNN) is a brain-inspired model with more spatio-temporal information processing capacity and computational energy efficiency. However, with the increasing depth of SNNs, the memory problem caused by the weights of SNNs has gradually attracted attention. In this study, we propose an ultra-low latency adaptive local binary spiking neural network (ALBSNN) with accuracy loss estimators, which dynamically selects the network layers to be binarized to ensure a balance between quantization degree and classification accuracy by evaluating the error caused by the binarized weights during the network learning process. At the same time, to accelerate the training speed of the network, the global average pooling (GAP) layer is introduced to replace the fully connected layers by combining convolution and pooling. Finally, to further reduce the error caused by the binary weight, we propose binary weight optimization (BWO), which updates the overall weight by directly adjusting the binary weight. This method further reduces the loss of the network that reaches the training bottleneck. The combination of the above methods balances the network's quantization and recognition ability, enabling the network to maintain the recognition capability equivalent to the full precision network and reduce the storage space by more than 20%. So, SNNs can use a small number of time steps to obtain better recognition accuracy. In the extreme case of using only a one-time step, we still can achieve 93.39, 92.12, and 69.55% testing accuracy on three traditional static datasets, Fashion- MNIST, CIFAR-10, and CIFAR-100, respectively. At the same time, we evaluate our method on neuromorphic N-MNIST, CIFAR10-DVS, and IBM DVS128 Gesture datasets and achieve advanced accuracy in SNN with binary weights. Our network has greater advantages in terms of storage resources and training time.
Imaging and clinical predictors of acute constipation in patients with acute ischemic stroke
Authors: Han I Joon , Lee Ji-Eun , Song Ha-Na , Baek In-Young , Choi Jongun , Chung Jong-Won , Bang Oh Young , Kim Gyeong-Moon , Seo Woo-Keun
Published: September 2023

Background

Constipation symptoms are highly prevalent in acute ischemic stroke, but the clinical and neuroimaging predictors are unknown. This study aimed to identify lesions and clinical features associated with acute constipation.

Methods

Data from patients with acute ischemic stroke registered in a hospital-based stroke registry between January 2018 and December 2019 were analyzed. Clinical, laboratory, and imaging features were examined for associations with acute constipation. Using the topographic lesion on diffusion-weighted images, multivariate support vector regression-based lesion-symptom mapping (SVR-LSM) was conducted and compared between the non-constipation and acute constipation groups.

Results

A total of 256 patients (mean age 67 years, men: 64%) were included. Acute constipation was noted in 81 patients (32%). Initial stroke severity, represented by initial National Institutes of Health and Stroke Scale (NIHSS) scores, was associated with acute constipation. Laboratory parameters, including fibrin degradation products (FDP), fibrinogen, D-dimer, lipoprotein (a), and free fatty acid levels, also showed statistically significant differences between the non-constipation and constipation groups. FDP, D-dimer, and free fatty acid levels were independently associated with acute constipation in the logistic regression model after adjusting for initial NIHSS scores and potassium levels. SVR-LSM revealed that bilateral lesions in the precentral gyrus, insula, opercular part of the inferior frontal gyrus, the inferior parietal lobule, and lesions in the right middle frontal gyrus were significantly associated with acute constipation. The results were consistent after controlling for the initial NIHSS scores and poststroke potassium levels. When cardioembolic stroke subjects were excluded, the right insular and prefrontal cortex lesions lost their association with acute constipation.

Conclusion

Acute constipation symptoms after acute ischemic stroke are mainly related to bilateral lesions in the insula, precentral gyrus, postcentral gyrus, and inferior parietal lobule. Clinically important predictors of acute constipation include initial neurological severity and thromboembolic markers of stroke.
BMI and plasma lipid levels with risk of proliferative diabetic retinopathy: a univariable and multivariable Mendelian randomization study
Authors: Shu Yiyang , Zhou Qi , Shao Yuting , Lin Hui , Qu Shen , Han Wenting , Lv Xiao , Bi Yanlong
Published: September 2023

Background

The study aimed to determine whether a causal effect exists between body mass index (BMI) or plasma lipid levels and proliferative diabetic retinopathy (PDR) risk in humans.

Methods

We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analyses to confirm the effects of BMI and plasma lipid levels on the risk of PDR. Genetic variants associated with BMI and three plasma lipids were obtained from GWAS summary datasets generated by many different consortia and were deposited in the MR-Base database. The GWAS summary data for PDR from the FinnGen biobank included 2,12,889 participants of European ancestry (8,681 cases and 2,04,208 controls). Inverse variance weighted (IVW) was applied as the main MR analysis. Sensitivity analysis was used to evaluate the robustness of our findings.

Results

In the UVMR analysis, the causal associations of genetically predicted BMI with PDR presented a positive association (OR = 1.120, 95% CI = 1.076–1.167, P < 0.001), and the lower HDL-C level was associated with a higher risk of PDR (OR = 0.898, 95% CI = 0.811–0.995, P = 0.040). No evidence of an association between LDL-C or TG levels (P > 0.05) and PDR risk was found. In the MVMR analysis controlling for the HDL-C level, there was strong evidence for a direct causal effect of BMI on the risk of PDR (OR = 1.106, 95%CI = 1.049, 1.166, P < 0.001, IVW). After adjusting for BMI, there was no evidence for a direct causal effect of the HDL-C level on the risk of PDR (OR = 0.911, 95% CI = 0.823, 1.008, P = 0.072). Sensitivity analyses confirmed that the results were reliable and stable.

Conclusion

Robust evidence was demonstrated for an independent, causal effect of BMI in increasing the risk of PDR. Further studies are required to understand the potential biological mechanisms underlying this causal relationship.