bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Eyed Seeing as a strategic dichotomy for decolonial nursing knowledge development and practice
Authors: McFadden Alysha , Lynam M. Judith , Hawkins Lorelei
Published: July 2023

The profession of nursing has recognized the need for contextual and relational frameworks to inform knowledge development. Two‐Eyed Seeing is a framework developed by Mi'kmaw Elders to respectfully engage with Indigenous and non‐Indigenous knowledges. Some scholars and practitioners, however, are concerned that Two‐Eyed Seeing re‐instantiates dichotomized notions regarding Western and Indigenous knowledges. As dichotomies and binaries are often viewed as polarizing devices for nursing knowledge development, this paper explores the local worldviews in which Two‐Eyed Seeing emerged, proposing that the onto‐epistemological and axiological ‘roots’ of the framework are antithetical to divisiveness, paradoxically asserting space for the dichotomy to stand. Two‐Eyed Seeing, if understood as a relational, decolonial praxis, could fundamentally change the way nursing scholarship and practice operate by facilitating space for diverse knowledges, ways of being, doing and relating. In this paper, considerations for nursing scholarship and practice, as well as recommendations to support the uptake of Two‐Eyed Seeing are explored. The authors assert that conceptual divisiveness, dichotomization and exclusion can be mitigated if nursing is informed by contextual knowledge, seeks to enact accountable partnerships with Indigenous knowledge holders, and holds the Mi'kmaq worldview upon which the concept developed in positive regard.
From seed dispersal service to reproductive collapse: density‐dependent outcome of a palm–mammal interaction
Authors: Muñoz‐Gallego Raquel , Wiegand Thorsten , Traveset Anna , Fedriani Jose M.
Published: July 2023

Interspecific ecological interactions are inherently context‐dependent. They may vary in both magnitude and sign depending on the biotic and abiotic conditions, depicting a mutualism–antagonism continuum. However, how population abundances and the activity of interacting species modulate these interactions remains underexplored. Here, we chose the interaction between the Mediterranean palm Chamaerops humilis and the feral goat Capra hircus in Mallorca (Balearic Islands, Spain). We selected three study plots with low, intermediate and high intensities of goat activity where we characterized palm distribution, seed rain, seed predation and early palm recruitment during two consecutive years. Since goats can cause both costs (e.g. florivory) and benefits (e.g. seed dispersal) to C. humilis performance, we investigated the following three questions: 1) does the spatial distribution of adult palms vary depending on the intensity of goat activity? 2) Does the intensity of goat activity influence seed rain and its potential spatial association with adult palms? 3) To what extent does the intensity of goat activity determine post‐dispersal events such as seed predation and seedling emergence? We found that adult palms showed a more clumped and complex distribution (double‐cluster process) in plots with low and intermediate goat activity compared to that with high goat activity (simple‐cluster process). In the low goat activity plot, dispersed seeds were spatially aggregated around adult palms, showing twice as much insect‐seed predation and nearly three times lower seed germination success than those in the intermediate goat activity plot. Palm seed dispersal and recruitment were almost nil in the high goat activity plot due to heavy consumption of palm inflorescences and developing fruits by goats. Our findings demonstrate how the net outcome of plant–animal interactions can change from mutualism to antagonism, from reproductive service to reproductive collapse, depending on the abundance and the activity of the interacting species.
Computer‐assisted analysis of chaos in a three‐species food chain model
Authors: Hua Duo , Liu Xingbo
Published: July 2023

In this paper, a three‐species food chain model with Holling type IV and Beddington–DeAngelis functional responses is formulated. Numerical simulations show that this system can generate chaos for some parameter values. But the mechanism behind chaos is still unclear only through numerical simulations. Then, using the topological horseshoe theories and Conley–Moser conditions, we present a computer‐assisted analysis to show the chaoticity of this system in the topological sense, that is, it has positive topological entropy. We prove that the Poincaré map of this model possesses a closed uniformly hyperbolic chaotic invariant set, and it is topologically conjugate to a 2‐shift map. At last, we consider the impact of fear on this three‐species model. It is an important factor in controlling chaos in biological models, which has been validated in other models.
Chimeric HLA antibody receptor T cells for targeted therapy of antibody‐mediated rejection in transplantation
Authors: Betriu Sergi , Rovira Jordi , Arana Carolt , García‐Busquets Ainhoa , Matilla‐Martinez Marina , Ramirez‐Bajo Maria J. , Bañon‐Maneus Elisenda , Lazo‐Rodriguez Marta , Bartoló‐Ibars Ariadna , Claas Frans H. J. , Mulder Arend , Heidt Sebastiaan , Juan Manel , Bayés‐Genís Beatriu , Campistol Josep M. , Palou Eduard , Diekmann Fritz
Published: July 2023

The presence of donor‐specific antibodies (DSA), mainly against HLA, increases the risk of allograft rejection. Moreover, antibody‐mediated rejection (ABMR) remains an important barrier to optimal long‐term outcomes after solid organ transplantation. The development of chimeric autoantibody receptor T lymphocytes has been postulated for targeted therapy of autoimmune diseases. We aimed to develop a targeted therapy for DSA desensitization and ABMR, generating T cells with a chimeric HLA antibody receptor (CHAR) that specifically eliminates DSA‐producing B cells. We have genetically engineered an HLA‐A2‐specific CHAR (A2‐CHAR) and transduced it into human T cells. Then, we have performed in vitro experiments such as cytokine measurement, effector cell activation, and cytotoxicity against anti‐HLA‐A2 antibody‐expressing target cells. In addition, we have performed A2‐CHAR‐Tc cytotoxic assays in an immunodeficient mouse model. A2‐CHAR expressing T cells could selectively eliminate HLA‐A2 antibody‐producing B cells in vitro. The cytotoxic capacity of A2‐CHAR expressing T cells mainly depended on Granzyme B release. In the NSG mouse model, A2‐CHAR‐T cells could identify and eradicate HLA‐A2 antibody‐producing B cells even when those cells are localized in the bone marrow. This ability is effector:target ratio dependent. CHAR technology generates potent and functional human cytotoxic T cells to target alloreactive HLA class I antibody‐producing B cells. Thus, we consider that CHAR technology may be used as a selective desensitization protocol or an ABMR therapy in transplantation.
The new HLA‐DQB1*05:304 allele identified in an Italian patient
Authors: Troiano M. , Giustiniani P. , Pinto R. M. , Di Luzio A. , Andreani M.
Published: July 2023

DQB1*05:304 allele was identical to DQB1*05:02:01 except for a single nucleotide substitution.
How to … define clinical education research terminology: A glossary
Authors: Finn Gabrielle M. , Charmer Ben , Burton Oliver E. , Asif Aqua , Byrne Matthew H. V. , Brennan Nicola , Brown Megan E. L. ,   the NIHR Incubator for Clinical Education Research
Published: July 2023

Clinical education research (ClinEdR) utilises diverse terminology, which can lead to confusion. A common language is essential for enhancing impact. An expert panel drawn from various workstreams within the National Institute for Health and Care Research (NIHR) Incubator for Clinical Education Research was tasked with reviewing an initial list of terms for the development of a glossary of terms in the field of ClinEdR. The glossary was populated with terms, definitions and foundational papers by the authors and peer‐reviewed for accuracy. The glossary of terms developed for ClinEdR should enable researchers to use a common language, promoting consistency and improving communication. We anticipate this will be useful for ClinEdR students and early career researchers. The glossary could be integrated into educational research methods courses in ClinEdR, and through critical and reflective use, enhance the quality and subsequent impact of ClinEdR.
Population genetic structure of Dermatophagoides farinae (Acari: Pyroglyphidae) from different geographic populations based on mitochondrial cytochrome b gene
Authors: Ye Changjiang , Wang Yan , Li Xinmei , Chu Lingmiao , Fang Yu , Zhou Xiaoqian , Chen Huilin , Fan Haiye , Zhu Yonghang , Tao Xianglin , Sun Entao
Published: July 2023

Dermatophagoides farinae (Acari: Pyroglyphidae) has been regarded as an important source of indoor allergens due to its prevalence and close proximity to humans. This study serves as an introductory probe into the population genetic structure of D. farinae, for which a few related studies of population genetic structure are available. In this study, the genetic structure of seven D. farinae populations in China was investigated based on the 372 bp mitochondrial cytochrome b (cytb) gene. A total of 29 haplotypes of the 68 cytb gene sequences were detected. The network diagram could be divided into Branch I (regions north of the Yangtze River: SJZ, CZ, FY and HN) and Branch II (regions south of the Yangtze River: AQ, WX and WH). Analysis of molecular variance (AMOVA) conducted according to the results of the network diagram revealed major genetic differentiation among groups, indicating that a significant genetic structure existed among groups. The results of population genetic structure could be largely attributed to geographical isolation. The existence of gene flow in a few populations may be influenced by grain trade activities. This study may facilitate a better understanding of the population genetic structure of D. farinae and could be utilized as the foundation for the development of efficient management strategies for D. farinae.
Comparing sputter rates, depth resolution, and ion yields for different gas cluster ion beams (GCIB): A practical guide to choosing the best GCIB for every application
Authors: Sano N. , Bellew A. , Blenkinsopp P.
Published: July 2023

Molecular gas species for gas cluster ion beams (GCIBs), such as carbon dioxide and water, were examined with a range of beam energies and cluster sizes to compare with the “universal relation” of the sputter yield, Y, per cluster atom against incident beam energy, E, per cluster atom of Arn cluster beam using Irganox 1010. In this work, we compare Arn, (CO2)n, and (H2O)n gas clusters to the universal equations for Arn clusters. To discuss molecular gas species for GCIBs, energy per nucleon (E/N) needs to replace energy per atom. We monitored sputter rate, depth resolution, and secondary ion yield as a function of the beam parameters: gas species, beam energy, and cluster size. (H2O)n GCIB shows reduced sputter rates and improved depth resolution with high sensitivity compared to Arn and (CO2)n GCIBs. These initial results indicate the potential to achieve high-depth resolution with high sensitivity and suggest that (H2O)n cluster ion beam has the potential to play a significant role in surface analysis techniques with organic materials. Results also show that no single set of conditions will provide the “best gas cluster ion beam” for all applications. However, it is possible to choose a set of conditions that will be more or less optimal depending on the experimental goals, such as maximizing the sputter rate, depth resolution, and molecular ion yield. In this work, we recommend the following three guidelines for GCIB users to set their own conditions: (1) to maximize the sputter rate, select a smaller cluster (higher E/N), but be aware that this will increase fragmentation and reduce molecular ion yield; (2) to maximize the depth resolution, select a larger cluster (lower E/N), and use (H2O)n GCIB, if possible; and (3) to maximize the molecular ion signal, use the highest beam energy available, and select a cluster with 0.15–0.25 eV/nucleon for Ar and (CO2)n GCIBs or around 0.1 eV/nucleon if using (H2O)n GCIB. These results are valid for XPS, SIMS, and any technique that utilizes GCIBs.
Lectin-Seq: A method to profile lectin-microbe interactions in native communities
Authors: McPherson Robert L. , Isabella Christine R. , Walker Rebecca L. , Sergio Dallis , Bae Sunhee , Gaca Tony , Raman Smrithi , Nguyen Le Thanh Tu , Wesener Darryl A. , Halim Melanie , Wuo Michael G. , Dugan Amanda , Kerby Robert , Ghosh Soumi , Rey Federico E. , Dhennezel Catherine , Pishchany Gleb , Lensch Valerie , Vlamakis Hera , Alm Eric J. , Xavier Ramnik J. , Kiessling Laura L.
Published: July 2023

Soluble human lectins are critical components of innate immunity. Genetic models suggest that lectins influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins’ roles in regulating microbiota requires an understanding of which microbial species they bind within native communities. To profile human lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to human fecal microbiota using the soluble mannose-binding lectin (MBL) and intelectin-1 (hItln1). Although each lectin binds a substantial percentage of the samples (10 to 20%), the microbial interactomes of MBL and hItln1 differ markedly in composition and diversity. MBL binding is highly selective for a small subset of species commonly associated with humans. In contrast, hItln1’s interaction profile encompasses a broad range of lower-abundance species. Our data uncover stark differences in the commensal recognition properties of human lectins.
Clonally expanded CD38
hi
cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor–associated arthritis
Authors: Wang Runci , Singaraju Anvita , Marks Kathryne E. , Shakib Lorien , Dunlap Garrett , Adejoorin Ifeoluwakiisi , Greisen Stinne R. , Chen Lin , Tirpack Aidan K. , Aude Carlos , Fein Miriam R. , Todd Derrick J. , MacFarlane Lindsey , Goodman Susan M. , DiCarlo Edward F. , Massarotti Elena M. , Sparks Jeffrey A. , Jonsson A. Helena , Brenner Michael B. , Postow Michael A. , Chan Karmela K. , Bass Anne R. , Donlin Laura T. , Rao Deepak A.
Published: July 2023

Immune checkpoint inhibitor (ICI) therapies used to treat cancer, such as anti–PD-1 antibodies, can induce autoimmune conditions in some individuals. The T cell mechanisms mediating such iatrogenic autoimmunity and their overlap with spontaneous autoimmune diseases remain unclear. Here, we compared T cells from the joints of 20 patients with an inflammatory arthritis induced by ICI therapy (ICI-arthritis) with two archetypal autoimmune arthritides, rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Single-cell transcriptomic and antigen receptor repertoire analyses highlighted clonal expansion of an activated effector CD8 T cell population in the joints and blood of patients with ICI-arthritis. These cells were identified as CD38
hi
CD127
−
CD8 T cells and were uniquely enriched in ICI-arthritis joints compared with RA and PsA and also displayed an elevated interferon signature. In vitro, type I interferon induced CD8 T cells to acquire the ICI-associated CD38
hi
phenotype and enhanced cytotoxic function. In a cohort of patients with advanced melanoma, ICI therapy markedly expanded circulating CD38
hi
CD127
−
T cells, which were frequently bound by the therapeutic anti–PD-1 drug. In patients with ICI-arthritis, drug-bound CD8 T cells in circulation showed marked clonal overlap with drug-bound CD8 T cells from synovial fluid. These results suggest that ICI therapy directly targets CD8 T cells in patients who develop ICI-arthritis and induces an autoimmune pathology that is distinct from prototypical spontaneous autoimmune arthritides.
Fungal mechanisms of intracellular survival: what can we learn from bacterial pathogens?
Authors: Stuckey Peter V. , Santiago-Tirado Felipe H.
Published: July 2023

Fungal infections represent a major, albeit neglected, public health threat with serious medical and economic burdens globally. With unacceptably high mortality rates, invasive fungal pathogens are responsible for millions of deaths each year, with a steadily increasing incidence primarily in immunocompromised individuals. The poor therapeutic options and rise of antifungal drug resistance pose further challenges in controlling these infections. These fungal pathogens have adapted to survive within mammalian hosts and can establish intracellular niches to promote survival within host immune cells. To do that, they have developed diverse methods to circumvent the innate immune system attack. This includes strategies such as altering their morphology, counteracting macrophage antimicrobial action, and metabolic adaptation. This is reminiscent of how bacterial pathogens have adapted to survive within host cells and cause disease. However, relative to the great deal of information available concerning intracellular bacterial pathogenesis, less is known about the mechanisms fungal pathogens employ. Therefore, here we review our current knowledge and recent advances in our understanding of how fungi can evade and persist within host immune cells. This review will focus on the major fungal pathogens, including
Cryptococcus neoformans, Candida albicans
, and
Aspergillus fumigatus
, among others. As we discover and understand the strategies used by these fungi, similarities with their bacterial counterparts are becoming apparent, hence we can use the abundant information from bacteria to guide our studies in fungi. By understanding these strategies, new lines of research will open that can improve the treatments of these devastating fungal diseases.
Upregulation of IQGAP2 by EBV transactivator Rta and its influence on EBV life cycle
Authors: Lin Kai-Min , Weng Li-Fang , Chen Shi-Yo Jill , Lin Sue-Jane , Tsai Ching-Hwa
Published: July 2023

Epstein-Barr virus (EBV) is a human oncogenic γ-herpesvirus that establishes persistent infection in more than 90% of the world’s population. EBV has two life cycles, latency and lytic replication. Reactivation of EBV from latency to the lytic cycle is initiated and controlled by two viral immediate-early transcription factors, Zta and Rta, encoded by
BZLF1
and
BRLF1
, respectively. In this study, we found that IQGAP2 expression was elevated in EBV-infected B cells and identified Rta as a viral gene responsible for the IQGAP2 upregulation in both B cells and nasopharyngeal carcinoma cell lines. Mechanistically, we showed that Rta increases IQGAP2 expression through direct binding to the Rta-responsive element in the IQGAP2 promoter. We also demonstrated the direct interaction between Rta and IQGAP2 as well as their colocalization in the nucleus. Functionally, we showed that the induced IQGAP2 is required for the Rta-mediated Rta promoter activation in the EBV lytic cycle progression and may influence lymphoblastoid cell line clumping morphology through regulating E-cadherin expression.

IMPORTANCE

Elevated levels of antibodies against EBV lytic proteins and increased EBV DNA copy numbers in the sera have been reported in patients suffering from Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma, indicating that EBV lytic cycle progression may play an important role in the pathogenesis of EBV-associated diseases and highlighting the need for a more complete mechanistic understanding of the EBV lytic cycle. Rta acts as an essential transcriptional activator to induce lytic gene expression and thus trigger EBV reactivation. In this study, scaffolding protein IQGAP2 was found to be upregulated prominently following EBV infection via the direct binding of Rta to the RRE in the IQGAP2 promoter but not in response to other biological stimuli. Importantly, IQGAP2 was demonstrated to interact with Rta and promote the EBV lytic cycle progression. Suppression of IQGAP2 was also found to decrease E-cadherin expression and affect the clumping morphology of lymphoblastoid cell lines.
Supplemental Material: Eruptive dynamics reflect crustal structure and mantle productivity beneath volcanoes
Authors: Higgins Oliver , Caricchi Luca
Published: July 2023

Published data tables and their sources used in this study as well as an extended methods description.  
Supplemental Material: Paleogeographical reconstruction of the South China Block during Gondwana assembly using detrital apatite: Pan-African source affinity concealed by detrital zircon
Authors: Xue Er-Kun , Wang, Wei , et al.
Published: July 2023

Table S1: U-Pb isotopic compositions of detrital apatites. Table S2: Trace elemental compositions of detrital apatites. Table S3: References for data of detrital zircon, and igneous, and metamorphic apatite and monazite from the potential source terranes.
Differences in type 2 diabetes risk between East, South, and Southeast Asians living in Singapore: the multi-ethnic cohort
Authors: Seah Jowy Yi Hoong , Sim Xueling , Khoo Chin Meng , Tai E Shyong , van Dam Rob M
Published: July 2023

Introduction

Prospective data on differences in type two diabetes (T2D) risk between Asian ethnic groups are sparse. We, therefore, compared T2D risk for East (Chinese), South (Indian), and Southeast (Malay) Asians and examined biological factors that may contribute to ethnic differences.

Research design and methods

We included 7427 adults of Chinese, Malay, and Indian origin participating in the Singapore multi-ethnic cohort. Information on sociodemographic, lifestyle, and biological risk factors (body mass index (BMI), waist circumference, blood lipids, blood pressure, C reactive protein, adiponectin, and homeostasis model assessment for insulin resistance and beta-cell function) were collected using standardized interviews and physical examinations. T2D cases were based on physician diagnoses, a national medical registry, fasting plasma glucose, or glycated hemoglobin A1c. We used multivariable logistic association and mediation analyses.

Results

During an average follow-up of 7.2 years (SD 2.2 years), we documented 595 cases of incident diabetes. Ethnic Malays (OR 2.08, 95% CI 1.69 to 2.56) and Indians (OR 2.22, 95% CI 1.80 to 2.74) had an approximately twofold higher risk of T2D compared with ethnic Chinese. Higher BMI explained the higher risk for Malay compared with Chinese ethnicity. Higher BMI, waist circumference, inflammation, and insulin resistance, and lower beta-cell function and high-density lipoprotein-cholesterol significantly contributed to the higher T2D risk for Indian compared with Chinese ethnicity. However, part of the higher T2D risk associated with Indian ethnicity remained unexplained. Despite their lower diabetes risk, Chinese participants had the lowest adiponectin levels.

Conclusions

Different Asian ethnic groups have unique biological risk factor profiles related to T2D development that may warrant targeted approaches for prevention and treatment.
Blood pressure medication and acute kidney injury after intracerebral haemorrhage: an analysis of the ATACH-II trial
Authors: Naidech Andrew M , Wang Hanyin , Hutch Meghan , Murphy Julianne , Paparello James , Bath Philip , Srivastava Anand , Luo Yuan
Published: July 2023

Background

Acute blood pressure (BP) reduction is standard of care after acute intracerebral haemorrhage (ICH). More acute BP reduction is associated with acute kidney injury (AKI). It is not known if the choice of antihypertensive medications affects the risk of AKI.

Methods

We analysed data from the ATACH-II clinical trial. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. We analysed antihypertensive medication from two sources. The first was a case report form that specified the use of labetalol, diltiazem, urapidil or other. We tested the hypothesis that the secondary medication was associated with AKI with χ2test. Second, we tested the hypotheses the dosage of diltiazem was associated with AKI using Mann-Whitney U test.

Results

AKI occurred in 109 of 1000 patients (10.9%). A higher proportion of patients with AKI received diltiazem after nicardipine (12 (29%) vs 21 (12%), p=0.03). The 95%ile (90%–99% ile) of administered diltiazem was 18 (0–130) mg in patients with AKI vs 0 (0–30) mg in patients without AKI (p=0.002). There was no apparent confounding by indication for diltiazem use.

Conclusions

The use of diltiazem, and more diltiazem, was associated with AKI in patients with acute ICH.
Growth rates and histopathological outcomes of small (6–9 mm) colorectal polyps based on CT colonography surveillance and endoscopic removal
Authors: Pooler B Dustin , Kim David H , Matkowskyj Kristina A , Newton Michael A , Halberg Richard B , Grady William M , Hassan Cesare , Pickhardt Perry J
Published: July 2023

Background and aims

The natural history of small polyps is not well established and rests on limited evidence from barium enema studies decades ago. Patients with one or two small polyps (6–9 mm) at screening CT colonography (CTC) are offered CTC surveillance at 3 years but may elect immediate colonoscopy. This practice allows direct observation of the growth of subcentimetre polyps, with histopathological correlation in patients undergoing subsequent polypectomy.

Design

Of 11 165 asymptomatic patients screened by CTC over a period of 16.4 years, 1067 had one or two 6–9 mm polyps detected (with no polyps ≥10 mm). Of these, 314 (mean age, 57.4 years; M:F, 141:173; 375 total polyps) elected immediate colonoscopic polypectomy, and 382 (mean age 57.0 years; M:F, 217:165; 481 total polyps) elected CTC surveillance over a mean of 4.7 years. Volumetric polyp growth was analysed, with histopathological correlation for resected polyps. Polyp growth and regression were defined as volume change of ±20% per year, with rapid growth defined as +100% per year (annual volume doubling). Regression analysis was performed to evaluate predictors of advanced histology, defined as the presence of cancer, high-grade dysplasia (HGD) or villous components.

Results

Of the 314 patients who underwent immediate polypectomy, 67.8% (213/314) harboured adenomas, 2.2% (7/314) with advanced histology; no polyps contained cancer or HGD. Of 382 patients who underwent CTC surveillance, 24.9% (95/382) had polyps that grew, while 62.0% (237/382) remained stable and 13.1% (50/382) regressed in size. Of the 58.6% (224/382) CTC surveillance patients who ultimately underwent colonoscopic resection, 87.1% (195/224) harboured adenomas, 12.9% (29/224) with advanced histology. Of CTC surveillance patients with growing polyps who underwent resection, 23.2% (19/82) harboured advanced histology vs 7.0% (10/142) with stable or regressing polyps (OR: 4.0; p<0.001), with even greater risk of advanced histology in those with rapid growth (63.6%, 14/22, OR: 25.4; p<0.001). Polyp growth, but not patient age/sex or polyp morphology/location were significant predictors of advanced histology.

Conclusion

Small 6–9 mm polyps present overall low risk to patients, with polyp growth strongly associated with higher risk lesions. Most patients (75%) with small 6–9 mm polyps will see polyp stability or regression, with advanced histology seen in only 7%. The minority of patients (25%) with small polyps that do grow have a 3-fold increased risk of advanced histology.
Targeting MS4A4A on tumour-associated macrophages restores CD8+ T-cell-mediated antitumour immunity
Authors: Li Yongsheng , Shen Zhiyong , Chai Zhen , Zhan Yizhi , Zhang Yaowei , Liu Zhengyu , Liu Yuechen , Li Zhenkang , Lin Mingdao , Zhang Zhanqiao , Liu Wei , Guan Shenyuan , Zhang Jinchao , Qian Junying , Ding Yi , Li Guoxin , Fang Yuan , Deng Haijun
Published: July 2023

Objective

Checkpoint immunotherapy unleashes T-cell control of tumours but is suppressed by immunosuppressive myeloid cells. The transmembrane protein MS4A4A is selectively highly expressed in tumour-associated macrophages (TAMs). Here, we aimed to reveal the role of MS4A4A+TAMs in regulating the immune escape of tumour cells and to develop novel therapeutic strategies targeting TAMs to enhance the efficacy of immune checkpoint inhibitor (ICI) in colorectal cancer.

Design

The inhibitory effect of MS4A4A blockade alone or combined with ICI treatment on tumour growth was assessed using murine subcutaneous tumour or orthotopic transplanted models. The effect of MS4A4A blockade on the tumour immune microenvironment was assessed by flow cytometry and mass cytometry. RNA sequencing and western blot analysis were used to further explore the molecular mechanism by which MS4A4A promoted macrophages M2 polarisation.

Results

MS4A4A is selectively expressed by TAMs in different types of tumours, and was associated with adverse clinical outcome in patients with cancer. In vivo inhibition of MS4A4A and anti-MS4A4A monoclonal antibody treatment both curb tumour growth and improve the effect of ICI therapy. MS4A4A blockade treatment reshaped the tumour immune microenvironment, resulting in reducing the infiltration of M2-TAMs and exhausted T cells, and increasing the infiltration of effector CD8+T cells. Anti-MS4A4A plus anti-programmed cell death protein 1 (PD-1) therapy remained effective in large, treatment-resistant tumours and could induce complete regression when further combined with radiotherapy. Mechanistically, MS4A4A promoted M2 polarisation of macrophages by activating PI3K/AKT pathway and JAK/STAT6 pathway.

Conclusion

Targeting MS4A4A could enhance the ICI efficacy and represent a new anticancer immunotherapy.
Assessment and management of asymptomatic atrial fibrillation
Authors: Andrade Jason G. , Deyell Marc W. , Bennett Richard , Macle Laurent
Published: July 2023

Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia encountered in practice. It is currently estimated that AF affects approximately 2% of the general population; however, the true prevalence of AF is likely to be at least 3%–4% when asymptomatic AF is considered. For clinically apparent AF, the investigations and management are relatively well established. The identification of minimally symptomatic patients is challenging, and furthermore, the optimal management is less certain. Although there is some debate about the ideal treatment pathway for asymptomatic AF, in most cases, the investigations and comprehensive management follow the same recommendations as clinically apparent AF. In contrast, beyond risk factor optimisation, the ideal management of subclinical or device-detected AF remains undefined. The purpose of the current review is to discuss the assessment and management of asymptomatic AF.
Age, period and cohort-related trends in prescription opioid use in the USA, 1999–2018
Authors: Shiue Kristin Y , Austin Anna E , Naumann Rebecca B , Aiello Allison E , Marshall Stephen W , Golightly Yvonne M
Published: July 2023

Background

To provide insight into the longitudinal dynamics of opioid use throughout the overdose crisis, this study estimated the separate influences of age, period and cohort on prescription opioid use during 1999–2018 in the USA.

Methods

Data from 10 cycles of the cross-sectional National Health and Nutrition Examination Survey were used to conduct an age–period–cohort analysis of the prevalence of prescription opioid use (n=63 500 across 1999–2018). Temporal trends were graphically visualised. The median polish approach was used to estimate age, period and cohort-related effects on prescription opioid use.

Results

Prescription opioid use broadly increased across the lifespan, with steeper prevalence increases observed from young adulthood to mid-adulthood. Period-related variation was consistent with recognised nationwide declines in opioid prescribing. While there was no evidence of systematic cohort effects, compared with individuals born in 1951–1954, those born during 1963–1966 had greater prescription opioid use (prevalence ratio (PR)=1.23, 95% CI: 1.05 to 1.43), whereas the 1991–1994 and 1999–2002 cohorts had lower prescription opioid use (PR91-94=0.70, 95% CI: 0.50 to 0.98; PR99-02=0.72, 95% CI: 0.63 to 0.81).

Conclusion

In the USA, longitudinal trends in prescription opioid use during 1999–2018 were predominantly driven by age and period influences. The cohort of youngest baby boomers experienced greater prescription opioid use, whereas recent-born cohorts have had lower use. As the overdose crisis continues evolving, such population-level characterisations of age, period and cohort dynamics are instrumental in understanding opioid use and can inform prevention and intervention approaches by identifying population groups more likely to use opioids who, thus, may also experience related outcomes.
Rationale and design of the NEO-NORMAL-AF study examination of the usefulness of implantable loop recorder for arrhythmia detection including atrial fibrillation in heart failure with non-reduced ejection fraction cases: a pilot study
Authors: Sugiura Junichi , Kasama Syu , Ueda Tomoya , Nishida Taku , Kawata Hiroyuki , Horii Manabu , Ozu Naoki , Kasahara Masato , Saito Yoshihiko
Published: July 2023

Introduction

The incidence of arrhythmia in heart failure with non-reduced ejection fraction (HFnon-rEF) in patients who have a history of hospitalisation is unclear. The aim of this study is to investigate the usefulness of an implantable loop recorder (ILR) for arrhythmia detection including atrial fibrillation (AF) in HFnon-rEF patients after discharge.

Methods and analysis

This is a multicentre single arm study to evaluate the usefulness of ILR for detecting arrhythmia. The eligible patients are HFnon-rEF patients (left ventricular ejection fraction ≥40%) aged ≥20 years with a history of hospitalisation. The ILR will be implanted for qualified patients, and ECGs will be monitored and recorded for 1 year to check for arrhythmias. The primary endpoint is new-onset 6 min or more persistent AF detected by ILR. Secondary endpoints are 30 s or more persistent supraventricular tachycardia and ventricular tachycardia, 3 s or more persistent pause, bradycardia with 40 beats per minutes or lower heart rate, AF burden, all-cause death, cardiovascular death, hospital readmission due to exacerbation of HF, acute coronary syndrome, ischaemic or haemorrhagic stroke, non-pharmacological therapy such as pacemaker implantation and ablation.

Conclusions

This study is expected to provide valuable findings regarding arrhythmia in HFnon-rEF patients, and elucidate a potential new therapeutic approach for HFnon-rEF.

Trial registration number

This trial has been registered in the Japan Registry of Clinical Trials (jRCT) (Trial Registration: jRCTs052210060).
Cardiac magnetic relaxometry versus ejection fraction in anthracycline-related cardiac changes: a systematic review and meta-analysis
Authors: Yu Christopher , Pathan Shahab , Jeyaprakash Prajith , Kritharides Leonard , Pathan Faraz , Negishi Kazuaki
Published: July 2023

Purpose

The purpose of this meta-analysis is to compare the magnitude of the changes in left ventricular ejection fraction (LVEF) and cardiac magnetic resonance (CMR) relaxometry techniques soon after the completion of anthracycline therapy. Anthracyclines are associated with myocardial functional and morphological changes. LVEF is currently used to identify the functional changes. Anthracyclines can also cause myocardial inflammation and oedema. This can be assessed using CMR relaxometry techniques; T1 and T2 mapping and extracellular volume (ECV) fraction.

Methods

Three databases were systematically searched for studies evaluating CMR relaxometry parameter at baseline and 1±1 months after anthracycline completion (the last search date 17 March 2023). CMR parameters pre and post anthracycline-based chemotherapy were abstracted. A random effects model was used to pool mean difference (MD) in LVEF and ECV. Standardised mean difference (SMD) was also calculated for T1 and T2 mapping due to the variations in techniques, normal ranges and for the comparison among the parameters.

Results

A total of 296 patients were included from 10 studies. 84% were female with a mean age of 54.9 years. Statistically significant alterations were observed in LVEF (MD −3.38% (95% CI −5.13%, −1.62%)) and ECV (1.92% (1.30%, 2.53%)). The pooled SMDs were also significant in LVEF, T1, T2 and ECV with −0.61 (–0.91, –0.30), 0.53 (0.16, 0.90), 0.59 (0.22, 0.96) and 0.74 (0.41, 1.06), respectively.

Conclusions

Our meta-analysis demonstrated small but significant alterations in CMR relaxometry parameters soon after anthracycline therapy, where ECV was superior to LVEF and T1 or T2 mapping. However, these short-term MDs were below the minimal detectable differences.

PROSPERO registration number

CRD42020196296.
Oral opioid prescribing to active duty US military personnel: a cross-sectional population
Authors: Junge Joshua M , Murray Hailey , Goldman Ashton H , Booth Gregory J , Balazs George C
Published: July 2023

Introduction

While civilian opioid prescriptions have seen a dramatic decline in recent years, there are few studies investigating trends in opioid prescription in the active duty military population. We evaluated oral opioid prescribing patterns to active duty military personnel in the Military Health System (MHS) from 2017 to 2020 to determine the incidence of opioid prescriptions as well as demographic and military-specific risk factors for receiving an oral opioid prescription.

Methods

The MHS Data Repository was queried from 2017 to 2020 to identify all outpatient oral opioid prescriptions to active duty military personnel in August of each year as well as demographic information on the study population. Data were evaluated in a logistic regression model, and ORs of receiving an oral opioid prescription were calculated for each factor.

Results

The proportion of active duty military personnel receiving an oral opioid prescription declined from 2.71% to 1.26% (53% relative reduction) over the study period. Within the logistic regression model, female military personnel were significantly more likely to receive opioid prescriptions compared with men, and there was a stepwise increase in likelihood of an opioid prescription with increasing age. Army and Marine personnel, personnel without a history of military deployment and those stationed within the continental USA were significantly more likely to receive an opioid prescription.

Discussion

The substantial decrease in oral opioid prescriptions to active duty military personnel mirrors data published in the civilian community. The identified risk factors for receiving an opioid prescription may be potential targets for future interventions to further decrease prescribing.
Impact of sex on spinal radiographic progression in axial spondyloarthritis: a longitudinal Swiss cohort analysis over a period of 10 years
Authors: Ensslin Caroline , Micheroli Raphael , Kissling Seraphina , Götschi Andrea , Bürki Kristina , Bräm René , de Hooge Manouk , Baraliakos Xenofon , Nissen Michael J , Möller Burkhard , Exer Pascale , Andor Michael , Distler Oliver , Scherer Almut , Ciurea Adrian
Published: July 2023

Objective

To investigate sex differences in spinal radiographic progression in axial spondyloarthritis (axSpA).

Methods

AxSpA patients in the Swiss Clinical Quality Management cohort with available spinal radiographs every 2 years were included. Paired radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Progression was defined as an increase of ≥2 mSASSS units in 2 years. The relationship between sex and progression was investigated with binomial generalised estimating equation models, considering baseline spinal damage as an intermediate covariate. Additional analyses included adjustments for explanatory variables and multiple imputations for missingness.

Results

In a total of 505 axSpA patients (317 men and 188 women), mean±SD radiographic progression over 2 years was 1.0±2.8 years in men and 0.3±1.1 years in women (p<0.001). Male sex was associated with enhanced progression in a small model not including baseline damage (OR 3.41, 95% CI 1.87 to 6.21). Both a direct effect of male sex on spinal progression, and an indirect effect, via enhancement of baseline spinal damage were significant (OR 2.06, 95% CI 1.15 to 3.67 and OR 1.04, 95% CI 1.01 to 1.07, respectively). A significant impact of male sex on spinal radiographic progression was still demonstrated after multiple adjustments for covariates known to potentially affect spinal radiographic progression (OR 1.97, 95% CI 1.04 to 3.71).

Conclusions

Spinal radiographic progression in axSpA is more severe in men than in women, with three times higher odds of progression in male patients and an effect that is mediated in part through an increase in baseline radiographic damage.
The Pixel Luminosity Telescope: a detector for luminosity measurement at CMS using silicon pixel sensors
Authors: Ayala E. , CarreraJarrin E. , Ahmed I. , Campbell A. , Danilov V. , EstevezBanos L. I. , Giraldi A. , Guthoff M. , Hempel M. , Henschel H. , Knolle J. , Lange W. , Leonard J. , Lohmann W. , Meyer A. B. , Myronenko V. , Penno M. , Ribeiro Lopes B. , Rübenach J. , Saggio A. , Scheurer V. , Sosa Ricardo R. E. , Turkot O. , Walter D. , Kassel F. , Mallows S. , Bartók M. , Chudasama R. , Farkas K. , Fejes M. , Gadallah M. M. A. , Major P. , Mehta A. , Pásztor G. , Rádl A. J. , Veres G. I. , Bakhshiansohi H. , Gholami A. , Khazaie E. , Sedghi M. , Zeinali M. , Fabbri F. , Tosi N. , Bacchetta N. , Trapani P. P. , Daugalas J. , Benitez J. F. , Castaneda Hernandez A. , Encinas Acosta H. A. , Gallegos Maríñez L. G. , León Coello M. , Murillo Quijada J. A. , Sehrawat A. , Valencia Palomo L. , Oropeza Barrera C. , Bheesette S. , Butler A. P. H. , Butler P. H. , Lokhovitskiy A. , Lujan P. , Auzinger G. , Ball A. H. , Çekmecelioğlu Y. C. , Dabrowski A. , Damanakis K. , Donadon Servelle A. , Eble F. , Haranko M. , Hegeman J. , Kessaci K. , Kornmayer A. , Loos R. , Miraglia M. , Nicolini J. , Orfanelli S. , Orsini L. , Petrucci A. , Ryjov V. , Saariokari S. , Schwick C. , Schneider B. , Tsoukias S. , Tsrunchev P. , Wanczyk J. , Zagoździńska-Bochenek A. A. , Zeuner W. D. , Rohe T. , Krintiras G. , Palmer C. , Jain Sh. , Mans J. , Rusack R. , Bueghly J. , Chen Z. , Gunter T. , Odell N. , Pozdnyakov A. , Velasco M. , Harrop B. , Higginbotham S. , Kalogeropoulos A. , Luo J. , Marlow D. , Stickland D. , Xie Z. , Bartz E. , Hidas D. , Karacheban O. , Schnetzer S. , Stone R. , Acharya H. , Delannoy A. G. , Heideman J. , Karunarathna N. , Riley G. , Rose K. , Spanier S. , Thapa K. , Gurrola A. , Johns W. , Romeo F. , Soubasis B. , Farrow M. C. , Azhgirey I. , Ershov A. , Gribushin A. , Kaminskiy A. , Kurochkin I. , Okhotnikov V. , Popova E. , Riabchikova A. , Selivanova D. , Shevelev A. ,   CMS BRIL Collaboration
Published: July 2023

The Pixel Luminosity Telescope is a silicon pixel detector dedicated to luminosity measurement at the CMS experiment at the LHC. It is located approximately 1.75 m from the interaction point and arranged into 16 “telescopes”, with eight telescopes installed around the beam pipe at either end of the detector and each telescope composed of three individual silicon sensor planes. The per-bunch instantaneous luminosity is measured by counting events where all three planes in the telescope register a hit, using a special readout at the full LHC bunch-crossing rate of 40 MHz. The full pixel information is read out at a lower rate and can be used to determine calibrations, corrections, and systematic uncertainties for the online and offline measurements. This paper details the commissioning, operational history, and performance of the detector during Run 2 (2015–18) of the LHC, as well as preparations for Run 3, which will begin in 2022.
Instanton induced spin–spin correlations
Authors: Ryskin M. G.
Published: July 2023

The QCD instanton can be observed at relatively low energies at Nica collider by studying the spin-spin correlations between the incoming proton and the produced $$\Lambda $$
Λ
or $$\Sigma $$
Σ
hyperons (or the $$\Lambda $$
Λ
and $$\bar{\Lambda }$$

Λ

¯

hyperons). Low Nica energy will allow to better record and to measure the polarization of the hyperon originated by the polarized valence quark(s) in the proton fragmentation region.
A linear mass and energy conserving numerical scheme for two-phase flows with thermocapillary effects
Authors: Shao Lihua , Guo Zhenlin , Sun Yanxiao
Published: July 2023

In this paper, a thermodynamically consistent phase-field model is employed to simulate the thermocapillary migration of a droplet. The model equations consist of a general Navier–Stokes equation for the two-phase flows, a Cahn–Hilliard equation for the diffuse interface, and a heat equation, and meanwhile satisfy the balance laws of mass, energy and entropy. In particular, the total energy of the system includes kinetic energy, potential energy and internal energy, which leads to a highly coupled and nonlinear equation system. We therefore develop a linear mass and energy conserving, semi-decoupled numerical method for the numerical simulations. As the model contains a heat (energy) equation, a simple error term introduced by the temporal discretization of the momentum equation can be absorbed into the heat equation, such that the numerical solutions satisfy the conservation laws of mass and energy exactly at the temporal discrete level. Several numerical tests are carried out to validate our numerical method.
SENPR disinformation spreading model to discuss the control of the spread of disinformation in emergencies
Authors: Tian Xin , Mai Qiang , An Shi
Published: July 2023

The spread of disinformation in online social networks (OSNs) poses a significant threat to maintaining normal social order. It is important to understand when and how intervention measures can control the spread of disinformation. We propose a novel information spreading model called susceptible, exposed, negative-infected, positive-infected, recovered population (SENPR) to describe the disinformation dynamics in OSNs under the intervention strategy. The model in this study considers that the susceptible population in the network is transformed into an exposed population through the influence of two information-dissemination methods that affect other susceptible people in the network. Subsequently, the stability of the model was analyzed to verify the validity of the obtained theoretical results. Finally, the influence of different parameters on the spread of disinformation is described, and corresponding management strategies to suppress the spread of false information in emergency situations are discussed. The results show that word-of-mouth is the main mode of communication in the “development” and “burst” stages of information spreading. The earlier the intervention is implemented, the sooner the number of people affected by word-of-mouth begins to decline and the sooner the spreading of disinformation reaches the saturation and decay stages.
Counting with Self-Weighted Multi-Scale Fusion Networks
Authors: Xiong Xin , Shen Jie , Li Ying , He Wei , Li Peng , Yan Wenjie
Published: July 2023

Because of the large-scale variation, counting in scenes of different densities is an extremely difficult task. In this paper, based on the attention mechanism, we propose a new self-weighted multi-scale fusion network structure named SMFNet to solve the problem of multi-scale changes and can significantly improve the effect of crowd counting in monitoring scene. The proposed SMFNet uses VGG as the backbone network to extract multi-scale features, uses a SMFNet as the neck to fuse multiple-scale features, and uses the atrous spatial pyramid pooling (ASPP) network and ordinary convolution as the head to generate both the attention map and the density map. The attention map highlighting crowd regions in the image contributes to a high-quality density map, and the density map records the crowd distribution. The number of crowd in the image can be obtained by summing the pixel values of the density map. We conduct experiments on three crowd counting datasets and one vehicle counting dataset to show that our proposed SMFNet can improve the state-of-the-art counting methods.