bluuebunny/crossref_metadata_2025 huggingface dataset:
Extrinsic and intrinsic drivers of natural killer cell clonality
Authors: Rückert Timo , Romagnani Chiara
Published: March 2024

Clonal expansion of antigen‐specific lymphocytes is the fundamental mechanism enabling potent adaptive immune responses and the generation of immune memory. Accompanied by pronounced epigenetic remodeling, the massive proliferation of individual cells generates a critical mass of effectors for the control of acute infections, as well as a pool of memory cells protecting against future pathogen encounters. Classically associated with the adaptive immune system, recent work has demonstrated that innate immune memory to human cytomegalovirus (CMV) infection is stably maintained as large clonal expansions of natural killer (NK) cells, raising questions on the mechanisms for clonal selection and expansion in the absence of re‐arranged antigen receptors. Here, we discuss clonal NK cell memory in the context of the mechanisms underlying clonal competition of adaptive lymphocytes and propose alternative selection mechanisms that might decide on the clonal success of their innate counterparts. We propose that the integration of external cues with cell‐intrinsic sources of heterogeneity, such as variegated receptor expression, transcriptional states, and somatic variants, compose a bottleneck for clonal selection, contributing to the large size of memory NK cell clones.
RETRACTED: Effects of evidence‐based nursing on surgical site wound infection in patients undergoing acute appendicitis surgery: A meta‐analysis
Authors: Liu Feng , Zhou Juan , Wu Xue‐Lian
Published: March 2024

This study aimed to comprehensively evaluate the effects of evidence‐based nursing (EBN) intervention on wound infection and postoperative complications in patients after appendectomy for acute appendicitis (AA), with the expectation of providing a theoretical basis for postoperative care in AA. Randomised controlled trials (RCTs) on the postoperative application of EBN in patients with AA were searched in PubMed, Web of Science, Cochrane Library, Embase, China Biomedical Literature Database, Wanfang and China National Knowledge Infrastructure from the inception of databases to October 2023. Two authors screened and evaluated the literature based on the inclusion and exclusion criteria, and data were extracted from the final included literature. Stata software (version 17.0) was employed for data analysis. In total, 29 RCTs involving 2848 patients with AA were included, with 1424 in the EBN group and 1424 in the conventional care group. The analyses revealed that patients with AA who experienced EBN were significantly less likely to develop postoperative wound infections (odds ratio [OR] = 0.23, 95% confidence intervals [CIs]: 0.14–0.38, p < 0.001) and postoperative complications (OR = 0.20, 95% CI: 0.15–0.26, p < 0.001) as opposed to conventional care. Available evidence suggests that EBN can effectively reduce the risk of wound infection and postoperative complications in patients undergoing appendectomy for AA, thereby improving patient prognosis. This finding is worth promoting in the clinical practice.
MRPS16 promotes lung adenocarcinoma growth via the PI3K/AKT/Frataxin signalling axis
Authors: Cheng Zaixing , Xue Kaming , Xiong Cui , Zheng Zhikun , Li Jinsong , Qiao Xinwei
Published: March 2024

Although MRPS16 is involved in cancer development, its mechanisms in developing LAUD remain unclear. Herein, qRT‐PCR, WB and IHC were utilized for evaluating MRPS16 expression levels, while functional assays besides animal experiments were performed to measure MRPS16 effect on LAUD progression. Using WB, the MRPS16 effect on PI3K/AKT/Frataxin signalling pathway was tested. According to our study, MRPS16 was upregulated in LAUD and was correlated to the advanced TNM stage as well as poor clinical outcomes, which represent an independent prognostic factor. Based on functional assays, MRPS16 is involved in promoting LAUD growth, migration and invasion, which was validated further in subsequent analyses through PI3K/AKT/Frataxin pathway activation. Moreover, MRPS16‐knockdown‐mediated Frataxin overexpression was shown to restore the reduction in tumour cells proliferation, migration and invasion. Our results revealed that MRPS16 caused an aggressive phenotype to LAUD and was a poor prognosticator; thus, targeting MRPS16 may be effectual in LAUD treatment.
Research progress on the regulatory mechanism of integrin‐mediated mechanical stress in cells involved in bone metabolism
Authors: Yang Li , Chen Hong , Yang Chanchan , Hu Zhengqi , Jiang Zhiliang , Meng Shengzi , Liu Rong , Huang Lan , Yang Kun
Published: March 2024

Mechanical stress is an internal force between various parts of an object that resists external factors and effects that cause an object to deform, and mechanical stress is essential for various tissues that are constantly subjected to mechanical loads to function normally. Integrins are a class of transmembrane heterodimeric glycoprotein receptors that are important target proteins for the action of mechanical stress stimuli on cells and can convert extracellular physical and mechanical signals into intracellular bioelectrical signals, thereby regulating osteogenesis and osteolysis. Integrins play a bidirectional regulatory role in bone metabolism. In this paper, relevant literature published in recent years is reviewed and summarized. The characteristics of integrins and mechanical stress are introduced, as well as the mechanisms underlying responses of integrin to mechanical stress stimulation. The paper focuses on integrin‐mediated mechanical stress in different cells involved in bone metabolism and its associated signalling mechanisms. The purpose of this review is to provide a theoretical basis for the application of integrin‐mediated mechanical stress to the field of bone tissue repair and regeneration.
Indoxyl sulphate‐initiated activation of cardiac fibroblasts is modulated by aryl hydrocarbon receptor and nuclear factor‐erythroid‐2‐related factor 2
Authors: Barisione Chiara , Verzola Daniela , Garibaldi Silvano , Altieri Paola , Furfaro Anna Lisa , Nitti Mariapaola , Pratesi Giovanni , Palombo Domenico , Ameri Pietro
Published: March 2024

In the last decade, extensive attention has been paid to the uremic toxin indoxyl sulphate (IS) as an inducer of cardiac fibroblast (cFib) activation and cardiac fibrosis in chronic kidney disease. At cellular level, IS engages aryl hydrocarbon receptor (AhR) and regulates many biological functions. We analysed how AhR inhibition by CH‐223191 (CH) and overexpression of non‐functional (dominant negative, DN) nuclear factor‐erythroid‐2‐related factor 2 (NRF2), a transcription factor recruited by AhR, modulate the response of neonatal mouse (nm) cFib to IS. We also evaluated nm‐cardiomyocytes after incubation with the conditioned medium (CM) of IS±CH‐treated nm‐cFib. IS induced activation, collagen synthesis, TLR4 and–downstream–MCP‐1, and the genes encoding angiotensinogen, angiotensin‐converting enzyme, angiotensin type 1 receptor (AT1r) and neprilysin (Nepr) in nm‐cFib. CH antagonized IS‐initiated nm‐cFib activation, but did not affect or even magnified the other features. IS promoted NRF2 nuclear translocation and expression the NRF2 target Nqo1. Both pre‐incubation with CH and transfection of DN‐NRF2 resulted in loss of NRF2 nuclear localization. Moreover, DN‐NRF2 overexpression led to greater TLR4 and MCP‐1 levels following exposure to IS. The CM of IS‐primed nm‐cFib and to a larger extent the CM of IS+CH‐treated nm‐cFib upregulated AT1r, Nepr and TNFα and myostatin genes in nm‐cardiomyocytes. Hence, IS triggers pro‐inflammatory activation of nm‐cFib partly via AhR, and AhR‐NRF2 counteract it. Strategies other than AhR inhibition are needed to target IS detrimental actions on cardiac cells.
Reduced chemokine C‐C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites
Authors: Iwata Miku , Haraguchi Ryuma , Kitazawa Riko , Ito Chihiro , Ogawa Kohei , Takada Yasutsugu , Kitazawa Sohei
Published: March 2024

Colorectal cancer (CRC) liver metastasis, albeit a stage‐IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin‐embedded surgical specimens. Chemokine C‐C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C‐C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1‐positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1‐CCR8 axis in CRC, CCR8‐positive CRC cell line Colo320DM was used to assess the effect of the CCL1‐CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP‐2 levels demonstrated by RT‐qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1‐CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.
Long noncoding RNA Glis2 regulates podocyte mitochondrial dysfunction and apoptosis in diabetic nephropathy via sponging miR‐328‐5p
Authors: Wang Ting , Chen Yanxia , Liu Zhihong , Zhou Jing , Li Na , Shan Yue , He Yinxi
Published: March 2024

Podocyte apoptosis exerts a crucial role in the pathogenesis of DN. Recently, long noncoding RNAs (lncRNAs) have been gradually identified to be functional in a variety of different mechanisms associated with podocyte apoptosis. This study aimed to investigate whether lncRNA Glis2 could regulate podocyte apoptosis in DN and uncover the underlying mechanism. The apoptosis rate was detected by flow cytometry. Mitochondrial membrane potential (ΔΨM) was measured using JC‐1 staining. Mitochondrial morphology was detected by MitoTracker Deep Red staining. Then, the histopathological and ultrastructure changes of renal tissues in diabetic mice were observed using periodic acid‐Schiff (PAS) staining and transmission electron microscopy. We found that lncRNA Glis2 was significantly downregulated in high‐glucose cultured podocytes and renal tissues of db/db mice. LncRNA Glis2 overexpression was found to alleviate podocyte mitochondrial dysfunction and apoptosis. The direct interaction between lncRNA Glis2 and miR‐328‐5p was confirmed by dual luciferase reporter assay. Furthermore, lncRNA Glis2 overexpression alleviated podocyte apoptosis in diabetic mice. Taken together, this study demonstrated that lncRNA Glis2, acting as a competing endogenous RNA (ceRNA) of miRNA‐328‐5p, regulated Sirt1‐mediated mitochondrial dysfunction and podocyte apoptosis in DN.
Circular RNAs as biomarkers and therapeutic targets for gastrointestinal cancers
Authors: Botwe Godwin , Fang Xinjian , Mukhtar Yusif Mohammed , Zhou Yue , Tang Haozhou , Wang Maoye , Zhang Jiahui , Fu Min , Jiang Pengcheng , Gu Jianmei , Zhang Xu
Published: March 2024

Circular RNAs are a class of noncoding RNAs with covalently linked 5′ and 3′ ends that arise from backsplicing events. The absence of a 5′ cap and a 3′ poly(A) tail makes circular RNAs relatively more stable than their linear counterparts. They are evolutionary conserved and tissue‐specific, and some show disease‐specific expression patterns. Although their biological functions remain largely unknown, circular RNAs have been shown to play regulatory roles by acting as microRNA sponges, regulators of RNA‐binding proteins, alternative splicing, and parental gene expression, and they could even encode proteins. Over the past few decades, circular RNAs have attracted wide attention in oncology owing to their implications in various tumors. Many circular RNAs have been characterized as key players in gastrointestinal cancers and influence cancer growth, progression, metastasis, and therapeutic resistance. Accumulating evidence reveals that their unique characteristics, coupled with their critical roles in tumorigenesis, make circular RNAs promising non‐invasive clinical biomarkers for gastrointestinal cancers. In the present review, we summarized the biological roles of the emerging circular RNAs and their potential as biomarkers and therapeutic targets, which may help better understand their clinical significance in the management of gastrointestinal cancers.
Ignorance of critical race theory predicts White Americans’ opposition to it
Authors: Richmond Brianna S. , Toosi Negin R. , Wellman Joseph D. , Wilkins Clara L.
Published: March 2024

Acknowledging systemic racism, a key tenet of Critical Race Theory (CRT), may be threatening to many Americans but it can also reduce racial biases. However, anti‐CRT legislation prohibits learning about racism, thus highlighting the mutually reinforcing relationship between systemic racism and the production of ignorance. We assessed White Americans’ knowledge about CRT through participant‐generated definitions (Study 1, N = 199) and via a true/false questionnaire (Study 2, N = 194), and its relation to opposition to CRT. Opposition to CRT was associated with a less accurate understanding of CRT, even when controlling for political orientation. Content analyses revealed that opponents of CRT deny anti‐Black racism, believe CRT harms Whites, and view discussing race as divisive. Based on these themes, we developed a meta‐cognitive corrective intervention in Study 3 (N = 289). Participants who received corrective feedback after taking a multiple‐choice test about CRT showed a larger decrease in their opposition to CRT than those in the control condition.
Sex differences in mortality and liver‐related events in non‐alcoholic fatty liver disease: A systematic review and meta‐analysis
Authors: Zhou Huimin , Chen Haiyan , Lu Hanxiao , Wu Bo , Zhang Shuo , Gu Yuanlong , Zhou Guangwen , Xiang Jie , Yang Jun
Published: March 2024

Background & Aims

Many systematic reviews explore the association of non‐alcoholic fatty liver disease (NAFLD) with mortality, but none of them explores sex‐based differences in detail. We aimed to assess whether NAFLD is associated with cause‐specific mortality, all‐cause mortality, and cancer incidence in both men and women.

Methods

The PubMed, Embase, and Medline databases were searched from inception through April 2023 for eligible studies. We separately pooled relative risks (RRs) for men and women using a random effects model. Subsequently, the RRs and 95% CIs (confidence intervals) in each study were used to calculate the women‐to‐men ratio of RRs (RRR). Furthermore, subgroup analyses were performed to explore the robustness of outcomes. The random‐effects model was employed to conduct sensitivity analyses to determine the impact of specific studies on the overall findings.

Results

The meta‐analysis included nine cohort studies comprising 557 614 patients with NAFLD were chosen. Women were 44% more likely than men to get cancer among those with NAFLD (RRR: 1.44; 95% CI: 1.02–2.04; p = .039). However, no sex‐related differences were observed between NAFLD and all‐cause mortality (RRR: 1.06; 95% CI: 0.56–2.01; p = .861), liver‐related mortality (RRR: 1.06; 95% CI: 0.02–69.82; p = .977), cardiovascular mortality (RRR: 1; 95% CI: 0.65–1.53; p = .987) and liver cancer (RRR: 0.76; 95% CI: 0.43–1.36; p = .36).

Conclusions

There may be sex variations between NAFLD and the risk of cancer, with the connection being stronger in females than in males.
Effects of web‐based diabetes education on knowledge retention in adult general population: An experiment
Authors: Cenčič Ajda , Bajec Saša , Žvanut Boštjan
Published: March 2024

Objective

To conduct a study to improve diabetes knowledge through a web‐based diabetes course in the general adult population. We hypothesised that participation in a web‐based diabetes course would have a positive impact on diabetes knowledge retention.

Methods

Participants were randomly assigned to an experimental or control group. Participants in the experimental group attended an interactive web‐based diabetes course. The Diabetes Knowledge Questionnaire (DKQ24) was used to assess the diabetes knowledge levels. The DKQ24 was completed at the beginning and end of the observation period of 3 months. The experimental group also completed it immediately after the intervention.

Results

At the end of the observation period, a statistically significant difference in the mean rank of DKQ24 scores was found in favor of the experimental group (p < .001). The results of the experimental group had a lower interquartile range (IQR = 3) than those of the control group (IQR = 5).

Conclusions

This study suggests that providing a web‐based diabetes course to the general population is effective and can improve diabetes knowledge and retention.
Jasmonic acid (JA)‐mediating MYB transcription factor1, JMTF1, coordinates the balance between JA and auxin signalling in the rice defence response
Authors: Uji Yuya , Suzuki Go , Fujii Yumi , Kashihara Keita , Yamada Shoko , Gomi Kenji
Published: March 2024

The plant hormone jasmonic acid (JA) is a signalling compound involved in the regulation of cellular defence and development in plants. In this study, we investigated the roles of a JA‐responsive MYB transcription factor, JMTF1, in the JA‐regulated defence response against rice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). JMTF1 did not interact with any JASMONATE ZIM‐domain (JAZ) proteins. Transgenic rice plants overexpressing JMTF1 showed a JA‐hypersensitive phenotype and enhanced resistance against Xoo. JMTF1 upregulated the expression of a peroxidase, OsPrx26, and monoterpene synthase, OsTPS24, which are involved in the biosynthesis of lignin and antibacterial monoterpene, γ‐terpinene, respectively. OsPrx26 was mainly expressed in the vascular bundle. Transgenic rice plants overexpressing OsPrx26 showed enhanced resistance against Xoo. In addition to the JA‐hypersensitive phenotype, the JMTF1‐overexpressing rice plants showed a typical auxin‐related phenotype. The leaf divergence and shoot gravitropic responses were defective, and the number of lateral roots decreased significantly in the JMTF1‐overexpressing rice plants. JMTF1 downregulated the expression of auxin‐responsive genes but upregulated the expression of OsIAA13, a suppressor of auxin signalling. The rice gain‐of‐function mutant Osiaa13 showed high resistance against Xoo. Transgenic rice plants overexpressing OsEXPA4, a JMTF1‐downregulated auxin‐responsive gene, showed increased susceptibility to Xoo. JMTF1 is selectively bound to the promoter of OsPrx26 in vivo. These results suggest that JMTF1 positively regulates disease resistance against Xoo by coordinating crosstalk between JA‐ and auxin‐signalling in rice.
Two‐field resolution on‐call HLA typing for deceased donors using nanopore sequencing
Authors: Devriese Magali , Da Silva Sephora , Le Mene Melchior , Rouquie Julien , Allain Vincent , Kolesar Libor , Rigo Krisztina , Creary Lisa E. , Lauterbach Nina , Usureau Cedric , Dewez Mathieu , Caillat‐Zucman Sophie , Werner Gregory , Taupin Jean‐Luc
Published: March 2024

The current practice of HLA genotyping in deceased donors poses challenges due to limited resolution within time constraints. Nevertheless, the assessment of compatibility between anti‐HLA sensitized recipients and mismatched donors remains a critical medical need, particularly when dealing with allele‐specific (second field genotyping level) donor‐specific antibodies. In this study, we present a customized protocol based on the NanoTYPE® HLA typing kit, employing the MinION® sequencer, which enables rapid HLA typing of deceased donors within a short timeframe of 3.75 h on average at a three‐field resolution with almost no residual ambiguities. Through a prospective real‐time analysis of HLA typing in 18 donors, we demonstrated the efficacy and precision of our nanopore‐based method in comparison to the conventional approach and without delaying organ allocation. Indeed, this duration was consistent with the deceased donor organ donation procedure leading to organ allocation via the French Biomedicine Agency. The improved resolution achieved with our protocol enhances the security of organ allocation, particularly benefiting highly sensitized recipients who often present intricate HLA antibody profiles. By overcoming technical challenges and providing comprehensive genotyping data, this approach holds the potential to significantly impact deceased donor HLA genotyping, thereby facilitating optimal organ allocation strategies.
Strain-induced modulation of electronic structure in correlated Dirac semimetal Pv-CaIrO3 epitaxial thin films
Authors: Ding Jianyang , Liu Zhengtai , Liu Jiayu , Yuan Jian , Wei Liyang , Jiang Zhicheng , Yang Yichen , Li Chihao , Wang Yilin , Guo Yanfeng , Ye Mao , Liu Jishan , Shen Dawei
Published: March 2024

Perovskite CaIrO3 is theoretically predicted to be a Dirac node semimetal near the Mott transition, which possesses a considerable interplay between electron correlations and spin–orbit coupling. Electron correlations can significantly tune the behavior of relativistic Dirac fermions. Here, we have grown high-quality perovskite CaIrO3 thin films on different substrates using oxide molecular beam epitaxy to modulate both electron correlations and Dirac electron states. Through in situ angle-resolved photoemission spectroscopy, we demonstrate a systematic evolution of the bandwidth and effective mass of Jeff=1/2 band in perovskite CaIrO3 induced by strain. The bandwidth of the Jeff=1/2 band undergoes an evident increase under in-plane compressive strain, which could be attributed to the weakening of electron correlations. The compressive strain can potentially shift the position of the Dirac node relative to the Fermi level and play a vital role in the transition from hole-type to electron-type transport characteristics. Our work provides a feasible approach for manipulating the topological Dirac electron states by engineering the strength of electron correlations.
Effect of high-temperature postannealing atmosphere on the properties of BaSi2 films
Authors: Iwai Ai , Aonuki Sho , Narita Shunsuke , Takayanagi Kaori , Toko Kaoru , Suemasu Takashi
Published: March 2024

We evaluated the effect of O atoms on the postannealed BaSi2 films grown by molecular beam epitaxy. Postannealing (PA) in an Ar atmosphere at a pressure of 1.9 × 105 Pa increased the O concentration to 7 × 1020 cm−3 in the bulk region and further increased to ∼1022 cm−3 at the BaSi2/Si interface. Cracks formed during the PA process, allowing O to enter more easily to the BaSi2 films. In the x-ray photoelectron spectroscopy spectrum of the Si 2s core level measured at 10 nm from the surface, a shift of the peak related to SiOx was detected, indicating a change in the bonding state of Si and O in this region. When PA was performed in vacuum at 10−3 Pa, the photoresponsivity in the short wavelength region was enhanced, with a maximum value of 6.6 A W−1 at 790 nm. The O concentration in the film decreased in the sample annealed in vacuum, and the PL peak intensity at 0.85 eV decreased, suggesting that this was due to a decrease in O-related defects compared to the Ar atmosphere. However, agglomeration of BaSi2 caused significant surface roughness, indicating the importance of PA conditions that minimize O uptake and keep the surface smooth for improved performance of BaSi2 solar cells.
An anti–TNF–glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases
Authors: McPherson Michael J. , Hobson Adrian D. , Hernandez Axel , Marvin Christopher C. , Waegell Wendy , Goess Christian , Oh Jason Z. , Shi Dan , Hayes Martin E. , Wang Lu , Wang Lu , Schmidt Diana , Wang Zhi , Pitney Victoria , McCarthy Kimberley , Jia Ying , Wang Ce , Kang Bit Na , Bryant Shaughn , Mathieu Suzanne , Ruzek Melanie , Parmentier Julie , D’Cunha Ronilda R. , Pang Yinuo , Phillips Lucy , Brown Nathan J. , Xu Jianwen , Graff Candace , Tian Yu , Longenecker Kenton L. , Qiu Wei , Zhu Haizhong , Liu Wei , Zheng Pingping , Bi Yingtao , Stoffel Robert
Published: March 2024

Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti–tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity. Consequently, we have generated an anti–TNF-GRM ADC with the aim of inhibiting pro-inflammatory cytokine production from stimulated human immune cells. In an acute mouse model of contact hypersensitivity, a murine surrogate anti–TNF-GRM ADC inhibited inflammatory responses with minimal effect on systemic GC biomarkers. In addition, in a mouse model of collagen-induced arthritis, single-dose administration of the ADC, delivered at disease onset, was able to completely inhibit arthritis for greater than 30 days, whereas an anti-TNF monoclonal antibody only partially inhibited disease. ADC treatment at the peak of disease was also able to attenuate the arthritic phenotype. Clinical data for a human anti–TNF-GRM ADC (ABBV-3373) from a single ascending dose phase 1 study in healthy volunteers demonstrated antibody-like pharmacokinetic profiles and a lack of impact on serum cortisol concentrations at predicted therapeutic doses. These data suggest that an anti–TNF-GRM ADC may provide improved efficacy beyond anti-TNF alone in immune mediated diseases while minimizing systemic side effects associated with standard GC treatment.
Symptomatic presentation of cancer in primary care: a scoping review of patients’ experiences and needs during the cancer diagnostic pathway
Authors: Wheelwright Sally J , Russ Stephanie , Mold Freda , Armes Jo , Harder Helena
Published: March 2024

Objectives

The objective was to map the experiences and needs of patients presenting with symptoms of suspected cancer in the primary care interval (from when they first present to primary care to their first appointment or referral to a secondary or tertiary level healthcare facility).

Design

This was a scoping review.

Inclusion criteria

Studies or reports written in English which included primary data on the primary care interval experiences and/or needs of adult patients presenting with new symptoms of suspected cancer were eligible. Studies which only included patients with secondary or recurring cancer, conference abstracts and reviews were excluded. No date limits were applied.

Methods

The Joanna Briggs Institute method for Scoping Reviews guided screening, report selection and data extraction. At least two independent reviewers contributed to each stage. Medline, CINAHL, PsychInfo, Embase and Web of Science were searched and several grey literature resources. Relevant quantitative findings were qualitised and integrated with qualitative findings. A thematic analysis was carried out.

Results

Of the 4855 records identified in the database search, 18 were included in the review, along with 13 identified from other sources. The 31 included studies were published between 2002 and 2023 and most (n=17) were conducted in the UK. Twenty subthemes across four themes (patient experience, interpersonal, healthcare professional (HCP) skills, organisational) were identified. No studies included patient-reported outcome measures. Patients wanted (1) to feel heard and understood by HCPs, (2) a plan to establish what was causing their symptoms, and (3) information about the next stages of the diagnostic process.

Conclusions

Scoping review findings can contribute to service planning as the cancer diagnostic pathway for symptomatic presentation of cancer evolves. The effectiveness of this pathway should be evaluated not only in terms of clinical outcomes, but also patient-reported outcomes and experience, along with the perspectives of primary care HCPs.
Evolution of the data and methods in real-world COVID-19 vaccine effectiveness studies on mortality: ascopingreview protocol
Authors: Stehlik Paulina , Dowsett Caroline , Camacho Ximena , Falster Michael O , Lim Renly , Nasreen Sharifa , Pratt Nicole L , Pearson Sallie-Anne , Henry David
Published: March 2024

Background

Early evidence on COVID-19 vaccine efficacy came from randomised trials. Many important questions subsequently about vaccine effectiveness (VE) have been addressed using real-world studies (RWS) and have informed most vaccination policies globally. As the questions about VE have evolved during the pandemic so have data, study design, and analytical choices. This scoping review aims to characterise this evolution and provide insights for future pandemic planning—specifically, what kinds of questions are asked at different stages of a pandemic, and what data infrastructure and methods are used?

Methods and analysis

We will identify relevant studies in the Johns Hopkins Bloomberg School of Public Health VIEW-hub database, which curates both published and preprint VE RWS identified from PubMed, Embase, Scopus, Web of Science, the WHO COVID Database, MMWR, Eurosurveillance, medRxiv, bioRxiv, SSRN, Europe PMC, Research Square, Knowledge Hub, and Google. We will include RWS of COVID-19 VE that reported COVID-19-specific or all-cause mortality (coded as ‘death’ in the ‘effectiveness studies’ data set).

Information on study characteristics; study context; data sources; design and analytic methods that address confounding will be extracted by single reviewer and checked for accuracy and discussed in a small group setting by methodological and analytic experts. A timeline mapping approach will be used to capture the evolution of this body of literature.

By describing the evolution of RWS of VE through the COVID-19 pandemic, we will help identify options for VE studies and inform policy makers on the minimal data and analytic infrastructure needed to support rapid RWS of VE in future pandemics and of healthcare strategies more broadly.

Ethics and dissemination

As data is in the public domain, ethical approval is not required. Findings of this study will be disseminated through peer-reviewed publications, conference presentations, and working-papers to policy makers.

Registration

https://doi.org/10.17605/OSF.IO/ZHDKR
Role of physical activity in the relationship between recovery from work and insomnia among early childhood education and care professionals: a cross-sectional study
Authors: Karihtala Tiina , Puttonen Sampsa , Valtonen Anu M , Kautiainen Hannu , Hopsu Leila , Heinonen Ari
Published: March 2024

Objectives

This study aimed to investigate the association between recovery from work and insomnia and the role of objectively measured leisure-time physical activity and occupational physical activity in this association.

Design

Cross-sectional.

Setting and participants

Study with female early childhood education and care professionals (N=224) in Finland was conducted between April 2017 and September 2018.

Methods

Recovery from work was measured with the Need for Recovery scale and insomnia with the Jenkins Sleep Scale. Physical activity was measured with an accelerometer for 7 days and analysed to represent leisure-time physical activity and occupational physical activity (min/day).

Results

Both Jenkins Sleep Scale and occupational physical activity significantly predicted Need for Recovery (β=0.29; 95% CI 0.17 to 0.42 and β=0.14; 95% CI 0.01 to 0.27, respectively). A low relationship was observed between the Need for Recovery and Jenkins Sleep Scale (r=0.32, 95% Cl 0.19 to 0.44). After categorising participants into four groups based on median splits of occupational and leisure-time physical activity, relationships between the Need for Recovery and Jenkins Sleep Scale were low to moderate in the high occupational physical activity and leisure time physical activity group (r=0.38, 95% Cl 0.14 to 0.61), and in the high occupational physical activity and low leisure-time physical activity group (r=0.40, 95% Cl 0.18 to 0.63).

Conclusion

Both insomnia and physical activity at work seem to be relevant in recovery from work. To enhance recovery, especially those involved in high physical activity at work, should seek methods to improve recovery, by incorporating activities that promote recuperation both during their workday and in their leisure time. Further research on the relevance of physical activity in recovery with longitudinal setting is warranted.

Trial registration number

NCT03854877.
Artificial intelligence tools for optimising recruitment and retention in clinical trials: a scoping review protocol
Authors: Lu Xiaoran , Chen Mingan , Lu Zhuolin , Shi Xiaoting , Liang Lu
Published: March 2024

Introduction

In recent years, the influence of artificial intelligence technology on clinical trials has been steadily increasing. It has brought about significant improvements in the efficiency and cost reduction of clinical trials. The objective of this scoping review is to systematically map, describe and summarise the current utilisation of artificial intelligence in recruitment and retention process of clinical trials that has been reported in research. Additionally, the review aims to identify benefits and drawbacks, as well as barriers and facilitators associated with the application of artificial intelligence in optimising recruitment and retention in clinical trials. The findings of this review will provide insights and recommendations for future development of artificial intelligence in the context of clinical trials.

Methods and analysis

The review of relevant literature will follow the methodological framework for scoping studies provided by the Joanna Briggs Institute. A comprehensive electronic search will be conducted using the search strategy developed by the authors. Leading medical and computer science databases such as PubMed, Embase, Scopus, IEEE Xplore and Web of Science Core Collection will be searched. The search will encompass analytical observational studies, descriptive observational studies, experimental and quasi-experimental studies published in all languages, without any time limitations, which use artificial intelligence tools in the recruitment and retention process of clinical trials. The review team will screen the identified studies and import them into a dedicated electronic library specifically created for this review. Data extraction will be performed using a data charting table.

Ethics and dissemination

Secondary data will be attained in this scoping review; therefore, no ethical approval is required. The results of the final review will be published in a peer-reviewed journal. It is expected that results will inform future artificial intelligence and clinical trials research.
REKOVER study protocol: a pRospective patient treatment rEgistry of tramadol and dexKetoprofen trometamol oral fixed-dose combination (SKUDEXA) in mOderate to seVere acutE pain in Real-world setting in Asia
Authors: Ho Kok Yuen , Gyanwali Bibek , Dimayuga Cesar , Eufemio Edgar Michael , Bernardo Edwin , Raju Gopinathan , Chong Keen Wai , Waithayayothin Kritsadakorn , Ona Leonardo , Castro Marc Anthony L , Sawaddiruk Passakorn , Salvador Roehl C , Roohi Sharifah Ahmad , Tangwiwat Suwimon , Wilairatana Vajara , Oon Zhi Hao , Gupta Ankur , Nagrale Dinesh
Published: March 2024

Introduction

Satisfactory management of acute pain remains a major medical challenge despite the availability of multiple therapeutic options including the fixed-dose combination (FDC) drugs. Tramadol and dexketoprofen trometamol (TRAM/DKP) 75/25 mg FDC was launched in 2018 in Asia and is widely used in the management of moderate to severe acute pain. There are limited data on its effectiveness and safety in Asian patients, and therefore, a need to better understand its usage patterns in clinical practice. We aim to understand the usage pattern of TRAM/DKP FDC, its effectiveness and tolerability in patients with moderate to severe acute pain in Asia.

Methods and analysis

REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18–80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app.

Ethics and dissemination

The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.
Can glycated haemoglobin (HbA1c) be used as a predictor of left ventricular diastolic dysfunction in non-hypertensive patients with newly diagnosed type 2 diabetes mellitus: a cross-sectional study at a tertiary care centre in Eastern India
Authors: Porel Rajdeep , Shyama Shyama , Ahmad Shaheen , Kumar Neeraj , Ahmad Shamshad , Biswas Ratnadeep , Ojha Vishnu Shankar
Published: March 2024

Objectives

This study was conducted to establish the association between glycated haemoglobin (HbA1c) and left ventricular diastolic dysfunction (LVDD) in non-hypertensive patients with newly diagnosed type 2 diabetes mellitus (DM) and determine the cut-off value of HbA1c for detecting LVDD.

Design

Cross-sectional study.

Setting

This study was conducted in General Medicine Department in collaboration with the Cardiology Department at All India Institute of Medical Sciences, Patna.

Participants

The study population comprised patients with newly diagnosed type 2 DM within the past 3 months, aged between 18 years and 80 years, who were not hypertensive and without any systemic diseases and who presented to the General Medicine Department.

Primary and secondary outcome measures

The presence of LVDD was the primary outcome measure.

Results

Among the total of 60 participants, it was observed that age (adjusted odds ratio (AOR): 1.169, 95% CI: 1.066 to 1.283) and HbA1c (AOR: 2.625, 95% CI: 1.264 to 5.450) were found to be independent predictors for the presence of LVDD. Receiver operating characteristic analysis identified a cut-off value of HbA1c at 9.5% (80 mmol/mol) for detecting LVDD, with a specificity of 96.43%, a sensitivity of 37.5% and a positive predictive value (PPV) of 91.62%.

Conclusions

This study demonstrated that age and HbA1c levels are independent predictors of LVDD in patients with newly diagnosed type 2 DM without hypertension. A cut-off value of 9.5% for HbA1c was identified with a high specificity and PPV for predicting LVDD in patients with newly diagnosed type 2 diabetes. This underscores the importance of conducting echocardiography in patients with newly diagnosed asymptomatic type 2 diabetes with HbA1c 9.5% or more to assess LVDD, allowing for prompt interventions if necessary and to decelerate the progression towards heart failure.
SCALE-UP II: protocol for a pragmatic randomised trial examining population health management interventions to increase the uptake of at-home COVID-19 testing in community health centres
Authors: Del Fiol Guilherme , Orleans Brian , Kuzmenko Tatyana V , Chipman Jonathan , Greene Tom , Martinez Anna , Wirth Jennifer , Meads Ray , Kaphingst Kimberly K , Gibson Bryan , Kawamoto Kensaku , King Andy J , Siaperas Tracey , Hughes Shlisa , Pruhs Alan , Pariera Dinkins Courtney , Lam Cho Y , Pierce Joni H , Benson Ryzen , Borsato Emerson P , Cornia Ryan , Stevens Leticia , Bradshaw Richard L , Schlechter Chelsey R , Wetter David W
Published: March 2024

Introduction

SCALE-UP II aims to investigate the effectiveness of population health management interventions using text messaging (TM), chatbots and patient navigation (PN) in increasing the uptake of at-home COVID-19 testing among patients in historically marginalised communities, specifically, those receiving care at community health centres (CHCs).

Methods and analysis

The trial is a multisite, randomised pragmatic clinical trial. Eligible patients are >18 years old with a primary care visit in the last 3 years at one of the participating CHCs. Demographic data will be obtained from CHC electronic health records. Patients will be randomised to one of two factorial designs based on smartphone ownership. Patients who self-report replying to a text message that they have a smartphone will be randomised in a 2×2×2 factorial fashion to receive (1) chatbot or TM; (2) PN (yes or no); and (3) repeated offers to interact with the interventions every 10 or 30 days. Participants who do not self-report as having a smartphone will be randomised in a 2×2 factorial fashion to receive (1) TM with or without PN; and (2) repeated offers every 10 or 30 days. The interventions will be sent in English or Spanish, with an option to request at-home COVID-19 test kits. The primary outcome is the proportion of participants using at-home COVID-19 tests during a 90-day follow-up. The study will evaluate the main effects and interactions among interventions, implementation outcomes and predictors and moderators of study outcomes. Statistical analyses will include logistic regression, stratified subgroup analyses and adjustment for stratification factors.

Ethics and dissemination

The protocol was approved by the University of Utah Institutional Review Board. On completion, study data will be made available in compliance with National Institutes of Health data sharing policies. Results will be disseminated through study partners and peer-reviewed publications.

Trial registration number

ClinicalTrials.gov:NCT05533918andNCT05533359.
Growth trajectory of full-term small-for-gestational-age infants: a 3-year longitudinal study in China
Authors: Zhang Jianwei , He Xinyu , Ma Lujia , Li Ziqiao , Shen Wenxia , Hua Mengdi , Sun Lidan , Bai Guannan
Published: March 2024

Objective

Small-for-gestational-age (SGA) infants are at risk of impaired growth and developmental outcomes, even for those who were born at full term. The growth trajectory of full-term SGA infants remains unknown. Therefore, this study aimed to evaluate the growth trajectory of full-term SGA infants from birth to 3 years old in East China.

Methods

Full-term SGA infants were followed up from birth to 3 years old. The weight and length were measured at 3, 6, 12, 18, 24, 30 and 36 months. Rate of catch-up growth and rates of growth deviations including short stature, emaciation, underweight, overweight and obesity, were calculated at different time points. Latent class analysis was applied to describe growth trajectories from birth to 36 months.

Results

A total of 816 full-term SGA infants were enrolled in this study and 303 had complete follow-up data at 3, 6, 12, 18, 24, 30 and 36 months. At 24 months, the rate of catch-up growth was 42.4% in girls and 48.6% in boys; while at 36 months, this rate was 43.3% in girls and 52.1% in boys. The latent class analysis identified two trajectories of weight and length in boys and girls. Girls showed different growth trajectories of weight since 12 months compared with boys.

Conclusions

Our study reported a relatively low rate of catch-up growth in full-term SGA infants and has identified different growth trajectories of length and weight in boys and girls. We call for attention from health professionals on the growth trajectory of full-term SGA infants to eventually promote their health potentials.
Multimorbidity in patients with atrial fibrillation
Authors: Lobeek Michelle , Middeldorp Melissa E , Van Gelder Isabelle C , Rienstra Michiel
Published: March 2024

There is an escalating trend in both the incidence and prevalence of atrial fibrillation (AF). AF is linked to numerous other comorbidities, contributing to the emergence of multimorbidity. The sustained rise in multimorbidity and AF prevalences exerts a significant strain on healthcare systems globally. The understanding of the relation between multimorbidity and AF is essential to determine effective healthcare strategies, improve patient outcomes to adequately address the burden of AF. It not only begins with the accurate identification of comorbidities in the setting of AF. There is also the need to understand the pathophysiology of the different comorbidities and their common interactions, and how multimorbidity influences AF perpetuation. To manage the challenges that rise from the increasing incidence and prevalence of both multimorbidity and AF, such as adverse events and hospitalisations, the treatment of comorbidities in AF has already gained importance and will need to be a primary focus in the forthcoming years. There are numerous challenges to overcome in the treatment of multimorbidity in AF, whereby the identification of comorbidities is essential. Integrated care strategies focused on a comprehensive multimorbidity management with an individual-centred approach need to be determined to improve healthcare strategies and reduce the AF-related risk of frailty, cardiovascular diseases and improve patient outcomes.