bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare exposures and associated risk of endocarditis after open-heart cardiac valve surgery
Authors: Kwan Timothy N. , Brieger David , Chow Vincent , Ng Arnold Chin Tse , Kwan Gemma , Hyun Karice , Sy Raymond , Kritharides Leonard , Ng Austin Chin Chwan
Published: February 2024

Background

Infective endocarditis (IE) following cardiac valve surgery is associated with high morbidity and mortality. Data on the impact of iatrogenic healthcare exposures on this risk are sparse. This study aimed to investigate risk factors including healthcare exposures for post open-heart cardiac valve surgery endocarditis (PVE).

Methods

In this population-linkage cohort study, 23,720 patients who had their first cardiac valve surgery between 2001 and 2017 were identified from an Australian state-wide hospital-admission database and followed-up to 31 December 2018. Risk factors for PVE were identified from multivariable Cox regression analysis and verified using a case-crossover design sensitivity analysis.

Results

In 23,720 study participants (median age 73, 63% male), the cumulative incidence of PVE 15 years after cardiac valve surgery was 7.8% (95% CI 7.3–8.3%). Thirty-seven percent of PVE was healthcare-associated, which included red cell transfusions (16% of healthcare exposures) and coronary angiograms (7%). The risk of PVE was elevated for 90 days after red cell transfusion (HR = 3.4, 95% CI 2.1–5.4), coronary angiogram (HR = 4.0, 95% CI 2.3–7.0), and healthcare exposures in general (HR = 4.0, 95% CI 3.3–4.8) (all p < 0.001). Sensitivity analysis confirmed red cell transfusion (odds ratio [OR] = 3.9, 95% CI 1.8–8.1) and coronary angiogram (OR = 2.6, 95% CI 1.5–4.6) (both p < 0.001) were associated with PVE. Six-month mortality after PVE was 24% and was higher for healthcare-associated PVE than for non-healthcare-associated PVE (HR = 1.3, 95% CI 1.1–1.5, p = 0.002).

Conclusions

The risk of PVE is significantly higher for 90 days after healthcare exposures and associated with high mortality.
Quantified pathway mutations associate epithelial-mesenchymal transition and immune escape with poor prognosis and immunotherapy resistance of head and neck squamous cell carcinoma
Authors: Huang Yuhong , Liu Han , Liu Bo , Chen Xiaoyan , Li Danya , Xue Junyuan , Li Nan , Zhu Lei , Yang Liu , Xiao Jing , Liu Chao
Published: February 2024

Background

Pathway mutations have been calculated to predict the poor prognosis and immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC). To uncover the unique markers predicting prognosis and immune therapy response, the accurate quantification of pathway mutations are required to evaluate epithelial-mesenchymal transition (EMT) and immune escape. Yet, there is a lack of score to accurately quantify pathway mutations.

Material and methods

Firstly, we proposed Individualized Weighted Hallmark Gene Set Mutation Burden (IWHMB, https://github.com/YuHongHuang-lab/IWHMB) which integrated pathway structure information and eliminated the interference of global Tumor Mutation Burden to accurately quantify pathway mutations. Subsequently, to further elucidate the association of IWHMB with EMT and immune escape, support vector machine regression model was used to identify IWHMB-related transcriptomic features (IRG), while Adversarially Regularized Graph Autoencoder (ARVGA) was used to further resolve IRG network features. Finally, Random walk with restart algorithm was used to identify biomarkers for predicting ICI response.

Results

We quantified the HNSCC pathway mutation signatures and identified pathway mutation subtypes using IWHMB. The IWHMB-related transcriptomic features (IRG) identified by support vector machine regression were divided into 5 communities by ARVGA, among which the Community 1 enriching malignant mesenchymal components promoted EMT dynamically and regulated immune patterns associated with ICI responses. Bridge Hub Gene (BHG) identified by random walk with restart was key to IWHMB in EMT and immune escape, thus, more predictive for ICI response than other 70 public signatures.

Conclusion

In summary, the novel pathway mutation scoring-IWHMB suggested that the elevated malignancy mediated by pathway mutations is a major cause of poor prognosis and immunotherapy failure in HNSCC, and is capable of identifying novel biomarkers to predict immunotherapy response.
The airway neuro-immune axis as a therapeutic target in allergic airway diseases
Authors: Wu Wanhua , Li Jianing , Chen Su , Ouyang Suidong
Published: February 2024

Recent evidence has increasingly underscored the importance of the neuro-immune axis in mediating allergic airway diseases, such as allergic asthma and allergic rhinitis. The intimate spatial relationship between neurons and immune cells suggests that their interactions play a pivotal role in regulating allergic airway inflammation. Upon direct activation by allergens, neurons and immune cells engage in interactions, during which neurotransmitters and neuropeptides released by neurons modulate immune cell activity. Meanwhile, immune cells release inflammatory mediators such as histamine and cytokines, stimulating neurons and amplifying neuropeptide production, thereby exacerbating allergic inflammation. The dynamic interplay between the nervous and immune systems suggests that targeting the neuro-immune axis in the airway could represent a novel approach to treating allergic airway diseases. This review summarized recent evidence on the nervous system’s regulatory mechanisms in immune responses and identified potential therapeutic targets along the peripheral nerve-immune axis for allergic asthma and allergic rhinitis. The findings will provide novel perspectives on the management of allergic airway diseases in the future.
The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode
Authors: Verhulst Clementine E. M. , van Heck Julia I. P. , Fabricius Therese W. , Stienstra Rinke , Teerenstra Steven , McCrimmon Rory J. , Tack Cees J. , Pedersen-Bjergaard Ulrik , de Galan Bastiaan E. ,   the Hypo-RESOLVE consortium
Published: February 2024

Background

Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans.

Methods

Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP.

Results

In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16+-monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1β, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia.

Conclusion

Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia.

Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019).
Ipragliflozin and sitagliptin differentially affect lipid and apolipoprotein profiles in type 2 diabetes: the SUCRE study
Authors: Nagao Mototsugu , Sasaki Jun , Tanimura-Inagaki Kyoko , Sakuma Ichiro , Sugihara Hitoshi , Oikawa Shinichi ,   on behalf of the SUCRE Study Investigators
Published: February 2024

Background

SGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other clinical parameters.

Methods

This is a multicenter, open-label, randomized, controlled trial. Patients with type 2 diabetes (20–74 years old) with HbA1c levels of 7.0-10.5% and serum triglyceride levels of 120–399 mg/dL (1.35–4.50 mmol/L) on diet and/or oral hypoglycemic agents were enrolled. Subjects were randomized to treatment with ipragliflozin (50 mg/day, n = 77) or sitagliptin (50 mg/day, n = 83). Laboratory measurements were performed at 0, 1, 3, and 6 months of treatment.

Results

Ipragliflozin and sitagliptin reduced fasting plasma glucose, glycoalbumin, and HbA1c almost equally. Ipragliflozin increased HDL-C and decreased apo E. Sitagliptin decreased TG, apo B48, CII, and CIII, but increased LDL-C. The between-treatment differences were significant for HDL-C (P = 0.02) and apo B48 (P = 0.006), and nearly significant for apo A1 (P = 0.06). In addition, ipragliflozin reduced body weight, blood pressure, serum liver enzymes, uric acid, and leptin, and increased serum ketones compared with sitagliptin.

Conclusions

While ipragliflozin and sitagliptin showed similar effects on glycemic parameters, the effects on serum lipid and apolipoprotein profiles were different. Ipragliflozin may have an anti-atherogenic effect through modulation of HDL-C and apo E compared to sitagliptin through TG and apo B48, CII, and CIII in patients with type 2 diabetes.
Protein production dynamics and physiological adaptation of recombinant Komagataella phaffii at near-zero growth rates
Authors: Rebnegger Corinna , Coltman Benjamin L. , Kowarz Viktoria , Peña David A. , Mentler Axel , Troyer Christina , Hann Stephan , Schöny Harald , Koellensperger Gunda , Mattanovich Diethard , Gasser Brigitte
Published: February 2024

Background

Specific productivity (qP) in yeast correlates with growth, typically peaking at intermediate or maximum specific growth rates (μ). Understanding the factors limiting productivity at extremely low μ might reveal decoupling strategies, but knowledge of production dynamics and physiology in such conditions is scarce. Retentostats, a type of continuous cultivation, enable the well-controlled transition to near-zero µ through the combined retention of biomass and limited substrate supply. Recombinant Komagataella phaffii (syn Pichia pastoris) secreting a bivalent single domain antibody (VHH) was cultivated in aerobic, glucose-limited retentostats to investigate recombinant protein production dynamics and broaden our understanding of relevant physiological adaptations at near-zero growth conditions.

Results

By the end of the retentostat cultivation, doubling times of approx. two months were reached, corresponding to µ = 0.00047 h−1. Despite these extremely slow growth rates, the proportion of viable cells remained high, and de novo synthesis and secretion of the VHH were observed. The average qP at the end of the retentostat was estimated at 0.019 mg g−1 h−1. Transcriptomics indicated that genes involved in protein biosynthesis were only moderately downregulated towards zero growth, while secretory pathway genes were mostly regulated in a manner seemingly detrimental to protein secretion. Adaptation to near-zero growth conditions of recombinant K. phaffii resulted in significant changes in the total protein, RNA, DNA and lipid content, and lipidomics revealed a complex adaptation pattern regarding the lipid class composition. The higher abundance of storage lipids as well as storage carbohydrates indicates that the cells are preparing for long-term survival.

Conclusions

In conclusion, retentostat cultivation proved to be a valuable tool to identify potential engineering targets to decouple growth and protein production and gain important insights into the physiological adaptation of K. phaffii to near-zero growth conditions.
Elevated serum LDL-C increases the risk of Lewy body dementia: a two-sample mendelian randomization study
Authors: Liu Pengdi , Liu Jin , Zhang Yafei , Xing Xin , Zhou Le , Qu Jianqiang , Yan Xianxia
Published: February 2024

Background

Lewy body dementia (LBD) ranks second among prevalent neurodegenerative dementias. Previous studies have revealed associations of serum lipid measures with several neurodegenerative diseases. Nevertheless, the potential connection between serum lipids and LBD remains undetermined. In this study, Mendelian randomization (MR) analyses were carried out to assess the causal relationships of several serum lipid measures with the risk of developing LBD.

Methods

Genome-wide association study (GWAS) data for serum lipids and LBD in European descent individuals were acquired from publicly available genetic summary data. A series of filtering procedures were conducted to identify the genetic variant candidates that are related to serum lipids, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). The causal effects were primarily determined through inverse-variance weighting (IVW)-based analyses.

Results

Neither TG (odds ratio [OR] = 1.149; 95% confidence interval [CI], 0.887–1.489; P = 0.293) nor HDL-C (OR = 0.864; 95% CI, 0.718–1.041; P = 0.124) had causal effects on LBD. However, a causal relationship was identified between LDL-C and LBD (OR = 1.343; 95% CI, 1.094–1.649; P = 0.005), which remained significant (OR = 1.237; 95% CI, 1.015–1.508; P = 0.035) following adjustment for HDL-C and TG in multivariable MR.

Conclusions

Elevated serum LDL-C increases the risk of LBD, while HDL-C and TG have no significant causal effects on LBD.
Beyond the barrier: the immune-inspired pathways of tumor extravasation
Authors: Di Russo Sara , Liberati Francesca Romana , Riva Agnese , Di Fonzo Federica , Macone Alberto , Giardina Giorgio , Arese Marzia , Rinaldo Serena , Cutruzzolà Francesca , Paone Alessio
Published: February 2024

Extravasation is a fundamental step in the metastatic journey, where cancer cells exit the bloodstream and breach the endothelial cell barrier to infiltrate target tissues. The tactics cancer cells employ are sophisticated, closely reflecting those used by the immune system for tissue surveillance. Remarkably, tumor cells have been observed to form distinct associations or clusters with immune cells where neutrophils stand out as particularly crucial partners. These interactions are not accidental; they are critical for cancer cells to exploit the immune functions of neutrophils and successfully extravasate. In another strategy, tumor cells mimic the behavior and characteristics of immune cells. They release a suite of inflammatory mediators, which under normal circumstances, guide the processes of endothelium reshaping and facilitate the entry and movement of immune cells within tissues. In this review, we offer a new perspective on the tactics employed by cancer cells to extravasate and infiltrate target tissues. We delve into the myriad mechanisms that tumor cells borrow, adapt, and refine from the immune playbook.
Peritoneal sepsis caused by Escherichia coli triggers brainstem inflammation and alters the function of sympatho-respiratory control circuits
Authors: Kola Gjinovefa , Clifford Caitlyn W. , Campanaro Cara K. , Dhingra Rishi R. , Dutschmann Mathias , Jacono Frank J. , Dick Thomas E.
Published: February 2024

Background

Sepsis has a high mortality rate due to multiple organ failure. However, the influence of peripheral inflammation on brainstem autonomic and respiratory circuits in sepsis is poorly understood. Our working hypothesis is that peripheral inflammation affects central autonomic circuits and consequently contributes to multiorgan failure in sepsis.

Methods

In an Escherichia coli (E. coli)–fibrin clot model of peritonitis, we first recorded ventilatory patterns using plethysmography before and 24 h after fibrin clot implantation. To assess whether peritonitis was associated with brainstem neuro-inflammation, we measured cytokine and chemokine levels in Luminex assays. To determine the effect of E. coli peritonitis on brainstem function, we assessed sympatho-respiratory nerve activities at baseline and during brief (20 s) hypoxemic ischemia challenges using in situ-perfused brainstem preparations (PBPs) from sham or infected rats. PBPs lack peripheral organs and blood, but generate vascular tone and in vivo rhythmic activities in thoracic sympathetic (tSNA), phrenic and vagal nerves.

Results

Respiratory frequency was greater (p < 0.001) at 24 h post-infection with E. coli than in the sham control. However, breath-by-breath variability and total protein in the BALF did not differ. IL-1β (p < 0.05), IL-6 (p < 0.05) and IL-17 (p < 0.04) concentrations were greater in the brainstem of infected rats. In the PBP, integrated tSNA (p < 0.05) and perfusion pressure were greater (p < 0.001), indicating a neural-mediated pathophysiological high sympathetic drive. Moreover, respiratory frequency was greater (p < 0.001) in PBPs from infected rats than from sham rats. Normalized phase durations of inspiration and expiration were greater (p < 0.009, p < 0.015, respectively), but the post-inspiratory phase (p < 0.007) and the breath-by-breath variability (p < 0.001) were less compared to sham PBPs. Hypoxemic ischemia triggered a biphasic response, respiratory augmentation followed by depression. PBPs from infected rats had weaker respiratory augmentation (p < 0.001) and depression (p < 0.001) than PBPs from sham rats. In contrast, tSNA in E. coli-treated PBPs was enhanced throughout the entire response to hypoxemic ischemia (p < 0.01), consistent with sympathetic hyperactivity.

Conclusion

We show that peripheral sepsis caused brainstem inflammation and impaired sympatho-respiratory motor control in a single day after infection. We conclude that central sympathetic hyperactivity may impact vital organ systems in sepsis.
Surgical outcomes and perioperative risk factors of patients with interstitial lung disease after pulmonary resection
Authors: Huang Chuan , Sun Yao-Guang , Ma Chao , Jiao Peng , Wu Qing-Jun , Tian Wen-Xin , Yu Han-Bo , Tong Hong-Feng
Published: February 2024

Background

Patients of interstitial lung disease (ILD) combined with pulmonary lesions are increasingly common in clinical practice. Patients with ILD are at significantly higher risk for complications after pulmonary resection (including lobectomy and sublobar resection), especially acute exacerbations of ILD (AE-ILD). The purpose of this study is to summarize the short-term and long-term outcomes after pulmonary resection in ILD patients and to analyze the clinical factors affecting surgical safety.

Methods

From January 2004 to January 2022, a total of 78 patients who were diagnosed with ILD and underwent pulmonary resection at our center were enrolled in this study. Clinical data, pathological findings, surgical procedures, and intraoperative safety of these patients were collected retrospectively. Postoperative 90-day complications and mortality, long-term surgical outcomes from postoperative 90 days to 24 months, and changes in ILD condition were investigated. Logistic regression analysis was used to identify the risk factors associated with postoperative complications.

Results

The median age of patients was 66.5 (range 33–86) years, 82.1% (64/78) of patients were male, and 78.2% (61/78) of patients had comorbidities. Idiopathic ILD and secondary ILD accounted for 86% and 14%, thoracotomy and video-assisted thoracoscopic surgery accounted for 12.8% and 87.2%, and lobectomy and sublobar resection accounted for 37.2% and 62.8%, respectively. Postoperative 90-day complications occurred in 25.6% (20/78) of patients, with pulmonary complications and AE-ILD occurring in 15.4% and 9.0% of patients, respectively. The postoperative 90-day mortality rate was 5.1% (4/78), and the cause of death was AE-ILD. Exacerbation of ILD or other complications occurred in 12.8% (10/78) of patients from postoperative 90 days to 24 months. Univariate logistic regression analysis showed that comorbidity, extent of resection, systemic lymph node dissection, operation time, intraoperative blood loss, and pathology of pulmonary lesion were associated with postoperative 90-day complications. In multivariate logistic regression analysis, age-adjusted Charlson Comorbidity Index and intraoperative blood loss were identified as independent risk factors of postoperative 90-day complications.

Conclusions

Patients with ILD have a significantly higher risk of postoperative 90-day complications and mortality after pulmonary resection, especially pulmonary complications and AE-ILD. After postoperative 90 days, the risk of deterioration of pulmonary status remains high, including exacerbation of ILD and complications associated with long-term use of glucocorticoids and immunosuppressant. Age, comorbidity and intraoperative blood loss are high risk factors for postoperative 90-day complications.
Electroreduction of divanillin to polyvanillin in an electrochemical flow reactor
Authors: Kunkel Robin , Fath Maximilian , Schmiedl Detlef , Schmidt Volkmar M. , Tübke Jens
Published: February 2024

The electrochemical conversion of biobased intermediates offers an attractive and sustainable process for the production of green chemicals. One promising synthesis route is the production of the total vanillin-based polymer polyvanillin, which can be produced by electrochemical pinacolization of divanillin (5–5´bisvanillyl). Divanillin can be easily enzymatically generated from vanillin, a renewable intermediate accessible from lignin on an industrial scale. This study investigates systematically the electrochemical production of polyvanillin in a divided plane parallel flow reactor in recirculation mode. Several analytic methods, such as online UV–VIS spectroscopy, size exclusion chromatography (SEC), 2D-NMR (HSQC, 13C/1H), TGA and DSC were used to monitor the reaction progress and to characterize the reaction products under different galvanostatic reaction conditions revealing new insights into the reaction mechanism and structural features of the polymer. Further, by using an electrochemical engineering-based approach determining the limiting current densities, we readily achieved high current densities over 50 mA cm−2 for the polyvanillin synthesis and reached averaged molecular weights up to Mw = 4100 g mol−1 and Mn = 2700 g mol−1. The cathodic polymerization to polyvanillin offers an innovative approach for the electrochemical production of biobased polymers presented on flow cell level.

Graphical Abstract
Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity
Authors: Chuah Min H , Leask Megan P , Topless Ruth K , Gamble Gregory D , Sumpter Nicholas A , Stamp Lisa K , Merriman Tony R , Dalbeth Nicola
Published: February 2024

Background

Alcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single-nucleotide polymorphisms (SNPs) have been identified as associated with both alcohol consumption and serum urate or gout in separate genome-wide association studies (GWAS). This study aimed to identify and characterise interactions between these shared signals of genetic association and alcohol consumption for serum urate level, hyperuricaemia, and gout.

Methods

This research was conducted using the UK Biobank resource. The association of alcohol consumption with serum urate and gout was tested among 458,405 European participants. Candidate SNPs were identified by comparing serum urate, gout, and alcohol consumption GWAS for shared signals of association. Multivariable-adjusted linear and logistic regression analyses were conducted with the inclusion of interaction terms to identify SNP-alcohol consumption interactions for association with serum urate level, hyperuricaemia, and gout. The nature of these interactions was characterised using genotype-stratified association analyses.

Results

Alcohol consumption was associated with elevated serum urate and gout. For serum urate level, non-additive interactions were identified between alcohol consumption and rs1229984 at the ADH1B locus (P = 3.0 × 10−44) and rs6460047 at the MLXIPL locus (P = 1.4 × 10−4). ADH1B also demonstrated interaction with alcohol consumption for hyperuricaemia (P = 7.9 × 10−13) and gout (P = 8.2 × 10−9). Beer intake had the most significant interaction with ADH1B for association with serum urate and gout among men, while wine intake had the most significant interaction among women. In the genotype-stratified association analyses, ADH1B and MLXIPL were associated with serum urate level and ADH1B was associated with hyperuricaemia and gout among consumers of alcohol but not non-consumers.

Conclusions

In this large study of European participants, novel interactions with alcohol consumption were identified at ADH1B and MLXIPL for association with serum urate level and at ADH1B for association with hyperuricaemia and gout. The association of ADH1B with serum urate and gout may occur through the modulation of alcohol metabolism rate among consumers of alcohol.
Diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT in detecting lymph node metastases in clinically early-stage cervical cancer — a nationwide Dutch cohort study
Authors: Olthof Ester P. , Bergink-Voorthuis Brenda J. , Wenzel Hans H. B. , Mongula Jordy , van der Velden Jacobus , Spijkerboer Anje M. , Adam Judit A. , Bekkers Ruud L. M. , Beltman Jogchum J. , Slangen Brigitte F. M. , Nijman Hans W. , Smolders Ramon G. V. , van Trommel Nienke E. , Zusterzeel Petra L. M. , Zweemer Ronald P. , Stalpers Lukas J. A. , Mom Constantijne H. , van der Aa Maaike A.
Published: February 2024

Objectives

Imaging is increasingly used to assess lymph node involvement in clinically early-stage cervical cancer. This retrospective study aimed to evaluate the diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT.

Methods

Women with International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage IA2-IIA cervical cancer and pretreatment imaging between 2009 and 2017 were selected from the Netherlands Cancer Registry. Patient-based and region-based (i.e. pelvic and common iliac) nodal status was extracted from radiology reports. Pathology results were considered the reference standard for calculating accuracy indices. Multiple imputation was used for missing pathology to limit verification bias risk.

Results

Nodal assessment was performed in 1676 patients with MRI, 926 with CT, and 379 with [18F]FDG-PET-CT, with suspicious nodes detected in 17%, 16%, and 48%, respectively. [18F]FDG-PET-CT was used to confirm MRI/CT results in 95% of patients. Pathology results were imputed for 30% of patients. [18F]FDG-PET-CT outperformed MRI and CT in detecting patient-based nodal metastases with sensitivities of 80%, 48%, and 40%, and AUCs of 0.814, 0.706, and 0.667, respectively, but not in specificity: 79%, 92%, and 92%. Region-based analyses showed similar indices in the pelvic region, but worse performance in the common iliac region with AUCs of 0.575, 0.554, and 0.517, respectively.

Conclusions

[18F]FDG-PET-CT outperformed MRI and CT in detecting nodal metastases, which may be related to its use as a verification modality. However, MRI and CT had the highest specificity. As MRI is generally performed routinely to assess local and regional spread of cervical cancer, [18F]FDG-PET-CT can be used to confirm suspicious nodes.

Critical relevance statement

Accurate assessment of the nodal status in clinically early-stage cervical cancer is essential for tumour staging, treatment decision making and prognosis.

Key points

• The accuracy of MRI, CT or [18F]FDG-PET-CT for nodal staging in early cervical cancer is a subject of discussion.

• Overall, [18F]FDG-PET-CT outperformed MRI, followed by CT, when used as a verification modality.

• Staging with MRI and the addition of [18F]FDG-PET-CT to verify high-risk cases seems to be a good approach.

Graphical Abstract
Adipose-derived stem cells in immune-related skin disease: a review of current research and underlying mechanisms
Authors: Sun Tianyi , Zhou Cheng , Lu Feng , Dong Ziqing , Gao Jianhua , Li Bin
Published: February 2024

Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell–cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell–cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.
The utility of behavioral biometrics in user authentication and demographic characteristic detection: a scoping review
Authors: Finnegan O. L. , White J. W. , Armstrong B. , Adams E. L. , Burkart S. , Beets M. W. , Nelakuditi S. , Willis E. A. , von Klinggraeff L. , Parker H. , Bastyr M. , Zhu X. , Zhong Z. , Weaver R. G.
Published: February 2024

Background

Objective measures of screen time are necessary to better understand the complex relationship between screen time and health outcomes. However, current objective measures of screen time (e.g., passive sensing applications) are limited in identifying the user of the mobile device, a critical limitation in children’s screen time research where devices are often shared across a family. Behavioral biometrics, a technology that uses embedded sensors on modern mobile devices to continuously authenticate users, could be used to address this limitation.

Objective

The purpose of this scoping review was to summarize the current state of behavioral biometric authentication and synthesize these findings within the scope of applying behavioral biometric technology to screen time measurement.

Methods

We systematically searched five databases (Web of Science Core Collection, Inspec in Engineering Village, Applied Science & Technology Source, IEEE Xplore, PubMed), with the last search in September of 2022. Eligible studies were on the authentication of the user or the detection of demographic characteristics (age, gender) using built-in sensors on mobile devices (e.g., smartphone, tablet). Studies were required to use the following methods for authentication: motion behavior, touch, keystroke dynamics, and/or behavior profiling. We extracted study characteristics (sample size, age, gender), data collection methods, data stream, model evaluation metrics, and performance of models, and additionally performed a study quality assessment. Summary characteristics were tabulated and compiled in Excel. We synthesized the extracted information using a narrative approach.

Results

Of the 14,179 articles screened, 122 were included in this scoping review. Of the 122 included studies, the most highly used biometric methods were touch gestures (n = 76) and movement (n = 63), with 30 studies using keystroke dynamics and 6 studies using behavior profiling. Of the studies that reported age (47), most were performed exclusively in adult populations (n = 34). The overall study quality was low, with an average score of 5.5/14.

Conclusion

The field of behavioral biometrics is limited by the low overall quality of studies. Behavioral biometric technology has the potential to be used in a public health context to address the limitations of current measures of screen time; however, more rigorous research must be performed in child populations first.

Systematic review registration

The protocol has been pre-registered in the Open Science Framework database (https://doi.org/10.17605/OSF.IO/92YCT).
Role of hydroxyurea therapy in the prevention of organ damage in sickle cell disease: a systematic review and meta-analysis
Authors: Khargekar Naveen , Banerjee Anindita , Athalye Shreyasi , Mahajan Namrata , Kargutkar Neha , Tapase Prashant , Madkaikar Manisha
Published: February 2024

Background

Hydroxyurea is an affordable drug that reduces vaso-occlusive crises and transfusion requirements in sickle cell disease. However, its effectiveness in preventing chronic organ damage is still unclear. This systematic review and meta-analysis aimed to evaluate the role of hydroxyurea in preventing organ morbidity.

Method

We included original articles published in English from 1st January 1990 to 31st January 2023, reporting hydroxyurea therapy and organ damage from PubMed, Google Scholar, Scopus, and CrossRef databases. A total of 45 studies with 4681 sickle cell disease patients were evaluated for organ damage.

Results

Our analysis showed that hydroxyurea intervention significantly lowered transcranial Doppler and tricuspid regurgitant velocity, with a standardized mean difference of − 1.03 (− 1.49; − 0.58); I2 = 96% and − 1.37 (CI − 2.31, − 0.42); I2 = 94%, respectively. Moreover, the pooled estimate for albuminuria showed a beneficial effect post-hydroxyurea therapy by reducing the risk of albuminuria by 58% (risk ratio of 0.42 (0.28; 0.63); I2 = 28%).

Conclusion

Our study found that a hydroxyurea dose above 20 mg/kg/day with a mean rise in HbF by 18.46% post-hydroxyurea therapy had a beneficial role in reducing transcranial doppler velocity, tricuspid regurgitant velocity, albuminuria, and splenic abnormality.

Systematic review registration

PROSPERO CRD42023401187.
The effect of acupuncture on oxidative stress in animal models of vascular dementia: a systematic review and meta-analysis
Authors: Bao Qiong-Nan , Xia Man-Ze , Xiong Jing , Liu Yi-Wei , Li Ya-Qin , Zhang Xin-Yue , Chen Zheng-Hong , Yao Jin , Wu Ke-Xin , Zhong Wan-Qi , Xu Shao-Jun , Yin Zi-Han , Liang Fan-Rong
Published: February 2024

Background

Growing evidence showed that acupuncture may improve cognitive function by reducing oxidative stress, key to the pathogenesis in vascular dementia (VaD), but this is yet to be systematically analysed. This study aimed to summarize and evaluate the effect of acupuncture on oxidative stress in animal models of VaD.

Method

Eight databases including PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, CBM, and VIP were searched since their establishment until April 2023, for studies that reported the effect of acupuncture on oxidative stress in VaD animal models. Relevant literature was screened, and information was extracted by two reviewers. The primary outcomes were the levels of oxidative stress indicators. The methodological quality was assessed via the SYRCLE Risk of Bias Tool. Statistical analyses were performed using the RevMan and Stata software.

Results

In total, 22 studies with 747 animals were included. The methodology of most studies had flaws or uncertainties. The meta-analysis indicated that, overall, acupuncture significantly reduced the expression of pro-oxidants including reactive oxygen species (standardized mean differences [SMDs] = -4.29, 95% confidence interval [CI]: -6.26, -2.31), malondialdehyde (SMD = -2.27, 95% CI: -3.07, -1.47), nitric oxide (SMD = -0.85, 95% CI: -1.50, -0.20), and nitric oxide synthase (SMD = -1.01, 95% CI: -1.69, -0.34) and enhanced the levels of anti-oxidants including super oxide dismutase (SMD = 2.80, 95% CI: 1.98, 3.61), glutathione peroxidase (SMD = 1.32, 95% CI: -0.11, 2.76), and catalase (SMD = 1.31, 95% CI: 0.05, 2.58) in VaD animal models. In subgroup analyses, acupuncture showed significant effects on most variables. Only partial modelling methods and treatment duration could interpret the heterogeneity of some outcomes.

Conclusion

Acupuncture may inhibit oxidative stress to improve cognitive deficits in animal models of VaD. Nevertheless, the methodological quality is unsatisfactory. More high-quality research with a rigorous design and further experimental researches and clinical trials are needed to confirm these findings.

Systematic review registration

This study was registered in PROSPERO (CRD42023411720).
Safinamide, an inhibitor of monoamine oxidase, modulates the magnitude, gating, and hysteresis of sodium ion current
Authors: Hung Te-Yu , Wu Sheng-Nan , Huang Chin-Wei
Published: February 2024

Background

Safinamide (SAF), an α-aminoamide derivative and a selective, reversible monoamine oxidase (MAO)-B inhibitor, has both dopaminergic and nondopaminergic (glutamatergic) properties. Several studies have explored the potential of SAF against various neurological disorders; however, to what extent SAF modulates the magnitude, gating, and voltage-dependent hysteresis [Hys(V)] of ionic currents remains unknown.

Methods

With the aid of patch-clamp technology, we investigated the effects of SAF on voltage-gated sodium ion (NaV) channels in pituitary GH3 cells.

Results

SAF concentration-dependently stimulated the transient (peak) and late (sustained) components of voltage-gated sodium ion current (INa) in pituitary GH3 cells. The conductance–voltage relationship of transient INa [INa(T)] was shifted to more negative potentials with the SAF presence; however, the steady-state inactivation curve of INa(T) was shifted in a rightward direction in its existence. SAF increased the decaying time constant of INa(T) induced by a train of depolarizing stimuli. Notably, subsequent addition of ranolazine or mirogabalin reversed the SAF-induced increase in the decaying time constant. SAF also increased the magnitude of window INa induced by an ascending ramp voltage Vramp. Furthermore, SAF enhanced the Hys(V) behavior of persistent INa induced by an upright isosceles-triangular Vramp. Single-channel cell-attached recordings indicated SAF effectively increased the open-state probability of NaV channels. Molecular docking revealed SAF interacts with both MAO and NaV channels.

Conclusion

SAF may interact directly with NaV channels in pituitary neuroendocrine cells, modulating membrane excitability.
Iranian EFL teachers’ self-efficacy: structural equation modeling of the consequences
Authors: Mossafaie Mohammadnasser , Alibakhshi Goudarz , Tabrizi Hossein Heidari
Published: February 2024

Within the field of teacher education, the concept of self-efficacy—which includes teachers' self-perceptions of their competence and abilities in particular tasks—has attracted a lot of attention. It shows how confident a teacher is in their ability to help students achieve the learning objectives. In spite of its critical importance, there hasn't been a single study that thoroughly examines the underlying effects of self-efficacy among English as a Foreign Language (EFL) teachers. To carefully examine these effects and verify a theoretical model, this study uses a mixed methods approach. 26 articles are found to be eligible after a meta-analysis method is used to thoroughly review pertinent articles from Elsevier, Google Scholar, and ERIC. The following outcomes are linked to the self-efficacy of EFL teachers: burnout, instructional success, psychological well-being, engagement and job satisfaction, communication readiness, teaching commitment, emotion regulation, professional development, and motivational teaching behavior. Using structural equation modeling, the proposed model is evaluated in the quantitative phase. The researchers' 10-factor scale is used to collect data. The model's divergent validity, convergent validity, and reliability are all shown to be at acceptable levels by the results. These findings have both theoretical and practical ramifications, offering useful information.
A framework for more equitable, diverse, and inclusive Patient and Public Involvement for palliative care research
Authors: Mitchell Sarah , Turner Nicola , Fryer Kate , Beng Jude , Ogden Margaret E. , Watson Melanie , Gardiner Clare , Bayly Joanne , Sleeman Katherine E. , Evans Catherine J.
Published: February 2024

Background

There are marked inequalities in palliative care provision. Research is needed to understand how such inequalities can be addressed, so that everyone living with advanced illness can receive the care they need, when they need it. Research into inequalities in palliative care should be guided by Patient and Public Involvement (PPI) that includes people from diverse backgrounds, who are less likely to receive specialist services. Multi-disciplinary research partnerships, bringing together primary care (the main providers of palliative care to diverse communities) and specialist palliative care, have the potential to work together in new ways to do research to address inequalities and improve palliative care in practice. This report describes a research partnership between primary care and palliative care that aimed to: (1) create opportunities for more inclusive PPI in palliative care research, (2) co-design new resources to support more equitable, diverse and inclusive PPI for palliative care, (3) propose a new framework for inclusive PPI in palliative care research.

Methods

PPI members were recruited via primary care and palliative care research networks from three diverse areas of the UK. A pragmatic, collaborative approach was taken to achieve the partnership aims. Online workshops were carried out to understand barriers to inclusive PPI in palliative care and to co-design resources. Evaluation included a “you said, we did” impact log and a short survey. The approach was informed by good practice principles from previous PPI, and existing theory relating to equity, equality, diversity, and inclusion.

Results

In total, 16 PPI members were recruited. Most were White British (n = 10), other ethnicities were Asian (n = 4), Black African (n = 1) and British mixed race (n = 1). The research team co-ordinated communication and activities, leading to honest conversations about barriers to inclusive PPI. Resources were co-designed, including a role description for an Equity, Equality, Diversity and Inclusion Champion, a “jargon buster”, an animation and an online recipe book (http://www.re-equipp.co.uk/) to inform future PPI. Learning from the partnership has been collated into a new framework to inform more inclusive PPI for future palliative care research.

Conclusion

Collaboration and reciprocal learning across a multi-disciplinary primary care and palliative care research partnership led to the development of new approaches and resources. Research team commitment, shared vision, adequate resource, careful planning, relationship building and evaluation should underpin approaches to increase equality, diversity and inclusivity in future PPI for palliative care research.
Moving towards deep equity, diversity, inclusivity and accessibility in simulation: a call to explore the promises and perils
Authors: Dieckmann Peter , Nirula Latika
Published: February 2024

Principles and issues of equity, diversity, inclusivity, and accessibility (EDIA) are being explored currently in simulation designs and trainings but with limited depth, often raising more questions than answers. This editorial invites the broader healthcare simulation community to move beyond the superficial to explore more expansively and deeply these issues of EDIA within simulation. Simulation is the very environment and context from which we may confront how existing (power) structures can be dismantled and re-envisioned for more optimal redistribution of participation, power, and benefits. We can use simulation to experiment with variations of these realities, and start exploring consequences of such alternatives to benefit our broader health systems and societies. Simulation uniquely combines opportunities for experience, reflection, application and active experimentation, enabling a ripe ground for this study. In fact, it is the responsibility of simulation educators to take up this challenge, and to engage in meaningful scholarship to understand more about the impact of simulation in exploring EDIA topics. This editorial invites contributions of empirical and theoretical works that advance our collective understanding of EDIA, while also cautioning against complacency. The simulation community is urged to look inwards and also examine its own practices critically, in spite of the uncertainty, vulnerability and risks that this presents.
First malaria in pregnancy followed in Philippine real-world setting: proof-of-concept of probabilistic record linkage between disease surveillance and hospital administrative data
Authors: Kinoshita Takuya , Espino Fe , Bunagan Raymart , Lim Dodge , Daga Chona , Parungao Sabrina , Balderian Aileen , Micu Katherine , Laborera Rutchel , Basilio Ramon , Inobaya Marianette , Baquilod Mario , Dy Melecio , Chiba Hitoshi , Matsumoto Takehiro , Nakayama Takeo , Kita Kiyoshi , Hirayama Kenji
Published: February 2024

Background

Although the Philippines targets malaria elimination by 2030, it remains to be a disease that causes considerable morbidity in provinces that report malaria. Pregnant women residing in endemic areas are a vulnerable population, because in addition to the risk of developing severe malaria, their pregnancy is not followed through, and the outcome of their pregnancy is unknown. This study determined the utility of real-world data integrated with disease surveillance data set as real-world evidence of pregnancy and delivery outcomes in areas endemic for malaria in the Philippines.

Methods

For the period of 2015 to 2019, electronic data sets of malaria surveillance data and Ospital ng Palawan hospital admission log of pregnant women residing in the four selected barangays of Rizal, Palawan were merged using probabilistic linkage. The source data for record linkage were first and last names, birth date, and address as the mutual variable. The data used for characteristics of the pregnant women from the hospital data set were admission date, discharge date, admitting and final diagnosis and body weight on admission. From the malaria surveillance data these were date of consultation, and malaria parasite species. The Levenshtein distance formula was used for a fuzzy string-matching algorithm. Chi-square test, and Mann–Whitney U test were used to compare the means of the two data sets.

Results

The prevalence of pregnant women admitted to the tertiary referral hospital, Ospital ng Palawan, was estimated to be 8.34/100 overall, and 11.64/100 from the four study barangays; that of malaria during pregnancy patients was 3.45/100 and 2.64/100, respectively. There was only one true-positive matched case from 238 women from the hospital and 54 women from the surveillance data sets. The overall Levenshstein score was 97.7; for non-matched cases, the mean overall score was 36.6 (35.6–37.7). The matched case was a minor who was hospitalized for severe malaria. The outcome of her pregnancy was detected from neither data set but from village-based records.

Conclusions

This proof-of-concept study demonstrated that probabilistic record linkage could match real-world data in the Philippines with further validation required. The study underscored the need for more integrated and comprehensive database to monitor disease intervention impact on pregnancy and its outcome in the Philippines.