bluuebunny/crossref_metadata_2025 huggingface dataset:
O226: OTD is cytotoxic to A-375 melanoma cells without compromising fibroblast migratory wound healing function – a potential role in perioperative melanoma surgery
Authors: O'Callaghan Stephanie Kate , Foley Cathriona , Redmond Henry Paul
Published: March 2024

Introduction

Melanoma incidence is increasing with 325,000 new cases reported in 2020 worldwide and 57,000 deaths. High recurrence rates are associated with prolonged inflammation and subsequent immunosuppression post-operatively. Surgical adjuvants may play a role in mitigating these adverse immune responses while increasing the cytotoxicity of cancer cells. Our previous research demonstrated anti-inflammatory effects of 1,4,5-oxathiazinane-4,4-dioxide (OTD) on Human Dermal Fibroblasts (HDFs) by the reduction of cytokine production. This study evaluates its cytotoxicity on melanoma cells.

Methods

OTD treatments of 0.25mM, 0.5mM, 0.75mM, 1mM and 1.25mM were applied to A-375 primary melanoma cells in triplicate for 24h and an MTT assay assessed cell viability. The absorbance was measured at 570nm wavelength. Cell viability was expressed as a percentage of the control. Results were compared using one-way analysis of variance (ANOVA) with GraphPad Prism software.

Results

Application of OTD treatments demonstrated a cytotoxic effect on melanoma cells at all concentrations. Relative optical density (OD) value was compared for each concentration against the control. A significant difference in cytotoxicity, relative to untreated control, was observed for each concentration; 56.8% at 0.25mM OTD (p*** = 0.001) and 68 to 71.6% at 0.5mM to 1.25mM OTD (p****<0.001).

Conclusion

OTD induces cytotoxicity in primary melanoma cells at all concentrations. Whereas our previous research demonstrated at 0.75mM it reduced inflammatory cytokine production in HDFs without adversely affecting migration. Therefore, OTD as a surgical adjuvant has the potential to be cytotoxic towards primary melanoma cells, reduce HDF inflammation and preserve migratory wound healing function.
O198: Cytosponge: Innovative technology in Barrett’s oesophagus surveillance
Authors: Khan Saadia , Brown Ayla , Ghoneima Ahmed , Bonner Clare , Farrah Nima , Hammett Felix , Sowemimo Sinmidele , Asarbakhsh Mariam , Saha Arin
Published: March 2024

Introduction

British Society of Gastroenterology guidance recommends oesophagogastroduodenoscopy (OGD) for Barrett’s oesophagus surveillance with quandrantic biopsies for every 2cm length of Barrett’s. The Covid pandemic led to delays in Barrett's surveillance and prolongation of surveillance intervals. This study assessed the potential role of Cytosponge, a novel cytology sampling device, in Barrett's surveillance.

Methodology

All patients due Barrett's surveillance in 2022/23 were identified and screened to assess suitability for Cytosponge. Cytology results and associated early clinical outcomes were assessed.

Results

193 patients (77%) were suitable for Cytosponge, and 175 of these (90%) did not require OGD. 18 patients (10%) required urgent OGD for inadequate cytology samples (3), cellular atypia (8), aberrant p53 (3) or dysplasia (4). 2 patients had high grade dysplasia on subsequent OGD, successfully treated with radiofrequency ablation. No diagnosis of oesophago-gastric cancer was made during the follow-up period. By July 2023, 282 patients with Barrett’s oesophagus had completed Cytosponge assessment; minimum follow-up was 4 months and no patients had developed ‘inter-test’ malignancy.

Conclusion

These data are promising and suggest that endoscopy and biopsy may not be required for all Barrett’s surveillance. Cytology samples alone may be sufficient to assess for epithelial dysplastic and neoplastic change in Barrett’s surveillance, with judicious utilisation of endoscopy resources where indicated and necessary. Patients who received a Cytosponge in 2022 will be due for endoscopic surveillance in 2024 – these data will provide valuable additional information about the role of Cytosponge in Barrett’s surveillance and whether endoscopy can be replaced altogether.
O105: Evaluating Surgical Approaches in Non-Small Cell Lung Cancer: Lobectomy vs Sublobar Resection
Authors: Faruqi Duaa , Faruqi Azn , Omran Kareem , Salmasi Yousuf , Asadi Nizar
Published: March 2024

Background

Lung Cancer remains the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Lobectomy has long been regarded as the gold-standard treatment for early-stage NSCLC. A shifting paradigm towards lung-sparing procedures such as sublobar resection, may benefit patients with limited respiratory reserve or high comorbidity index. This study aims to compare survival outcomes between patients undergoing lobectomy and sublobar resection.

Methods

This was a tertiary retrospective cohort study comparing disease-free survival (DFS), overall survival (OS) and postoperative outcomes in lobectomy and sublobar patients between 2013 and 2023 (n=3983). Propensity matched analysis was employed to adjust for treatment selection bias, calculated using a logistic regression model and incorporated eight covariates (n=528). Baseline, post-operative, and survival data were extracted from the hospital database. Comparison of baseline and post-operative characteristics involved Wilcoxon rank sum test, Fisher’s exact test and Pearson’s Chi-squared test. Kaplan Meier estimates and Multivariate Cox Regression were used to evaluate survival. p<0.05 was considered significant.

Results

No significant inter-cohort differences were observed in either DFS (log-rank p=0.32), OS (log-rank p=0.47), or 90-day mortality (log-rank p=0.78). Sublobar resection exhibited shorter post-operative length of stay (p<0.05). Conversely, both approaches demonstrated comparable resection margins and complication rates. Significant predictors of survival were age, gender and low Eastern Cooperative Oncology Group (ECOG) performance status (p<0.05).

Conclusion

These findings further support the non-inferiority of sublobar resection to lobectomy for stage 1 lung cancer. Additionally, improved perioperative outcomes may make sublobar resection more desirable for higher risk patients.
O113: Predictors of textbook outcome following oesophagogastric cancer surgery
Authors: Velayudham Ganesh , Dermanis Alexander , Kamarajah Sivesh , Griffiths Ewen
Published: March 2024

Textbook outcome (TO) is a multidimensional composite measure representing an ideal perioperative course, which has been utilised to assess the quality of care in oesophagogastric cancer surgery. We aim to determine TO rates among oesophagogastric cancer patients in a UK tertiary centre, investigate predictors of TO attainment, and evaluate the relationship between TO and survival. A retrospective analysis of a prospectively collected departmental database between 2006-2021 was conducted. Patients that underwent radical oesophagogastric cancer surgery with curative intent were included. TO attainment required margin-negative resection, adequate lymphadenectomy, uncomplicated postoperative course, and no hospital readmission. Predictors of TO were investigated using multivariable logistic regression. The association between TO and survival was evaluated using Kaplan-Meier analysis and Cox regression modelling. 667 oesophageal cancer and 312 gastric cancer patients were included. TO was achieved in 35.1% of oesophagectomy patients and 51.3% of gastrectomy patients. Several factors were independently associated with a low likelihood of TO attainment: T3 stage (OR:0.41, 95% CI [0.22-0.79], p=0.008) and T4 stage (OR:0.26, 95% CI [0.08-0.72], p=0.013) in the oesophagectomy cohort and high BMI (OR:0.93, 95% CI [0.88-0.98], p=0.011) in the gastrectomy cohort. TO attainment was associated with greater overall survival in oesophagectomy and gastrectomy cohorts, however, it was not associated with recurrence-free survival in the gastrectomy cohort. TO is a useful multidimensional quality improvement metric that can be utilised to compare surgical quality between centres and investigate patients at risk of TO failure. Implementation of preoperative care measures can improve rates of TO and long-term survival.
P34: The prognostic value of pre-treatment sarcopenia in overall survival in head and neck cancer patients: A systematic review
Authors: Syziu Anxhela , Schache Andrew
Published: March 2024

Background

This study aims to determine the prognostic value of pre-treatment sarcopenia, defined radiologically at the cervical (C3) or lumbar (L3) region, in head and neck (HNC) adult patient population undergoing treatment with curative intention.

Methods

A systematic search in the PubMed and Scopus databases was performed before February 2022. The inclusion criteria applied were adult patients with locally advanced HNC, sarcopenia defined radiologically at the C3 and/or L3 level, and patients receiving primary treatment with curative intent. The certainty of study evidence was assessed using the ROBINS-I scale, the Cochrane method for assessing bias in non-randomised trials.

Results

Twenty-six studies were included in this review, totalling 6395 adult patients with HNC. It was evident that pre-treatment sarcopenia was associated with worse overall survival outcomes in 22 out of 26 (85%) studies across all the treatment modalities with curative intent. In addition, the gender-specific skeletal muscle index (SMI) sarcopenic cut-off value of <52.4 cm2/m2 for men and <38.5 cm2/m2 for women, was significantly associated with worse OS compared to other cut-off values seen in a minority of studies.

Conclusions

Despite the retrospective design of the studies and inconsistency in SMI cut-off values, these findings suggest that sarcopenia is a strong prognostic factor of overall survival in HNC patients undergoing primary curative treatment. The clinical implications of these findings suggest that sarcopenia evaluation is a good prognostic marker in the HNC population. Future nutritional interventional studies might focus on reversing the muscle loss and improving the overall outcomes in identified sarcopenic individuals.
P240: Sarcopenia of the lower limb on Magnetic Resonance Imaging in patients with Diabetes Mellitus – a systematic review
Authors: Ahmad Manal , Mohamed Abdulla , Amiras Dimitri , Davies Alun , Shalhoub Joseph
Published: March 2024

Introduction

Sarcopenia is defined by low measures of muscle quantity and quality and physical performance. Accelerated sarcopenic changes in diabetic patients leads to biomechanical changes in the foot and limb loss.

Aim

To systematically review the literature on Magnetic Resonance Imaging (MRI) and sarcopenia in the lower limb in patients with diabetes.

Methods

A literature review was conducted in accordance with PRISMA guidelines. Embase and Medline databases were searched with Ovid interface, as well as Pubmed and Cochrane. The grey literature was also reviewed on ClinicalTrials.gov, WHO international clinical trials registry platform, Cochrane library and the NIHR journals library and ProQuest. The MeSH terms “sarcopenia” AND “diabetes mellitus” AND “magnetic resonance imaging” were employed in the primary search string. The articles were reviewed by two independent reviewers.

Results

874 studies were screened. 20 articles were included in the final review. Methods of measurement included cross sectional area measurements, stereological muscle measurements, muscle volume estimation, adipose infiltration, signal intensity cut-off, Goutallier grading, semiquantitative 5-point scale. Reduction in cross-sectional area and volumes and greater intramuscular fat infiltration was noted in patients with diabetes Sarcopenia ++ in Diabetic polyneuropathy (DPN) compared to non-diabetic and diabetic but non-DPN counterparts. MRI findings correlate with neuropathy disability scores and physical tests. Single study using a semi-automated process to measure sarcopenia.

Conclusion

MRI has its merit in providing accurate and detailed information on skeletal muscle volume and assessment of fat infiltration in muscle. This is relevant to reducing complications associated with changes in the biomechanics of the foot.
General dermatology and dermatology in primary healthcare
Authors: Kaur Amreeta , Nixon Rosemary
Published: March 2024

A 24-year-old male tiler with bilateral hand dermatitis was referred for assessment and patch testing. His rash was aggravated by contact with cement and by latex gloves.
Elephantiasis nostras verrucosa of a limb stump: is there room for dermoscopy?
Authors: Marino Andrea , Baffa Maria Efenesia , Grandi Vieri , Salvini Camilla , Tinunin Luca , Difonzo Elisa Margherita , Francalanci Stefano
Published: March 2024

Elephantiasis nostras verrucosa (ENV) is a rare and dramatic sequela of chronic nonfilarial lymphoedema. Here we would like to share a case of ENV that appeared as a late complication of limb amputation.
Ultraviolet light and eyelash extensions: does convenience outweigh theoretical risk?
Authors: O’Malley Seán , Feighery Cliona
Published: March 2024

Recent newspaper articles have attracted attention to the growing use of ultraviolet (UV) lamps in the fixation of eyelash extensions. This practice involves a polymer that acts as an adhesive when exposed briefly to UV light and sets rapidly, bonding the extension to the eyelash. Although industry statements attest to the safety of these systems, the nature of this process raises significant concerns.
Multipattern graph convolutional network-based autism spectrum disorder identification
Authors: Zhou Wenhao , Sun Mingxiang , Xu Xiaowen , Ruan Yudi , Sun Chenhao , Li Weikai , Gao Xin
Published: March 2024

The early diagnosis of autism spectrum disorder (ASD) has been extensively facilitated through the utilization of resting-state fMRI (rs-fMRI). With rs-fMRI, the functional brain network (FBN) has gained much attention in diagnosing ASD. As a promising strategy, graph convolutional networks (GCN) provide an attractive approach to simultaneously extract FBN features and facilitate ASD identification, thus replacing the manual feature extraction from FBN. Previous GCN studies primarily emphasized the exploration of topological simultaneously connection weights of the estimated FBNs while only focusing on the single connection pattern. However, this approach fails to exploit the potential complementary information offered by different connection patterns of FBNs, thereby inherently limiting the performance. To enhance the diagnostic performance, we propose a multipattern graph convolution network (MPGCN) that integrates multiple connection patterns to improve the accuracy of ASD diagnosis. As an initial endeavor, we endeavored to integrate information from multiple connection patterns by incorporating multiple graph convolution modules. The effectiveness of the MPGCN approach is evaluated by analyzing rs-fMRI scans from a cohort of 92 subjects sourced from the publicly accessible Autism Brain Imaging Data Exchange database. Notably, the experiment demonstrates that our model achieves an accuracy of 91.1% and an area under ROC curve score of 0.9742. The implementation codes are available at https://github.com/immutableJackz/MPGCN.
“Walking selectivity” in the occipital place area in 8-year-olds, not 5-year-olds
Authors: Jung Yaelan , Hsu Debbie , Dilks Daniel D
Published: March 2024

A recent neuroimaging study in adults found that the occipital place area (OPA)—a cortical region involved in “visually guided navigation” (i.e. moving about the immediately visible environment, avoiding boundaries, and obstacles)—represents visual information about walking, not crawling, suggesting that OPA is late developing, emerging only when children are walking, not beforehand. But when precisely does this “walking selectivity” in OPA emerge—when children first begin to walk in early childhood, or perhaps counterintuitively, much later in childhood, around 8 years of age, when children are adult-like walking? To directly test these two hypotheses, using functional magnetic resonance imaging (fMRI) in two groups of children, 5- and 8-year-olds, we measured the responses in OPA to first-person perspective videos through scenes from a “walking” perspective, as well as three control perspectives (“crawling,” “flying,” and “scrambled”). We found that the OPA in 8-year-olds—like adults—exhibited walking selectivity (i.e. responding significantly more to the walking videos than to any of the others, and no significant differences across the crawling, flying, and scrambled videos), while the OPA in 5-year-olds exhibited no walking selectively. These findings reveal that OPA undergoes protracted development, with walking selectivity only emerging around 8 years of age.
Public–Private engagement and health systems resilience in times of health worker strikes: a Ghanaian case study
Authors: Buabeng-Baidoo Bettina , Olivier Jill
Published: March 2024

In low and middle-income countries like Ghana, private providers, particularly the grouping of faith-based non-profit health providers networked by the Christian Health Association of Ghana (CHAG), play a crucial role in maintaining service continuity during health worker strikes. Poor engagement with the private sector during such strikes could compromise care quality and impose financial hardships on populations, especially the impoverished. This study delves into the engagement between CHAG and the Government of Ghana (GoG) during health worker strikes from 2010 to 2016, employing a qualitative descriptive and exploratory case study approach. By analysing evidence from peer-reviewed literature, media archives, grey literature and interview transcripts from a related study using a qualitative thematic analysis approach, this study identifies health worker strikes as a persistent chronic stressor in Ghana. Findings highlight some system-level interactions between CHAG and GoG, fostering adaptive and absorptive resilience strategies, influenced by CHAG’s non-striking ethos, unique secondment policy between the two actors and the presence of a National Health Insurance System. However, limited support from the government to CHAG member facilities during strikes and systemic challenges with the National Health Insurance System pose threats to CHAG’s ability to provide quality, affordable care. This study underscores private providers’ pivotal role in enhancing health system resilience during strikes in Ghana, advocating for proactive governmental partnerships with private providers and joint efforts to address human-resource-related challenges ahead of strikes. It also recommends further research to devise and evaluate effective strategies for nations to respond to strikes, ensuring preparedness and sustained quality healthcare delivery during such crises.
The Rumble of a Locomotive, Traumatizing Screams, and Mortal Dance: Firsthand Poetic Testimonies Haunted by the Sounds of the Holocaust
Authors: Lisak-Gębala Dobrawa
Published: March 2024

This article analyzes the relationship between Holocaust trauma and firsthand poetic testimonies through the lens of literary acoustics. Specifically, it explores the work of three Jewish poets, Stanisław Wygodzki, Ilona Karmel, and Stanisław Jerzy Lec, who wrote in Polish of their tragic experiences in the Nazi camps. The article compares these poetical works to involuntary flashbacks composed of haunting sounds that recall trauma and violence and applies the concept of thantosonics to these auditory memories. In particular, the author notes the importance of trains as not only an auditory motif, but also as the metrical underpinning of the verses, and as a point of juxtaposition against sounds of innocence in the Holocaust soundscape. Furthermore, the article also explores the imagery of folk dance as a kind of danse macabre, as well as instances of involuntary sonic identification with the perpetrators.
Genome-wide variants and optimal allelic combinations for citric acid in tomato
Authors: Gai Wenxian , Yuan Liangdan , Yang Fan , Ahiakpa John Kojo , Li Fangman , Ge Pingfei , Zhang Xingyu , Tao Jinbao , Wang Fei , Yang Yang , Zhang Yuyang
Published: March 2024

Citric acid (CA) plays a crucial role as a fruit flavor enhancer and serves as a mediator in multiple metabolic pathways in tomato fruit development. Understanding factors influencing CA metabolism is essential for enhancing fruit flavor and CA-mediated biological processes. The accumulation of CA, however, is influenced by a complex interplay of genetic and environmental factors, leading to challenges in accurately predicting and regulating its levels. In this study, we conducted a genome-wide association study (GWAS) on CA, employing six landmark models based on genome-wide variations including structural variants, insertions and deletions, and single nucleotide polymorphisms. The identification of 11 high-confidence candidate genes was further facilitated by leveraging linkage disequilibrium and causal variants associated with CA. The transcriptome data from candidate genes were examined, revealing higher correlations between the expression of certain candidate genes and changes in CA metabolism. Three CA-associated genes exerted a positive regulatory effect on CA accumulation, while the remaining genes exhibited negative impacts based on gene cluster and correlation analyses. The CA content of tomatoes is primarily influenced by improvement sweeps with minimal influence from domestication sweeps in the long-term breeding history, as evidenced by population differentiation and variants distribution. The presence of various causal variants within candidate genes is implicated in the heterogeneity of CA content observed among the tomato accessions. This observation suggests a potential correlation between the number of alternative alleles and CA content. This study offers significant function-based markers that can be utilized in marker-assisted breeding, thereby enhancing their value and applicability.
Acute type A aortic dissection features and outcomes in octogenarians: a propensity score analysis
Authors: Park You Kyeong , Lee Jae Hang , Kim Kang Min , Jung Joon Chul , Chang Hyoung Woo , Kim Dong Jung , Kim Jun Sung , Lim Cheong , Park Kay-Hyun
Published: March 2024

OBJECTIVES

The clinical characteristics and early outcomes of surgical repair in octogenarians with acute type A aortic dissection were compared with those in nonoctogenarians.

METHODS

All patients who underwent emergency surgical repair for acute type A aortic dissection in our institution between 2003 and 2022 were included in this study. The patients were divided into an octogenarian group and a nonoctogenarian group. The patients in the 2 groups were propensity score matched at a ratio of 1:1. Before matching, the baseline characteristics were compared between 2 groups. The major complication and 30-day mortality rates were compared in the matched population.

RESULTS

A total of 495 patients were screened, and 471 were included in the analysis, with 48 in the octogenarian group and 423 in the nonoctogenarian group. Before matching, DeBakey type II dissection was significantly more prevalent in the octogenarians (42% vs 14% in the octogenarians and nonoctogenarians, respectively, P < 0.001). Additionally, intramural haematomas (39.6% vs 14.4%, P < 0.001) were more prevalent in the octogenarians. However, severe aortic regurgitation (4.2% vs 15.4%, P = 0.046) and root enlargement (0% vs 13.7%, P = 0.009) were less prevalent in the octogenarians. After matching (36 pairs), the incidence of postoperative delirium was higher in the octogenarians (56% vs 25%, P = 0.027). However, there were no significant differences in 30-day and in-hospital mortality rates, intensive care unit stay or major complications, including stroke, paraplegia, respiratory complications, mediastinitis and haemodialysis.

CONCLUSIONS

The octogenarians with acute type A aortic dissection had higher incidences of DeBakey type II dissection and intramural haematomas and lower incidences of severe aortic regurgitation and aortic root enlargement than the nonoctogenarians. Being an octogenarian was not associated with an increased risk of early major complications or mortality after surgery for acute type A aortic dissection.
Early and long-term outcomes following redo mitral valve surgery in patients with prior minimally invasive mitral valve surgery
Authors: Schumacher Katja , Marin Cuartas Mateo , de la Cuesta Manuela , Noack Thilo , Kiefer Philipp , Leontyev Sergey , Borger Michael A , Vollroth Marcel , Misfeld Martin
Published: March 2024

OBJECTIVES

The frequency of minimally invasive mitral valve surgery (MVS) has steadily increased over the last decades and therefore surgeons are now encountering an increasing number of patients requiring mitral valve (MV) reoperations post-minimally invasive MVS. The aim of this study was to analyse the early postoperative outcomes and the long-term survival in patients who undergo reoperative MVS following previous minimally invasive surgery.

METHODS

Patients who underwent redo MVS following prior minimally invasive MVS between January 2002 and December 2021 were included in our analysis. Study data were prospectively collected and retrospectively analysed. The primary outcomes were 30-day mortality and long-term survival.

RESULTS

Among the 187 included patients, 34 (18.2%) underwent repeat MV repair and 153 (81.8%) MV replacement. The median age was 66 years (interquartile range 56–74) and 80 (42.8%) patients were female. Redo MVS was performed through median sternotomy in 169 patients (90.4%). A total of 77 (41.2%) patients had additional concomitant procedures. The median intensive care unit stay was 1 day (1–5). The 30-day mortality was 6.4% (12/187). Estimated survival at 5 and 12 years was 61.8% and 38.3%, respectively. Preoperative stroke (hazard ratio 3.28, 95% confidence interval 1.37–7.85, P = 0.007) as well as infective endocarditis (hazard ratio 1.85; 95% confidence interval 1.09-3.11, P = 0.021) were independent predictors of long-term mortality.

CONCLUSIONS

Redo MVS following prior minimally invasive MVS can be performed safely with low early perioperative mortality and acceptable long-term survival. Preoperative stroke, infective endocarditis and concomitant tricuspid valve surgery are independent predictors of long-term mortality.
Corynebacterium diphtheriae and Corynebacterium ulcerans: development of EUCAST methods and generation of data on which to determine breakpoints
Authors: Berger Anja , Badell Edgar , Åhman Jenny , Matuschek Erika , Zidane Nora , Kahlmeter Gunnar , Sing Andreas , Brisse Sylvain
Published: March 2024

Background

Evidence-based clinical susceptibility breakpoints have been lacking for antimicrobial agents used for diphtheria.

Objectives

We aimed to evaluate broth microdilution and disc diffusion methods and create a dataset of MIC values and inhibition zone diameters (ZDs) from which breakpoints could be determined.

Methods

We included 400 recent clinical isolates equally distributed by species (Corynebacterium diphtheriae and Corynebacterium ulcerans) and by national surveillance programmes (France and Germany). Non-duplicate toxigenic and non-toxigenic isolates were chosen to enable the inclusion of a diversity of susceptibility levels for the 13 agents tested. Broth microdilution and disc diffusion, using EUCAST methodology for fastidious organisms, were used.

Results

The distributions of MIC and ZD values were largely in agreement among methods and countries. Breakpoints to allow categorization of WT isolates as susceptible, i.e. susceptible (S) or susceptible, increased exposure (I) were determined for 12 agents. The data supported a breakpoint for benzylpenicillin and amoxicillin of resistant (R) > 1 mg/L since WT isolates were inhibited by 1 mg/L or less. WT isolates were categorized as I (S ≤ 0.001 mg/L) for benzylpenicillin, emphasizing the need for increased exposure, and S (S ≤ 1 mg/L) for amoxicillin. Erythromycin breakpoints were set at S ≤ 0.06 mg/L and R > 0.06 mg/L. The corresponding ZD breakpoints were determined for all agents except amoxicillin, for which categorization was based on benzylpenicillin results.

Conclusions

This work provided a large set of antimicrobial susceptibility data for C. diphtheriae and C. ulcerans, using a harmonized methodology. The dataset allowed EUCAST and experts in the diphtheria field to develop evidence-based breakpoints in January 2023.
Factors influencing voriconazole plasma level in intensive care patients
Authors: Hinze Christopher Alexander , Fuge Jan , Grote-Koska Denis , Brand Korbinian , Slevogt Hortense , Cornberg Markus , Simon Susanne , Joean Oana , Welte Tobias , Rademacher Jessica
Published: March 2024

Background

In clinical routine, voriconazole plasma trough levels (Cmin) out of target range are often observed with little knowledge about predisposing influences.

Objectives

To determine the distribution and influencing factors on voriconazole blood levels of patients treated on intensive- or intermediate care units (ICU/IMC).

Patients and methods

Data were collected retrospectively from patients with at least one voriconazole trough plasma level on ICU/IMC (n = 153) to determine the proportion of sub-, supra- or therapeutic plasma levels. Ordinal logistic regression analysis was used to assess factors hindering patients to reach voriconazole target range.

Results

Of 153 patients, only 71 (46%) reached the target range at the first therapeutic drug monitoring, whereas 66 (43%) patients experienced too-low and 16 (10%) too-high plasma levels. Ordinal logistic regression analysis identified the use of extra corporeal membrane oxygenation (ECMO), low international normalized ratio (INR) and aspartate-aminotransferase (AST) serum levels as predictors for too-low plasma levels.

Conclusion

Our data highlight an association of ECMO, INR and AST levels with voriconazole plasma levels, which should be considered in the care of critically ill patients to optimize antifungal therapy with voriconazole.
An interpretable predictive deep learning platform for pediatric metabolic diseases
Authors: Javidi Hamed , Mariam Arshiya , Alkhaled Lina , Pantalone Kevin M , Rotroff Daniel M
Published: March 2024

Objectives

Metabolic disease in children is increasing worldwide and predisposes a wide array of chronic comorbid conditions with severe impacts on quality of life. Tools for early detection are needed to promptly intervene to prevent or slow the development of these long-term complications.

Materials and Methods

No clinically available tools are currently in widespread use that can predict the onset of metabolic diseases in pediatric patients. Here, we use interpretable deep learning, leveraging longitudinal clinical measurements, demographical data, and diagnosis codes from electronic health record data from a large integrated health system to predict the onset of prediabetes, type 2 diabetes (T2D), and metabolic syndrome in pediatric cohorts.

Results

The cohort included 49 517 children with overweight or obesity aged 2-18 (54.9% male, 73% Caucasian), with a median follow-up time of 7.5 years and mean body mass index (BMI) percentile of 88.6%. Our model demonstrated area under receiver operating characteristic curve (AUC) accuracies up to 0.87, 0.79, and 0.79 for predicting T2D, metabolic syndrome, and prediabetes, respectively. Whereas most risk calculators use only recently available data, incorporating longitudinal data improved AUCs by 13.04%, 11.48%, and 11.67% for T2D, syndrome, and prediabetes, respectively, versus models using the most recent BMI (P < 2.2 × 10–16).

Discussion

Despite most risk calculators using only the most recent data, incorporating longitudinal data improved the model accuracies because utilizing trajectories provides a more comprehensive characterization of the patient’s health history. Our interpretable model indicated that BMI trajectories were consistently identified as one of the most influential features for prediction, highlighting the advantages of incorporating longitudinal data when available.
Leveraging large language models for generating responses to patient messages—a subjective analysis
Authors: Liu Siru , McCoy Allison B , Wright Aileen P , Carew Babatunde , Genkins Julian Z , Huang Sean S , Peterson Josh F , Steitz Bryan , Wright Adam
Published: March 2024

Objective

This study aimed to develop and assess the performance of fine-tuned large language models for generating responses to patient messages sent via an electronic health record patient portal.

Materials and Methods

Utilizing a dataset of messages and responses extracted from the patient portal at a large academic medical center, we developed a model (CLAIR-Short) based on a pre-trained large language model (LLaMA-65B). In addition, we used the OpenAI API to update physician responses from an open-source dataset into a format with informative paragraphs that offered patient education while emphasizing empathy and professionalism. By combining with this dataset, we further fine-tuned our model (CLAIR-Long). To evaluate fine-tuned models, we used 10 representative patient portal questions in primary care to generate responses. We asked primary care physicians to review generated responses from our models and ChatGPT and rated them for empathy, responsiveness, accuracy, and usefulness.

Results

The dataset consisted of 499 794 pairs of patient messages and corresponding responses from the patient portal, with 5000 patient messages and ChatGPT-updated responses from an online platform. Four primary care physicians participated in the survey. CLAIR-Short exhibited the ability to generate concise responses similar to provider’s responses. CLAIR-Long responses provided increased patient educational content compared to CLAIR-Short and were rated similarly to ChatGPT’s responses, receiving positive evaluations for responsiveness, empathy, and accuracy, while receiving a neutral rating for usefulness.

Conclusion

This subjective analysis suggests that leveraging large language models to generate responses to patient messages demonstrates significant potential in facilitating communication between patients and healthcare providers.
Levodopa attenuates the feed intake reduction caused by ergot alkaloids in cattle
Authors: Valente Eriton E L , Klotz James L , Markmann Ryana C , Trotta Ronald J , Edwards J Lannett , May John B , Harmon David L
Published: March 2024

Consumption of ergot alkaloids from endophyte-infected tall fescue results in losses to the livestock industry in many countries and a means to mitigate these losses is needed. The objective of this study was to evaluate intra-abomasal infusion of the dopamine precursor, levodopa (L-DOPA), on dopamine metabolism, feed intake, and serum metabolites of steers exposed to ergot alkaloids. Twelve Holstein steers (344.9 ± 9.48 kg) fitted with ruminal cannula were housed with a cycle of heat challenge during the daytime (32 °C) and thermoneutral at night (25 °C). The steers received a basal diet of alfalfa cubes containing equal amounts of tall fescue seed composed of a mixture of endophyte-free (E−) or endophyte-infected tall fescue seeds (E+) equivalent to 15 µg ergovaline/kg body weight (BW) for 9 d followed by intra-abomasal infusion of water (L-DOPA−) or levodopa (L-DOPA+; 2 mg/kg BW) for an additional 9 d. Afterward, the steers were pair-fed for 5 d to conduct a glucose tolerance test. The E+ treatment decreased (P = 0.005) prolactin by approximately 50%. However, prolactin increased (P = 0.050) with L-DOPA+. Steers receiving E+ decreased (P < 0.001) dry matter intake (DMI); however, when supplemented with L-DOPA+ the decrease in DMI was less severe (L-DOPA × E, P = 0.003). Also, L-DOPA+ infusion increased eating duration (L-DOPA × E, P = 0.012) when steers were receiving E+. The number of meals, meal duration, and intake rate were not affected (P > 0.05) by E+ or L-DOPA+. The L-DOPA+ infusion increased (P < 0.05) free L-DOPA, free dopamine, total L-DOPA, and total dopamine. Conversely, free epinephrine and free norepinephrine decreased (P < 0.05) with L-DOPA+. Total epinephrine and total norepinephrine were not affected (P > 0.05) by L-DOPA+. Ergot alkaloids did not affect (P > 0.05) circulating free or total L-DOPA, dopamine, or epinephrine. However, free and total norepinephrine decreased (P = 0.046) with E+. Glucose clearance rates at 15 to 30 min after glucose infusion increased with L-DOPA+ (P < 0.001), but not with E+ (P = 0.280). Administration of L-DOPA as an agonist therapy to treat fescue toxicosis provided a moderate increase in DMI and eating time and increased plasma glucose clearance for cattle dosed with E+ seed.
Interactions between γδ T cells and neutrophils in cancer: knowns and unknowns
Authors: Hao Jianlei , Granot Zvi
Published: March 2024

The tumor microenvironment provides a unique opportunity to gain insight into the relationship and crosstalk between different cell types. In this context, little is known about the interaction between γδ T cells and neutrophils, which are innate immune cells abundant in the tumor microenvironment. Interestingly, both γδ T cells and neutrophils are heterogeneous, may play diverse regulatory roles, and have been shown to have both protumor and antitumor functions. In this editorial, we discuss recent advances in the understanding of interplay between γδ T cells and neutrophils in cancer and provide insights and future directions highlighting the role these interactions may play in cancer.
Changing tactics in negotiating refugee assistance policies and practices: A case study of an asylum seeker-led organization in Hong Kong
Authors: Lam Ka Wang Kelvin
Published: March 2024

This article examines the tactical changes made by the asylum seeker community in Hong Kong in negotiating local refugee assistance policies and practices. The analysis presented in this paper is grounded in my ethnographic fieldwork with an asylum seeker-led organization and supplemented by archival study and informal interviews. In recent years, the asylum seeker community has adopted a pragmatic approach to advocacy, increasingly asking the local community for support in providing humanitarian aid rather than calling for changes to the assistance system, a tactic that this group used in the past. I argue that these tactical changes cannot be separated from the social and political contexts of Hong Kong. The presence of stimulating events, particularly those involving local and global refugee and migrant communities, the space available for voicing dissent, and the level of institutional responsiveness, all affect how the asylum seeker community in Hong Kong participates in policy discussions.
Retractions in arts and humanities: an analysis of the retraction notices
Authors: Heibi Ivan , Peroni Silvio
Published: March 2024

The aim of this work is to understand the retraction phenomenon in the arts and humanities domain through an analysis of the retraction notices—formal documents stating and describing the retraction of a particular publication. The retractions and the corresponding notices are identified using the data provided by Retraction Watch. Our methodology for the analysis combines a metadata analysis and a content analysis (mainly performed using a topic modelling process) of the retraction notices. Considering 343 cases of retraction, we found that many retraction notices are neither identifiable nor findable. In addition, these were not always separated from the original papers, introducing ambiguity in understanding how these notices were perceived by the community (i.e. cited). Also, we noticed that there is no systematic way to write a retraction notice. Indeed, some retraction notices presented a complete discussion of the reasons for retraction, while others tended to be more direct and succinct. We have also reported many notices having similar text while addressing different retractions. We think a further study with a larger collection should be done using the same methodology to confirm and investigate our findings further.
E-XQR-30: The evolution of Mg ii, C ii, and O i across 2 < z < 6
Authors: Sebastian Alma Maria , Ryan-Weber Emma , Davies Rebecca L , Becker George D , Keating Laura C , D’Odorico Valentina , Meyer Romain A , Bosman Sarah E I , Cupani Guido , Kulkarni Girish , Haehnelt Martin G , Lai Samuel , Eilers Anna–Christina , Bischetti Manuela , Gallerani Simona
Published: March 2024

Intervening metal absorbers in quasar spectra at z > 6 can be used as probes to study the chemical enrichment of the Universe during the Epoch of Reionization. This work presents the comoving line densities (dn/dX) of low-ionization absorbers, namely, Mg ii (2796 Å), C ii (1334 Å), and O  i (1302 Å) across 2 < z < 6 using the E-XQR-30 metal absorber catalogue prepared from 42 XSHOOTER quasar spectra at 5.8 < z < 6.6. Here, we analyse 280 Mg ii (1.9 < z < 6.4), 22 C ii (5.2 < z < 6.4), and 10 O i (5.3 < z < 6.4) intervening absorbers, thereby building up on previous studies with improved sensitivity of 50 per cent completeness at an equivalent width of W > 0.03 Å. For the first time, we present the comoving line densities of 131 weak (W < 0.3 Å) intervening Mg ii absorbers at 1.9 < z < 6.4 which exhibit constant evolution with redshift similar to medium (0.3 < W < 1.0 Å) absorbers. However, the cosmic mass density of Mg ii – dominated by strong Mg ii systems – traces the evolution of global star formation history from redshift 1.9 to 5.5. E-XQR-30 also increases the absorption path-length by a factor of 50 per cent for C ii and O i whose line densities show a rising trend towards z > 5, in agreement with previous works. In the context of a decline in the metal enrichment of the Universe at z > 5, the overall evolution in the incidence rates of absorption systems can be explained by a weak – possibly soft fluctuating – ultraviolet background. Our results, thereby, provide evidence for a late reionization continuing to occur in metal-enriched and therefore, biased regions in the Universe.
POLARIS: A phase 2 trial of encorafenib plus binimetinib evaluating high-dose and standard-dose regimens in patients with BRAF V600-mutant melanoma with brain metastasis
Authors: Menzies Alexander M , Long Georgina V , Kohn Amiee , Tawbi Hussein , Weber Jeffrey , Flaherty Keith , McArthur Grant A , Ascierto Paolo A , Pfluger Yanina , Lewis Karl , Tsai Katy K , Hamid Omid , Prenen Hans , Fein Luis , Wang Erjian , Guenzel Carolin , Zhang Fan , Kleha Joseph F , di Pietro Alessandra , Davies Michael A
Published: March 2024

Background

POLARIS (phase 2 [ph2]; NCT03911869) evaluated encorafenib (BRAF inhibitor) in combination with binimetinib (MEK1/2 inhibitor) in BRAF/MEK inhibitor-naïve patients with BRAF V600-mutant melanoma with asymptomatic brain metastases.

Methods

The safety lead-in (SLI) assessed tolerability for high-dose encorafenib 300 mg twice daily (BID) plus binimetinib 45 mg BID. If the high dose was tolerable in ph2, patients would be randomized to receive high or standard dose (encorafenib 450 mg once daily [QD] plus binimetinib 45 mg BID). Otherwise, standard dose was evaluated as the recommended ph2 dose (RP2D). Patients who tolerated standard dosing during Cycle 1 could be dose escalated to encorafenib 600 mg QD plus binimetinib 45 mg BID in Cycle 2. Safety, efficacy, and pharmacokinetics were examined.

Results

RP2D was standard encorafenib dosing, as >33% of evaluable SLI patients (3/9) had dose-limiting toxicities. Overall, of 13 safety-evaluable patients (10 SLI, 3 ph2), 9 had prior immunotherapy. There were 9 treatment-related adverse events in the SLI and 3 in ph2. Of the SLI efficacy-evaluable patients (n = 10), 1 achieved complete response and 5 achieved partial responses (PR); the brain metastasis response rate (BMRR) was 60% (95% CI: 26.2, 87.8). In ph2, 2 of 3 patients achieved PR (BMRR, 67% [95% CI: 9.4, 99.2]). Repeated encorafenib 300 mg BID dosing did not increase steady-state exposure compared with historical 450 mg QD data.

Conclusions

Despite small patient numbers due to early trial termination, BMRR appeared similar between the SLI and ph2, and the ph2 safety profile appeared consistent with previous reports of standard-dose encorafenib in combination with binimetinib.
Developmental outcomes of preschool children requiring craniosynostosis surgery in Manitoba: a cohort study
Authors: Ripstein Yael , Pylypjuk Christy , Conway Alexandra , Ricci M Florencia
Published: March 2024

Craniosynostosis is a congenital abnormality resulting in the premature fusion of one or more cranial sutures and usually requires surgical correction in the first year of life. While the majority of craniosynostosis cases represent isolated, nonsyndromic defects, approximately 25% are linked to a genetic diagnosis. Craniosynostosis has been associated with developmental delay. Therefore, historically in Manitoba, all children with surgically managed craniosynostosis were referred to the Child Development Clinic (CDC) for developmental assessment. There are currently prolonged wait times for neurodevelopmental assessments at CDC, leading to the need to better prioritize children who require neurodevelopmental assessment. The aim of the study was then to determine the developmental outcomes of preschool children requiring craniosynostosis surgery in Manitoba from July 1, 2016 through December 1, 2021. In this retrospective cohort study, clinical records were reviewed to evaluate the developmental outcomes of patients who were assessed at CDC for surgically managed craniosynostosis. Out of 67 children included in this study, 18% demonstrated global developmental delay, 24% demonstrated mild developmental delay, and 58% were developmentally appropriate across all levels. The presence of a genetic syndrome, multisutural craniosynostosis, and parental socioeconomic status were associated with risk of global developmental delay. The findings of this study suggest that while not all children with craniosynostosis present with developmental delay, those with suspected or confirmed syndromic involvement, multisutural cranyosinostosis, and/or low SES, should be referred for neurodevelopmental evaluation.
Scaling laws for lattice distortions: Application to high entropy alloys
Authors: Wang Zhaowei , Pattamatta A S L Subrahmanyam , Han Jian , Srolovitz David J
Published: March 2024

Lattice distortions are intrinsic features of all solid solution alloys associated with varying atomic radii; this phenomenon facilitates the formation of single-phase solid solutions. Using high-entropy alloys (HEAs), as an example, we investigate the influence of variations in inter-atomic separations for stabilizing and controlling their structural, mechanical, and thermodynamic properties. This is done through a combination of statistical mechanics analysis and molecular dynamics simulations on simplified 2D systems, as well as a 3D crystals with harmonic and anharmonic inter-atomic bonds with varying natural inter-atomic separations. We demonstrate that the impact of this inter-atomic length disorder (representing static lattice distortion) and temperature fluctuations (representing dynamic lattice distortion) on fundamental and universal thermodynamic, structural, and elastic characteristics are similar and can be unified through effective temperature; i.e. a scaling law for HEAs that establishes a relationship between these factors. This scaling law reveals that different HEAs (i.e. varying degrees of local lattice distortions) collapse onto a single curve when plotted against the effective temperature. We demonstrate that lattice distortion significantly enhances the stability of solid solution alloys (relative to phase separation or ordering by effectively increasing the temperature of the system; this stabilization effect is particularly pronounced in HEAs).