bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photochemical inactivation as an alternative method to produce a whole-cell vaccine for uropathogenic
Escherichia coli
(UPEC)
Authors: Westcott Marlena M. , Morse Alexis E. , Troy Gavin , Blevins Maria , Wierzba Thomas , Sanders John W. 
Published: February 2024

ABSTRACT

Uropathogenic
Escherichia coli
(UPEC) is the primary causative agent of lower urinary tract infection (UTI). UTI presents a serious health risk and has considerable secondary implications including economic burden, recurring episodes, and overuse of antibiotics. A safe and effective vaccine would address this widespread health problem and emerging antibiotic resistance. Killed, whole-cell vaccines have shown limited efficacy to prevent recurrent UTI in human trials. We explored photochemical inactivation with psoralen drugs and UVA light (PUVA), which crosslinks nucleic acid, as an alternative to protein-damaging methods of inactivation to improve whole-cell UTI vaccines. Exposure of UPEC to the psoralen drug AMT and UVA light resulted in a killed but metabolically active (KBMA) state, as reported previously for other PUVA-inactivated bacteria. The immunogenicity of PUVA-UPEC as compared to formalin-inactivated UPEC was compared in mice. Both generated high UPEC-specific serum IgG titers after intramuscular delivery. However, using functional adherence as a measure of surface protein integrity, we found differences in the properties of PUVA- and formalin-inactivated UPEC. Adhesion mediated by Type-1 and P-fimbriae was severely compromised by formalin but was unaffected by PUVA, indicating that PUVA preserved the functional conformation of fimbrial proteins, which are targets of protective immune responses.
In vitro
assays indicated that although they retained metabolic activity, PUVA-UPEC lost virulence properties that could negatively impact vaccine safety. Our results imply the potential for PUVA to improve killed, whole-cell UTI vaccines by generating bacteria that more closely resemble their live, infectious counterparts relative to vaccines generated with protein-damaging methods.

IMPORTANCE

Lower urinary tract infection (UTI), caused primarily by uropathogenic
Escherichia coli
, represents a significant health burden, accounting for 7 million primary care and 1 million emergency room visits annually in the United States. Women and the elderly are especially susceptible and recurrent infection (rUTI) is common in those populations. Lower UTI can lead to life-threatening systemic infection. UTI burden is manifested by healthcare dollars spent (1.5 billion annually), quality of life impact, and resistant strains emerging from antibiotic overuse. A safe and effective vaccine to prevent rUTI would address a substantial healthcare issue. Vaccines comprised of inactivated uropathogenic bacteria have yielded encouraging results in clinical trials but improvements that enhance vaccine performance are needed. To that end, we focused on inactivation methodology and provided data to support photochemical inactivation, which targets nucleic acid, as a promising alternative to conventional protein-damaging inactivation methods to improve whole-cell UTI vaccines.
Establishing consensus on nutrition competencies for medicine: a Delphi study
Authors: Lepre Breanna , Mansfield Kylie J , Ray Sumantra , Beck Eleanor J 
Published: February 2024

BackgroundSignificant research, regulatory bodies and even governmental resolutions have identified meaningful nutrition education for medical and other healthcare professionals as a priority. Doctors are well placed to provide nutrition care, yet nutrition education in medicine remains inadequate regardless of country, setting, or year of training. There remains a need to establish an accepted benchmark on nutrition competencies for medicine, as without consensus standards there is little likelihood of uniform adoption.ObjectiveThis study aimed to establish consensus on nutrition competencies using a Delphi process to inform a framework for nutrition education in medicine.MethodsA three-round modified online Delphi survey of experts in healthcare practice, education and training, and experts by experience (service users) was conducted to provide a comprehensive consensus on nutrition competencies for medical practice.ResultsFifty-two experts (15.1% response rate) participated in Round 1, 42 completed Round 2 and 47 completed Round 3. Participants included medical professionals, dietitians, academics working in health professions education and policymakers from Australia, New Zealand, the UK and Northern Ireland. Twenty-seven service users (57.5% response rate) completed the Round 1 questionnaire, 19 completed Round 2 and 16 completed Round 3. By consensus, 25 nutrition competencies for medicine were defined. The service user panel identified an additional seven skills and attributes considered important in the receipt of nutrition care. Competencies that achieved consensus broadly fell into themes of team-based care, communication, professionalism (eg, attributes) and health promotion and disease prevention. This informs broad skills that may be taught in a nutrition context but could be included in other domains.ConclusionsThe findings suggest doctors need the knowledge and skills to consider the findings from nutrition screening and assessment, coordinate nutrition care when an individual may benefit from further assessment or intervention and provide support for advice delivered by other experts as part of a multidisciplinary approach.
Occupational stress and its correlates among healthcare workers of a tertiary level teaching hospital in Kathmandu, Nepal, during COVID-19 pandemic: a cross-sectional study
Authors: Thapa Suchana , Pradhan Pranil Man Singh 
Published: February 2024

BackgroundHealthcare workers experience high job stress, contributing to negative health outcomes and poor patient care. This study aims to assess occupational stress and its associated factors among healthcare workers at a tertiary hospital during COVID-19 pandemic in Kathmandu, Nepal.MethodsA cross-sectional quantitative study was conducted among doctors and nurses in a tertiary hospital. A self-administered questionnaire was used to collect data from 368 participants. Bivariate and multiple linear regression analysis identified the predictors associated with occupational stress.ResultsThe mean occupational stress index score was 149.56±22.01. It was significantly higher among female participants (151.59±19.12 vs 144.2±27.6, p=0.004), married individuals (152.06±19.79 vs 147.01±23.86, p=0.028), those with over 1 year of employment duration (152.17±21.28 vs 145.45±22.60, p=0.004), health workers attending more than four night shift a month (152.30±19.44 vs 135.52±28.45, p<0.001), those working in rotating shift (151.68±21.12 vs 142.17±23.57, p=0.006), those working 48 hours or more per week (152.39±19.28 vs 145.97±24.66, p=0.005), those lacking support from other staff (157.81±18.70 vs 148.17±22.25, p=0.003) and those who consumed alcohol (152.14±21.25 vs 147.18±22.49, p=0.031). Multiple linear regression revealed associations with employment duration over 1 year (β=0.174, p=0.001), rotating shift (β=−0.106, p=0.006), night shifts (β=0.251, p<0.001), working hours of 48 hours or more per week (β=0.175, p=0.001), lack of support from other staff (β=0.130, p=0.010) and low-wealth quintile (β=0.161, p=0.006).ConclusionOccupational stress is associated with employment duration, night shift, rotating shift, working hours, support mechanisms and socioeconomic profile among healthcare workers. There is a crucial need to establish evidence-based actions to prevent occupational stress and promote the overall health of healthcare workers.
Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease
Authors: Sato Tomonori , Furukawa Taiki , Teramachi Ryo , Fukihara Jun , Yamano Yasuhiko , Yokoyama Toshiki , Matsuda Toshiaki , Kataoka Kensuke , Kimura Tomoki , Sakamoto Koji , Ishii Makoto , Kondoh Yasuhiro 
Published: February 2024

BackgroundPulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD.MethodsWe retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed.ResultsAmong 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 20<MPAP<25 mm Hg, and ≥25 mm Hg were 26.2%, 60.4% and 86.4%, respectively. In Cox proportional hazards analyses with adjustment for ILD–Gender, Age and Physiology Index, PVR but not MPAP was associated with a higher mortality rate (HR 1.37, 95% CI 1.23 to 1.52, p<0.0001; HR 0.98, 95% CI 0.96 to 1.01, p=0.1671, respectively). PVR>2 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg.ConclusionsMild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.
The Web-Based Portal SpatialTME Integrates Histological Images with Single-Cell and Spatial Transcriptomics to Explore the Tumor Microenvironment
Authors: Shi Jintong , Wei Xia , Xun Zhenzhen , Ding Xinyu , Liu Yao , Liu Lianxin , Ye Youqiong 
Published: February 2024

Abstract

The tumor microenvironment (TME) represents a complex network in which tumor cells communicate not only with each other but also with stromal and immune cells. The intercellular interactions in the TME contribute to tumor initiation, progression, metastasis, and treatment outcome. Recent advances in spatial transcriptomics (ST) have revolutionized the molecular understanding of the TME at the spatial level. A comprehensive interactive analysis resource specifically designed for characterizing the spatial TME could facilitate further advances using ST. In this study, we collected 296 ST slides covering 19 cancer types and developed a computational pipeline to delineate the spatial structure along the malignant–boundary–nonmalignant axis. The pipeline identified differentially expressed genes and their functional enrichment, deconvoluted the cellular composition of the TME, reconstructed cell type–specific gene expression profiles at the sub-spot level, and performed cell–cell interaction analysis. Finally, the user-friendly database SpatialTME (http://www.spatialtme.yelab.site/) was constructed to provide search, visualization, and downloadable results. These detailed analyses are able to reveal the heterogeneous regulatory network of the spatial microenvironment and elucidate associations between spatial features and tumor development or response to therapy, offering a valuable resource to study the complex TME.

Significance:
SpatialTME provides spatial structure, cellular composition, expression, function, and cell–cell interaction information to enable investigations into the tumor microenvironment at the spatial level to advance understanding of cancer development and treatment.
Otolith as a tool to differentiate juveniles of two species Centropomidae
Authors: Carvalho Barbara Maichak de , Bot Neto Renato Luiz , Schwarz Júnior Roberto , Spach Henry Louis , Volpedo Alejandra Vanina 
Published: February 2024

Centropomus undecimalis and Centropomus ensifurus are a species belonging to the family Centropomidae, which has an important role in estuarine ecosystem. The present study aimed at comparing the otoliths shape of juveniles both species collected in in the lower São Francisco River (10°28′34.02″S, 36°24′27.02″W). In the laboratory, 52 otoliths were extracted, photographed, measured and the contour was analyzed by the wavelet method. The otolith contours varied between species (n = 28 C. ensiferus and n = 24 C. undecimalis). The Linear Discriminant Analysis correctly reclassified 92.3% of all otoliths among species. MANOVA also evidenced significant differences in contour between species (F = 3.73; p < 0.0001). The results suggest that C. ensiferus is adapted to enviroments with higher turbidity and the C. undecimalis tends to colonize environments with lower turbidity and spends more time in the water column.
Food is a Love Language: An Analysis of Connection and Desire in Stir-Fry
Authors: Borges Esther 
Published: February 2024

This paper aims at analysing the Irish contemporary novel Stir-fry (1994), written by Emma Donoghue. The story is set in rural Ireland in the early 1990s, and this study focusses on how food, and the room of the kitchen, is used throughout the novel as a way to represent the emotional connections between the characters as well as the sexual awakening of the main character, Maria. The parallels between Maria’s relationship with food and the kitchen back at her original home in opposition to her new home in Dublin help create an understanding of how the character changes perspective on society and her own sexuality, exploring her new Self away from suffocating expectations and prejudices imposed by a highly religious, misogynistic and homophobic society.
Breaking Silences: Women, Citizenship and Theatre In Northern Ireland
Authors: Fitzpatrick Lisa 
Published: February 2024

This essay seeks to weave together an analysis of women’s citizenship and its dependency on certain silences, and the exploration of this tension in two recent productions by Belfast- based Kabosh Theatre Company. Kabosh, and company Artistic Director Paula McFetridge, stage work that examines the realities of the region in the post-conflict era. In constructing the theoretical frame for the analysis, the concept of “silence” and “silencing” draws from Kristie Dotson (2015), and from work on violence such as Gayatri Spivak’s concept of “epistemic violence” and a wide range of sources on the performance of violence in theatre. Chantal Mouffe’s concept of agonistic democracy shapes the discussion of the Northern Irish state, and Wendy Brown and Joane Butler are the key scholars for the consideration of citizenship and nation.
Pediatric ECG-Based Deep Learning to Predict Left Ventricular Dysfunction and Remodeling
Authors: Mayourian Joshua , La Cava William G. , Vaid Akhil , Nadkarni Girish N. , Ghelani Sunil J. , Mannix Rebekah , Geva Tal , Dionne Audrey , Alexander Mark E. , Duong Son Q. , Triedman John K. 
Published: February 2024

BACKGROUND:
Artificial intelligence–enhanced ECG analysis shows promise to detect ventricular dysfunction and remodeling in adult populations. However, its application to pediatric populations remains underexplored.

METHODS:
A convolutional neural network was trained on paired ECG–echocardiograms (≤2 days apart) from patients ≤18 years of age without major congenital heart disease to detect human expert–classified greater than mild left ventricular (LV) dysfunction, hypertrophy, and dilation (individually and as a composite outcome). Model performance was evaluated on single ECG–echocardiogram pairs per patient at Boston Children’s Hospital and externally at Mount Sinai Hospital using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC).

RESULTS:
The training cohort comprised 92 377 ECG–echocardiogram pairs (46 261 patients; median age, 8.2 years). Test groups included internal testing (12 631 patients; median age, 8.8 years; 4.6% composite outcomes), emergency department (2830 patients; median age, 7.7 years; 10.0% composite outcomes), and external validation (5088 patients; median age, 4.3 years; 6.1% composite outcomes) cohorts. Model performance was similar on internal test and emergency department cohorts, with model predictions of LV hypertrophy outperforming the pediatric cardiologist expert benchmark. Adding age and sex to the model added no benefit to model performance. When using quantitative outcome cutoffs, model performance was similar between internal testing (composite outcome: AUROC, 0.88, AUPRC, 0.43; LV dysfunction: AUROC, 0.92, AUPRC, 0.23; LV hypertrophy: AUROC, 0.88, AUPRC, 0.28; LV dilation: AUROC, 0.91, AUPRC, 0.47) and external validation (composite outcome: AUROC, 0.86, AUPRC, 0.39; LV dysfunction: AUROC, 0.94, AUPRC, 0.32; LV hypertrophy: AUROC, 0.84, AUPRC, 0.25; LV dilation: AUROC, 0.87, AUPRC, 0.33), with composite outcome negative predictive values of 99.0% and 99.2%, respectively. Saliency mapping highlighted ECG components that influenced model predictions (precordial QRS complexes for all outcomes; T waves for LV dysfunction). High-risk ECG features include lateral T-wave inversion (LV dysfunction), deep S waves in V1 and V2 and tall R waves in V6 (LV hypertrophy), and tall R waves in V4 through V6 (LV dilation).

CONCLUSIONS:
This externally validated algorithm shows promise to inexpensively screen for LV dysfunction and remodeling in children, which may facilitate improved access to care by democratizing the expertise of pediatric cardiologists.
Multiorgan Dysfunction and Associated Prognosis in Transthyretin Cardiac Amyloidosis
Authors: Ioannou Adam , Nitsche Christian , Porcari Aldostefano , Patel Rishi K. , Razvi Yousuf , Rauf Muhammad U. , Martinez‐Naharro Ana , Venneri Lucia , Accietto Antonella , Netti Lucrezia , Bandera Francesco , Virsinskaite Ruta , Kotecha Tushar , Knight Dan , Petrie Aviva , Whelan Carol , Wechalekar Ashutosh , Lachmann Helen , Hawkins Philip N. , Gillmore Julian D. , Fontana Marianna 
Published: February 2024

Background
Transthyretin cardiac amyloidosis (ATTR‐CA) is a progressive and ultimately fatal cardiomyopathy. Biomarkers reflecting multiorgan dysfunction are of increasing importance in patients with heart failure; however, their significance in ATTR‐CA remains largely unknown. The aims of this study were to characterize the multifaceted nature of ATTR‐CA using blood biomarkers and assess the association between blood biomarkers and prognosis.

Methods and Results

This is a retrospective cohort study of 2566 consecutive patients diagnosed with ATTR‐CA between 2007 and 2023. Anemia (39%), high urea (52%), hyperbilirubinemia (18%), increased alkaline phosphatase (16%), increased CRP (C‐reactive protein; 27%), and increased troponin (98.2%) were common findings in the overall population, whereas hyponatremia (6%) and hypoalbuminemia (2%) were less common. These abnormalities were most common in patients with p.(V142I) hereditary ATTR‐CA, and became more prevalent as the severity of cardiac disease increased. Multivariable Cox regression analysis demonstrated that anemia (hazard ratio [HR], 1.19 [95% CI, 1.04–1.37];
P
=0.01), high urea (HR, 1.23 [95% CI, 1.04–1.45];
P
=0.01), hyperbilirubinemia (HR, 1.32 [95% CI, 1.13–1.57;
P
=0.001), increased alkaline phosphatase (HR, 1.20 [95% CI, 1.01–1.42;
P
=0.04), hyponatremia (HR, 1.65 [95% CI, 1.28–2.11];
P
<0.001), and troponin‐T >56 ng/L (HR, 1.72 [95% CI, 1.46–2.03];
P
<0.001) were all independently associated with mortality in the overall population. The association between biomarkers and mortality varied across the spectrum of genotypes and left ventricular ejection fraction, with anemia remining independently associated with mortality in p.(V142I) hereditary ATTR‐CA (HR, 1.58 [95% CI, 1.17–2.12];
P
=0.003) and in a subgroup of the overall population with a left ventricular ejection fraction ≤40% (HR, 1.39 [95% CI, 1.08–1.81];
P
=0.01).

Conclusions
Cardiac and noncardiac biomarker abnormalities were common and reflect the complex and multifaceted nature of ATTR‐CA, with a wide range of biomarkers remaining independently associated with mortality. Clinical trials are needed to investigate whether biomarker abnormalities represent modifiable risk factors that if specifically targeted could improve outcomes.
Ketogenic Diet: Parental Experiences and Expectations
Authors: Orr Elizabeth , Whitney Robyn , Nandeesha Nandini , Kossoff Eric H. , RamachandranNair Rajesh 
Published: February 2024

Background The ketogenic diet may be difficult for some patients and their families to implement and can impact physical, emotional, and social well-being. Methods Through principles of fundamental qualitative description, we completed an exploratory study on parents’ experiences and expectations on the use and efficacy of the ketogenic diet for children with medically refractory epilepsy. Results Seventeen parents (10 mothers and 7 fathers) of 12 children with epilepsy participated. At the time of the interview, parents had experienced an average of 25 months of ketogenic diet treatment for their child (range 2 months to 98 months). Half of the caregivers learned about the ketogenic diet from their neurologist, whereas the remainder had heard about it from another source (ie, the internet). Most caregivers’ (n = 13) diet expectations were related to seizure control. However, child development (n = 5) and quality of life (n = 5) were also crucial to some. Physical impacts of the diet were most commonly gastrointestinal for children (n = 9). Social and emotional effects were noted in some older children with typical development. Most caregivers described negative impacts on finances (n = 15), relationships (n = 14), and emotional well-being (ie, stress) (n = 12). Caregivers benefited from the ketogenic diet team's regular communication, close follow-up, and family-centered care. Conclusions Despite the impacts that the ketogenic diet may have on caregivers’ emotional and social well-being, the positive impacts of the diet were felt to outweigh any perceived risks. Effects (both positive and negative) on quality of life and child development (eg, social, emotional, cognitive) are essential for caregivers and require additional investigation.