bluuebunny/crossref_metadata_2025 huggingface dataset:
O62: Five year followup of the abdominal aortic aneurysm Get Fit Trial: a randomised controlled trial of exercise to improve fitness in patients with AAA
Authors: Tay Tricia , Haque Adam
Published: March 2024

Aims

Improved fitness of patients on Abdominal Aortic Aneurysm(AAA) surveillance is predicted to reduce cardiovascular events and improve perioperative morbidity and mortality. The AAA GetFit Trial was a randomised control trial comparing community exercise programme(CEP) with standard care which demonstrated improved CardioPulmonary Exercise Test-related fitness in AAA patients to inform a definitive RCT. This study aims to investigate longer-term five-year clinical outcomes of these individuals.

Methods

The AAA GetFit trial recruited participants from Greater Manchester’s AAA Surveillance programme, and randomly assigned participants to either i)24-week CEP with choice of gym or home exercises, or ii) standard clinical care. We performed a retrospective analysis of clinical outcomes from this trial over five-year follow-up reviewing whether they underwent operative repair, 30-day postoperative morbidity, cardiovascular event, and mortality. We defined 30-day post-operative morbidity using Clavien-Dindo classification≥3.

Results

In total, 56 participants were recruited, 28 were randomised to CEP group, 86% were males. Mean age at time of enrolment was 72.8(SD5.7) years. At five-year follow-up, mortality in control and CEP were 60%(n=6) and 40%(n=4). In each group, 36%(n=20) underwent operative repair. There was no perioperative mortality. One perioperative morbidity occurred in control subject. Cardiovascular events(n=8) occurred in 7% and 21% control and CEP, respectively. Mean diameter of aneurysm increased in both CEPvsControl(0.89vs0.82cm).

Conclusions

The AAA GetFit trial showed significant benefits in cardiovascular fitness through community-based exercise. Clinical outcomes thus far were similar in both groups, there is an indication CEP improves perioperative outcomes.
O25: Accuracy of NELA score in predicting the risk of mortality following emergency laparotomy in patients aged above and below 80: A cohort study
Authors: Linganathan Saranya , Saji Alwin Puthiyakunnel , Hughes Ioan , Mitra Kalyan , Hajibandeh Shahin , Hajibandeh Shahab
Published: March 2024

Objectives

To compare accuracy of National Emergency Laparotomy Audit (NELA) score in predicting the risk of mortality following emergency laparotomy in patients aged above and below 80.

Methods

In compliance with STROCSS statement standards a retrospective cohort study was conducted. The study period was between January 2017 and January 2022. All adult patients with non-traumatic acute abdominal pathology who underwent emergency laparotomy in two centres were included. The Receiver Operating Characteristic (ROC) curve analysis and Hosmer & Lemeshow test were conducted to evaluate the discrimination and calibration of NELA score in predicting the risk of 30-day mortality in patients aged above and below 80 years.

Results

A total of 1458 eligible patients were included; 289 patients were aged above 80 with median age of 84 (IQR 81-87) and 1168 patients were aged below 80 with median age of 60 (IQR 46-71). The risk of 30-day mortality was 13.5 % in the above 80 group and 8% in the below 80 group. ROC curve analysis showed that the AUC of NELA score was 0.78 (95% CI 0.73-0.83) in the above 80 group and 0.89 (95% CI 0.87-0.91) in the below 80 group. The score was not well-calibrated for either groups.

Conclusions

The NELA score is less accurate in predicting the risk of mortality following emergency laparotomy in patients aged above 80 compared to younger patients. This may be explained by the fact that it does not take into account the measures of age-related decline in physical status of the patients.
O160: Novel Monitoring of General Surgeons' Intraoperative Cognitive Load following Surgical Sabermetrics Principles
Authors: Howie Emma , Dias Roger , Wigmore Stephen , Skipworth Richard , Yule Steven
Published: March 2024

Introduction

Surgeons strive to continually enhance performance. Currently, assessment relies on subjective, retrospective methods-hindering real-time improvement and error prevention. Learning from sports, surgeons can utilise surgical sabermetrics for data-driven analysis. Cognitive load(CogL) impacts performance, with overload impairing skills and judgement. Sabermetrics can be leveraged to measure CogL objectively(e.g.Electrodermal activity(EDA)) and subjectively. This study aimed to combine these measures and explore their relationship with surgeon factors and patient outcomes.

Methods

Fourteen surgeons conducting 58 benign surgery cases participated. Surgeons’ intraoperative EDA was captured using a digital sensor. Subjective data collected included (i)Surgery Task-Load-Index(SURG-TLX)), (ii)mood, (iii)sleep-disturbance and (iv)risk-aversion. EDA underwent decomposition into (a)tonic (background autonomic arousal) and (b) phasic(response to events) components. Patient outcomes included (i)30-day morbidity and (ii)case difficulty.

Results

Overall, mean phasic-EDA was 0.038μS and mean tonic-EDA was 0.483μS(ranges 0-1:1 indicating highest CogL). Mean SURG-TLX was 47.128(/120, where 120 is the highest workload). Negative mood related to changes in tonic-EDA(p<0.05,F=11.84). EDA climbed throughout each case (Tonic:p<0.05,F=2.035;Phasic:p<0.05,F=1.626). SURG-TLX were weakly correlated with sleep(p<0.05,ϱ=-0.273) and moderately correlated with case duration(p<0.05, ϱ=0.598), but not EDA(p>0.50).

Discussion

This study is the first in the UK to report combined CogL measures gathered during live surgery. Awareness of factors that affect CogL crucially allows for the management of factors to prevent overload and to inform targeted interventions for performance improvement. Using digital sensors to measure CogL provides opportunity for automated, real-time performance assessment, advanced feedback, and behavioural modifications.
O140: How clinically relevant are prostate cancer cell lines? A comprehensive multiomics analysis.
Authors: Ahmed Zahra , Mosabbir Warda , Tandon Devansh , Pereira Snehal Pinto , Cheema Umber , Loizidou Marilena , Whithington John , Moore Caroline , Heavey Susan
Published: March 2024

Introduction

Cell lines remain a heavily used resource in cancer research despite their questionable clinical relevance, mainly due to their feasibility and affordability. A range of in silico, in vivo and ex vivo approaches are gaining popularity to potentially replace cell lines, however, we cannot ignore the plethora of historical data from cell lines, nor write off their future use. Therefore, we question if and how cell lines hold clinical relevance.

Methods

The clinical characteristics of 45 PCa cell lines were compared against worldwide data and the biological features of seven cell lines were compared to over 10,000 well-characterised cases from 23 studies in eight countries. Clinical comparisons included age, race, Gleason grade, cancer type and multiomics variables included mutations, copy number alterations, structural variants, microsatellite instability, mRNA and protein expression, and tumour mutational burden. Using this, cell-line-like patients were identified and characterised.

Results

The most used cell lines were derived from metastases over 40 years ago and accurately represented very few patients. The most common alterations in clinical datasets were not necessarily altered in cell lines and 24% of key PCa gene alterations were not altered in any cell line. From the seven cell lines analysed, the greatest number of patients were found to be biologically similar to VCaP.

Conclusion

Cell lines are valuable in cancer research, but they must hold biological and clinical relevance. PCa cell lines should either be applicable to typical PCa patients or representative of specific cancer subtypes to increase the relevance of translational research.
O167: 3D-TIPS Printed Nanohybrid Composite Vascular Grafts for Evaluation of Human Umbilical Vein Endothelial Cell Response
Authors: Imran Maryam , Li Johanne , Ibrahim Maryam , Huang Xia , Song Wenhui
Published: March 2024

Introduction

Cardiovascular disease is a global killer. For progressive disease coronary artery bypass grafting is used, which is limited by suboptimal vasculature and patency. Alternatively, tissue engineered scaffolds are cell seeded structures supporting neovascularization. Poly(ethylene-diethylene glycol succinate)urea-urethane-polyhedral oligomeric silsesquioxane [P(EDS)UU-POSS] shows potential for its elastic and degradation properties. In this study, we manufacture a P(EDS)UU-POSS scaffold and assess human umbilical vein endothelial cell (HUVEC) attachment.

Method

3D printed thermally induced phase separated (3DTIPS) scaffolds were manufactured. Mechanical testing was employed to compare scaffold stress-strain curves with those of currently utilised vessels and synthetic grafts. HUVEC were seeded onto scaffolds coated with type I collagen and peptide hydrogel respectively. Surface functionalization in this way, is hypothesised to optimise cell attachment. Assessment of cell viability was with PrestoBlueTM and total DNA assay. Confocal imaging was also performed.

Results

Tensile properties of 3D-TIPS scaffolds match the greater saphenous vein. 3D-TIPS scaffolds exhibit higher elasticity than synthetic PCL grafts, meeting stretch and strength requirements of vessels. Metabolism data shows an initial increase followed by a decrease for both types of coating. This indicates a decrease in overall metabolism but not cell death, attributed to cellular adaptation to the scaffold microenvironment, with collagen coating performing better. Visualisation of type I collagen samples demonstrates increases in cellular attachment.

Conclusions

There is potential for optimised 3DTIPS P(EDS)UU-POSS scaffolds with suitable mechanical properties. Further study of HUVEC and smooth muscle cell co-culture will better mimic in vivo environments, assessing sustained potential as vascular grafts.
O193: Drains versus No Drain in Thyroid Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials
Authors: Ahmad Mohammad , Sarwar Safdar , Shaikh Shahzeb , Ashrafian Hutan , Siddiqui Muhammed , Khwaja Sadie , Kumar Nirmal
Published: March 2024

Introduction

Thyroid surgery does not come without its risks of complications of post-operative haemorrhage, haematoma and seroma, for which drains may be used. Placement of a drain may prevent these complications, which may be life-threatening due to vascular compromise and airway compression.

Objective

This study aims to evaluate the outcomes and complications in patients undergoing thyroid surgery with a drain and without a drain.

Methods

Systematic review of all studies up to October 2023. These studies were identified from all major databases including MEDLINE, Cochrane (1960–2023), and EMBASE (1991–2023). All studies reporting a comparison between drain and no drain thyroid surgery were searched; all studies were included. Post-operative complications and outcomes were recorded and analysed.

Results

35 studies with 4089 patients contributed to the summative outcome measures. The no drain group showed a statistically significant superiority compared to the drain group when it came to infection rates (p=0.0001), re-operation rates (p=0.05), pain score (p<0.00001) and length of stay (p<0.00001). There was no statistical difference for haematoma (p=0.52), haemorrhage (p=0.39) or seroma rates (p=0.38).

Conclusion

There is a superiority in postoperative outcomes and reduced complications in favour of patients without a drain compared to patients with a drain following thyroid surgery. A large number of studies with a large patient population were included; further studies are required to assess the individual suitable indications for a drain in thyroid surgery.
O79: Adjuvant chemotherapy following surgery for adenocarcinoma arising from intraductal papillary mucinous neoplasia and impact on recurrence and survival: ADENO-IPMN study
Authors: Lucocq James ,   Adeno-IPMN Collaborative, Pandanaboyana Sanjay
Published: March 2024

Background

The clinical impact of giving adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia (IPMN) is unclear. The present study aims to identify factors related to receipt of adjuvant chemotherapy, the type and its impact on recurrence, site specific recurrence and survival in a large international cohort of patients.

Method

Patients undergoing pancreatic resection for adenocarcinoma arising from IPMN between 2010-2020 at 18 pancreatic centres were identified. Propensity score matching (PSM) and survival analyses were performed to identify the impact of adjuvant chemotherapy on recurrence and survival.

Results

A total of 459 patients underwent pancreatic resection and 275 patients (59.9%) received adjuvant chemotherapy (Gemcitabine,51.3%; Gemcitabine-capecitabine,21.8%; Folfirinox,8.0%; and other,18.9%). In multivariate analysis, poor differentiation (30.2%vs.19.0%; p=0.007) was associated with adjuvant chemotherapy use. Adjuvant chemotherapy was not associated with all, locoregional, systemic or site-specific recurrence compared to no adjuvant chemotherapy on Kaplan-Meier analysis (median time to recurrence 26 versus 50 months; p=0.14), multivariate analysis (HR 0.79, p=0.175), and on propensity score matching (HR 0.76, p=0.111). No particular subgroup had lower rates of recurrence with adjuvant chemotherapy. No particular chemotherapy regime resulted in lower recurrence rates or longer survival. The overall or disease-free survival rates were not significantly different in multivariate analysis.

Conclusion

Based on the contemporary data, adjuvant chemotherapy after pancreatic resection for adenocarcinoma arising from IPMN does not appear to impact on recurrence rates, recurrence patterns and long term survival. However, data on the most potent chemotherapy (Folfirinox) is limited and warrants further studies
Does internal validity play a factor in ChatGPT’s success?
Authors: Ahuja Kripa Raj , Lio Peter
Published: March 2024

We elaborated on our previously published article by asking ChatGPT to create images for each of the diagnoses previously asked in our article. We assessed ChatGPT’s internal validity by calculating the accuracy of the responses provided to its own images.
Practical applications of artificial intelligence in dermatology residency training
Authors: Sachedina Dilshad , Hooda Rohan , Fawaz Bilal
Published: March 2024

Artificial intelligence (AI) is revolutionizing healthcare, notably in dermatology diagnostics using deep learning, such as convolutional neural networks. This piece spotlights AI’s potential in dermatology training: (i) enhancing academic training with tailored, interactive learning; (ii) boosting surgical proficiency via virtual reality and real-time AI feedback; and (iii) customizing training through AI-identified clinical gaps. However, integrating AI requires substantial investments, a paradigm shift in teaching methods, and an understanding of the evolving dynamics of dermatological practices as AI becomes integral.
Prevalence and clinical outcomes of isolated or combined moderate to severe mitral and tricuspid regurgitation in patients with cardiac amyloidosis
Authors: Tomasoni Daniela , Aimo Alberto , Porcari Aldostefano , Bonfioli Giovanni Battista , Castiglione Vincenzo , Saro Riccardo , Di Pasquale Mattia , Franzini Maria , Fabiani Iacopo , Lombardi Carlo Mario , Lupi Laura , Mazzotta Marta , Nardi Matilde , Pagnesi Matteo , Panichella Giorgia , Rossi Maddalena , Vergaro Giuseppe , Merlo Marco , Sinagra Gianfranco , Emdin Michele , Metra Marco , Adamo Marianna
Published: March 2024

Aims

Evidence on the epidemiology and prognostic significance of mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with cardiac amyloidosis (CA) is scarce.

Methods and results

Overall, 538 patients with either transthyretin (ATTR, n = 359) or immunoglobulin light-chain (AL, n = 179) CA were included at three Italian referral centres. Patients were stratified according to isolated or combined moderate/severe MR and TR. Overall, 240 patients (44.6%) had no significant MR/TR, 112 (20.8%) isolated MR, 66 (12.3%) isolated TR, and 120 (22.3%) combined MR/TR. The most common aetiologies were atrial functional MR, followed by primary infiltrative MR, and secondary TR due to right ventricular (RV) overload followed by atrial functional TR. Patients with isolated or combined MR/TR had a more frequent history of heart failure (HF) hospitalization and atrial fibrillation, worse symptoms, and higher levels of NT-proBNP as compared to those without MR/TR. They also presented more severe atrial enlargement, atrial peak longitudinal strain impairment, left ventricular (LV) and RV systolic dysfunction, and higher pulmonary artery systolic pressures. TR carried the most advanced features. After adjustment for age, sex, CA subtypes, laboratory, and echocardiographic markers of CA severity, isolated TR and combined MR/TR were independently associated with an increased risk of all-cause death or worsening HF events, compared to no significant MR/TR [adjusted HR 2.75 (1.78–4.24) and 2.31 (1.44–3.70), respectively].

Conclusion

In a large cohort of patients with CA, MR, and TR were common. Isolated TR and combined MR/TR were associated with worse prognosis regardless of CA aetiology, LV, and RV function, with TR carrying the highest risk.
Development and validation of a prognostic score integrating remote heart failure symptoms and clinical variables in mortality risk prediction after myocardial infarction: the PragueMi score
Authors: Wohlfahrt Peter , Jenča Dominik , Melenovský Vojtěch , Stehlik Josef , Mrázková Jolana , Šramko Marek , Kotrč Martin , Želízko Michael , Adámková Věra , Piťha Jan , Kautzner Josef
Published: March 2024

Aims

While heart failure (HF) symptoms are associated with adverse prognosis after myocardial infarction (MI), they are not routinely used for patients’ stratification. The primary objective of this study was to develop and validate a score to predict mortality risk after MI, combining remotely recorded HF symptoms and clinical risk factors, and to compare it against the guideline-recommended Global Registry of Acute Coronary Events (GRACE) score.

Methods and results

A cohort study design using prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart centre between June 2017 and September 2022 was used. Data from 1135 patients (aged 64 ± 12 years, 26.7% women), were split into derivation (70%) and validation cohort (30%). Components of the 23-item Kansas City Cardiomyopathy Questionnaire and clinical variables were used as possible predictors. The best model included the following variables: age, HF history, admission creatinine and heart rate, ejection fraction at hospital discharge, and HF symptoms 1 month after discharge including walking impairment, leg swelling, and change in HF symptoms. Based on these variables, the PragueMi score was developed. In the validation cohort, the PragueMi score showed superior discrimination to the GRACE score for 6 months [the area under the receiver operating curve (AUC) 90.1, 95% confidence interval (CI) 81.8–98.4 vs. 77.4, 95% CI 62.2–92.5, P = 0.04) and 1-year risk prediction (AUC 89.7, 95% CI 83.5–96.0 vs. 76.2, 95% CI 64.7–87.7, P = 0.004).

Conclusion

The PragueMi score combining HF symptoms and clinical variables performs better than the currently recommended GRACE score.
Identification of chemosensory genes in the stingless bee Tetragonisca fiebrigi
Authors: Balbuena María Sol , Latorre-Estivalis Jose M , Farina Walter M
Published: March 2024

Reception of chemical information from the environment is crucial for insects' survival and reproduction. The chemosensory reception mainly occurs by the antennae and mouth parts of the insect, when the stimulus contacts the chemoreceptors located within the sensilla. Chemosensory receptor genes have been well-studied in some social hymenopterans such as ants, honeybees, and wasps. However, although stingless bees are the most representative group of eusocial bees, little is known about their odorant, gustatory, and ionotropic receptor genes. Here, we analyze the transcriptome of the proboscis and antennae of the stingless bee Tetragonisca fiebrigi. We identified and annotated 9 gustatory and 15 ionotropic receptors. Regarding the odorant receptors, we identified 204, and we were able to annotate 161 of them. In addition, we compared the chemosensory receptor genes of T. fiebrigi with those annotated for other species of Hymenoptera. We found that T. fiebrigi showed the largest number of odorant receptors compared with other bees. Genetic expansions were identified in the subfamilies 9-exon, which was also expanded in ants and paper wasps; in G02A, including receptors potentially mediating social behavior; and in GUnC, which has been related to pollen and nectar scent detection. Our study provides the first report of chemosensory receptor genes in T. fiebrigi and represents a resource for future molecular and physiological research in this and other stingless bee species.
Age, Political Participation, and Political Context in Africa
Authors: Dim Eugene Emeka , Schafer Markus H
Published: March 2024

Objectives

Political participation differs across the age range, but little is known about these patterns outside of developed countries. Political context is a particularly important consideration for all political behavior in Africa, where only a few countries are fully democratic. Drawing from political opportunity structures theory, we investigate how political freedom conditions the age-based pattern of electoral and nonelectoral political engagement, as well as protesting.

Methods

This study merges the fifth, sixth, and seventh rounds of the Afrobarometer data sets, spanning 36 African countries, with country-level data on political freedom from Freedom House. Using multilevel regression models, we examine how political freedom shapes the relationship between age and 3 forms of political participation.

Results

Africans aged from 18 to 60 years and living in nonfree countries are most engaged in electoral and nonelectoral political activities, though participation begins to drop markedly past age 60. For protest participation, young Africans living in partially and non-free countries are the most engaged in protests; yet limited political freedom again means a sharp age-based decline.

Discussion

The impact of political context on the age–participation association is nuanced in ways not anticipated by mainstream research on the developed West. Repressive regimes, while spurring engagement at younger ages, appear to disproportionately deter older Africans from political engagement, especially its riskiest forms. We conclude by calling for more country-comparative gerontological research with careful attention to contextual heterogeneity, particularly in the understudied Global South.
Agency is Positionally Distributed: Practice Theory and (Post)Colonial Structures
Authors: Pingeot Lou , Pouliot Vincent
Published: March 2024

Why are some practices available to some actors in world politics, but not to others? In this theory note, we develop a theory of agency as positionally distributed: In global politics, the action potentials of groups and individuals vary depending on their location in the macrostructures inherited from common histories of colonial domination and exploitation. We contribute to the understanding of subordinate agency by exploiting the many synergies between International Practice Theory and Postcolonial Theory. Where the former sometimes struggles to capture deep macrostructures, the latter emphasizes the constitutive effects of coloniality. Conversely, where the postcolonial gaze faces the aporia of giving voice to the subordinate, a practice approach helps make sense of the indexicality of agency, including defiance and subversion. Based on these complementarities, we develop a structural concept according to which agency, including subordinate forms, is a relational effect of an unequal playing field characterized by centuries of (post)colonial dynamics. Overall, the theory note helps explain why the very same practices, such as border crossing, seem to be distributed unequally across groups depending not on their competence but on their position in social and international structures such as the North–South divide or the global color line.
Prediction of pyrazinamide resistance in Mycobacterium tuberculosis using structure-based machine-learning approaches
Authors: Carter Joshua J , Walker Timothy M , Walker A Sarah , Whitfield Michael G , Morlock Glenn P , Lynch Charlotte I , Adlard Dylan , Peto Timothy E A , Posey James E , Crook Derrick W , Fowler Philip W
Published: March 2024

Background

Pyrazinamide is one of four first-line antibiotics used to treat tuberculosis; however, antibiotic susceptibility testing for pyrazinamide is challenging. Resistance to pyrazinamide is primarily driven by genetic variation in pncA, encoding an enzyme that converts pyrazinamide into its active form.

Methods

We curated a dataset of 664 non-redundant, missense amino acid mutations in PncA with associated high-confidence phenotypes from published studies and then trained three different machine-learning models to predict pyrazinamide resistance. All models had access to a range of protein structural-, chemical- and sequence-based features.

Results

The best model, a gradient-boosted decision tree, achieved a sensitivity of 80.2% and a specificity of 76.9% on the hold-out test dataset. The clinical performance of the models was then estimated by predicting the binary pyrazinamide resistance phenotype of 4027 samples harbouring 367 unique missense mutations in pncA derived from 24 231 clinical isolates.

Conclusions

This work demonstrates how machine learning can enhance the sensitivity/specificity of pyrazinamide resistance prediction in genetics-based clinical microbiology workflows, highlights novel mutations for future biochemical investigation, and is a proof of concept for using this approach in other drugs.
Cryo-EM advances in GPCR structure determination
Authors: Shihoya Wataru , Iwama Aika , Sano Fumiya K , Nureki Osamu
Published: March 2024

G-protein-coupled receptors (GPCRs) constitute a prominent superfamily in humans and are categorized into six classes (A–F) that play indispensable roles in cellular communication and therapeutics. Nonetheless, their structural comprehension has been limited by challenges in high-resolution data acquisition. This review highlights the transformative impact of cryogenic electron microscopy (cryo-EM) on the structural determinations of GPCR–G-protein complexes. Specific technologies, such as nanobodies and mini-G-proteins, stabilize complexes and facilitate structural determination. We discuss the structural alterations upon receptor activation in different GPCR classes, revealing their diverse mechanisms. This review highlights the robust foundation for comprehending GPCR function and pave the way for future breakthroughs in drug discovery and therapeutic targeting.
Metabolic regulation of the host–fungus interaction: from biological principles to therapeutic opportunities
Authors: Silva-Gomes Rita , Caldeira Inês , Fernandes Raquel , Cunha Cristina , Carvalho Agostinho
Published: March 2024

Fungal infections present a significant global public health concern, impacting over 1 billion individuals worldwide and resulting in more than 3 million deaths annually. Despite considerable progress in recent years, the management of fungal infections remains challenging. The limited development of novel diagnostic and therapeutic approaches is largely attributed to our incomplete understanding of the pathogenetic mechanisms involved in these diseases. Recent research has highlighted the pivotal role of cellular metabolism in regulating the interaction between fungi and their hosts. In response to fungal infection, immune cells undergo complex metabolic adjustments to meet the energy demands necessary for an effective immune response. A comprehensive understanding of the metabolic circuits governing antifungal immunity, combined with the integration of individual host traits, holds the potential to inform novel medical interventions for fungal infections. This review explores recent insights into the immunometabolic regulation of host–fungal interactions and the infection outcome and discusses how the metabolic repurposing of immune cell function could be exploited in innovative and personalized therapeutic approaches.
Spatial Pattern Analysis using Closest Events (SPACE)—A Nearest Neighbor Point Pattern Analysis Framework for Assessing Spatial Relationships from Digital Images
Authors: Soltisz Andrew M , Craigmile Peter F , Veeraraghavan Rengasayee
Published: March 2024

The quantitative description of biological structures is a valuable yet difficult task in the life sciences. This is commonly accomplished by imaging samples using fluorescence microscopy and analyzing resulting images using Pearson's correlation or Manders’ co-occurrence intensity-based colocalization paradigms. Though conceptually and computationally simple, these approaches are critically flawed due to their reliance on signal overlap, sensitivity to cursory signal qualities, and inability to differentiate true and incidental colocalization. Point pattern analysis provides a framework for quantitative characterization of spatial relationships between spatial patterns using the distances between observations rather than their overlap, thus overcoming these issues. Here we introduce an image analysis tool called Spatial Pattern Analysis using Closest Events (SPACE) that leverages nearest neighbor-based point pattern analysis to characterize the spatial relationship of fluorescence microscopy signals from image data. The utility of SPACE is demonstrated by assessing the spatial association between mRNA and cell nuclei from confocal images of cardiac myocytes. Additionally, we use synthetic and empirical images to characterize the sensitivity of SPACE to image segmentation parameters and cursory image qualities such as signal abundance and image resolution. Ultimately, SPACE delivers performance superior to traditional colocalization methods and offers a valuable addition to the microscopist's toolbox.
Evolutionary and functional insights into the Ski2-like helicase family in Archaea: a comparison of Thermococcales ASH-Ski2 and Hel308 activities
Authors: Batista Manon , Langendijk-Genevaux Petra , Kwapisz Marta , Canal Isabelle , Phung Duy Khanh , Plassart Laura , Capeyrou Régine , Moalic Yann , Jebbar Mohamed , Flament Didier , Fichant Gwennaele , Bouvier Marie , Clouet-d’Orval Béatrice
Published: March 2024

RNA helicases perform essential housekeeping and regulatory functions in all domains of life by binding and unwinding RNA molecules. The Ski2-like proteins are primordial helicases that play an active role in eukaryotic RNA homeostasis pathways, with multiple homologs having specialized functions. The significance of the expansion and diversity of Ski2-like proteins in Archaea, the third domain of life, has not yet been established. Here, by studying the phylogenetic diversity of Ski2-like helicases among archaeal genomes and the enzymatic activities of those in Thermococcales, we provide further evidence of the function of this protein family in archaeal metabolism of nucleic acids. We show that, in the course of evolution, ASH-Ski2 and Hel308-Ski2, the two main groups of Ski2-like proteins, have diverged in their biological functions. Whereas Hel308 has been shown to mainly act on DNA, we show that ASH-Ski2, previously described to be associated with the 5′-3′ aRNase J exonuclease, acts on RNA by supporting an efficient annealing activity, but also an RNA unwinding with a 3′-5′ polarity. To gain insights into the function of Ski2, we also analyse the transcriptome of Thermococcus barophilus ΔASH-Ski2 mutant strain and provide evidence of the importance of ASH-Ski2 in cellular metabolism pathways related to translation.
Chest X-ray Features of HIV-Associated Pneumocystis Pneumonia (PCP) in Adults: A Systematic Review and Meta-analysis
Authors: Wills Nicola K , Adriaanse Marguerite , Erasmus Shandri , Wasserman Sean
Published: March 2024

Background

The performance of chest x-ray (CXR) features for Pneumocystis pneumonia (PCP) diagnosis has been evaluated in small studies. We conducted a systematic review and meta-analysis to describe CXR changes in adults with HIV-associated laboratory-confirmed PCP, comparing these with non-PCP respiratory disease.

Methods

We searched databases for studies reporting CXR changes in people >15 years old with HIV and laboratory-confirmed PCP and those with non-PCP respiratory disease. CXR features were grouped using consensus terms. Proportions were pooled and odds ratios (ORs) generated using random-effects meta-analysis, with subgroup analyses by CD4 count, study period, radiology review method, and study region.

Results

Fifty-one studies (with 1821 PCP and 1052 non-PCP cases) were included. Interstitial infiltrate (59%; 95% CI, 52%–66%; 36 studies, n = 1380; I2 = 85%) and ground-glass opacification (48%; 95% CI, 15%–83%; 4 studies, n = 57; I2 = 86%) were common in PCP. Cystic lesions, central lymphadenopathy, and pneumothorax were infrequent. Pleural effusion was rare in PCP (0%; 95% CI, 0%–2%). Interstitial infiltrate (OR, 2.3; 95% CI, 1.4–3.9; I2 = 60%), interstitial–alveolar infiltrate (OR, 10.2; 95% CI, 3.2–32.4; I2 = 0%), and diffuse CXR changes (OR, 7.3; 95% CI, 2.7–20.2; I2 = 87%) were associated with PCP diagnosis. There was loss of association with alveolar infiltrate in African studies.

Conclusions

Diffuse CXR changes and interstitial–alveolar infiltrates indicate a higher likelihood of PCP. Pleural effusion, lymphadenopathy, and focal alveolar infiltrates suggest alternative causes. These findings could be incorporated into clinical algorithms to improve diagnosis of HIV-associated PCP.
Impact of the COVID-19 Pandemic on Candida auris Infections: A Retrospective Analysis in an Academic Medical Center in New York City
Authors: Schaefer Sarah , Walits Emily , Thaler Kalani , Patel Gopi
Published: March 2024

Background

Candida auris (C. auris), a multidrug-resistant fungus first described in Japan in 2009, has since spread rapidly around the world. More recently, cases of C. auris have increased substantially, which may have been affected by the strain the coronavirus disease 2019 (COVID-19) pandemic placed on health care resources. We describe the epidemiology of C. auris infection and colonization at a tertiary care hospital in New York City before, during, and after the peak of the COVID-19 pandemic and describe our approach to surveillance.

Methods

We performed a retrospective chart review for all incident cases of C. auris, defined as a patient without a known history of infection or colonization who had a positive surveillance or clinical culture detected at our institution from 2019 through 2022. Clinical and demographic data were collected using the electronic medical record.

Results

Sixty-four incident cases of C. auris were identified. Thirty-four of these were identified by surveillance and 30 by clinical culture. There was a statistically significant increase in the number of cases identified in 2022 compared with 2019, with incidence rates of 2.6 cases per 10 000 admissions in 2019 and 7.8 cases per 10 000 admissions in 2022 (p = .002), respectively.

Conclusions

The incidence of C. auris colonization or infection increased significantly at our institution during the COVID-19 pandemic, reflecting the potential impact the pandemic had on C. auris transmission. Targeted admission surveillance allows for the early identification of C. auris cases and can serve as a valuable tool to combat the increasing transmission of C. auris.
Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia
Authors: Wang Dao Sen , Phu Amy , McKee Kristen , Strasser Simone I , Sheils Sinead , Weltman Martin , Sellar Sue , Davis Joshua S , Young Mel , Braund Alicia , Farrell Geoffrey C , Blunn Anne , Harding Damian , Ralton Lucy , Muller Kate , Davison Scott A , Shaw David , Wood Marnie , Hajkowicz Krispin , Skolen Richard , Davies Jane , Tate-Baker Jaclyn , Doyle Adam , Tuma Rhoda , Hazeldine Simon , Lam Wendy , Edmiston Natalie , Zohrab Krista , Pratt William , Watson Belinda , Zekry Amany , Stephens Carlie , Clark Paul J , Day Melany , Park Gordon , Kim Hami , Wilson Mark , McGarity Bruce , Menzies Natalie , Russell Darren , Lam Thao , Boyd Peter , Kok Jen , George Jacob , Douglas Mark W
Published: March 2024

Background

Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported.

Methods

We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome.

Results

Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir.

Conclusions

In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.
An Explicit Vinogradov–Korobov Zero-Free Region for Dirichlet L-Functions
Authors: Khale Tanmay
Published: March 2024

We establish the first explicit form of the Vinogradov–Korobov zero-free region for Dirichlet L-functions.
Does attitudes toward own aging explain more variance in aging-related outcomes than chronological age and subjective age? A meta-analysis
Authors: Yang Huan , Shi Junqi , Zhao Xinyuan (Roy) , Pryor Christopher , Tian Mengwei
Published: March 2024

Significant research efforts have been devoted to explaining why and how aging impacts employees’ attitudes and behaviors. However, age itself has been subject to a range of conceptualizations and measurements, which has resulted in a fragmented literature. Chronological age (CA) captures biological differences, and subjective age (SA) captures people’s perceptions of their own chronological aging. Not surprisingly, these constructs have different effects on aging-related outcomes. More recently, a relatively newer construct, attitudes toward own aging (ATOA), has gained research traction. In this study, we synthesize the empirical evidence concerning ATOA, and we establish criterion-related and incremental validity of ATOA using meta-analytical techniques. We found that ATOA not only predicted health, cognitive function, well-being, and self-efficacy, but also provided additional explanatory power regarding these aging-related outcomes above and beyond CA and SA. The theoretical and practical implications of these studies are discussed.
Seasonal Fluctuations in Plant-Parasitic Nematode Vertical Distributions and Their Interactions with Edaphic Factors in Vegetable Fields of South Georgia, U.S.A.
Authors: Marquez Josiah , Hajihassani Abolfazl
Published: March 2024

Plant-parasitic nematodes (PPNs) can be found deep in the soil profile, compounding nematode management decisions and detection. This study aimed to understand how seasonal fluctuations in edaphic factors are associated with the vertical distribution of PPNs in south Georgia's vegetable cropping systems. Five-core composite soil samples were taken monthly (March 2020 to February 2022) at three random locations in six vegetable fields. Fields represented three cropping systems (vegetable plasticulture, bare ground cucumber, and plastic bed watermelon rotation) and two regions (north and south) sampled from five 15-cm strata (0 to 15, 15 to 30, 30 to 45, 45 to 60, and 60 to 75 cm). Only soil temperatures and precipitation had seasonal fluctuations; the other edaphic factors were vertically stratified. Latitude and stratum had the strongest associations with nematode composition, showing a clear separation between the north and south regions. Variations in soil texture, porosity, moisture, and PPN vertical distribution suggested that the illuvial zone in the north region was the main factor in the differences observed between regions and strata. Seasonal fluctuations in vertical distribution were found among Meloidogyne incognita and Nanidorus spp. Higher abundances of deep-dwelling PPNs were limited to the south region in the winter for deep-dwelling M. incognita and summer and winter for Nanidorus spp., probably due to the illuvial zone barrier in the north region. Because most root-knot nematodes dwell at ≤30 cm during the summer, fumigant/nematicide applications are recommended during this season to minimize the risk of deep-dwelling escapees.
Sustainability in Obstetrics and Gynecology
Authors: Wright Kelly N. , Melnyk Alexandra I. , Emont Jordan , Van Dis Jane
Published: March 2024

The greatest threat to human health, otherwise known as the climate crisis, disproportionately affects women and pregnant people via exposure to air pollution, heat, extreme weather events, and toxic substances. These effects lead to increased mortality and morbidity in patient populations, but the overall role of the healthcare system and its contribution remains unknown to medical professionals. This review aims to educate clinicians on the effects of the climate crisis on health outcomes and how the current US healthcare system practices drive climate change. Solutions for decarbonizing operating rooms (ORs), neonatal intensive care units (and nurseries), and labor and delivery units are also addressed.

The impact on health can be categorized by the effect of heat (rising temperatures), air pollution, and toxic substances such as microplastics. These have variously been shown to impact fertility; rates of miscarriage, stillbirth, and preterm birth; and hypertensive disorders of pregnancy.

Notably, the healthcare industry contributes more carbon emissions than even global aviation, with the US healthcare industry producing 27% of the world’s healthcare carbon emissions through its energy and water usage, but also via the supply chain, its waste, and pharmaceuticals. Petroleum-based plastic single-use supplies (ie, gowns, instruments, drapes) in hospitals are also a major contributor to this crisis. Up to 95% of the environmental imprint of the healthcare supply chain stems from these single-use supplies. In addition, biohazard waste must be incinerated prior to landfill disposal, further adding to the environmental impact.

Evidence supports the immediate impact of systemic change in terms of decarbonizing healthcare. Replacing single-use instruments with sterilized reusable ones, for instance, has a major impact, such as replacing acrylic specula with stainless steel ones. Another study indicated lower rates of surgical site infections when single-use materials were unavailable in the OR. Beyond this, many single-use supplies are never utilized for patients and go directly to waste. In addition, over carbon dioxide, inhaled anesthetics such as desflurane have 2540 times the potential for global warming while lacking noticeable benefit over other anesthetics. Instead, intravenous anesthetic use can greatly decarbonizing surgeries due to the lower carbon footprint of these medications.

Finally, decreasing energy use in climate control measures within buildings can also impact the environment for the better. Powering down unused ORs saved one institution $33,000 annually. Powering down computers over weekends and on nights can also greatly reduce carbon emissions.
Evidence for the Role of Selection for Reproductively Advantageous Alleles in Human Aging
Authors: Long Erping , Zhang Jianzhi
Published: March 2024

The antagonistic pleiotropy hypothesis is one of the leading theories in the evolutionary origin of aging. It states that mutations contributing to aging could be positively selected for if they are advantageous early in life and promote earlier reproduction or more offspring. The evidence supporting the antagonistic pleiotropy hypothesis in humans is mixed and lacks unambiguous genome-wide support. The UK Biobank contains the genotypes and various phenotypes of 500,000 participants, offering an opportunity to test the antagonistic pleiotropy hypothesis in humans.

This analysis aimed to use the UK Biobank to determine whether genetic variants influencing reproduction are likely to affect lifespan, whether pleiotropy between reproduction and lifespan are largely antagonistic, and whether pleiotropic mutations promoting reproduction but causing aging are favored by natural selection. In addition, potential molecular mechanisms linking reproduction to aging were investigated. Genetic correlation between 2 phenotypic traits was defined as the proportion of variance that the 2 traits share due to genetic causes and is a measure of the contribution of pleiotropy to the covariation of the traits. Four reproductive traits were focused on negative age at first birth, negative age at first sex, number of children fathers, and age at menopause, with larger values of these traits corresponding to higher reproduction. Two life span traits were examined: father's age at death and mother's age at death.

Data were available for a total of 276,406 UK Biobank participants, and 583 genetic variants were reported to be associated with at least 1 reproductive trait. A strong, negative genetic correlation was observed between the 3 reproductive traits and 2 life span traits, supporting the antagonistic pleiotropy hypothesis. Individuals ranked in the top third in polygenic score (PGS) for the 3 reproductive traits had a significantly lower probability of survival to age 76 (SV76) than that of individuals ranked in the bottom third. Compared with randomly selected polymorphisms, those impacting reproduction were 5 times more likely to affect life span and 7.5 times more likely to affect life span antagonistically. Among individuals with the same number of children ever born, SV76 was negatively correlated with the PGS for each of the 4 reproductive traits. In this study, the evidence shows a strong negative genetic correlation between reproduction and parental life span, as well as between parental reproduction and parental life span. This supports the antagonistic pleiotropy hypothesis of aging in humans.