bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the Prediction of 1-Year Right Ventricular Failure After Left Ventricular Assist Device Implantation
Authors: Movahedi Faezeh , Antaki James F.
Published: February 2024

Previous predictive models for postimplant right heart failure (RHF) following left ventricular assist device (LVAD) implantation have demonstrated limited performance on validation datasets and are susceptible to overfitting. Thus, the objective of this study was to develop an improved predictive model with reduced overfitting and improved accuracy in predicting RHF in LVAD recipients. The study involved 11,967 patients who underwent continuous-flow LVAD implantation between 2008 and 2016, with an RHF incidence of 9% at 1 year. Using an eXtreme Gradient Boosting (XGBoost) algorithm, the training data were used to predict RHF at 1 year postimplantation, resulting in promising area under the curve (AUC)-receiver operating characteristic (ROC) of 0.8 and AUC-precision recall curve (PRC) of 0.24. The calibration plot showed that the predicted risk closely corresponded with the actual observed risk. However, the model based on data collected 48 hours before LVAD implantation exhibited high sensitivity but low precision, making it an excellent screening tool but not a diagnostic tool.
Bacteriophages for bronchiectasis: treatment of the future?
Authors: Dominic Catherine , Pye Hannah V. , Mishra Eleanor K. , Adriaenssens Evelien M.
Published: February 2024

Purpose of review

Bronchiectasis is a chronic respiratory disease characterized by dilated airways, persistent sputum production and recurrent infective exacerbations. The microbiology of bronchiectasis includes various potentially pathogenic microorganisms including Pseudomonas aeruginosa which is commonly cultured from patients’ sputum. P. aeruginosa is difficult to eradicate and frequently exhibits antimicrobial resistance. Bacteriophage therapy offers a novel and alternative method to treating bronchiectasis and can be used in conjunction with antibiotics to improve patient outcome.

Recent findings

Thirteen case reports/series to date have successfully used phages to treat infections in bronchiectasis patients, however these studies were constrained to few patients (n = 32) and utilized personalized phage preparations and adjunct antibiotics. In these studies, phage therapy was delivered by inhalation, intravenously or orally and was well tolerated in most patients without any unfavourable effects. Favourable clinical or microbiological outcomes were seen following phage therapy in many patients. Longitudinal patient follow-up reported regrowth of bacteria and phage neutralization in some studies. There are five randomized clinical controlled trials ongoing aiming to use phage therapy to treat P. aeruginosa associated respiratory conditions, with limited results available to date.

More research, particularly robust clinical trials, into how phages can clear respiratory infections, interact with resident microbiota, and how bacteria might develop resistance will be important to establish to ensure the success of this promising therapeutic alternative.
Length of Stay Prediction With Standardized Hospital Data From Acute and Emergency Care Using a Deep Neural Network
Authors: Lequertier Vincent , Wang Tao , Fondrevelle Julien , Augusto Vincent , Polazzi Stéphanie , Duclos Antoine
Published: February 2024

Objective:

Length of stay (LOS) is an important metric for the organization and scheduling of care activities. This study sought to propose a LOS prediction method based on deep learning using widely available administrative data from acute and emergency care and compare it with other methods.

Patients and Methods:

All admissions between January 1, 2011 and December 31, 2019, at 6 university hospitals of the Hospices Civils de Lyon metropolis were included, leading to a cohort of 1,140,100 stays of 515,199 patients. Data included demographics, primary and associated diagnoses, medical procedures, the medical unit, the admission type, socio-economic factors, and temporal information. A model based on embeddings and a Feed-Forward Neural Network (FFNN) was developed to provide fine-grained LOS predictions per hospitalization step. Performances were compared with random forest and logistic regression, with the accuracy, Cohen kappa, and a Bland-Altman plot, through a 5-fold cross-validation.

Results:

The FFNN achieved an accuracy of 0.944 (CI: 0.937, 0.950) and a kappa of 0.943 (CI: 0.935, 0.950). For the same metrics, random forest yielded 0.574 (CI: 0.573, 0.575) and 0.602 (CI: 0.601, 0.603), respectively, and 0.352 (CI: 0.346, 0.358) and 0.414 (CI: 0.408, 0.422) for the logistic regression. The FFNN had a limit of agreement ranging from −2.73 to 2.67, which was better than random forest (−6.72 to 6.83) or logistic regression (−7.60 to 9.20).

Conclusion:

The FFNN was better at predicting LOS than random forest or logistic regression. Implementing the FFNN model for routine acute care could be useful for improving the quality of patients’ care.
MicroRNA Signatures for Pancreatic Cancer and Chronic Pancreatitis
Authors: Singh Nidhi , Khan Imteyaz Ahmad , Rashid Safoora , Rashid Sumaira , Roy Shikha , Kaushik Kriti , Kumar Amit , Das Prasenjit , Lalwani Sanjeev , Gupta Dinesh , Gunjan Deepak , Dash Nihar Ranjan , Chauhan Shyam S. , Gupta Surabhi , Saraya Anoop
Published: February 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease due to the lack of early detection. Because chronic pancreatitis (CP) patients are a high-risk group for pancreatic cancer, this study aimed to assess the differential miRNA profile in pancreatic tissue of patients with CP and pancreatic cancer.

Methods

MiRNAs were isolated from formalin-fixed paraffin-embedded pancreatic tissue of 22 PDAC patients, 18 CP patients, and 10 normal pancreatic tissues from autopsy (C) cases and processed for next-generation sequencing. Known and novel miRNAs were identified and analyzed for differential miRNA expression, target prediction, and pathway enrichment between groups.

Results

Among the miRNAs identified, 166 known and 17 novel miRNAs were found exclusively in PDAC tissues, while 106 known and 10 novel miRNAs were found specifically in CP tissues. The pathways targeted by PDAC-specific miRNAs and differentially expressed miRNAs between PDAC versus CP tissues and PDAC versus control tissues were the proteoglycans pathway, Hippo signaling pathway, adherens junction, and transforming growth factor-β signaling pathway.

Conclusions

This study resulted in a set of exclusive and differentially expressed miRNAs in PDAC and CP can be assessed for their diagnostic value. In addition, studying the role of miRNA-target gene interactions in carcinogenesis may open new therapeutic avenues.
Fatty Liver, Statin Therapy, and the Risk of Hypertriglyceridemic Acute Pancreatitis
Authors: Chen Chunyan , Zhang Yu , Ding Zhengdong , Zhu Suyan
Published: February 2024

Objectives

Identifying patients with severe hypertriglyceridemia (HTG) who are prone to developing hypertriglyceridemic pancreatitis (HTGP) is essential for facilitating preventative interventions. This research aims to explore which part of the HTG patients is easy to develop into HTGP.

Materials and Methods

An observational cohort study was conducted in patients with serum triglycerides (TGs) ≥ 5.65 mmol/L. Propensity score matching (PSM) and logistic regression were used to adjust for potential confounding factors. Receiver operating characteristic (ROC) curves were applied to evaluate the predictive potential for HTGP.

Results

A total of 283 patients were included finally with a PSM cohort consisting of 55 HTGP matched with 77 non-HTGP. In multivariate logistic regression analysis, fatty liver (FL) (odds ratio, 2.535; P = 0.019) showed statistically significant association with HTGP, whereas statin use was correlated with a lower rate of HTGP (odds ratio, 0.203; P = 0.009). Finally, the ROC analysis showed that the TGs threshold thought to be causal of HTGP in patients with FL was significantly lower (9.31 vs 14.67 mmol/L) than that in patients without FL.

Conclusions

Although with lower TGs levels, patients with FL are much more prone to generate HTGP, and our findings suggest a potential role of statin as protective agents against HTGP.
Pancreatic Paragonimiasis in Children
Authors: Mu Xiaolong , Zhao Mingjun , Zhao Junbo
Published: February 2024

A few pediatric cases of abdominal paragonimiasis have been described. Here we describe a case of pulmonary and abdominal paragonimiasis with involvement of the pancreas in a 9-year-old boy. The aim of this study was to analyze the clinical and radiological features of pancreatic paragonimiasis in children and raise the awareness of this disease.
Examining the psychometric characteristics of the metacognition questionnaire in teaching: a cross-sectional study
Authors: Rezaeisharif Ali , Ghorbani Mehdi , Naeim Mahdi , Imannezhad Shima
Published: February 2024

Background:

The role of metacognition as a common concept in education is undeniable. One of the challenges in the field of metacognition is to measure the impact of metacognition in teaching with practical tools. Therefore, this study aimed to investigate the psychometric characteristics of the metacognition questionnaire in teaching.

Methods:

In this cross-sectional study, the statistical population of the study included all teachers in 2020 which was selected by an available sampling method of 137 people. The data were collected using a teacher’s metacognition questionnaire (TMI). A Confirmatory, Pearson correlation coefficient was used to analyze the data. For this purpose, the use of SPSS-25 and LISREL software has been used.

Results:

of exploratory and confirmatory factor analysis indicate that. The validity and retest of the total score were calculated to be 0.93 and 0.86, respectively. The credibility of its subscales was also acceptable.

Conclusion:

As a result, it can be stated that the questionnaire has the proper psychometric properties for use in Iranian society and can be used as a valid tool for identifying teachers with teaching problems and teaching methods.
Improving Direct Admissions to Internal Medicine Services
Authors: Scheetz Seth , Prochaska Micah , Roy Rukmini , Nguyen Khanh T.
Published: February 2024

Background

Direct admissions from clinic or home to the hospital may improve efficiency and reduce emergency room utilization, but nonoptimized processes may increase the risk of harm during the transition of care. Our multidisciplinary team aimed to understand and improve the process of directly admitting patients to inpatient medicine services at a large academic medical center.

Methods

In this single-institution quality improvement initiative, we identified key communication gaps within the direct admission process and implemented a handoff tool in the form of a templated note and order set to bridge those communication gaps. The primary outcome measure was the monthly utilization rate of the handoff note as a surrogate for handoffs and uptake of the intervention.

Results

We launched our intervention in April 2022. We achieved sustained use of the SmartText and a peak of 24% of direct admissions utilizing the SmartText in January 2023. Based on feedback during Plan-Do-Study-Act cycles, we added direct admission instructions for outpatient teams to follow in the order set and reduced text in the handoff note.

Conclusions

This study demonstrates the design and implementation of a quality improvement initiative to identify and address communication gaps for direct admissions of adult medicine patients.
Comparison of WHO-UMC and Naranjo Scales for Causality Assessment of Reported Adverse Drug Reactions
Authors: Pandit Sukant , Soni Dhruve , Krishnamurthy Bhaskar , Belhekar Mahesh N.
Published: February 2024

Objectives

The 2 most commonly used scales worldwide are the World Health Organization–Uppsala Monitoring Centre (WHO-UMC) and the Naranjo scales. The present study was planned to assess the degree of agreement between the 2 scales when the same adverse drug reactions (ADR) were assessed by 5 raters independently.

Methods

One hundred individual case safety reports were selected randomly from the ADR database of our institute and the details were emailed to 5 different experts (raters), who were DM Clinical Pharmacology residents from different institutes in India. An independent causality assessment of these ADRs was performed independently by these raters using both the WHO-UMC and Naranjo causality assessment scales. The agreement between the 2 scales was assessed for each rater using Cohen κ, and the overall interrater agreement was assessed using Fleiss κ.

Results

The Cohen κ level of agreement between the 2 scales for the 5 raters were substantial, fair, substantial, moderate, and substantial, respectively. The most common causality assessment category as per WHO-UMC scale was “possible” but varied among the raters on the Naranjo scale. No ADR was categorized as “certain” by any rater on the Naranjo scale. The Fleiss κ value for agreement among the 5 raters was found to be 0.2 (slight) for the WHO-UMC scale and 0.297 (fair) for the Naranjo scale.

Conclusions

A moderate level of agreement was observed in this study between the WHO-UMC and Naranjo scales. The level of agreement among these 5 raters was found to be similar for the WHO-UMC and the Naranjo scales, indicating a similar degree of subjectivity for the 2 scales. Hence, more robust and less subjective scales are required for causality assessment.
Maxillary Artery Traversing Through the Temporal Muscle
Authors: Dumitru Cătălin C. , Rusu Mugurel C. , Vrapciu Alexandra D.
Published: February 2024

Few previous dissection reports demonstrated the possible course of the maxillary artery (MA) through the temporalis muscle (TM). A dissection study performed a long time ago established a 2% prevalence of this variant. As the variant was not studied on angiograms, we decided to do so. One hundred seventy archived computed tomography angiograms were used on 95 male and 75 female patients. The MA course through the TM was found in 11/170 cases (6.47%) but in 16/340 sides (5.58%). This is because, in 5/11 cases, the variant was bilateral. Therefore, preoperative computed tomography angiography could be helpful when surgical procedures using either the TM or the MA are designed. The course of the MA is variable, either deep or through the TM.
Should opioids be used for breathlessness and in whom? A PRO and CON debate of the evidence
Authors: Ekström Magnus , Janssen Daisy J.A.
Published: February 2024

Purpose of review

The net clinical benefit of opioids for chronic breathlessness has been challenged by recent randomized clinical trials. The purpose was to review and weigh the evidence for and against opioid treatment for chronic breathlessness in people with serious disease.

Recent findings

Evidence to date on the efficacy and safety of opioids for chronic breathlessness was reviewed. Findings supporting a benefit from opioids in meta-analyses of earlier, mostly smaller trials were not confirmed by recent larger trials. Evidence pertains mostly to people with chronic obstructive pulmonary disease but also to people with pulmonary fibrosis, heart failure, and advanced cancer. Taken together, there is no consistent evidence to generally recommend opioids for severe breathlessness or to identify people who are more likely to benefit. Opioid treatment may be tested in patients with intractable breathlessness and limited other treatment options, such as in end-of-life care. Knowledge gaps were identified and recommendations were made for future research.

Opioids cannot be generally recommended for treating breathlessness based on insufficient evidence for net clinical benefit.
Case studies associated with the 10 major geodiversity-related topics
Authors: Gray Murray
Published: February 2024

This paper outlines the 10 major topics related to geodiversity that have emerged since the concept was first introduced in 1993, 30 years ago. After a short introduction, each of the 10 topics is then illustrated by a relevant case study. The 10 topics (italics) and their case studies (bold) are as follows: 1.
Celebrating
,
International Geodiversity Day
; 2.
Measurement/Assessment
,
Potential role of remote sensing
; 3.
Natural Capital and Geosystem Services
,
Coastal geosystem services
; 4.
Biodiversity
,
Mangue de Pedra, Brazil
; 5.
Geomaterials
,
The circular economy
; 6.
Geotourism
,
World's top geotourism sites?
; 7.
Geoheritage
,
Landscape restoration
; 8.
National Geoconservation
,
Trump golf course and an SSSI, Scotland
; 9.
World Heritage Sites and Global Geoparks
,
Azores Global Geopark, Portugal
; 10.
Sustainability
,
Xitle Volcano, Mexico City
. It is concluded that, given the way in which geodiversity has developed as a concept, leading to new insights and avenues of research and advancing our understanding of the world since its first use, it clearly now constitutes a significant, geoscientific paradigm.

This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Quantitative measurement of geodiversity uniqueness: research implications and conservation applications
Authors: Alahuhta Janne , García-Girón Jorge , Hjort Jan , Salminen Henriikka , Tukiainen Helena , Heino Jani
Published: February 2024

Quantitative approaches are needed to complement qualitative explorations to identify sites with unique geodiversity and thereby guide geoconservation and geoheritage programmes. Here, we introduce the concept and associated index of ‘geodiversity uniqueness’. This index is based on a numerical analysis of geofeatures and allows the identification of sites with unique geodiversity in a study area. We applied this approach to geofeature data from three areas in Finland. Our results showed that patterns of geodiversity uniqueness varied profoundly among the three study areas and across sites within each area. This was due to different sets of geofeatures and distinct characteristics of each study area. More importantly, the approach presented here was robust across the datasets and selection criteria for sets of sites, showing potential for geoconservation in each study area. The geodiversity uniqueness approach is a promising starting point to identify and map sites with unique geodiversity that can be further verified using field observations. To improve our knowledge of geodiversity variation, complementary approaches providing objective information on contributions to total beta geodiversity are needed to advance geoconservation programmes across areas and different spatial scales.

This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Geodiversity data for Europe
Authors: Toivanen M. , Maliniemi T. , Hjort J. , Salminen H. , Ala-Hulkko T. , Kemppinen J. , Karjalainen O. , Poturalska A. , Kiilunen P. , Snåre H. , Leppiniemi O. , Makopoulou E. , Alahuhta J. , Tukiainen H.
Published: February 2024

Geodiversity is an essential part of nature's diversity. However, geodiversity is insufficiently understood in terms of its spatial distribution and its relationship to biodiversity over large spatial extents. Here, we present European geodiversity data at resolutions of 1 km and 10 km. We assess terrestrial geodiversity quantitatively as a richness variable (georichness) using a commonly employed grid-based approach. The data incorporate aspects of geological, pedological, geomorphological and hydrological diversity, which are also available as separate richness variables. To evaluate the data, we correlated European georichness with empirically tested national georichness data from Finland, revealing a positive correlation at both 1 km (

r
p

 = 0.37,
p
 < 0.001) and 10 km (

r
p

 = 0.59,
p
 < 0.001) resolutions. We also demonstrate potential uses of the European data by correlating georichness with vascular plant species richness in two contrasting example areas: Finland and Switzerland. The positive correlations between georichness and species richness in Finland (

r
p

 = 0.34,
p
 < 0.001) and Switzerland (

r
p

 = 0.26,
p
 < 0.001) further support the use of our data in geodiversity–biodiversity research. Moreover, there is great potential beyond geodiversity–biodiversity questions, as the data can be exploited across different regions, ecosystems and scales. These geodiversity data provide an insight on abiotic diversity in Europe and establish a quantitative large-scale geodiversity assessment method applicable worldwide.

This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Extra-intestinal pathogenic lineages of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are associated with prolonged ESBL gene carriage
Authors: van der Putten Boas C.L. , van Hattem Jarne M. , Penders John , Consortium COMBAT , Mende Daniel R. , Schultsz Constance
Published: February 2024

Objectives. Extended-spectrum β-lactamase-producing

Escherichia coli

(ESBL-Ec) are frequently acquired during international travel, contributing to the global spread of antimicrobial resistance. Human-adapted ESBL-Ec are predicted to exhibit increased intestinal carriage duration, resulting in a higher likelihood of onward human-to-human transmission. Yet, bacterial determinants of increased carriage duration are unknown. Previous studies analysed small traveller cohorts, with short follow-up times, or did not employ high-resolution molecular typing, and were thus unable to identify bacterial traits associated with long-term carriage after recent acquisition. We aimed to identify which ESBL-Ec lineages are associated with increased carriage duration after return from international travel.

Methods. In a prospective cohort study of 2001 international travellers, we analysed 160 faecal ESBL-Ec isolates from all 38 travellers who acquired ESBL-Ec during travel and subsequently carried ESBL-Ec for at least 12 months after return, by whole-genome sequencing. For 17 travellers, we confirmed the long-term carriage of ESBL-Ec strains through single nucleotide variant typing. To identify determinants of increased carriage duration, we compared the 17 long-term carriers (≥12 months of carriage) with 33 age-, sex- and destination-matched short-term carriers (<1 month of carriage). Long-read sequencing was employed to investigate long-term ESBL plasmid carriage.

Results. We show that in healthy travellers with very low antibiotic usage, extra-intestinal pathogenic lineages of

E. coli

(ExPEC) are significantly more likely to persist than other

E. coli

lineages. The long-term carriage of

E. coli

from ExPEC lineages is mainly driven by sequence type 131 and phylogroup D

E. coli

.

Conclusions. Although ExPEC lineages frequently cause extra-intestinal infections such as bloodstream infections, our results indicate that ExPEC lineages are also efficient intestinal colonizers, which potentially contributes to their onward transmission.
Age, not body size, influences flight distance in the bumble beeBombus terrestrisL. (Hymenoptera: Apidae)
Authors: Gilgenreiner Milena , Kurze Christoph
Published: February 2024

Bumble bees and honey bees provide crucial pollination service and have become important insect model system. Despite their close relation, they differ in their morphology, physiology, and social organisation. Notably, honey bees workers exhibit age-based polyethism, while bumble bees display considerable body size variation. Though body size is known to affect foraging range, behaviour, and flight ability, the influence of age remains less explored. Here we studied the flight performance (distance and speed) in aging bumble bee workers using tethered flight mills. Additionally, we measured their intertegular distance (ITD), dry mass, and fat content. Flight distance was predominantly influenced by age, challenging assumptions that age does not play a role in foraging and task allocation. Between 7 to 14 days, flight distance increased six-fold before a slight decline at the age of 21 days, aligning with age-dependent flight physiology in honey bees. Larger workers had decreasing mass-specific fat reserves, challenging the notion about their energy preservation for oocyte development. Our findings indicate that age substantially influences flight distance, impacting foraging performance and potentially altering task allocation strategies. This underscores the need to consider individual age and physiological changes alongside body size and mass in experiments involving bumble bee workers.
Genome-wide association study reveals different T cell distributions in peripheral blood of healthy individuals at high genetic risk of type 1 diabetes and long COVID
Authors: Deecke Laura , Homann Jan , Goldeck David , Luessi Felix , Vandebergh Marijne , Ohlei Olena , Toepfer Sarah , Zipp Frauke , Demuth Ilja , Morgan Sarah L. , Bertram Lars , Pawelec Graham , Lill Christina M.
Published: February 2024

The immune system plays a crucial role in many human diseases. In this context, genome-wide association studies (GWAS) offer valuable insights to elucidate the role of immunity in health and disease. The present multi-omics study aimed to identify genetic determinants of immune cell type distributions in the blood of healthy individuals and to assess whether the distributions of these cells may play a role for autoimmune and COVID-19 disease risk.

To this end, the frequencies of different immune cells in 483 healthy individuals from the Berlin Aging Study II were quantified using flow cytometry, and GWAS was performed for 92 immune cell phenotypes. Additionally, we performed linear regression analyses of immune cell distributions using polygenic risk scores (PRS) based on prior GWAS for five autoimmune diseases as well as for COVID-19 infection and post-COVID syndrome (“long COVID”).

We validated seven previously described immune loci and identified 13 novel loci showing genome-wide significant (α=5.00E-8) association with different immune cell phenotypes. The most significant novel signal was conferred by theSLC52A3locus, encoding for a riboflavin transporter protein, which was associated with naïve CD57+ CD8+ T cells (p=4.13E-17) and colocalized withSLC52A3expression. Several novel loci contained immunologically plausible candidate genes, e.g., variants nearTBATAandB3GAT1representing genes associated with T cell phenotypes. The PRS of type 1 diabetes were significantly associated with CD8+ T cells at different differentiation states (p≤7.02E-4), and PRS of long COVID were associated with early-differentiated CD4+ T cells (p≤1.54E-4).

In conclusion, our extensive immune cell GWAS analyses highlight several novel genetic loci of likely relevance for immune system function. Furthermore, our PRS analyses point to a shared genetic basis between immune cell distributions in healthy adults and T1D (CD8+ T cells) as well as long COVID (CD4+ T cells).
High Throughput Deep Learning Detection of Mitral Regurgitation
Authors: Vrudhula Amey , Duffy Grant , Vukadinovic Milos , Liang David , Cheng Susan , Ouyang David
Published: February 2024

Background

Diagnosis of mitral regurgitation (MR) requires careful evaluation of echocardiography with Doppler imaging. This study presents the development and validation of a fully automated deep learning pipeline for identifying apical-4-chamber view videos with color Doppler and detection of clinically significant (moderate or severe) mitral regurgitation from transthoracic echocardiography studies.

Methods

A total of 58,614 studies (2,587,538 videos) from Cedars-Sinai Medical Center (CSMC) were used to develop and test an automated pipeline to identify apical-4-chamber view videos with color Doppler across the mitral valve and then assess mitral valve regurgitation severity. The model was tested on an internal test set of 1,800 studies (80,833 videos) from CSMC and externally evaluated in a geographically distinct cohort of 915 studies (46,890 videos) from Stanford Healthcare (SHC).

Results

In the held-out CSMC test set, the view classifier demonstrated an AUC of 0.998 (0.998 - 0.999) and correctly identified 3,452 of 3,539 MR color Doppler videos (sensitivity of 0.975 (0.968-0.982) and specificity of 0.999 (0.999-0.999) compared with manually curated videos). In the external test cohort from SHC, the view classifier correctly identified 1,051 of 1,055 MR color Doppler videos (sensitivity of 0.996 (0.990 – 1.000) and specificity of 0.999 (0.999 – 0.999) compared with manually curated videos). For evaluating clinically significant MR, in the CSMC test cohort, moderate-or-severe MR was detected with AUC of 0.916 (0.899 - 0.932) and severe MR was detected with an AUC of 0.934 (0.913 - 0.953). In the SHC test cohort, the model detected moderate-or-severe MR with an AUC of 0.951 (0.924 - 0.973) and severe MR with an AUC of 0.969 (0.946 - 0.987).

Conclusions

In this study, we developed and validated an automated pipeline for identifying clinically significant MR from transthoracic echocardiography studies. Such an approach has potential for automated screening of MR and precision evaluation for surveillance.
MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn’s disease
Authors: Layunta Elena , Jäverfelt Sofia , van de Koolwijk Fleur C. , Sivertsson Molly , Dolan Brendan , Arike Liisa , Thulin Sara , Vallance Bruce A. , Pelaseyed Thaher
Published: February 2024

Crohn’s disease (CD) is the chronic inflammation of the ileum and colon triggered by bacteria, but insights into molecular perturbations at the bacteria-epithelium interface are limited. We report that membrane mucin MUC17 protects small intestinal enterocytes against commensal and pathogenic bacteria. In non-inflamed CD ileum, reduced MUC17 levels correlated with a compromised glycocalyx, allowing bacterial contact with enterocytes.Muc17deletion in mice rendered the small intestine prone to atypical infection while maintaining resistance to colitis. The loss of Muc17 resulted in spontaneous deterioration of epithelial homeostasis and extra-intestinal translocation of bacteria. Finally, Muc17-deficient mice harbored specific small intestinal bacterial taxa observed in CD. Our findings highlight MUC17 as an essential line of defense in the small intestine with relevance for early epithelial defects in CD.

One-sentence summary

Membrane mucin MUC17 protects enterocytes against bacterial attachment and constitutes an early defect in Crohn’s disease.
UXS1 regulates UDP-GlcA levels to support growth of UGDH-high cancer cells
Authors: Wang Yunyi , Zhou Chen , Bou-Tayeh Berna , Lisle Richard , Kriaucionis Skirmantas , Shi Yang
Published: February 2024

Identifying genes that are crucial for cancer cell survival but dispensable in normal cells holds immense therapeutic potential. The DepMap Consortium’s extensive datasets have paved the way for uncovering such selectively essential genes in cancer. However, it remained challenging to efficiently prioritize understudied, selectively essential genes for validation and characterization. To this end, our lab has previously ranked and prioritized potentially understudied, selectively essential genes based on their PubMed publication numbers. This approach led to successful identification and detailed characterization of two top understudied genes. Building on this methodology, our current research identified UXS1, an enzyme responsible for catalyzing the conversion from UDP-glucuronic acid (UDP-GlcA) to UDP-xylose, as a selectively essential gene in cancer cells expressing elevated levels of UGDH, an enzyme responsible for producing UDP-GlcA. Through an integrated approach combining genetic and biochemical assays, we discovered that UXS1 plays a critical role in these UGDH-overexpressing cancer cells by preventing the harmful buildup of UDP-GlcA, which otherwise would lead to cellular toxicity. Our findings not only validate our strategy for prioritizing underexplored but potentially pivotal selectively essential genes but also highlight UXS1 as a potential vulnerability and therapeutic target in cancers characterized by high UGDH expression.
Investigating EMT-mediated resistance to EGFR tyrosine kinase inhibitors in NSCLC using innovative organoid models
Authors: Kobayashi Nobuaki , Katakura Seigo , Fukuda Nobuhiko , Teranishi Shuhei , Kubo Sousuke , Kamimaki Chisato , Matsumoto Hiromi , Somekawa Kohei , Kaneko Ayami , Ishikawa Yoshihiro , Okudela Koji , Sekine Keisuke , Kaneko Takeshi
Published: February 2024

Background

Epithelial-mesenchymal transition (EMT) has emerged as a key mechanism underlying resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). However, the intricacies of EMT-mediated resistance, driven by tumor microenvironment (TME) interactions, remain enigmatic. This study aimed to probe EMT-induced resistance in NSCLC using innovative in vitro organoid models.

Methods

We generated organoids by co-culturing EGFR-mutant NSCLC cells (HCC827, H1975), mesenchymal stem cells and endothelial cells. Drug susceptibility was compared between organoids and spheroids (cancer cells only) using EGFR TKIs - Gefitinib, Afatinib, Osimertinib. EMT marker (E-cadherin, ZEB1) expression was analyzed via immunofluorescence and western blotting. The effects of Bevacizumab and miR200c on overcoming resistance were also investigated.

Results

The study identified a significant link between EMT and EGFR-TKI resistance. Notable findings included the decrease of E-cadherin and an increase in ZEB1, both of which influenced EMT and resistance to treatment. Bevacizumab showed promise in improving drug resistance and mitigating EMT, suggesting an involvement of the VEGF cascade. Transfection with miR200c was associated with improved EMT and drug resistance, further highlighting the role of EMT in TKI resistance.

Conclusions

This study offered vital insights into EMT-driven EGFR TKI resistance, highlighting the utility of organoid models in evaluating resistance modulated by TME interactions. Our findings reveal promising directions for overcoming EMT-mediated resistance involving Bevacizumab and miR200c, warranting further in vivo validation.
Polygenic architecture of adaptation to a high-altitude environment forDrosophila melanogasterwing shape and size
Authors: Pelletier Katie , Bilodeau Megan , Pellizzari-Delano Isabella , Siemon M. Daniel , Huang Yuheng , Pool John E. , Dworkin Ian
Published: February 2024

As is typical of small insects, populations ofDrosophila melanogasteradapted to high altitude environments evolved increased body size, disproportionality large wings, and differing wing shape compared to low-altitude ancestors. In one instance the colonization of high-altitude environments in Ethiopia is recent (2000-3000 years ago), and is a useful system to study alleles contributing to adaptive divergence. Unlike predictions derived from formulations Fisher-Kimura-Orr geometric model based onde novomutations concurrent with selection, recent models predict segregating alleles in a population are more likely to contribute to adaptation on short time scales, particularly when populations are large and genetically diverse, likeD. melanogaster. Strains derived from lowland (∼500m above sea level – ASL) and highland (∼3000m ASL) populations were used to generate F20 advanced-intercrosses. From each cross, phenotypically extreme individuals for size and shape were pool-sequenced, and genetic differentiation among pools of individuals demonstrated a polygenic architecture of divergence for size and shape. We identified one QTL of large effect, contributing to adaptive divergence in shape. This QTL is not observed in all crosses, pointing to the importance of examining independent genetic backgrounds when mapping alleles contributing to adaptation. Despite the intrinsic links between shape and size, we find a unique genetic basis of adaptation for these traits. This work demonstrates that many alleles, throughout the genome, rather than single, large effect alleles, contribute to adaption forDrosophilawing shape and size, adding to the growing body of evidence for polygenic adaptation.
Using machine learning to integrate genetic and environmental data to model genotype-by-environment interactions
Authors: Fernandes Igor K. , Vieira Caio C. , Dias Kaio O. G. , Fernandes Samuel B.
Published: February 2024

Complementing phenotypic traits and molecular markers with high-dimensional data such as climate and soil information is becoming a common practice in breeding programs. This study explored new ways to integrate non-genetic information in genomic prediction models using machine learning (ML). Using the multi-environment trial data from the Genomes To Fields initiative, different models to predict maize grain yield were adjusted using various inputs: genetic, environmental, or a combination of both, either in an additive (genetic-and-environmental; G+E) or a multiplicative (genotype-by-environment interaction; GEI) manner. When including environmental data, the mean predictive ability of machine learning genomic prediction models increased from 7-9% over the well-established Factor Analytic Multiplicative Mixed Model (FA) among the three cross-validation scenarios evaluated. Moreover, using the G+E model was more advantageous than the GEI model given the superior, or at least comparable, predictive ability, the lower usage of computational memory and time, and the flexibility of accounting for interactions by construction. Our results illustrate the flexibility provided by the ML framework, particularly with feature engineering. We show that the featured engineering stage offers a viable option for envirotyping and generates valuable information for machine learning-based genomic prediction models. Furthermore, we verified that the genotype-by-environment interactions may be considered using tree-based approaches without explicitly including interactions in the model. These findings support the growing interest in merging high-dimensional genotypic and environmental data into predictive modeling.

Key message

Incorporating feature-engineered environmental data into machine learning-based genomic prediction models is an efficient approach to model genotype-by-environment interactions.
TopoQual polishes circular consensus sequencing data and accurately predicts quality scores
Authors: Weerakoon Minindu , Lee Sangjin , Mitchell Emily , Heaton Haynes
Published: February 2024

Pacific Biosciences (PacBio) circular consensus sequencing (CCS) aka high fidelity (HiFi) technology has revolutionized modern genomics by producing long (10+kb) and highly accurate reads by sequencing circularized DNA molecules multiple times and combining them into a consensus sequence. Currently the accuracy and quality value estimation is more than sufficient for genome assembly and germline variant calling, but the estimated quality scores are not accurate enough for confident somatic variant calling on single reads. Here we introduce TopoQual, a tool utilizing partial order alignments (POA), topologically parallel bases, and deep learning to polish consensus sequences and more accurately predict base qualities. We correct ~31.9% of errors in PacBio consensus sequences and validate base qualities up to q59 which is one error in 0.9 million bases enabling accurate somatic variant calling with HiFi data.

Availability and implementation

The source code and installation instructions as well as validation dataset used are freely available athttps://github.com/lorewar2/TopoQual
Physiotherapy Under Pressure: A Cross-Sectional Study on The Interplay Between Perfectionism, Moral Injury, and Burnout
Authors: Biggs Daniel , Blackburn Laura , Black Cameron , Shanmugam Sivaramkumar
Published: February 2024

Background

Given the escalating challenges for UK-based physiotherapists in workload pressures, budget constraints, staff shortages and patient wait times, the profession (of 65,000 registered physiotherapists) requires immediate care and review of therapist health. This pioneering study aims to examine perfectionism, moral injury, and burnout among UK-based physiotherapists across the NHS, private practice, sports, and academia.

Method

This cross-sectional study utilised an online survey and implementation of Structure Equation Modelling (SEM) to assess the interplay of Perfectionism (Multidimension Perfectionism Scale-Short Form), Moral Injury (Moral Injury Symptoms Scale-Healthcare Professionals) and Burnout (Shirom-Melamed Burnout Questionnaire). Our sample size calculation shows representation of the UK physiotherapy profession via utilisation of 95% confidence interval with a 5% margin of error.

Findings

Our analysis conducted on (n=402) UK-based physiotherapists reveals significant burnout levels – 96% are categorised as moderate to high. Furthermore, associations and SEM of Perfectionism and Moral Injury collectively account for a substantial proportion of burnout variability (r2.62), highlighting their sequential impact on burnout manifestation.

Interpretation

With such high levels of burnout, urgent intervention is paramount. Elevated burnout presents challenges for the physiotherapy profession as staff retention, accurate and effective patient care, and overall health are severely impacted due to burnout. Recognising and addressing perfectionism and moral injury becomes pivotal to mitigate its impact on individual and collective health.

Funding

No funding was acquired for this research project.
Conformal Triage for Medical Imaging AI Deployment
Authors: Angelopoulos Anastasios N. , Pomerantz Stuart , Do Synho , Bates Stephen , Bridge Christopher P. , Elton Daniel C. , Lev Michael H. , González R. Gilberto , Jordan Michael I. , Malik Jitendra
Published: February 2024

Background

The deployment of black-box AI models in medical imaging presents significant challenges, especially in maintaining reliability across different clinical settings. These challenges are compounded by distribution shifts that can lead to failures in reproducing the accuracy attained during the AI model’s original validations.

Method

We introduce the conformal triage algorithm, designed to categorize patients into low-risk, high-risk, and uncertain groups within a clinical deployment setting. This method leverages a combination of a black-box AI model and conformal prediction techniques to offer statistical guarantees of predictive power for each group. The high-risk group is guaranteed to have a high positive predictive value, while the low-risk group is assured a high negative predictive value. Prediction sets are never constructed; instead, conformal techniques directly assure high accuracy in both groups, even in clinical environments different from those in which the AI model was originally trained, thereby ameliorating the challenges posed by distribution shifts. Importantly, a representative data set of exams from the testing environment is required to ensure statistical validity.

Results

The algorithm was tested using a head CT model previously developed by Do and col-leagues [9] and a data set from Massachusetts General Hospital. The results demonstrate that the conformal triage algorithm provides reliable predictive value guarantees to a clinically significant extent, reducing the number of false positives from 233 (45%) to 8 (5%) while only abstaining from prediction on 14% of data points, even in a setting different from the training environment of the original AI model.

Conclusions

The conformal triage algorithm offers a promising solution to the challenge of deploying black-box AI models in medical imaging across varying clinical settings. By providing statistical guarantees of predictive value for categorized patient groups, this approach significantly enhances the reliability and utility of AI in optimizing medical imaging workflows, particularly in neuroradiology.
Will ChatGPT-4 improve the quality of medical abstracts?
Authors: Gravel Jocelyn , Dion Chloé , Fadaei Kermani Mandana , Mousseau Sarah , Osmanlliu Esli
Published: February 2024

Background

ChatGPT received recognition for medical writing. Our objective was to evaluate whether ChatGPT 4.0 could improve the quality of abstracts submitted to a medical conference by clinical researchers.

Methods

This was an experimental study involving 24 international researchers who provided one original abstract intended for submission at the 2024 Pediatric Academic Society (PAS) conference. We created a prompt asking ChatGPT-4 to improve the quality of the abstract while adhering PAS submission guidelines. Researchers received the revised version and were tasked with creating a final abstract. The quality of each version (original, ChatGPT and final) was evaluated by the researchers themselves using a numeric scale (0-100). Additionally, three co-investigators assessed abstracts blinded to the version. The primary analysis focused on the mean difference in scores between the final and original abstracts.

Results

Abstract quality varied between the three versions with mean scores of 82, 65 and 90 for the original, ChatGPT and final versions, respectively. Overall, the final version displayed significantly improved quality compared to the original (mean difference 8.0 points; 95% CI: 5.6-10.3). Independent ratings by the co-investigator confirmed statistical improvements (mean difference 1.10 points; 95% CI: 0.54-1.66). Researchers identified minor (n=10) and major (n=3) factual errors in ChatGPT’s abstracts.

Conclusion

While ChatGPT 4.0 does not produce abstracts of better quality then the one crafted by researchers, it serves as a valuable tool for researchers to enhance the quality of their own abstracts. The utilization of such tools is a potential strategy for researchers seeking to improve their abstracts.

Funding

None