bluuebunny/crossref_metadata_2025_split huggingface dataset:
CASCC: a co-expression-assisted single-cell RNA-seq data clustering method
Authors: Cai Lingyi , Anastassiou Dimitris 
Published: April 2024

Abstract

Summary
Existing clustering methods for characterizing cell populations from single-cell RNA sequencing are constrained by several limitations stemming from the fact that clusters often cannot be homogeneous, particularly for transitioning populations. On the other hand, dominant cell populations within samples can be identified independently by their strong gene co-expression signatures using methods unrelated to partitioning. Here, we introduce a clustering method, CASCC (co-expression-assisted single-cell clustering), designed to improve biological accuracy using gene co-expression features identified using an unsupervised adaptive attractor algorithm. CASCC outperformed other methods as evidenced by multiple evaluation metrics, and our results suggest that CASCC can improve the analysis of single-cell transcriptomics, enabling potential new discoveries related to underlying biological mechanisms.

Availability and implementation
The CASCC R package is publicly available at https://github.com/LingyiC/CASCC and https://zenodo.org/doi/10.5281/zenodo.10648327.
RecGraph: recombination-aware alignment of sequences to variation graphs
Authors: Avila Cartes Jorge , Bonizzoni Paola , Ciccolella Simone , Della Vedova Gianluca , Denti Luca , Didelot Xavier , Monti Davide Cesare , Pirola Yuri 
Published: April 2024

Abstract

Motivation
Bacterial genomes present more variability than human genomes, which requires important adjustments in computational tools that are developed for human data. In particular, bacteria exhibit a mosaic structure due to homologous recombinations, but this fact is not sufficiently captured by standard read mappers that align against linear reference genomes. The recent introduction of pangenomics provides some insights in that context, as a pangenome graph can represent the variability within a species. However, the concept of sequence-to-graph alignment that captures the presence of recombinations has not been previously investigated.

Results
In this paper, we present the extension of the notion of sequence-to-graph alignment to a variation graph that incorporates a recombination, so that the latter are explicitly represented and evaluated in an alignment. Moreover, we present a dynamic programming approach for the special case where there is at most a recombination—we implement this case as RecGraph. From a modelling point of view, a recombination corresponds to identifying a new path of the variation graph, where the new arc is composed of two halves, each extracted from an original path, possibly joined by a new arc. Our experiments show that RecGraph accurately aligns simulated recombinant bacterial sequences that have at most a recombination, providing evidence for the presence of recombination events.

Availability and implementation
Our implementation is open source and available at https://github.com/AlgoLab/RecGraph.
Improving traumatic fracture detection on radiographs with artificial intelligence support: a multi-reader study
Authors: Bachmann Rikke , Gunes Gozde , Hangaard Stine , Nexmann Andreas , Lisouski Pavel , Boesen Mikael , Lundemann Michael , Baginski Scott G 
Published: April 2024

Abstract

Objectives
The aim of this study was to evaluate the diagnostic performance of nonspecialist readers with and without the use of an artificial intelligence (AI) support tool to detect traumatic fractures on radiographs of the appendicular skeleton.

Methods
The design was a retrospective, fully crossed multi-reader, multi-case study on a balanced dataset of patients (≥2 years of age) with an AI tool as a diagnostic intervention. Fifteen readers assessed 340 radiographic exams, with and without the AI tool in 2 different sessions and the time spent was automatically recorded. Reference standard was established by 3 consultant radiologists. Sensitivity, specificity, and false positives per patient were calculated.

Results
Patient-wise sensitivity increased from 72% to 80% (P &lt; .05) and patient-wise specificity increased from 81% to 85% (P &lt; .05) in exams aided by the AI tool compared to the unaided exams. The increase in sensitivity resulted in a relative reduction of missed fractures of 29%. The average rate of false positives per patient decreased from 0.16 to 0.14, corresponding to a relative reduction of 21%. There was no significant difference in average reading time spent per exam. The largest gain in fracture detection performance, with AI support, across all readers, was on nonobvious fractures with a significant increase in sensitivity of 11 percentage points (pp) (60%-71%).

Conclusions
The diagnostic performance for detection of traumatic fractures on radiographs of the appendicular skeleton improved among nonspecialist readers tested AI fracture detection support tool showed an overall reader improvement in sensitivity and specificity when supported by an AI tool. Improvement was seen in both sensitivity and specificity without negatively affecting the interpretation time.

Advances in knowledge
The division and analysis of obvious and nonobvious fractures are novel in AI reader comparison studies like this.
Current prescribing for pyoderma gangrenosum in the UK and access to biologic medications: results from a UK Dermatology Clinical Trials Network survey of dermatologists
Authors: Jenkins Myfanwy , Watson Nicola , McPhee Margaret , Levell Nick J , Arden-Jones Mike , D Ormerod Anthony , Hampton Philip J 
Published: April 2024

Abstract
Pyoderma gangrenosum (PG) is an ulcerative inflammatory disorder affecting the lower legs in 80% of patients. The use of biologic medications to treat PG is increasing, although there is a limited evidence base to guide treatment choices. In some health systems, such as the UK National Health Service, limitations are placed on biologic prescribing for PG, leading to wide variations in prescribing. A survey of mainly UK clinicians showed that prednisolone remains the first-line treatment for PG (90%, 34/38). Biologics have been used by 66% (25/38) of clinicians as second-line therapy, but 19% (7/38) have had prescribing requests declined. Further research is needed to determine optimal treatment strategies for PG.
Predictive Value of Microfilariae-Based Stop-MDA Thresholds After Triple Drug Therapy With IDA Against Lymphatic Filariasis in Treatment-Naive Indian Settings
Authors: James Ananthu , Coffeng Luc E , Blok David J , King Jonathan D , de Vlas Sake J , Stolk Wilma A 
Published: April 2024

Abstract
Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.
Improving the Cost-efficiency of Preventive Chemotherapy: Impact of New Diagnostics on Stopping Decisions for Control of Schistosomiasis
Authors: Coffeng Luc E , Graham Matthew , Browning Raiha , Kura Klodeta , Diggle Peter J , Denwood Matthew , Medley Graham F , Anderson Roy M , de Vlas Sake J 
Published: April 2024

Abstract

Background
Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These “stopping decisions” are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed.

Methods
Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni.

Results
We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection).

Conclusions
We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.
An Updated Economic Assessment of Moxidectin Treatment Strategies for Onchocerciasis Elimination
Authors: Turner Hugo C , Kura Klodeta , Roth Barbara , Kuesel Annette C , Kinrade Sally , Basáñez Maria-Gloria 
Published: April 2024

Abstract

Background
Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies.

Methods
We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs.

Results
aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI.

Conclusions
Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.
Echocardiographic findings in cancer-associated non-bacterial thrombotic endocarditis: clinical series of 111 patients from a single institution
Authors: Kurmann Reto D , Klarich Kyle W , Wysokinska Ewa , Houghton Damon , Kaminska Alicja , Patrzalek Patryk , Hodge David , Wysokinski Waldemar E 
Published: April 2024

Abstract

Aims
Echocardiographic assessment of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE) is limited to case reports and small clinical series. The study aimed to identify heart valve abnormalities and its relation to embolic complications and cancer types.

Methods and results
Manual review of echocardiographic images and medical records of Mayo Clinic patients (31 March 2002–30 June 2022) was performed. Ca-NBTE in 111 patients (mean age 63.2 ± 9.7 years, 66.7% female) predominantly affected mitral valves (MV) (69), 56 aortic (AV), 8 tricuspid (TV), and rarely pulmonic (PV) (1). In 18 patients, 2 valves were involved, 3 and 4 valve involvement in only a single patient each. Embolic complications were prevalent (n = 102, 91.9%). Ca-NBTE affected MV more frequently on the upstream (atrial) (90% vs. 49.3%) and TV downstream (ventricular) side (75% vs. 37.5%). NBTE size (cm) varied significantly among valves, with TV hosting the largest masses (0.63–2.40 × 0.39–1.77), compared with MV [(0.11–1.81 × 0.11–1.62), (length P = 0.001; width P = 0.03)] and AV [(0.20–2.70 × 0.11–1.51), (length P = 0.001; width P = 0.056)]; MV masses were borderline longer in systemic compared with cerebral emboli (P = 0.057). Majority of MV (79.6%) and AV (69.6%) had thickened leaflets. NBTE lesions commonly affected closing margins (73.9% MV, 85.7% AV, and 62.5% of TV) but rarely commissures of MV (8.7%), yet fairly frequently of AV (41.1%). Five patients had severe regurgitation of MV and 5 AV.

Conclusion
Ca-NBTE manifests mainly as thrombotic mobile masses attached to thickened MV and AV, with distinct variations in size based on valve type. Embolic destination but not cancer type is associated with NBTE mass size and location.
High-output heart failure due to a giant left circumflex coronary aneurysm with a left atrial fistula and atrial septal defect: a case report
Authors: Lee Moses , Thomas Mariam , Joodi Golsa , Koppula Anthony , Soverow Jonathan 
Published: April 2024

Abstract

Background
A coronary artery aneurysm is a rare cardiac anomaly that may be incidentally detected on echocardiography. When associated with a coronary cameral fistula, an aneurysm can become symptomatic. We present a unique case of a giant left circumflex coronary aneurysm with a fistula to the left atrium and a large atrial septal defect causing acute heart failure in a young woman during the peripartum period.

Case summary
A 32 year-old woman who presented with hypoxia after the delivery of her fourth child was found to have heart failure with severe mitral regurgitation and multiple abnormal intracardiac shunts. Echocardiography showed a large circular structure with Doppler color flow into the left atrium and between the atria. Cardiac computed tomography showed multiple dilated coronary arteries including a left circumflex coronary artery aneurysm measuring &gt;10 cm in diameter with fistulous communication to the left atrium and a large atrial septal defect. A right heart catheterization was performed, and the patient was diagnosed with high-output heart failure. Surgical closure of the coronary cameral fistula was deferred due to the risk of worsening pressure in the coronary aneurysm, and the patient was referred for cardiac transplantation.

Discussion
This case illustrates severe heart failure as a complication of a giant coronary artery aneurysm with fistulization to the left atrium and subsequent shunting through a large atrial defect. Echocardiography allows for the detection of a coronary aneurysm and shunting, and cardiac computed tomography provides detailed visualization of a coronary cameral fistula.
Selection maintains a nonadaptive floral polyphenism
Authors: Gómez José María , González-Megías Adela , Armas Cristina , Narbona Eduardo , Navarro Luis , Perfectti Francisco 
Published: April 2024

Abstract
Adaptive phenotypic plasticity evolves in response to the contrasting selection pressures that arise when organisms face environmental heterogeneity. Despite its importance for understanding how organisms successfully cope with environmental change, adaptive plasticity is often assumed but rarely demonstrated. We study here the adaptive nature of the extreme seasonal within-individual floral polyphenism exhibited by the crucifer Moricandia arvensis, a Mediterranean species that produces two different types of flowers depending on the season of the year. During spring, this species has large, cross-shaped, lilac flowers, while during summer, it develops small, rounded, white flowers. Although floral polyphenism was associated with increased plant fitness, selection moved floral traits away from their local optimum values during the harsh summer. This result strongly suggests that floral polyphenism is not adaptive in M. arvensis. The main factor selecting against floral polyphenism was pollinators, as they select for the same floral morph in all environments. Despite not being adaptive, floral polyphenism occurs throughout the entire distribution range of M. arvensis and has probably been present since the origin of the species. To solve this paradox, we explored the factors causing floral polyphenism, finding that floral polyphenism was triggered by summer flowering. Summer flowering was beneficial because it led to extra seed production and was favored by adaptive plasticity in leaf functional traits. Taken together, our study reveals a complex scenario in which nonadaptive floral polyphenism has been indirectly maintained over M. arvensis evolutionary history by selection operating to favor summer flowering. Our study provides thus strong evidence that nonadaptive plasticity may evolve as a byproduct of colonizing stressful environments.
The genome of the Arctic snow alga Limnomonas spitsbergensis (Chlamydomonadales)
Authors: Hulatt Chris J , Suzuki Hirono , Détain Alexandre , Wijffels René H , Leya Thomas , Posewitz Matthew C 
Published: April 2024

Abstract
Snow algae are a diverse group of extremophilic microeukaryotes found on melting polar and alpine snowfields. They play an important role in the microbial ecology of the cryosphere, and their propagation on snow and ice surfaces may in part accelerate climate-induced melting of these systems. High-quality snow algae genomes are needed for studies on their unique physiology, adaptive mechanisms, and genome evolution under multiple forms of stress, including cold temperatures and intense sunlight. Here, we assembled and annotated the genome of Limnomonas spitsbergensis, a cryophilic biciliate green alga originally isolated from melting snow on Svalbard, in the Arctic. The L. spitsbergensis genome assembly is based primarily on the use of PacBio long reads and secondly Illumina short reads, with an assembly size of 260.248 Mb in 124 contigs. A combination of 3 alternative annotation strategies was used including protein homology, RNA-seq evidence, and PacBio full-length transcript isoforms. The best merged set of annotations identified 18,277 protein-coding genes, which were 95.2% complete based on Benchmarking Universal Single-Copy Orthologs analysis. We also provide the annotated mitogenome, which is a relatively large 77.942 kb circular mapping sequence containing extensive repeats. The L. spitsbergensis genome will provide a new resource for research on snow algae adaptation, behavior, and natural selection in unique, low-temperature terrestrial environments that are under threat from climate change.
The Affordable Care Act and income-based disparities in health care coverage and spending among nonelderly adults with cancer
Authors: Olateju Olajumoke A , Shen Chan , Thornton James Douglas 
Published: April 2024

Abstract
The Patient Protection and Affordable Care Act (ACA) significantly reduced uninsured individuals and improved financial protection; however, escalating costs of cancer treatment has led to substantial out-of-pocket expenses, causing severe financial and mental health distress for individuals with cancer. Mixed evidence on the ACA's ongoing impact highlights the necessity of assessing health-spending changes across income groups for informed policy interventions. In our nationally representative survey evaluating the early- and long-term effects of the ACA on nonelderly adult patients with cancer, we categorized individuals-based income subgroups defined by the ACA for eligibility. We found that ACA implementation increased insurance coverage, which was particularly evident after 2 years of implementation. Early post-ACA (within two years of implementation), there were declines in out-of-pocket spending for the lowest and low-income groups by 26.52% and 38.31%, respectively, persisting long-term only for the lowest-income group. High-income groups experienced continuously increased out-of-pocket and premium spending by 25.39% and 34.28%, respectively, with a notable 122% increase in the risk of high-burden spending. This study provides robust evidence of income-based disparities in financial burden for cancer care, emphasizing the need for health care policies promoting equitable care and addressing spending disparities across income brackets.
Four novel Cit7GlcTs functional in flavonoid 7-O-glucoside biosynthesis are vital to flavonoid biosynthesis shunting in citrus
Authors: Yuan Ziyu , Li Gu , Zhang Huixian , Peng Zhaoxin , Ding Wenyu , Wen Huan , Zhou Hanxin , Zeng Jiwu , Chen Jiajing , Xu Juan 
Published: April 2024

Abstract
Citrus fruits have abundant flavonoid glycosides (FGs), an important class of natural functional and flavor components. However, there have been few reports about the modification of UDP-glycosyltransferases (UGTs) on flavonoids in citrus. Notably, in flavonoid biosynthesis, 7-O-glucosylation is the initial and essential step of glycosylation prior to the synthesis of flavanone disaccharides, the most abundant and iconic FGs in citrus fruits. Here, based on the accumulation of FGs observed at the very early fruit development stage of two pummelo varieties, we screened six novel flavonoid 7-O-glucosyltransferase genes (7GlcTs) via transcriptomic analysis and then characterized them in vitro. The results revealed that four Cg7GlcTs possess wide catalytic activities towards various flavonoid substrates, with CgUGT89AK1 exhibiting the highest catalytic efficiency. Transient overexpression of CgUGT90A31 and CgUGT89AK1 led to increases in FG synthesis in pummelo leaves. Interestingly, these two genes had conserved sequences and consistent functions across different germplasms. Moreover, CitUGT89AK1 was found to play a role in the response of citrus to Huanglongbing infection by promoting FG production. The findings improve our understanding of flavonoid 7-O-glucosylation by identifying the key genes, and may help improve the benefits of flavonoid biosynthesis for plants and humans in the future.