bluuebunny/crossref_metadata_2025 huggingface dataset:
Inheritance of feed intake-based resilience traits and their correlation with production traits in Finnish pig breeds
Authors: Kavlak Alper T , Uimari Pekka
Published: February 2024

High resilience against diseases, changing environmental conditions, and other stress factors and the ability to efficiently recover to normal status, is becoming increasingly important in pig production. Finding new phenotypes that relate to resilience is a crucial step for improving the resilience of pigs through selection. The objective of this study was to extract resilience-related phenotypes based on fluctuations in daily feed intake (DFI, g) and time spent in feeding per day (TPD, min) and to estimate the heritability of these traits and genetic correlations with production traits (PT). Resilience-related traits with high enough heritability and with either favorable or neutral genetic correlation with PT could be used in the selection program to improve the productivity and welfare of pigs. In this study, we used data from 7,347 Finnish Yorkshire, Landrace, and crossbred pigs raised at the test station. Six pig-specific resilience-related phenotypes were extracted from the individual DFI and TPD: root mean square error (RMSE), quantile regression (QR), and coefficient of variation (CV). RMSE was calculated from the differences between the actual DFI (or TPD) and the pig-specific predicted values. QR was based on the number of days that a pig belonged to the group with the lowest 5% of pigs based on DFI (or TPD), and CV was calculated over the daily observations of DFI (or TPD). PT included average daily gain (ADG, g), backfat thickness (BF, mm), and feed conversion rate (FCR, g/g). The heritability estimates for resilience-related traits varied between 0.07 ± 0.02 (QRDFI) and 0.20 ± 0.03 (RMSETPD). The genetic correlations between resilience-related traits and PT were mostly neutral, but for example, RMSEDFI had a favorable genetic correlation with FCR and BF but an unfavorable correlation with ADG. Lastly, we observed that pigs belonging to the lowest 10% group based on their breeding value (BV) for QRTPD had a lower proportion (10% incidence) of sick days compared to the highest 10% BV group (30% incidence). Therefore, pigs exhibiting small TPD variation (related to high resilience) tend to be less susceptible to sickness than pigs with large TPD variation (related to low resilience). Given its moderate heritability, neutral genetic correlation with PT, and positive effect on health, QRTPD can be considered the most promising resilience-related trait in the Finnish production system.
Research on four-bar linkage trajectory synthesis using extreme gradient boosting and genetic algorithm
Authors: Wang Jianping , Chen Boyan , Wang Youchao , Pu Dexi , Jia Xiaoyue
Published: February 2024

The current study on the synthesis problems of four-bar mechanism trajectories primarily relies on establishing a numerical atlas based on trajectory characteristics and employing neural networks to synthesize mechanism parameters. However, this approach has several shortcomings, including a vast database, inefficient retrieval, and challenges in maintaining accuracy. This paper presents a method for synthesizing a trajectory-generation mechanism that combines the extreme gradient boosting (XGBoost) algorithm with a genetic algorithm (GA). The purpose is to synthesize, based on a particular trajectory, the dimensions and installation position parameters of a four-bar mechanism. The paper classifies the trajectories according to their shape features and geometric center placements, thereby improving the accuracy of the XGBoost model for synthesizing mechanisms. The XGBoost algorithm is employed to synthesize the basic dimensional parameters for the mechanism, with the relative slopes of trajectories as input features. The synthesized basic dimensional parameters are turned into parameters for the actual mechanism by researching the scaling, translation, and rotation relationships between mechanisms and the trajectories they generate. The accuracy of the generated trajectories from the synthesized mechanism can be improved by applying GA to optimize the mechanism parameters. Five comparative examples are provided in this research for the different scenarios of given trajectory curves and trajectory points. The effectiveness and accuracy of the proposed approach in this study are validated in comparison to existing research methods by comparing errors between the generated trajectories and the given trajectories.
Ganoderic acid A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to cisplatin
Authors: Gong Enhui , Pan Jiongwei , Ye Zaiting , Cai Xiaoping , Zheng Hao , Yin Zhangyong , Jiang Yiwei , Wang Xin , Cao Zhuo
Published: February 2024

Objectives

Reportedly, ganoderic acid A (GA-A) increases the sensitivity of hepatocellular carcinoma cells to cisplatin (DDP) chemotherapy. Therefore, this study aims to fathom the influence of GA-A on lung cancer cells.

Methods

After the construction of A549/DDP cells through exposure to DDP, the effects of GA-A on A549 and A549/DDP cells were revealed by cellular functional assays, western blot and quantitative reverse transcription PCR (qRT-PCR). The DDP-resistant lung cancer tumor was established in vivo, followed by further validation of the mechanism of GA-A.

Results

GA-A suppressed the viability, migration, and invasion while downregulating Beclin and autophagy marker LC3II/LC3I levels and upregulating P62 levels in A549 and A549/DDP cells. These effects were reversed by circFLNA overexpression. Also, GA-A reinforced the sensitivity of A549/DDP cells to DDP, elevated the apoptosis and regulated the circFLNA/miR-486-3p/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/X-ray repair cross-complementing 1 (XRCC1) axis. The reversal effects of circFLNA overexpression on GA-A-induced viability and apoptosis of A549/DDP cells could all be counteracted in the presence of 3MA. GA-A inhibited lung cancer tumor growth and blocked autophagy.

Conclusion

GA-A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to DDP.
Quantifying Chemotherapy Delivery in Older and Younger Women With Early-Stage Breast Cancer Using Longitudinal Cumulative Dose
Authors: Pak Joyce , Nyrop Kirsten A , Muss Hyman B , Forster Moriah K , Lund Jennifer L
Published: February 2024

Background

Delivery of cancer treatments, such as chemotherapy, requires a complex set of decisions that can change over time. Traditional measures of chemotherapy delivery, such as relative dose intensity, measure the amount of chemotherapy received by the end of treatment but mask the timing of dose reductions, delays, and discontinuation. These events may be important for delivering timely interventions to support adherence and lower the risk of recurrence.

Materials and Methods

We used an institutional database to identify women diagnosed with stage I-III breast cancer receiving adjuvant chemotherapy with a standard 4-cycle regimen of docetaxel + cyclophosphamide (TC, every 21 days) from April 2014 to December 2019. LCD was calculated as the amount of a given chemotherapy agent delivered at a specified time, t, divided by the total planned standard chemotherapy dose at time t. We visualized LCD curves for each chemotherapy agent and reported the median LCD and interquartile range (IQR) at the end of the regimen, overall and by age group (<65 years vs. 65+ years).

Results

The study population included 80 women. At the end of treatment, overall median LCDs for both cyclophosphamide and docetaxel were 100% (IQR: 99.6%, 100%), suggesting that TC was well tolerated. However, the lower quartile LCD for cyclophosphamide was 98.7% in older women treated with TC compared with 99.7% in younger women.

Conclusion

Within our cohort, adjuvant TC was well tolerated with LCD curves showing largely on-time and full-dose administration. Subgroup analyses showed only slight decreases in adjuvant TC LCD for patients aged 65+ versus <65 years.
Exploring the Fetal Origins Hypothesis Using Genetic Data
Authors: Trejo Sam
Published: February 2024

Birth weight is a robust predictor of valued life course outcomes, emphasizing the importance of prenatal development. But does birth weight act as a proxy for environmental conditions in utero, or do biological processes surrounding birth weight themselves play a role in healthy development? To answer this question, we leverage variation in birth weight that is, within families, orthogonal to prenatal environmental conditions: one’s genes. We construct polygenic scores in two longitudinal studies (Born in Bradford, N = 2008; Wisconsin Longitudinal Study, N = 8488) to empirically explore the molecular genetic correlates of birth weight. A 1 standard deviation increase in the polygenic score is associated with an ~100-grams increase in birth weight and a 1.4 pp (22 percent) decrease in low birth weight probability. Sibling comparisons illustrate that this association largely represents a causal effect. The polygenic score–birth weight association is increased for children who spend longer in the womb and whose mothers have higher body mass index, though we find no differences across maternal socioeconomic status. Finally, the polygenic score affects social and cognitive outcomes, suggesting that birth weight is itself related to healthy prenatal development.
An Agent-Based Model Shows How Mixed Infections Drive Multiyear Pathotype Dynamics in a Plant–Virus System
Authors: Cuevas-Zuviria Bruno , Fraile Aurora , García-Arenal Fernando
Published: February 2024

Mathematical models are widely used to understand the evolution and epidemiology of plant pathogens under a variety of scenarios. Here, we used this approach to analyze the effects of different traits intrinsic and extrinsic to plant-virus interactions on the dynamics of virus pathotypes in genetically heterogeneous plant–virus systems. For this, we propose an agent-based epidemiological model that includes epidemiologically significant pathogen life-history traits related to virulence, transmission, and survival in the environment and allows for integrating long- and short-distance transmission, primary and secondary infections, and within-host pathogen competition in mixed infections. The study focuses on the tobamovirus−pepper pathosystem. Model simulations allowed us to integrate pleiotropic effects of resistance-breaking mutations on different virus life-history traits into the net costs of resistance breaking, allowing for predictions on multiyear pathotype dynamics. We also explored the effects of two control measures, the use of host resistance and roguing of symptomatic plants, that modify epidemiological attributes of the pathogens to understand how their populations will respond to evolutionary pressures. One major conclusion points to the importance of pathogen competition within mixed-infected hosts as a component of the overall fitness of each pathogen that, thus, drives their multiyear dynamics.
Lumpy skin disease virus ORF127 protein suppresses type I interferon responses by inhibiting K63‐linked ubiquitination of tank binding kinase 1
Authors: Liang Zhengji , Wang Shasha , Yao Kaishen , Ren Shanhui , Cheng Pengyuan , Qu Min , Ma Xiaoqin , Gao Xin , Yin Xiangping , Wang Xiangwei , Sun Yuefeng
Published: February 2024

Lumpy skin disease (LSD) is a severe animal infectious disease caused by lumpy skin disease virus (LSDV), inducing extensive nodules on the cattle mucosa or the scarfskin. LSDV genome encodes multiple proteins to evade host innate immune response. However, the underlying molecular mechanisms are poorly understood. In this study, we found that LSDV could suppress the expression of IFN‐β and interferon‐stimulated genes (ISGs) in MDBK cells during the early stage of infection. Subsequently, an unbiased screen was performed to screen the LSDV genes with inhibitory effects on the type I interferon (IFN‐I) production. ORF127 protein was identified as one of the strongest inhibitory effectors on the expression of IFN‐β and ISGs, meanwhile, the 1–43 aa of N‐terminal of ORF127 played a vital role in suppressing the expression of IFN‐β. Overexpression of ORF127 could significantly promote LSDV replication through inhibiting the production of IFN‐β and ISGs in MDBK cells. Mechanism study showed that ORF127 specifically interacted with TBK1 and decreased the K63‐linked polyubiquitination of TBK1 which suppressed the phosphorylation of TBK1 and ultimately decreased the production of IFN‐β. In addition, truncation mutation analysis indicated that the 1–43 aa of N‐terminal of ORF127 protein was the key structural domain for its interaction with TBK1. In short, these results validated that ORF127 played a negative role in regulating IFN‐β expression through cGAS‐STING signaling pathway. Taken together, this study clarified the molecular mechanism of ORF127 gene antagonizing IFN‐I‐mediated antiviral, which will helpfully provide new strategies for the treatment and prevention of LSD.
Modified Scoring of the QuickDASH Can Achieve Previously-unattained Interval-level Measurement in Dupuytren Disease and Carpal Tunnel Syndrome
Authors: Stirling Paul H.C. , McEachan Jane E. , Rodrigues Jeremy N. , Geoghegan Luke , Harrison Conrad J.
Published: February 2024

Background:

Rasch measurement theory can be used to identify scales within questionnaires and to map responses to more precise continuous scales. The aim of this article was to use RMT to refine the scoring of the QuickDASH in patients with Dupuytren disease and carpal tunnel syndrome (CTS).

Methods:

Data were collected between 2013 and 2019 from a single center in the UK. Preoperative QuickDASH responses from patients diagnosed with Dupuytren disease and CTS were used. RMT was used to reduce the number of items in the QuickDASH and examine the reliability and validity of each subscale.

Results:

The preoperative QuickDASH responses of 750 patients with Dupuytren disease and 1916 patients with CTS were used. The median age of participants was 61 years, and 46% were men. Exploratory factor analysis suggested two distinct subscales within the QuickDASH: task items 1–6 and symptom items 9–11. These items were fitted to the Rasch model, and disordered response thresholds were collapsed. In Dupuytren disease, the two worst responses or each item were disordered. After collapsing these options, good Rasch model fit was demonstrated. CTS responses fitted without modification. Item targeting was more appropriate for CTS than Dupuytren disease.

Conclusions:

This study proposes a modification to the scoring system for the QuickDASH that provides high-quality, continuous, and condition-specific scales for the QuickDASH. The identification of distinct subscales within the QuickDASH can be used to identify distinct improvements in hand function and/or symptoms in previous, current, and future work.
Prognosis of uterine and extrauterine low-grade endometrial stromal sarcoma：an observational cohort study
Authors: Dai Qianwen , Xu Baolin , Wu Huanwen , You Yan , Li Lei
Published: February 2024

Objective:

Little is known about the survival differences between uterine and extrauterine low-grade endometrial stromal sarcoma (LGESS). Survival outcomes, consisting of disease-free survivals and overall survivals, were compared in these two entities.

Methods:

From February 2012 to June 2019, all primary LGESS cases and LGESS cases with first recurrence in the study center were reviewed. The clinicopathological characteristics and survival outcomes of extrauterine and uterine LGESS patients were compared for both primary and recurrent diseases.

Results:

During the study period, 143 patients with primary LGESS and 56 patients with recurrent LGESS were included and followed up to June 1, 2020, among whom 8 (5.6%) and 10 (17.8%) patients were identified as having extrauterine LGESS. Patients with primary and recurrent extrauterine LGESS had similar clinicopathological characteristics to those of patients with uterine LGESS. In primary or in recurrent LGESS cases, in univariate analysis, patients with uterine and extrauterine LGESS had similar disease-free intervals after the last treatment, and they also had similar overall survivals after the diagnosis. Ovarian preservation led to significantly increased recurrence for primary LGESS (hazard ratio [HR] 4.9, 95% confidence interval [95% CI] 2.3-10.1, P<0.001) and repeated recurrence for recurrent LGESS (HR 3.1, 95% CI 1.3-7.3, P=0.009). Surgical treatment for recurrent LGESS decreased repeated recurrence after the first recurrence (HR 0.2, 95% CI 0.1-0.7, P=0.006). No factors were found to be associated with the overall survival of primary or recurrent LGESS.

Conclusion:

The clinical characteristics and survival outcomes of extrauterine LGESS are similar to those of uterine LGESS. Surgery is the treatment of choice for recurrent LGESS. Ovarian preservation is detrimental to disease-free survival but not to overall survival in both uterine and extrauterine LGESS.
Impact of the presence of a mediator on patient violent or uncivil behaviours in emergency departments: a cluster randomised crossover trial
Authors: Touzet Sandrine , Buchet-Poyau Karine , Denis Angélique , Occelli Pauline , Jacquin Laurent , Potinet Véronique , Sigal Alain , Delaroche-Gaudin Marine , Fayard-Gonon Florence , Tazarourte Karim , Douplat Marion
Published: February 2024

Background and importance

Several studies reported that violent behaviours were committed by patients against healthcare professionals in emergency departments (EDs). The presence of mediators could prevent or resolve situations of tension.

Objective

To evaluate whether the presence of mediators in EDs would have an impact on violent behaviours committed by patients or their relatives against healthcare professionals. Design, settings and participants A 6-period cluster randomised crossover trial was performed in 4 EDs during 12 months. Patients aged ≥18 and their relatives were included.

Intervention

In order to prevent or resolve situations of tension and conflict, four mediators were recruited.Outcome measure and analysis Using a logistic regression mixed model, the rate of ED visits in which at least one act of violence was committed by a patient or their relatives, reported by healthcare professionals, was compared between the intervention group and the control group.

Results

A total of 50 429 ED visits were performed in the mediator intervention group and 50 851 in the control group. The mediators reported 1365 interventions; >50% of the interventions were to answer questions about clinical management or waiting time. In the intervention group, 173 acts of violence were committed during 129 ED visits, and there were 145 acts of violence committed during 106 ED visits in the control group. The rate of ED visits in which at least one act of violence was committed, was 0.26% in the intervention group and 0.21% in the control group (OR = 1.23; 95% CI [0.73–2.09]); on a 4-level seriousness scale, 41.6% of the acts of violence were rated level-1 (acts of incivility or rudeness) in the intervention group and 40.0% in the control group.

Conclusion

The presence of mediators in the ED was not associated with a reduction in violent or uncivil behaviours committed by patients or their relatives. However, the study highlighted that patients had a major need for information regarding their care; improving communication between patients and healthcare professionals might reduce the violence in EDs.

Trial registration

Clinicaltrials.gov (NCT03139110).
Inguinal hernia following the use of fluid anti-adhesive agents in laparoscopic surgery: a literature review and case report
Authors: Chu Man-Jung , Huang Pei-Shen
Published: February 2024

Introduction and importance:

Inguinal hernia is a rare complication in females occurring due to the use of common anti-adhesion agents, such as ADEPT. Some complications have been reported to date; however, there are no reported cases of ADEPT-induced inguinal hernia.

Case presentation:

A 39-year-old woman underwent laparoscopic ovarian cystectomy for a right ovarian endometrioma, using ADEPT as an anti-adhesion agent. Subsequently, she developed an inguinal hernia diagnosed using pelvic computed tomography. The inguinal mass gradually decreased in size and disappeared four months after, without intervention.

Clinical discussion:

While rare complications have been reported, no cases of inguinal hernias induced by anti-adhesion agents have been reported to date. To minimize the risk of this complication, avoiding excessive intra-abdominal pressure to prevent possible peritoneal fluid migration through small orifices into low-pressure areas is advised. Additionally, applying external pressure over the superficial/deep inguinal rings until CO2 is completely removed from the abdominal cavity might be helpful.

Conclusion:

Inguinal hernia is a rare anti-adhesion solution complication in females. Minimizing the risk involves avoiding excessive intra-abdominal pressure and applying external pressure over the superficial/deep inguinal rings.
Learner Perception of Disaster Simulation Modalities
Authors: Skaltsis Jessica , Sackett Ashlee , Ellis Kerri A. , Cohen Steven A.
Published: February 2024

Background:

Both simulation and tabletop exercises are used in disaster training, but the efficacy of one approach versus the other is lacking.

Purpose:

This pilot study explored the satisfaction, confidence, and perception of effectiveness among nursing students regarding 2 disaster preparedness training methods: simulation and tabletop exercises.

Methods:

A comparative quasi-experimental design assessed the effectiveness of 2 simulation experiences. Validated effectiveness and confidence survey tools were completed by 126 self-selected senior prelicensure baccalaureate nursing students after the completion of simulation experiences.

Results:

Tabletop exercises may be more effective to build confidence and understand pathophysiology. Full-scale simulations may be more effective in facilitating participant expression of feelings and providing a constructive evaluation of the simulation.

Conclusions:

Variability among facilitators may have impacted the results of this pilot project. Further research is needed to enhance understanding of the effectiveness of tabletop and full-scale simulations for disaster preparedness in nursing education.
Maternal Psychological Symptom Trajectories from 2 to 24 Months Postpartum: A Latent Class Growth Analysis
Authors: Scroggins Jihye Kim , Reuter-Rice Karin , Brandon Debra , Yang Qing
Published: February 2024

Background

Postpartum women experience an array of psychological symptoms that are associated with adverse health behaviors and outcomes including postpartum suicidal ideation and long-term depression. To provide early management of postpartum psychological symptoms, it is important to understand how the symptom experiences change over time.

Objective

To examine maternal psychological symptom trajectories over 2, 6, 15, and 24 months postpartum using latent class growth analysis (LCGA) and to examine how each trajectory is associated with maternal depression outcome at 24 months.

Methods

We used secondary data from the Family Life Project (N = 1,122) and performed multi-trajectory LCGA based on four observed symptom variables (depression, anxiety, somatization, and hostility). After the final model was identified, bivariate analyses were conducted to examine the association between each trajectory and (a) individual characteristics and (b) outcome (Center for Epidemiologic Studies Depression Scale [CES-D]) variables.

Results

A 4-class model was selected for the final model because it had better fit indices, entropy, and interpretability. The four symptom trajectories were: (1) No symptoms over 24 months, (2) low symptoms over 24 months, (3) moderate symptoms increasing over 15 months, and (4) high symptoms increasing over 24 months. More postpartum women with the trajectory of high symptoms increasing over 24 months (Trajectory 4) were in low economic status (92.16%), unemployed (68.63%), or did not complete 4-year college education (98.04%). Most postpartum women (95.56%) in trajectory 4 also had higher CES-D cut-off scores, indicating a possible clinical depression at 24 months postpartum.

Discussion

Postpartum women who experience increasing symptom trajectories over 15 to 24 months (Trajectories 3 and 4) could benefit from tailored symptom management interventions provided earlier in the postpartum period to prevent persistent and worsening symptom experiences.
Overdosing in a Motor Vehicle: Examination of Human, Geographic, and Environmental Factors
Authors: Lopez Dahianna , Parent Jason , Stegnicki Thomas , Kenyon Zachariah , Arcoleo Kimberly , Malloy Liam C. , Mello Michael
Published: February 2024

Background

Fentanyl, a type of opioid, in impaired driving cases increased across cities in the United States.

Objectives

No empirical studies have examined motor vehicle overdoses with fentanyl use. We investigated the magnitude of the motor vehicle overdose problem in Providence, RI, and the environmental, socioeconomic, and geographic conditions associated with motor vehicle overdose occurrence.

Methods

This was a retrospective observational study of emergency medical services data on all suspected opioid overdoses between January 1, 2017, and October 31, 2020. The data contain forced-choice fields, such as age and biological sex, and an open-ended narrative in which the paramedic documented clinical and situational information. The overdoses were geocoded, allowing for the extraction of sociodemographic data from the U.S. Census Bureau’s American Community Survey. Seven other data sources were included in a logistic regression to understand key risk factors and spatial patterns of motor vehicle overdoses.

Results

Of the 1,357 opioid overdose cases in this analysis, 15.2% were defined as motor vehicle overdoses. In adjusted models, we found a 61% increase in the odds of a motor vehicle overdose involvement for men versus women, a 16.8% decrease in the odds of a motor vehicle overdose for a one-unit increase in distance to the nearest gas station, and a 10.7% decrease in the odds of a motor vehicle overdose for a one-unit increase in distance to a buprenorphine clinic.

Conclusion

There is a need to understand the interaction between drug use in vehicles to design interventions for decreasing driving after illicit drug use.
Cardiac Critical Care Fellowship Training in the United States and Canada: Pediatric Cardiac Intensive Care Society-Endorsed Subcompetencies to the 2022 Entrustable Professional Activities*
Authors: Chlebowski Meghan M. , Migally Karl , Werho David K. , Sznycer-Taub Nathaniel , Rhodes Leslie A. , Szadkowski Adam , Hupp Susan , Sacks Loren D. , Chen Jodi , Zyblewski Sinai C.
Published: February 2024

OBJECTIVES:

We aimed to define and map subcompetencies required for pediatric cardiac critical care (PCCC) fellowship education and training under the auspices of the Pediatric Cardiac Intensive Care Society (PCICS). We used the 2022 frameworks for PCCC fellowship learning objectives by Tabbutt et al and for entrustable professional activities (EPAs) by Werho et al and integrated new subcompetencies to the EPAs. This complementary update serves to provide a foundation for standardized trainee assessment tools for PCCC.

DESIGN:

A volunteer panel of ten PCICS members who are fellowship education program directors in cardiac critical care used a modified Delphi method to develop the update and additions to the EPA-based curriculum. In this process, the experts rated information independently, and repetitively after feedback, before reaching consensus. The agreed new EPAs were later reviewed and unanimously accepted by all PCICS program directors in PCCC in the United States and Canada and were endorsed by the PCICS in 2023.

PROCEDURE AND MAIN RESULTS:

The procedure for defining new subcompetencies to the established EPAs comprised six consecutive steps: 1) literature search; 2) selection of key subcompetencies and curricular components; 3) written questionnaire; 4) consensus meeting and critical evaluation; 5) approval by curriculum developers; and 6) PCICS presentation and endorsement. Overall, 110 subcompetencies from six core-competency domains were mapped to nine EPAs with defined levels of entrustment and examples of simple and complex cases. To facilitate clarity and develop a future assessment tool, three EPAs were subcategorized with subcompetencies mapped to the appropriate subcategory. The latter covering common procedures in the cardiac ICU.

CONCLUSIONS:

This represents the 2023 update to the PCCC fellowship education and training EPAs with the defining and mapping of 110 subcompetencies to the nine established 2022 EPAs. This goal of this update is to serve as the next step in the integration of EPAs into a standardized competency-based assessment framework for trainees in PCCC.
The Small Pixel Effect in Ultra-High-Resolution Photon-Counting CT of the Lumbar Spine
Authors: Huflage Henner , Hendel Robin , Woznicki Piotr , Conrads Nora , Feldle Philipp , Patzer Theresa Sophie , Ergün Süleyman , Bley Thorsten Alexander , Kunz Andreas Steven , Grunz Jan-Peter
Published: February 2024

Objectives

Image acquisition in ultra-high-resolution (UHR) scan mode does not impose a dose penalty in photon-counting CT (PCCT). This study aims to investigate the dose saving potential of using UHR instead of standard-resolution PCCT for lumbar spine imaging.

Materials and Methods

Eight cadaveric specimens were examined with 7 dose levels (5–35 mGy) each in UHR (120 × 0.2 mm) and standard-resolution acquisition mode (144 × 0.4 mm) on a first-generation PCCT scanner. The UHR images were reconstructed with 3 dedicated bone kernels (Br68 [spatial frequency at 10% of the modulation transfer function 14.5 line pairs/cm], Br76 [21.0], and Br84 [27.9]), standard-resolution images with Br68 and Br76. Using automatic segmentation, contrast-to-noise ratios (CNRs) were established for lumbar vertebrae and psoas muscle tissue. In addition, image quality was assessed subjectively by 19 independent readers (15 radiologists, 4 surgeons) using a browser-based forced choice comparison tool totaling 16,974 performed pairwise tests. Pearson's correlation coefficient (r) was used to analyze the relationship between CNR and subjective image quality rankings, and Kendall W was calculated to assess interrater agreement.

Results

Irrespective of radiation exposure level, CNR was higher in UHR datasets than in standard-resolution images postprocessed with the same reconstruction parameters. The use of sharper convolution kernels entailed lower CNR but higher subjective image quality depending on radiation dose. Subjective assessment revealed high interrater agreement (W = 0.86; P < 0.001) with UHR images being preferred by readers in the majority of comparisons on each dose level. Substantial correlation was ascertained between CNR and the subjective image quality ranking (all r's ≥ 0.95; P < 0.001)

Conclusions

In PCCT of the lumbar spine, UHR mode's smaller pixel size facilitates a considerable CNR increase over standard-resolution imaging, which can either be used for dose reduction or higher spatial resolution depending on the selected convolution kernel.
Daily vocalization patterns of the Saipan Reed Warbler (Acrocephalus hiwae)
Authors: Gaul Willson , Lin Jie , Roark Ellie
Published: February 2024

We investigated how detectability and vocalization patterns of Saipan Reed Warblers (Acrocephalus hiwae) varied by time of day. We used long-duration sound recordings from eleven locations occupied by Saipan Reed Warblers to model the probability of detecting a vocalization in each hour of the day. We found that Saipan Reed Warblers sang during all daylight hours. We did not find evidence of a dawn or evening chorus in this species. These results are useful for determining what time of day surveys of Saipan Reed Warblers should be conducted, which is particularly relevant because Saipan Reed Warblers are protected by local and U.S. Federal laws.
Plant-on-a-chip: continuous, soilless electrochemical monitoring of salt uptake and tolerance among different genotypes of tomato
Authors: Coatsworth Philip , Cotur Yasin , Asfour Tarek , Zhou Zihao , Flauzino José M. R. , Bozkurt Tolga , Güder Firat
Published: February 2024

Tomatoes (Solanum lycopersicum), a high-value crop, exhibit a unique relationship with salt, where increased levels of NaCl can enhance flavor, aroma and nutritional quality but can cause oxidative damage and reduce yields. A drive for larger, better-looking tomatoes has reduced the importance of salt sensitivity, a concern considering that the sodium content of agricultural land is increasing over time. Currently, there are no simple ways of comparing salt tolerance between plants, where a holistic approach looking at [Na+] throughout the plant typically involves destructive, single time point measurements or expensive imaging techniques. Finding methods that collect rapid information in real time could improve the understanding of salt resistance in the field. Here we investigate the uptake of NaCl by tomatoes using TETRIS (Time-resolvedElectrochemicalTechnology for plantRoot environmentIn-situchemicalSensing), a platform used to measure chemical signals in the root area of living plants. Low-cost, screen-printed electrochemical sensors were used to measure changes in salt concentrationviaelectrical impedance measurements, facilitating the monitoring of the uptake of ions by roots. We not only demonstrated differences in the rate of uptake of NaCl between tomato seedlings under different growth conditions, but also showed differences in uptake between varieties of tomato with different NaCl sensitivities and the relatively salt-resistant “wild tomato” (Solanum pimpinellifolium) sister species. Our results suggest that TETRIS could be used to ascertain physiological traits of salt resistance found in adult plants but at the seedling stage of growth. This extrapolation, and the possibility to multiplex and change sensor configuration, could enable high-throughput screening of many hundreds or thousands of mutants or varieties.
Molecular structure discovery for untargeted metabolomics using biotransformation rules and global molecular networking
Authors: Martin Margaret R. , Bittremieux Wout , Hassoun Soha
Published: February 2024

Although untargeted mass spectrometry-based metabolomics is crucial for understanding life’s molecular underpinnings, its effectiveness is hampered by low annotation rates of the generated tandem mass spectra. To address this issue, we introduce a novel data-driven approach, Biotransformation-based Annotation Method (BAM), that leverages molecular structural similarities inherent in biochemical reactions. BAM operates by applying biotransformation rules to known ‘anchor’ molecules, which exhibit high spectral similarity to unknown spectra, thereby hypothesizing and ranking potential structures for the corresponding ‘suspect’ molecule. BAM’s effectiveness is demonstrated by its success in annotating suspect spectra in a global molecular network comprising hundreds of millions of spectra. BAM was able to assign correct molecular structures to 24.2 % of examined anchor-suspect cases, thereby demonstrating remarkable advancement in metabolite annotation.
AAclust:k-optimized clustering for selecting redundancy-reduced sets of amino acid scales
Authors: Breimann Stephan , Frishman Dmitrij
Published: February 2024

Amino acid scales are crucial for sequence-based protein prediction tasks, yet no gold standard scale set or simple scale selection methods exist. We developed AAclust, a wrapper for clustering models that require a pre-defined number of clustersk, such ask-means. AAclust obtains redundancy-reduced scale sets by clustering and selecting one representative scale per cluster, wherekcan either be optimized by AAclust or defined by the user. The utility of AAclust scale selections was assessed by applying machine learning models to 24 protein benchmark datasets. We found that top-performing scale sets were different for each benchmark dataset and significantly outperformed scale sets used in previous studies. Notably, model performance showed a strong positive correlation with the scale set size. AAclust enables a systematic optimization of scale-based feature engineering in machine learning applications.

Availability and implementation

The AAclust algorithm is part of AAanalysis, a Python-based framework for interpretable sequence-based protein prediction, which will be made freely accessible in a forthcoming publication.

Contact

Stephan Breimann (Stephan.Breimann@dzne.de) and Dmitrij Frishman (dimitri.frischmann@tum.de)

Supplementary information

Further details on methods and results are provided in Supplementary Material.
Chronospaces: an R package for the statistical exploration of divergence times promotes the assessment of methodological sensitivity
Authors: Mongiardino Koch Nicolas , Milla Carmona Pablo
Published: February 2024

Much of our understanding of the history of life hinges upon time calibration, the process of assigning absolute times to cladogenetic events. Bayesian approaches to time scaling phylogenetic trees have dramatically grown in complexity, and depend today upon numerous methodological choices. Arriving at objective justifications for all of these is difficult and time consuming. Thus, divergence times are routinely inferred under only one or a handful of parametric conditions, often times chosen arbitrarily. Progress towards building robust biological timescales necessitate the development of better methods to visualize and quantify the sensitivity of results to these decisions. Here, we present an R package that assists in this endeavor through the use of chronospaces, i.e., graphical representations summarizing variation in the node ages contained in time-calibrated trees. We further test this approach by estimating divergence times for three empirical datasets-spanning widely differing evolutionary timeframes-using the software PhyloBayes. Our results reveal large differences in the impact of many common methodological decisions, with the choice of clock (uncorrelated vs. autocorrelated) and loci having strong effects on inferred ages. Other decisions have comparatively minor consequences, including the use of the computationally intensive site-heterogeneous model CAT-GTR, whose effect might only be discernible for exceedingly old divergences (e.g., the deepest eukaryote nodes). The package chronospace implements a range of graphical and analytical tools that assist in the exploration of sensitivity and the prioritization of computational resources in the inference of divergence times.
C. elegansRIG-I-like receptor DRH-1 signals via CARDs to activate anti-viral immunity in intestinal cells
Authors: Batachari Lakshmi E. , Dai Alyssa Y. , Troemel Emily R.
Published: February 2024

Upon sensing viral RNA, mammalian RIG-I-like receptors activate downstream signals using caspase activation and recruitment domains (CARDs), which ultimately promote transcriptional immune responses that have been well-studied. In contrast, the downstream signaling mechanisms for invertebrate RIG-I-like receptors are much less clear. For example, theCaenorhabditis elegansRIG-I-like receptor DRH-1 lacks annotated CARDs and upregulates the distinct output of RNA interference (RNAi). Here we found that, similar to mammal RIG-I-like receptors, DRH-1 signals through two tandem caspase activation and recruitment domains (2CARD) to induce a transcriptional immune response. Expression of DRH-1(2CARD) alone in the intestine was sufficient to induce immune gene expression, increase viral resistance, and promote thermotolerance, a phenotype previously associated with immune activation. We also found that DRH-1 is required in the intestine to induce immune gene expression, and we demonstrate subcellular colocalization of DRH-1 puncta with double-stranded RNA inside the cytoplasm of intestinal cells upon viral infection. Altogether, our results reveal mechanistic and spatial insights into anti-viral signaling inC. elegans,highlighting unexpected parallels in RIG-I-like receptor signaling betweenC. elegansand mammals.

Significance

Viruses are ubiquitous pathogens that challenge diverse organisms, from bacteria to killer whales. While anti-viral defense has been well-studied in mammals, less is known about defense in invertebrates, including the roundwormCaenorhabditis elegans. Here we show that theC. elegansviral sensor DRH-1 shares similarities to a viral sensor in mammals called RIG-I. We find that DRH-1 has a signaling motif resembling the 2CARD motif, which is found in RIG-I and activates anti-viral immunity. We demonstrate that overexpression of DRH-1(2CARD) inC. eleganspromotes resistance to viral infection, and that DRH-1 forms clusters inside intestinal cells during viral infection, similar to RIG-I in humans. Overall, these findings provide insights intoC. elegansanti-viral immunity, highlighting similarities with mammalian anti-viral immunity.
Biotic interactions promote local adaptation to soil in plants
Authors: Dorey Thomas , Frachon Léa , Rieseberg Loren H. , Kreiner Julia , Schiestl Florian P.
Published: February 2024

Although different ecological factors shape adaptative evolution in natural habitats, we know little about how their interactions impact local adaptation. Here we used eight generations of experimental evolution with outcrossingBrassica rapaplants as a model system, in eight treatment groups that varied in soil type, herbivory (with/without aphids), and pollination mode (hand- or bumblebee-pollination), to study how biotic interactions affect local adaptation to soil. First, we show that several plant traits evolved in response to biotic interactions in a soil-specific way. Second, using a reciprocal transplant experiment, we demonstrate that significant local adaptation to soil-type evolved in the “number of open flowers”, a trait used as a fitness proxy, but only in plants that evolved with herbivory and bee pollination. Whole genome re-sequencing of experimental lines revealed that biotic interactions caused a 10-fold increase in the number of SNPs across the genome with significant allele frequency change, and that alleles with opposite allele frequency change in different soil types (antagonistic pleiotropy) were most common in plants with an evolutionary history of herbivory and bee pollination. Our results demonstrate that the interaction of mutualists and antagonists can facilitate local adaptation to soil type through antagonistic pleiotropy.
Spatial transcriptomic profiling of human retinoblastoma
Authors: Wang Luozixian , Hung Sandy , Urrutia-Cabrera Daniel , Kong Roy C. K. , Staffieri Sandra , Ludlow Louise E. , Lau Xianzhong , Wang Peng-Yuan , Hewitt Alex W. , Wong Raymond C.B.
Published: February 2024

Retinoblastoma (RB) represents one of the most prevalent intraocular cancers in children. Understanding the tumor heterogeneity in RB is important to design better targeted therapies. Here we used spatial transcriptomic to profile human retina and RB tumor to comprehensively dissect the spatial cell-cell communication networks. We found high intratumoral heterogeneity in RB, consisting of 10 transcriptionally distinct subpopulations with varying levels of proliferation capacity. Our results uncovered a complex architecture of the tumor microenvironment that predominantly consisted of cone precursors, as well as glial cells and cancer-associated fibroblasts. We delineated the cell trajectory underlying malignant progression of RB, and identified key signaling pathways driving genetic regulation across RB progression. We also explored the signaling pathways mediating cell-cell communications in RB subpopulations, and mapped the spatial networks of RB subpopulations and region neighbors. Altogether, we constructed the first spatial gene atlas for RB, which allowed us to characterize the transcriptomic landscape in spatially-resolved RB subpopulations, providing novel insights into the complex spatial communications involved in RB progression.
Fast and accurate modeling and design of antibody-antigen complex using tFold
Authors: Wu Fandi , Zhao Yu , Wu Jiaxiang , Jiang Biaobin , He Bing , Huang Longkai , Qin Chenchen , Yang Fan , Huang Ningqiao , Xiao Yang , Wang Rubo , Jia Huaxian , Rong Yu , Liu Yuyi , Lai Houtim , Xu Tingyang , Liu Wei , Zhao Peilin , Yao Jianhua
Published: February 2024

Accurate prediction of antibody-antigen complex structures holds significant potential for advancing biomedical research and the design of therapeutic antibodies. Currently, structure prediction for protein monomers has achieved considerable success, and promising progress has been made in extending this achievement to the prediction of protein complexes. However, despite these advancements, fast and accurate prediction of antibody-antigen complex structures remains a challenging and unresolved issue. Existing end-to-end prediction methods, which rely on homology and templates, exhibit sub-optimal accuracy due to the absence of co-evolutionary constraints. Meanwhile, conventional docking-based methods face difficulties in identifying the contact interface between the antigen and antibody and require known structures of individual components as inputs. In this study, we present a fully end-to-end approach for three-dimensional (3D) atomic-level structure predictions of antibodies and antibody-antigen complexes, referred to as tFold-Ab and tFold-Ag, respectively. tFold leverages a large protein language model to extract both intra-chain and inter-chain residue-residue contact information, as well as evolutionary relationships, avoiding the time-consuming multiple sequence alignment (MSA) search. Combined with specially designed modules such as the AI-driven flexible docking module, it achieves superior performance and significantly enhanced speed in predicting both antibody (1.6% RMSD reduction in the CDR-H3 region, thousand times faster) and antibody-antigen complex structures (37% increase in DockQ score, over 10 times faster), compared to AlphaFold-Multimer. Given the performance and speed advantages, we further extend the capability of tFold for structure-based virtual screening of binding antibodies, as well as de novo co-design of both structure and sequence for therapeutic antibodies. The experiment results demonstrate the potential of tFold as a high-throughput tool to enhance processes involved in these tasks. To facilitate public access, we release code and offer a web service for antibody and antigen-antibody complex structure prediction, which is available athttps://drug.ai.tencent.com/en.
Distinguishable topological properties of functional genome networks in HIV-1 reservoirs
Authors: Wiśniewski Janusz , Więcek Kamil , Ali Haider , Pyrc Krzysztof , Kula-Păcurar Anna , Wagner Marek , Chen Heng-Chang
Published: February 2024

HIV-1 reservoirs display heterogeneous nature, lodging both intact and defective proviruses. Recent evidence has shed light on their difference, particularly in the context of immune-mediated selection. To deepen our understanding of such heterogeneous HIV-1 reservoirs and their functional implications, we pioneered the integration of basic concepts of graph theory to characterize the composition of HIV-1 reservoirs. Our analysis revealed noticeable topological properties in networks, featuring immunologic signatures enriched by genes harboring intact and defective proviruses, when comparing antiretroviral therapy (ART)-treated HIV-1-infected individuals and elite controllers. The key variable, the rich factor, played a pivotal role in classifying distinct topological properties in networks. The host gene expression strengthened the accuracy of classification between elite controllers and ART-treated patients. Overall, our work provides a prime example of leveraging genomic approaches alongside mathematical tools to unravel the complexities of HIV-1 reservoirs.