bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating machine learning models for supernova gravitational wave signal classification
Authors: Abylkairov Y Sultan , Edwards Matthew C , Orel Daniil , Mitra Ayan , Shukirgaliyev Bekdaulet , Abdikamalov Ernazar
Published: December 2024

We investigate the potential of using gravitational wave (GW) signals from rotating core-collapse supernovae to probe the equation of state (EOS) of nuclear matter. By generating GW signals from simulations with various EOSs, we train machine learning models to classify them and evaluate their performance. Our study builds on previous work by examining how different machine learning models, parameters, and data preprocessing techniques impact classification accuracy. We test convolutional and recurrent neural networks, as well as six classical algorithms: random forest, support vector machines, naïve Bayes(NB), logistic regression, k-nearest neighbors, and eXtreme gradient boosting. All models, except NB, achieve over 90 per cent accuracy on our dataset. Additionally, we assess the impact of approximating the GW signal using the general relativistic effective potential (GREP) on EOS classification. We find that models trained on GREP data exhibit low classification accuracy. However, normalizing time by the peak signal frequency, which partially compensates for the absence of the time dilation effect in GREP, leads to a notable improvement in accuracy. Despite this, the accuracy does not exceed 70 per cent, suggesting that GREP lacks the precision necessary for EOS classification. Finally, our study has several limitations, including the omission of detector noise and the focus on a single progenitor mass model, which will be addressed in future works.
ZYG-12/Hook's dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain
Authors: Carvalho Cátia , Moreira Matilde , Barbosa Daniel J. , Chan Fung-Yi , Koehnen Carlota Boal , Teixeira Vanessa , Rocha Helder , Green Mattie , Carvalho Ana Xavier , Cheerambathur Dhanya K. , Gassmann Reto
Published: December 2024

The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS–Hook–FHIP (FHF) complex. By contrast, the Caenorhabditis elegans Hook homologue ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex. Here, we demonstrate that ZYG-12 recruits dynein to EE in epithelia. We identify and functionally characterize the homologues of FTS (UBC-19) and FHIP (FHIP-1) that constitute the C. elegans FHF complex, validate the predicted FHIP-1–RAB-5 binding interface in vivo, and show that ZYG-12 forms FHF via a conserved segment that precedes, and is distinct from, its C-terminal NE targeting domain. Finally, we show that C-terminal ZYG-12 splice isoforms differ in their ability to target to the NE and EE. We conclude that the C. elegans Hook adaptor evolved to recruit dynein to two distinct organelles, and that cargo specificity of ZYG-12 is regulated by alternative splicing.
Experimental analysis of genetic and environmental interactions on leaf elongation and reproductive development in Lolium perenne
Authors: Rouet Simon , Durand Jean-Louis , Troux Alice , Barillot Romain
Published: December 2024

Perennial grasses’ reproductive phenology profoundly impacts plant morphogenesis, biomass production, and perenniality in natural ecosystems and cultivated grasslands. Complex interactions between vegetative and reproductive development complicate grass phenology prediction for various environments and genotypes. This work aims to analyse genetic × environment interactions effects on tiller growth and reproductive development in Lolium perenne. Three perennial ryegrass cultivars, Bronsyn, Carvalis, and Tryskal, were grown from seedling to heading under four inductive conditions. T0 plants were continuously exposed to high temperatures and long days (HT–LD). T1, T2, and T3, plants were initially exposed to low temperatures and short days (LT–SD) for 9 weeks. Then, T1 plants were immediately transferred to high temperatures and long days (HT–LD). Before their exposure to HT–LD, T2, and T3 plants were first transferred to high temperatures and short days (HT–SD) for 3 and 6 weeks, respectively. Leaf length, leaf emergence, and heading were regularly monitored. Floral transition and heading only occurred in T1, T2, and T3, i.e. after successive exposure to low temperature and long photoperiod. Bronsyn had higher heading earliness and proportion of reproductive tillers than Carvalis and Tryskal. The duration of HT–SD exposure affected the final number of leaves and spikelets. The rate of leaf and spikelet production significantly increased once plants were exposed to LD. Our results suggest an additive effect of the photoperiod and floral transition on leaf elongation rate. These findings enhance our understanding of the genetic × environment interactions on the vegetative and reproductive development in perennial ryegrass.
QuICSeedR: an R package for analyzing fluorophore-assisted seed amplification assay data
Authors: Li Manci , Bryant Damani N , Gresch Sarah , Milstein Marissa S , Christenson Peter R , Lichtenberg Stuart S , Larsen Peter A , Oh Sang-Hyun
Published: December 2024

Motivation

Fluorophore-assisted seed amplification assays (F-SAAs), such as real-time quaking-induced conversion (RT-QuIC) and fluorophore-assisted protein misfolding cyclic amplification (F-PMCA), have become indispensable tools for studying protein misfolding in neurodegenerative diseases. However, analyzing data generated by these techniques often requires complex and time-consuming manual processes. In addition, the lack of standardization in F-SAA data analysis presents a significant challenge to the interpretation and reproducibility of F-SAA results across different laboratories and studies. There is a need for automated, standardized analysis tools that can efficiently process F-SAA data while ensuring consistency and reliability across different research settings.

Results

Here, we present QuICSeedR (pronounced as “quick seeder”), an R package that addresses these challenges by providing a comprehensive toolkit for the automated processing, analysis, and visualization of F-SAA data. Importantly, QuICSeedR also establishes the foundation for building an F-SAA data management and analysis framework, enabling more consistent and comparable results across different research groups.

Availability and implementation

QuICSeedR is freely available at: https://CRAN.R-project.org/package=QuICSeedR. Data and code used in this manuscript are provided in Supplementary Materials.
FuncFetch: an LLM-assisted workflow enables mining thousands of enzyme–substrate interactions from published manuscripts
Authors: Smith Nathaniel , Yuan Xinyu , Melissinos Chesney , Moghe Gaurav
Published: December 2024

Motivation

Thousands of genomes are publicly available, however, most genes in those genomes have poorly defined functions. This is partly due to a gap between previously published, experimentally characterized protein activities and activities deposited in databases. This activity deposition is bottlenecked by the time-consuming biocuration process. The emergence of large language models presents an opportunity to speed up the text-mining of protein activities for biocuration.

Results

We developed FuncFetch—a workflow that integrates NCBI E-Utilities, OpenAI’s GPT-4, and Zotero—to screen thousands of manuscripts and extract enzyme activities. Extensive validation revealed high precision and recall of GPT-4 in determining whether the abstract of a given paper indicates the presence of a characterized enzyme activity in that paper. Provided the manuscript, FuncFetch extracted data such as species information, enzyme names, sequence identifiers, substrates, and products, which were subjected to extensive quality analyses. Comparison of this workflow against a manually curated dataset of BAHD acyltransferase activities demonstrated a precision/recall of 0.86/0.64 in extracting substrates. We further deployed FuncFetch on nine large plant enzyme families. Screening 26 543 papers, FuncFetch retrieved 32 605 entries from 5459 selected papers. We also identified multiple extraction errors including incorrect associations, nontarget enzymes, and hallucinations, which highlight the need for further manual curation. The BAHD activities were verified, resulting in a comprehensive functional fingerprint of this family and revealing that ∼70% of the experimentally characterized enzymes are uncurated in the public domain. FuncFetch represents an advance in biocuration and lays the groundwork for predicting the functions of uncharacterized enzymes.

Availability and implementation

Code and minimally curated activities are available at: https://github.com/moghelab/funcfetch and https://tools.moghelab.org/funczymedb.
Understanding climate change response of plant–insect herbivore interactions from ecological traits
Authors: Chang Xinyue , Yang Yuchen , Ashton Louise A , Pang Hong , Xing Shuang
Published: December 2024

The interactions between plants and insect herbivores play crucial roles in ecosystem functions and services. Ongoing climate change can affect these interactions through different mechanisms either directly or indirectly. In this review, we outline key ecological traits through which organisms respond to climate change. These include morphology, physiology, and chemistry for plants, and morphology, physiology, and behaviour for insects. We highlight how the responses of those traits to a changing climate might consequently affect herbivory. We propose key ecological questions that need to be addressed for each perspective of plant and insect traits, and we suggest novel approaches for answering these questions. Looking forwards, we outline fruitful areas for exploration of the ecological mechanisms underlying how plant–insect herbivore interactions might respond to climate changes from trait-based approaches.
Clinical and patient-reported outcomes in women offered oncoplastic breast-conserving surgery as an alternative to mastectomy: ANTHEM multicentre prospective cohort study
Authors: Davies Charlotte , Johnson Leigh , Conefrey Carmel , Mills Nicola , Fairbrother Patricia , Holcombe Chris , Whisker Lisa , Hollingworth William , Skillman Joanna , White Paul , Macmillan Douglas , Comins Charles , Potter Shelley
Published: December 2024

Background

Oncoplastic breast-conserving surgery may be a better option than mastectomy, but high-quality comparative evidence is lacking. The aim of the ANTHEM study (ISRCTN18238549) was to explore clinical and patient-reported outcomes in a multicentre cohort of women offered oncoplastic breast-conserving surgery as an alternative to mastectomy with or without immediate breast reconstruction.

Methods

Women with invasive/pre-invasive breast cancer who were offered oncoplastic breast-conserving surgery with volume replacement or displacement techniques to avoid mastectomy were recruited prospectively. Demographic, operative, oncological, and 3- and 12-month complication data were collected. The proportion of women choosing oncoplastic breast-conserving surgery and the proportion in whom breast conservation was successful were calculated. Participants completed the validated BREAST-Q questionnaire at baseline, 3 months after surgery, and 12 months after surgery. Questionnaires were scored according to the developers’ instructions and scores for each group were compared over time.

Results

In total, 362 women from 32 UK breast units participated, of whom 294 (81.2%) chose oncoplastic breast-conserving surgery. Of the oncoplastic breast-conserving surgery patients in whom postoperative margin status was reported, 210 of 255 (82.4%) had clear margins after initial surgery and only 10 (3.9%) required completion mastectomy. Major complications were significantly more likely after immediate breast reconstruction. Women having oncoplastic breast-conserving surgery with volume displacement techniques reported significant improvements in baseline ‘satisfaction with breasts’ and ‘psychosocial well-being’ scores at 3 and 12 months, but both oncoplastic breast-conserving surgery groups reported significant decreases in ‘physical well-being: chest’ at 3 and 12 months.

Conclusion

Oncoplastic breast-conserving surgery allows greater than 95% of women to avoid mastectomy, with lower major complication rates than immediate breast reconstruction, and may improve satisfaction with outcome. Oncoplastic breast-conserving surgery should be offered as an alternative to mastectomy in all women in whom it is technically feasible.
Weakness acquired in the cardiac intensive care unit: still the elephant in the room?
Authors: Van Aerde Nathalie , Hermans Greet
Published: December 2024

Over the past two decades, the cardiac critical care population has shifted to increasingly comorbid and elderly patients often presenting with nonprimary cardiac conditions that exacerbate underlying advanced cardiac disease. Consequently, the modern cardiac intensive care unit (CICU) patient has poor outcome regardless of left ventricular ejection fraction. Importantly, delayed liberation from organ support, independent from premorbid health status and admission severity of illness, has been associated with increased morbidity and mortality up to years post-general critical care. Although a constellation of several acquired morbidities is at play, the most prominent enactor of poor long-term outcome in this population appears to be intensive care unit acquired weakness. Although the specific burden of ICU-acquired morbidities in CICU patients is yet to be clearly defined, it seems unfathomable that patients will not accrue some sort of ICU-related morbidity. There is hence an urgent need to better establish the exact benefit and cost of resource-intensive strategies in both short- and long-term survival of the CICU patient. Consequent and standardized documentation of admission comorbidities, severity of illness indicators, relevant ICU-related complications including weakness, and long-term post-ICU morbidity outcomes can help our understanding of the disease continuum and how to better care for the CICU survivor and their families and caregivers. Given increasing budgetary pressure on healthcare systems worldwide, interventions targeting CICU patients should focus on improving patient-centred long-term outcomes in a cost-effective manner. It will require a holistic and transmural continuity of care model to meet the challenges associated with treating critically ill cardiac patients in the future.
The impact of restricted chests on long-term lung function parameters following lung transplantation in patients with interstitial lung disease
Authors: Nakanishi Keita , Schweiger Thomas , Schwarz Stefan , Taghavi Shahrokh , Hillebrand Caroline , Begic Merjem , Auner Sophia , Boehm Panja M , Mosleh Berta , Jaksch Peter , Benazzo Alberto , Chen-Yoshikawa Toyofumi Fengshi , Hoetzenecker Konrad
Published: December 2024

OBJECTIVES

In patients with interstitial lung disease (ILD), the diaphragm typically rises as the lungs chronically shrink. However, the grade of restriction differs in each patient. It is currently unknown, how disparities between actual and predicted recipient total lung capacity (TLC), impact changes in lung function parameters and long-term outcomes following lung transplantation (LTx).

METHODS

This retrospective study included 170 LTx for the patients with ILD performed in a European high-volume LTx center between 09/2011 and 12/2022. The preoperative median ratio of recipient actual to predicted (a/p) TLC was 0.55. Patients were stratified into two groups: low a/p TLC ratio group, corresponding to a more restricted chest cavity (< 0.55: n = 85), and high a/p TLC ratio group, corresponding to a more preserved chest cavity (≥ 0.55: n = 85). Perioperative and long-term outcomes, including lung function and overall survival, were analyzed.

RESULTS

Between the two groups, tracheostomy and reintubation rates, length of mechanical ventilation, ICU-stay and hospital-stay were not significantly different. Although lung function measurements obtained early after LTx were better in the high a/p TLC ratio group, no significant differences were observed in the long term. 5-year overall survival was not significantly different between the two groups.

CONCLUSIONS

Although LTx for ILD patients with a restricted chest is considered technically more challenging, the perioperative course is similar to ILD patients with a preserved chest. In addition, no significant differences were observed between both groups in long-term lung function and overall survival, suggesting an improvement in chest wall compliance.
Arterial conduits for coronary bypass grafting: the set-point concept
Authors: Calafiore Antonio M , Prapas Sotirios , Gaudino Mario
Published: December 2024

Endothelial cells control the vascular tone of arterial grafts used for coronary artery bypass surgery and react to changes in local shear stress. The vascular adaptations induced by endothelial cell activation affect the outcome of surgical grafts and can be predicted based on the set-point theory. In this Hypothesis piece, it is proposed that the set-point concept should inform surgical decision making for coronary artery bypass surgery.
Stereotactic cardiac radiotherapy for refractory ventricular tachycardia in structural heart disease patients: a systematic review
Authors: Gupta Amulya , Sattar Zeeshan , Chaaban Nourhan , Ranka Sagar , Carlson Cameron , Sami Farhad , Robinson Clifford G , Cuculich Phillip S , Sheldon Seth H , Reddy Madhu , Akhavan David , Noheria Amit
Published: December 2024

Aims

Among patients with structural heart disease with ventricular tachycardia (VT) refractory to medical therapy and catheter ablation, cardiac stereotactic body radiotherapy (SBRT) is a paradigm-changing treatment option. This study aims to assess the efficacy of cardiac SBRT in refractory VT by comparing the rates of VT episodes, anti-tachycardia pacing (ATP) therapies, and implantable cardioverter-defibrillator (ICD) shocks post-SBRT with pre-SBRT.

Methods and results

We performed a comprehensive literature search and included all clinical studies reporting outcomes on cardiac SBRT for VT. Treatment efficacy was evaluated as random-effects pooled rate-ratios of VT episodes, ATP therapies and ICD shocks post-SBRT (after 6-week blanking) and pre-SBRT, with patients serving as their own controls. Post-SBRT overall survival was assessed using Kaplan–Meier method. We included 23 studies published 2017–24 reporting on 225 patients who received cardiac SBRT, with median follow-up 5.8–28 months. There was significant heterogeneity among the studies for all three efficacy endpoints (P < 0.00001). The random-effects pooled rate-ratios of VT episodes, ATP therapies and ICD shocks post- vs. pre-SBRT were 0.10 (95% CI 0.06, 0.16), 0.09 (0.05, 0.15), and 0.09 (0.05, 0.17), respectively (all P < 0.00001). The most common reported complications included pericardial (8.0%, including 0.9% late oesophagogastro-pericardial fistula) and pulmonary (5.8%). There was no change in left ventricular ejection fraction post-SBRT (P = 0.3) but some studies reported an increase in mitral regurgitation. The combined 3-, 12-, and 24-month overall patient survival was 0.86 (0.80, 0.90), 0.72 (0.65, 0.78), and 0.57 (0.47, 0.67), respectively.

Conclusion

Among patients with refractory VT in context of structural heart disease, VT burden and ICD shocks are dramatically reduced following cardiac SBRT. The overall mortality in this population with heart failure and refractory VT receiving palliative cardiac SBRT remains high.
Quantifying architectural uniqueness of Scots pine trees using terrestrial laser scanning: toward individual tree fingerprinting
Authors: Yrttimaa Tuomas , Junttila Samuli , Hyyppä Juha , Holopainen Markus , Wulder Michael A , Vastaranta Mikko
Published: December 2024

Tree architecture reflects a hierarchical growth pattern shaped by the interplay between genetics and the environment. Environmental variation leads to unique resource availability, resulting in each tree developing distinct structural features, akin to the uniqueness of a human fingerprint. In this study, we propose a nondestructive method for quantifying this architectural uniqueness using terrestrial laser scanning for tree identification. While tree identification is commonly based on their precise geospatial location, this information may not always be available. Instead, we hypothesized that a tree’s stem profile (diameters along the stem) and branching arrangement (locations of branch origins on the stem surface) could distinguish individuals within a population. The experimental setup included 65 Scots pine (Pinus sylvestris L.) trees in a managed boreal forest stand, scanned with terrestrial laser scanning in September 2021 (T1) and November 2022 (T2). We investigated whether individual trees could be identified based on architectural similarities between their point cloud reconstructions from T1 and T2. In total, 52 trees (80.0%) were identified based on their architectural characteristics. The results supported our hypothesis, showing that identifying ≥10 branch origins from independent reconstructions was sufficient to establish architectural uniqueness, resulting in 100% identification accuracy (n = 20 trees). These findings suggest that the complex three-dimensional tree architecture can be condensed into a two-dimensional pattern of points representing branch arrangement, which we term the “tree fingerprint.” These architectural characteristics, which can be reconstructed from the lower half of the tree, are well suited for acquisition via ground-based sensing techniques such as terrestrial or mobile laser scanning. If point cloud data capable of characterizing individual branches is acquired during forest operations, the proposed methodology can facilitate tree identification for applications such as wood tracking, even without geospatial coordinates.
The genome of the solitary bee Tetrapedia diversipes (Hymenoptera, Apidae)
Authors: Santos Priscila K F , de Souza Araujo Natalia , Françoso Elaine , Werren John H , Kapheim Karen M , Arias Maria Cristina
Published: December 2024

Tetrapedia diversipes is a Neotropical solitary bee commonly found in trap-nests, known for its morphological adaptations for floral oil collection and prepupal diapause during the cold and dry season. Here, we present the genome assembly of T. diversipes (332 Mbp), comprising 2,575 scaffolds, with 15,028 predicted protein-coding genes. Repetitive elements constitute 38.68% of the genome, notably Class II transposable elements. An investigation into lateral gene transfers identified a low frequency (0.037%) of nuclear copies of mitochondrial DNA and 18 candidate regions from bacterial origins. Furthermore, the annotation of 3 scaffolds reveals the presence of the Wolbachia endosymbiont genome, confirming the infection by 2 strains in T. diversipes populations. This genome contributes valuable insights into Neotropical bee genomics, offering a resource for comparative studies and enhancing our understanding of the molecular basis of solitary bee adaptations and interactions.
Monitoring slow uplift and subsidence in shallow seafloor environments using bottom pressure measurements
Authors: Morelli Rebecca Sveva , Riccio Rosario , Guardato Sergio , Chierici Francesco , Caliro Stefano , Macedonio Giovanni , Iannaccone Giovanni
Published: December 2024

Ultraslow seafloor deformations are frequent in several marine environments like volcanic calderas, offshore oil and gas extraction fields subject to subsidence and river delta regions; they can exhibit unpredictable behaviours, particularly in caldera systems situated along coastlines. However, offshore monitoring of seafloor uplift and subsidence is still very challenging. Here, we present a new method to recover vertical seafloor deformation at Campi Flegrei caldera, Southern Italy, using bottom pressure recorder (BPR) sensors, tide gauges and a barometer. Using data from two BPRs installed on the seabed within the multiparametric elastic-beacon devices and underwater sensors acquisition (MEDUSA) marine infrastructure of the Istituto Nazionale Geofisica e Vulcanologia (INGV) -‘Osservatorio Vesuviano’, we transform pressure measurements into equivalent water level changes to derive the vertical seafloor displacements. We obtain high-accuracy vertical deformation records from the BPR measurements by taking into account the high-resolution mean seawater density variation over time, estimated by applying an innovative procedure to the BPRs data and using additional barometric and sea level data. We obtained for the two BPRs an uplift of 22.8 cm over about 2 yr and 7 cm over about 18 months, respectively. We compare the results with data acquired by GPSs installed on the top of MEDUSA buoys, deployed at the same sites as the BPRs, which recorded the vertical seafloor deformation values of 22 and 6.9 cm, respectively, over the same periods. These independent data sets show a strong correlation, with correlation coefficient values of 0.98 and 0.87, and very good agreement in both the trend and amplitude of vertical motion, proving the reliability of BPRs in accurately measuring vertical seafloor deformation. The methodology we developed allows a cost-effective implementation of high-accuracy seafloor vertical deformation monitoring networks.
DNA Methylation Analysis on Anal Swabs for Anal Cancer Screening in People Living With Human Immunodeficiency Virus
Authors: Dias Gonçalves Lima Fernando , Rozemeijer Kirsten , van der Zee Ramon P , Dick Stèfanie , ter Braak Timo J , Geijsen Debby E , Meijnen Philip , Lissenberg-Witte Birgit I , van Noesel Carel J M , de Vries Henry J C , Prins Jan M , Steenbergen Renske D M
Published: December 2024

Background

High-resolution anoscopy (HRA) to prevent anal cancer is complex and screening capacity is limited. Previously, DNA methylation analysis of anal high-grade squamous intraepithelial lesion (HSIL) biopsies was shown to distinguish between HSIL with an increased and a low cancer risk, supporting personalized treatment. Here, methylation analysis on anal swabs was assessed to detect underlying HSIL with an increased cancer risk.

Methods

A cross-sectional series of paired anal swabs and biopsies of 215 persons with human immunodeficiency virus and swabs of 19 cancer patients were tested for 6 methylation markers. Data were analyzed by logistic regression analysis. The primary endpoint was methylation-positive biopsy HSIL (M+ HSIL), indicating increased cancer risk. Test performance of methylation markers, human papillomavirus (HPV), and/or cytology, and cancer detection and HRA referral, were calculated.

Results

Anal cancer swabs showed highest methylation. ZNF582 and panels ASCL1/ZNF582 and LHX8/ZNF582 yielded an area under the curve of 0.68–0.70 to detect underlying M+ HSIL. Methylation at 80% sensitivity corresponded to 43% fewer patients requiring HRA, without missing any cancers and detecting 79% of HPV-16–positive HSIL-AIN3. Methylation/HPV and cytology/HPV co-testing performed similarly.

Conclusions

Methylation levels in anal swabs reflect underlying anal disease. Methylation analysis could reduce HRA referrals substantially, while maintaining a high sensitivity for M+ HSIL and detecting all cancers. These results encourage screening on anal swabs to preselect patients needing HRA.
Staphylococcus aureus Tetracycline Resistance and Co-resistance in a Doxycycline Postexposure Prophylaxis–Eligible Population
Authors: Mittelstaedt Rachel , Kanjilal Sanjat , Helekal David , Robbins Gregory K , Grad Yonatan H
Published: December 2024

Among doxycycline postexposure prophylaxis (doxy-PEP)–eligible men, Staphylococcus aureus tetracycline nonsusceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select for multidrug-resistant S aureus, underscoring the importance of surveillance.
Addition of Macrolide Antibiotics for Hospital Treatment of Community-Acquired Pneumonia
Authors: Wei Jia , Walker A Sarah , Eyre David W
Published: December 2024

Background

Guidelines recommend combining macrolides with β-lactam antibiotics for moderate-to-high severity community-acquired pneumonia (CAP); however, macrolides pose risks of adverse events and anti-microbial resistance.

Methods

We analyzed electronic health data from 8872 adults hospitalized with CAP in Oxfordshire, UK (2016-2024), initially treated with amoxicillin or co-amoxiclav. Using inverse probability treatment weighting, we examined the effects of adjunctive macrolides on 30-day all-cause mortality, time to hospital discharge, and changes in Sequential Organ Failure Assessment (SOFA) score.

Results

There was no evidence of an association between adjunctive macrolides and 30-day mortality (marginal odds ratio 1.05 [95% CI 0.75-1.47] for amoxicillin with vs. without macrolide; 1.12 [0.93-1.34] for co-amoxiclav with vs. without macrolide); and no evidence of a difference in time to discharge (restricted mean days lost +1.76 days [−1.66, +5.19] for amoxicillin, +0.44 days [−1.63, +2.51] for co-amoxiclav). Macrolide use was not associated with SOFA score decreases. Results were consistent across severity sub-groups and sensitivity analyses with missing covariates imputed.

Conclusions

At a population level, the addition of macrolides was not associated with improved clinical outcomes for patients with CAP. The potential benefits of additional macrolides should be weighed against the risks of adverse effects and anti-microbial resistance.
Litter quality modulates changes in bacterial and fungal communities during the gut transit of earthworm species of different ecological groups
Authors: Chao Huizhen , Zhong Linlin , Schaefer Ina , Sun Mingming , Junggebauer André , Hu Feng , Scheu Stefan
Published: December 2024

Earthworms are keystone animals stimulating litter decomposition and nutrient cycling. However, earthworms comprise diverse species which live in different soil layers and consume different types of food. Microorganisms in the gut of earthworms are likely to contribute significantly to their ability to digest organic matter, but this may vary among earthworm species. Here, we analyse the effect of food (litter) quality on gut microbiota and their changes during the gut passage (from foregut to hindgut) of earthworms of different ecological groups. The endogeic (soil living) species Aporrectodea caliginosa and the anecic (litter feeding) species Lumbricus terrestris were fed with high- (rape leaves) and low-quality litter (wheat straw) in a microcosm experiment for 18 weeks. Irrespective of earthworm species, alpha diversity of bacterial and fungal communities changed little during the gut passage, with the composition and diversity of microbial communities in the gut generally resembling those in soil more than in litter. In addition, the low-quality litter supported higher alpha diversity and more complex communities than high-quality litter. Further, gut microbial communities of the anecic L. terrestris changed less during gut passage than those of the endogeic A. caliginosa, especially when fed low-quality litter. Our findings indicate that earthworm gut microbial communities are predominantly shaped by the soil they ingest, but are modulated by the quality of litter they feed on and earthworm ecological group. Overall, the results suggest that earthworms primarily influence soil microbiota by mixing and spreading microorganisms from different microhabitats through bioturbation rather than by digesting microorganisms.
Consumer Credit with Over-Optimistic Borrowers
Authors: Exler Florian , Livshits Igor , MacGee James , Tertilt Michèle
Published: December 2024

Do cognitive biases call for regulation to limit the use of credit? We incorporate over-optimistic and rational borrowers into an incomplete markets model with consumer bankruptcy. Over-optimists face worse income risk but incorrectly believe they are rational. Thus, both types behave identically. Lenders price loans forming beliefs-type scores-about borrower types. This gives rise to a tractable theory of type scoring. As lenders cannot screen types, borrowers are partially pooled. Over-optimists face cross-subsidized interest rates but make financial mistakes: borrowing too much and defaulting too little. In equilibrium, the welfare losses from mistakes are more than compensated by cross-subsidization. We calibrate the model to the US and quantitatively evaluate policies to address these frictions: financial literacy education, reducing default cost, increasing borrowing costs, and debt limits. While some policies lower debt and filings, only reducing default costs and financial literacy education improve welfare. However, financial literacy education benefits only rationals at the expense of over-optimists. Score-dependent borrowing limits can reduce financial mistakes but lower welfare.
Time-Varying Risk Aversion and Inflation-Consumption Correlation in an Equilibrium Term Structure Model
Authors: Bletzinger Tilman , Lemke Wolfgang , Renne Jean-Paul
Published: December 2024

Inflation risk premiums tend to be positive in an economy mainly hit by supply shocks, and negative if demand shocks dominate. Risk premiums also fluctuate with risk aversion. We shed light on this nexus in a linear-quadratic equilibrium macro-finance model featuring time variation in inflation-consumption correlation and risk aversion. We obtain analytical solutions for real and nominal yield curves and for risk premiums. While changes in the inflation-consumption correlation drive nominal yields, changes in risk aversion drive real yields and act as amplifier on nominal yields. Combining a trend-cycle specification of real consumption with hysteresis effects generates an upward-sloping real yield curve. Estimating the model on U.S. data from 1961 to 2019 confirms substantial time variation in inflation risk premiums: distinctly positive in the earlier part of our sample, especially during the 1980s, and turning negative with the onset of the new millennium.
DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation
Authors: Yang Yaqi , Wen Jiejun , Lou Susu , Han Yali , Pan Yi , Zhong Ying , He Qiao , Zhang Yinfeng , Mo Xi , Ma Jing , Shen Nan
Published: December 2024

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Despite treatment advances, the survival rates of high-risk NB patients remain low. This highlights the urgent need for a deeper understanding of the molecular mechanisms driving NB progression to support the development of new therapeutic strategies. In this study, we demonstrated that the reduced levels of DNAJC12, a protein involved in metabolic regulation, are associated with poor prognosis in NB patients. Our data indicate that low DNAJC12 expression activates glycolysis in NB cells, leading to increased lactic acid production and histone H4 lysine 5 lactylation (H4K5la). Elevated H4K5la upregulates the transcription of COL1A1, a gene implicated in cell metastasis. Immunohistochemistry staining of NB patient samples confirmed that high H4K5la levels correlate with poor clinical outcomes. Furthermore, we showed that inhibiting glycolysis, reducing H4K5la, or targeting COL1A1 can mitigate the invasive behavior of NB cells. These findings reveal a critical link between metabolic reprogramming and epigenetic modifications in the context of NB progression, suggesting that H4K5la could serve as a novel diagnostic and prognostic marker, and shed light on identifying new therapeutic targets within metabolic pathways for the treatment of this aggressive pediatric cancer.
A Bayesian approach to model local and temporal heterogeneity in repeated cross-sectional health surveys
Authors: Stival Mattia , Schiavon Lorenzo , Campostrini Stefano
Published: December 2024

In several countries, including Italy, a prominent approach to population health surveillance involves conducting repeated cross-sectional surveys at short intervals of time. These surveys gather information on the health status of individual respondents, including details on their behaviours, risk factors, and relevant socio-demographic information. While the collected data provides valuable information, modelling such data presents several challenges. For instance, in health risk models, it is essential to consider behavioural information, local and temporal dynamics, and disease co-occurrence. In response to these challenges, our work proposes a multivariate temporal logistic model for chronic disease diagnoses at local level. Linear predictors are modelled using individual risk factor covariates and a latent individual propensity to diseases. Leveraging a state space formulation of the model, we construct a framework in which temporal heterogeneity in regression coefficients is informed by exogenous information at local level, corresponding to different contextual risk factors that may affect the occurrence of chronic diseases in different ways. To explore the effectiveness of our method, we analyse behavioural and risk factor surveillance data collected in Italy (PASSI), which is well-known as a country characterized by high peculiar administrative, social and territorial diversities reflected on high variability in morbidity among population subgroups.
Tense logics based on posets
Authors: Chajda Ivan , LÄnger Helmut , Ledda Antonio , Paseka Jan , Vergottini Gandolfo
Published: December 2024

Quantum mechanics, initially formalized with orthomodular lattices, benefits from a simpler approach using just partially ordered sets (posets). This paper explores how logical connectives are introduced in poset-based logics. Building on prior work by the authors, we delve deeper into ‘dynamic’ logics where truth values can change over time. We consider time sets with a preference relation and propositions whose truth depends on time. Tense operators, introduced by J.Burgess and extended for various logics, become a valuable tool. This paper proposes several approaches to this topic, aiming to inspire a further stream of research.
ExoMol line lists – LXI. A trihybrid line list for rovibronic transitions of the hydroxyl radical (OH)
Authors: Mitev Georgi B , Bowesman Charles A , Zhang Jingxin , Yurchenko Sergei N , Tennyson Jonathan
Published: December 2024

The hydroxyl radical (OH) is a species of high importance in exoplanetary studies, the interstellar medium, and in stellar spectra. Terrestrially, it is a significant component of combustion chemistry, an oxidizer in the upper atmosphere, and a source of telluric bands. Internally contracted multireference configuration interaction potential energy curves, spin-orbit couplings, electronic angular momentum couplings, and (transition) dipole moments for eight electronic states of OH are computed and refined against empirical energy levels to produce an OH spectroscopic model. A line list consisting of rovibronic term values, allowed electronic dipole transitions, Einstein-A coefficients, and partition functions for varying temperature and a continuum absorption data set are then produced by variational solution of the coupled-channel Schrödinger equations using the nuclear motion code Duo. Marvel energy levels substitute equivalent levels in the OH line list, with estimated uncertainties in experimentally dark regions, following an established hybridization procedure. Predissociation lifetimes of the A $^2\Sigma ^+$ state are calculated using a stabilization method and convoluted with natural lifetimes to include predissociative effects. Continuum absorption cross-sections for $T \in [100,200,...,8000]~\textrm {K}$ and zero pressure are provided in the range of $0\rightarrow 80\, 000$ cm$^{-1}$ with a step size of 0.01 cm$^{-1}$. Comparison with available literature cross-sections exhibits strong agreement. The line list is suitable for high-resolution studies up to 8000 K. The OH MYTHOS data set is available for download via www.exomol.com.
A de novo Gene Promotes Seed Germination Under Drought Stress in Arabidopsis
Authors: Jin Guang-Teng , Xu Yong-Chao , Hou Xing-Hui , Jiang Juan , Li Xin-Xin , Xiao Jia-Hui , Bian Yu-Tao , Gong Yan-Bo , Wang Ming-Yu , Zhang Zhi-Qin , Zhang Yong E , Zhu Wang-Sheng , Liu Yong-Xiu , Guo Ya-Long
Published: December 2024

The origin of genes from noncoding sequences is a long-term and fundamental biological question. However, how de novo genes originate and integrate into the existing pathways to regulate phenotypic variations is largely unknown. Here, we selected 7 genes from 782 de novo genes for functional exploration based on transcriptional and translational evidence. Subsequently, we revealed that Sun Wu-Kong (SWK), a de novo gene that originated from a noncoding sequence in Arabidopsis thaliana, plays a role in seed germination under osmotic stress. SWK is primarily expressed in dry seed, imbibing seed and silique. SWK can be fully translated into an 8 kDa protein, which is mainly located in the nucleus. Intriguingly, SWK was integrated into an extant pathway of hydrogen peroxide content (folate synthesis pathway) via the upstream gene cytHPPK/DHPS, an Arabidopsis-specific gene that originated from the duplication of mitHPPK/DHPS, and downstream gene GSTF9, to improve seed germination in osmotic stress. In addition, we demonstrated that the presence of SWK may be associated with drought tolerance in natural populations of Arabidopsis. Overall, our study highlights how a de novo gene originated and integrated into the existing pathways to regulate stress adaptation.
Ectopic endometrial stromal cell-derived extracellular vesicles encapsulating microRNA-25-3p induce endometrial collagen I deposition impairing decidualization in endometriosis
Authors: Zhu Yuan , Zheng Bo , Zhang Yuting , Li Mengyun , Jiang Yuan , Zhou Jidong , Zhang Yang , Kang Nannan , Wu Min , Yan Yuan , Xing Jun , Zhou Jianjun
Published: December 2024

Endometrial collagen I undergoes dynamic degradation and remodelling in response to endometrial stromal cell (ESC) decidualization and embryo implantation. However, excessive collagen I deposition in the endometrium during the implantation window may impair decidualization, causing embryo implantation failure in patients with endometriosis (EMS). We found that endometrial collagen I expression during the mid-secretory phase was increased in the EMS group of patients. Collagen I stimulation resulted in decreased expression of the decidualization markers prolactin and insulin-like growth factor binding protein-1 in ESCs, impeding ESC transformation to a decidual morphology and decreasing the blastocyst-like spheroid expansion area in vitro. Treatment with extracellular vesicles (EVs) derived from the ectopic ESCs of EMS patients (EMS-EVs) increased collagen I expression in vivo and in vitro and decreased the blastocyst-like spheroid expansion area. Furthermore, EV microRNA (miRNA) sequencing revealed that there were 40 upregulated and 77 downregulated miRNAs in EMS-EVs when compared to the EVs derived from ESCs in the endometrium of control patients (CTL-EVs), including increased expression of miR-25-3p that targets phosphatase and tensin homolog (PTEN). We also found that PTEN expression was decreased and p-Akt expression was increased in the endometrium of EMS patients and EMS-EV-treated ESCs. miR-25-3p transfected ESCs exhibited increased collagen I, decreased PTEN, and increased p-Akt. Additionally, an EV uptake study further showed that EMS-EVs were preferentially taken up by ESCs rather than by endometrial epithelial cells. These results suggest that EMS-EVs encapsulating miR-25-3p might be preferentially taken up by eutopic ESCs where they may induce endometrial collagen I deposition to impair ESC decidualization in EMS.
A subcellular selective APEX2-based proximity labeling used for identifying mitochondrial G-quadruplex DNA binding proteins
Authors: Wang Xu , Qin Geng , Yang Jie , Zhao Chuanqi , Ren Jinsong , Qu Xiaogang
Published: December 2024

G-quadruplexes (G4s), as an important type of non-canonical nucleic acid structure, have received much attention because of their regulations of various biological processes in cells. Identifying G4s-protein interactions is essential for understanding G4s-related biology. However, current strategies for exploring G4 binding proteins (G4BPs) include pull-down assays in cell lysates or photoaffinity labeling, which are lack of sufficient spatial specificity at the subcellular level. Herein, we develop a subcellular selective APEX2-based proximity labeling strategy to investigate the interactome of mitochondrial DNA (mtDNA) G4s in living cells. By this method, we have identified several mtDNA G4BPs. Among them, a previously unrecognized mtDNA G4BP, DHX30 has been selected as an example to explore its important biofunctions. DHX30 localizes both in cytoplasm and mitochondria and can resolve mtDNA G4s. Further studies have demonstrated that DHX30 unfolds mtDNA G4 in living cells, which results in a decrease in glycolysis activity of tumor cells. Besides, RHPS4, a known mtDNA G4 stabilizer, will reverse this inhibition effect. Benefiting from the high spatiotemporal resolution and the ability of genetically encoded systems to perform the labeling with exquisite specificity within living cells, our approach can realize the identification of subcellular localized G4BPs. Our work provides a novel strategy to map protein interactions of specific nucleic acid features in subcellular compartments of living cells.