bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic associations of common waxbill gut and feather microbiome diversity in a shared environment
Authors: Marques Silva Sofia , Xavier Raquel , Gomes Ana Cristina R , Beltrão Patrícia , Cardoso Gonçalo C , Trigo Sandra
Published: September 2023

Microbial diversity may affect host phenotypes, including morphology and behaviour, but it remains unclear to which extent those could be mediated by host differences in diet or habitat use. We used a population of wild common waxbills living in a large open-air mesocosm to control for such differences and test whether phenotypic variation is associated with cloaca bacteria diversity. We also tested correlations between feather-associated bacteria diversity and plumage colour ornamentation. Albeit weakly correlated, individuals sharing more similar cloaca microbiotas were more similar in their carotenoid-based plumage and bill red colour, suggesting that the gut microbiota can influence ornamentation even when individuals are in the same habitat and have access to the same food resources, perhaps mediating individual differences in feeding or digestion. There were no associations between feather bacteria and plumage colour, nor between cloaca bacteria and body size or several behavioural phenotypes. These results further highlight that investigating associations between microbiota and behaviour in nature should account for variation in extrinsic factors.
Research progress of the Fanconi anemia pathway and premature ovarian insufficiency
Authors: Zhao Jingyu , Zhang Yixin , Li Wenbo , Yao Mengmeng , Liu Chuqi , Zhang Zihan , Wang Caiqin , Wang Xiaomei , Meng Kai
Published: September 2023

The Fanconi anemia pathway is a key pathway involved in the repair of deoxyribonucleic acidinterstrand crosslinking damage, which chiefly includes the following four modules: lesion recognition, Fanconi anemia core complex recruitment, FANCD2–FANCI complex monoubiquitination, and downstream events (nucleolytic incision, translesion synthesis, and homologous recombination). Mutations or deletions of multiple Fanconi anemia genes in this pathway can damage the interstrand crosslinking repair pathway and disrupt primordial germ cell development and oocyte meiosis, thereby leading to abnormal follicular development. Premature ovarian insufficiency is a gynecological clinical syndrome characterized by amenorrhea and decreased fertility due to decreased oocyte pool, accelerated follicle atresia, and loss of ovarian function in women <40 years old. Furthermore, in recent years, several studies have detected mutations in the Fanconi anemia gene in patients with premature ovarian insufficiency. In addition, some patients with Fanconi anemia exhibit symptoms of premature ovarian insufficiency and infertility. The Fanconi anemia pathway and premature ovarian insufficiency are closely associated.
Bayesian joint models for multi-regional clinical trials
Authors: Bean Nathan W , Ibrahim Joseph G , Psioda Matthew A
Published: September 2023

In recent years, multi-regional clinical trials (MRCTs) have increased in popularity in the pharmaceutical industry due to their ability to accelerate the global drug development process. To address potential challenges with MRCTs, the International Council for Harmonisation released the E17 guidance document which suggests the use of statistical methods that utilize information borrowing across regions if regional sample sizes are small. We develop an approach that allows for information borrowing via Bayesian model averaging in the context of a joint analysis of survival and longitudinal data from MRCTs. In this novel application of joint models to MRCTs, we use Laplace’s method to integrate over subject-specific random effects and to approximate posterior distributions for region-specific treatment effects on the time-to-event outcome. Through simulation studies, we demonstrate that the joint modeling approach can result in an increased rejection rate when testing the global treatment effect compared with methods that analyze survival data alone. We then apply the proposed approach to data from a cardiovascular outcomes MRCT.
MerTK is a mediator of alpha-synuclein fibril uptake by human microglia
Authors: Dorion Marie-France , Yaqubi Moein , Senkevich Konstantin , Kieran Nicholas W , MacDonald Adam , Chen Carol X Q , Luo Wen , Wallis Amber , Shlaifer Irina , Hall Jeffery A , Dudley Roy W R , Glass Ian A ,   Birth Defects Research Laboratory, Stratton Jo Anne , Fon Edward A , Bartels Tim , Antel Jack P , Gan-or Ziv , Durcan Thomas M , Healy Luke M
Published: September 2023

Mer tyrosine kinase (MerTK) is a receptor tyrosine kinase that mediates non-inflammatory, homeostatic phagocytosis of diverse types of cellular debris. Highly expressed on the surface of microglial cells, MerTK is of importance in brain development, homeostasis, plasticity and disease. Yet, involvement of this receptor in the clearance of protein aggregates that accumulate with ageing and in neurodegenerative diseases has yet to be defined. The current study explored the function of MerTK in the microglial uptake of alpha-synuclein fibrils which play a causative role in the pathobiology of synucleinopathies.

Using human primary and induced pluripotent stem cell-derived microglia, the MerTK-dependence of alpha-synuclein fibril internalization was investigated in vitro. Relevance of this pathway in synucleinopathies was assessed through burden analysis of MERTK variants and analysis of MerTK expression in patient-derived cells and tissues.

Pharmacological inhibition of MerTK and siRNA-mediated MERTK knockdown both caused a decreased rate of alpha-synuclein fibril internalization by human microglia. Consistent with the non-inflammatory nature of MerTK-mediated phagocytosis, alpha-synuclein fibril internalization was not observed to induce secretion of pro-inflammatory cytokines such as IL-6 or TNF, and downmodulated IL-1β secretion from microglia. Burden analysis in two independent patient cohorts revealed a significant association between rare functionally deleterious MERTK variants and Parkinson’s disease in one of the cohorts (P = 0.002). Despite a small upregulation in MERTK mRNA expression in nigral microglia from Parkinson’s disease/Lewy body dementia patients compared to those from non-neurological control donors in a single-nuclei RNA-sequencing dataset (P = 5.08 × 10−21), no significant upregulation in MerTK protein expression was observed in human cortex and substantia nigra lysates from Lewy body dementia patients compared to controls.

Taken together, our findings define a novel role for MerTK in mediating the uptake of alpha-synuclein fibrils by human microglia, with possible involvement in limiting alpha-synuclein spread in synucleinopathies such as Parkinson’s disease. Upregulation of this pathway in synucleinopathies could have therapeutic values in enhancing alpha-synuclein fibril clearance in the brain.
A painful ulcer on the dorsal aspect of the hand
Authors: Wang Wei-Yao , Lan Cheng-Che E , Chiu Szu-Hao
Published: September 2023

We present the case of a 77-year-old man who had a sudden onset of a painful ulcer on the dorsal aspect of the hand. The skin lesion exhibited a limited response to oral antibiotics. We discuss the distinct clinical and histopathological features necessary for diagnosing this disorder.
Dynamics in cardiac surgery: trends in population characteristics and the performance of the EuroSCORE II over time
Authors: van Dijk Wouter B , Leeuwenberg Artuur M , Grobbee Diederick E , Siregar Sabrina , Houterman Saskia , Daeter Edgar J , de Vries Martine C , Groenwold Rolf H H , Schuit Ewoud ,   Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration, Bramer Sander , van Boven Wim Jan , Vonk Alexander , Koene Bart , Bekkers Jos , Hoohenkerk Gerard , Markou Thanasie , de Weger Arend , Segers Patrique , Porta Fabiano , Speekenbrink Ron , Stooker Wim , Li Wilson , Daeter Edgar , van der Kaaij Niels , Douglas Yvonne
Published: September 2023

OBJECTIVES

The aim of this study was to investigate the performance of the EuroSCORE II over time and dynamics in values of predictors included in the model.

METHODS

A cohort study was performed using data from the Netherlands Heart Registration. All cardiothoracic surgical procedures performed between 1 January 2013 and 31 December 2019 were included for analysis. Performance of the EuroSCORE II was assessed across 3-month intervals in terms of calibration and discrimination. For subgroups of major surgical procedures, performance of the EuroSCORE II was assessed across 12-month time intervals. Changes in values of individual EuroSCORE II predictors over time were assessed graphically.

RESULTS

A total of 103 404 cardiothoracic surgical procedures were included. Observed mortality risk ranged between 1.9% [95% confidence interval (CI) 1.6–2.4] and 3.6% (95% CI 2.6–4.4) across 3-month intervals, while the mean predicted mortality risk ranged between 3.4% (95% CI 3.3–3.6) and 4.2% (95% CI 3.9–4.6). The corresponding observed:expected ratios ranged from 0.50 (95% CI 0.46–0.61) to 0.95 (95% CI 0.74–1.16). Discriminative performance in terms of the c-statistic ranged between 0.82 (95% CI 0.78–0.89) and 0.89 (95% CI 0.87–0.93). The EuroSCORE II consistently overestimated mortality compared to observed mortality. This finding was consistent across all major cardiothoracic surgical procedures. Distributions of values of individual predictors varied broadly across predictors over time. Most notable trends were a decrease in elective surgery from 75% to 54% and a rise in patients with no or New York Heart Association I class heart failure from 27% to 33%.

CONCLUSIONS

The EuroSCORE II shows good discriminative performance, but consistently overestimates mortality risks of all types of major cardiothoracic surgical procedures in the Netherlands.
Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis
Authors: Drexler Richard , Rotermund Roman , Smith Timothy R , Kilgallon John L , Honegger Jürgen , Nasi-Kordhishti Isabella , Gardner Paul A , Gersey Zachary C , Abdallah Hussein M , Jane John A , Marino Alexandria C , Knappe Ulrich J , Uksul Nesrin , Rzaev Jamil A , Galushko Evgeniy V , Gormolysova Ekaterina V , Bervitskiy Anatoliy V , Schroeder Henry W S , Eördögh Márton , Losa Marco , Mortini Pietro , Gerlach Rüdiger , Azab Mohammed , Budohoski Karol P , Rennert Robert C , Karsy Michael , Couldwell William T , Antunes Apio C M , Westphal Manfred , Ricklefs Franz L , Flitsch Jörg
Published: September 2023

Importance

Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available.

Objective

We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas.

Design

A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed.

Setting

Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values.

Results

Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%.

Conclusions

This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.
Process and sampling variance within fisheries stock assessment models: estimability, likelihood choice, and the consequences of incorrect specification
Authors: Fisch N , Shertzer K , Camp E , Maunder M , Ahrens R
Published: September 2023

Increasingly, mixed-effect fishery stock assessment models are being developed where deviations about functional forms of different processes are modelled as random effects and the extent of variance is estimated internal to the model. Concurrently, sampling variance parameters associated with likelihoods for fitting composition data within fisheries assessments are more often being estimated internal to the model as well. We examine the performance of stock assessment models when multiple process variance and sampling variance terms are simultaneously estimated within assessment models. We specifically examine how assessment performance is affected by the choice of composition likelihood, the degree of overdispersion in composition data, overparameterization, and modelling variation on the wrong process. In doing so, we build a simulation containing overdispersion and correlations in composition data, directional variation in catchability and/or selectivity, and estimation models which include random effects and composition likelihoods with theoretically estimable variances. Results suggest that with standard data available in fisheries assessments, process variance parameters associated with some commonly employed methods and sampling variance parameters can be simultaneously estimated internal to an assessment, and performance greatly improves with increased composition data. Our results also suggest little downside to overparameterization of selectivity and catchability when the true process is not time-varying, which largely agrees with previous research. However, when a process is truly time-varying and the assessment models time-variation on a different process, namely when selectivity is time-varying and instead natural mortality is modelled as potentially time-varying, we find a risk of severe increases in bias and decreases in confidence interval coverage for assessed quantities. This bias and decrease in coverage could, however, be partially mitigated by also modelling time-variation on the correct process.
Research progress and latest achievements of road piezoelectric vibration energy capture technology based on intelligent transportation construction
Authors: Zhou Mengqi , Wang Long , Wang Jun , Ding Guangya , Liu Zhiming
Published: September 2023

Developing smart transportation and advocating green transportation are the main directions of future transportation development. In recent years, with the rapid development of intelligent structures and intelligent materials, a variety of energy harvesting technologies in road environment have gradually become a research hotspot. However, due to the low energy conversion efficiency and high cost, the application of some energy harvesting technologies is limited. Among them, vibration energy capture technology based on piezoelectric effect has been widely concerned by scholars because it does not need external power supply and can supply power for low-power wireless sensors. Therefore, this paper summarizes the current state of road energy harvesting technology, with emphasis on piezoelectric systems. It includes the mechanism of piezoelectric effect, the structure of the collector, and its road application. Based on extensive review research, this paper provides a comprehensive insight into road energy harvesting technologies. Specifically, the paper discusses the social and environmental benefits and challenges of road energy harvesting technologies. Finally, research on the durability, safety, and life cycle cost of road piezoelectric energy capture technology is still scarce. It is recommended to carry out such research in order to promote the positive contribution of piezoelectric energy exchange technology in the construction of intelligent transportation.
Epiphytic microbiota in Swedish grass-clover herbage and the effect of silage additives on fermentation profiles and bacterial community compositions of the resulting silages
Authors: Eliasson Thomas , Sun Li , Lundh Åse , Höjer Annika , Saedén Karin Hallin , Hetta Mårten , Gonda Horacio
Published: September 2023

Aims

To investigate the epiphytic microbiota in grass-clover herbage harvested at different sites and occasions and to explore the effect of different silage additives on the resulting silage microbiota.

Methods and results

Herbage was harvested from grass-clover leys at geographically distributed sites in a long-term field experiment in Sweden, in early and late season of two consecutive years. Different silages were made from the herbage using: (1) no additive, (2) acid-treatment, and (3) inoculation by starter culture. Herbages were analysed for botanical and chemical composition, and the resulting silages for products of fermentation. Bacterial DNA was extracted from herbage and silage samples, followed by sequencing using Illumina 16S rRNA amplicon sequencing. Herbage microbiota showed no clear correlation to site or harvesting time. Silage additives had a major effect on the ensiling process; inoculation resulted in well fermented silages comprising a homogenous microbiota dominated by the genera Lactobacillus and Pediococcus. A minor effect of harvest time was also observed, with generally a more diverse microbiota in second-harvest silages. Untreated silages showed a higher relative abundance (RA) from non-lactic acid bacteria compared to acid-treated silages. In most silages, only a few bacterial amplicon sequence variants contributed to most of the RA.

Conclusions

The epiphytic microbiota in grass-clover herbage were found to be random and not dependent on site. From a microbial point of view, the most predictable and preferable silage outcome was obtained by inoculation with a starter culture. Acid-treatment with formic- and propionic acid surprisingly resulted in a less preferable silage. Silage making without additives cannot be recommended based on our results.
Image-encoded biological and non-biological variables may be used as shortcuts in deep learning models trained on multisite neuroimaging data
Authors: Souza Raissa , Wilms Matthias , Camacho Milton , Pike G Bruce , Camicioli Richard , Monchi Oury , Forkert Nils D
Published: September 2023

Objective

This work investigates if deep learning (DL) models can classify originating site locations directly from magnetic resonance imaging (MRI) scans with and without correction for intensity differences.

Material and Methods

A large database of 1880 T1-weighted MRI scans collected across 41 sites originally for Parkinson’s disease (PD) classification was used to classify sites in this study. Forty-six percent of the datasets are from PD patients, while 54% are from healthy participants. After preprocessing the T1-weighted scans, 2 additional data types were generated: intensity-harmonized T1-weighted scans and log-Jacobian deformation maps resulting from nonlinear atlas registration. Corresponding DL models were trained to classify sites for each data type. Additionally, logistic regression models were used to investigate the contribution of biological (age, sex, disease status) and non-biological (scanner type) variables to the models’ decision.

Results

A comparison of the 3 different types of data revealed that DL models trained using T1-weighted and intensity-harmonized T1-weighted scans can classify sites with an accuracy of 85%, while the model using log-Jacobian deformation maps achieved a site classification accuracy of 54%. Disease status and scanner type were found to be significant confounders.

Discussion

Our results demonstrate that MRI scans encode relevant site-specific information that models could use as shortcuts that cannot be removed using simple intensity harmonization methods.

Conclusion

The ability of DL models to exploit site-specific biases as shortcuts raises concerns about their reliability, generalization, and deployability in clinical settings.
A framework for understanding label leakage in machine learning for health care
Authors: Davis Sharon E , Matheny Michael E , Balu Suresh , Sendak Mark P
Published: September 2023

Introduction

The pitfalls of label leakage, contamination of model input features with outcome information, are well established. Unfortunately, avoiding label leakage in clinical prediction models requires more nuance than the common advice of applying “no time machine rule.”

Framework

We provide a framework for contemplating whether and when model features pose leakage concerns by considering the cadence, perspective, and applicability of predictions. To ground these concepts, we use real-world clinical models to highlight examples of appropriate and inappropriate label leakage in practice.

Recommendations

Finally, we provide recommendations to support clinical and technical stakeholders as they evaluate the leakage tradeoffs associated with model design, development, and implementation decisions. By providing common language and dimensions to consider when designing models, we hope the clinical prediction community will be better prepared to develop statistically valid and clinically useful machine learning models.
Dietary lysolecithin supplementation improves growth performance of weaned piglets via improving nutrients absorption, lipid metabolism, and redox status
Authors: Liu Yang , Wu Aimin , Mo Ruixia , Zhou Qiang , Song Lianghui , Li Zheng , Zhao Hua , Fang Zhengfeng , Lin Yan , Xu Shengyu , Feng Bin , Zhuo Yong , Wu De , Che Lianqiang
Published: September 2023

Lysolecithin is widely used as emulsifier to improve the digestibility and retention of fat. The current study aimed to investigate the effects of dietary lysolecithin supplementation on growth performance, nutrients absorption, lipid metabolism, and redox status of weaned pigs. A total of 60 weaned piglets were assigned into 2 dietary treatments in a randomized complete block design, receiving basal diet with 0 or 1,000 mg/kg lysolecithin for a period of 28 d. Each dietary treatment had 10 replicates with 3 piglets per replicate. Growth performance and fecal score were monitored during trial. Samples of blood, ileum, and liver tissues were collected and analyzed for serology, intestinal histomorphology, and lipid metabolism-related gene and protein expressions. Dietary lysolecithin supplementation increased average daily gain (+15%, P < 0.05) and tended to increase average daily feed intake (+14%, P = 0.08) in overall experimental period. At final, the average body weight of piglets in lysolecithin group was 10% greater than that of control group (P = 0.09). In addition, dietary lysolecithin supplementation improved the ability of nutrients absorption as indicated by the higher d-xylose level in plasma (P < 0.05). Moreover, piglets from lysolecithin group had higher concentration of high-density lipoprotein (P < 0.05), but lower triglyceride (P < 0.05) in plasma. The inclusion of lysolecithin in diet increased the level of reduced glutathione (GSH) and GSH to oxidized glutathione (GSSG) ratio in plasma and liver (P < 0.05), but attenuated the levels of malondialdehyde and GSSG in ileum (P < 0.05). The upregulation of lipogenesis-related genes (FAS and ACC), downregulation of lipolysis (PNPLA2 and PABP1), and lipid mobilization (PGC-1α and SRIT1) genes were observed in lysolecithin relative to control piglets. Compared with control group, dietary lysolecithin supplementation upregulated protein expressions of GPX4, SREBP1, and LPL in liver and LPL in ileum (P < 0.05). Collectively, our study indicates that dietary lysolecithin supplementation improved growth performance of weaned piglets, which may be associated with the improved nutrients absorption, redox status, and lipid metabolism.
Racism, public pedagogy, and the construction of a United States values infrastructure, 1661–2023: a critical reflection
Authors: Becnel Barbara
Published: September 2023

This paper argues that public pedagogy—an educational activity that takes place outside of the traditional classroom setting—has had a potent impact on the history of racism in the United States of America (USA). Yet this paper questions why the education academy’s scholarship has not shown a commensurate focus on the subdiscipline of public pedagogy, particularly racialized public pedagogy. I explore these topics by first examining a fateful confluence of historical circumstances involving slave codes and indentured servant laws governing low-income white workers, laws passed by the Barbados Assembly in 1661, that made their way across the Atlantic to be lifted, word for word, by leaders of colonial territories that became the USA. These laws ended up regulating not only the legal status of black slaves and white indentured servants in the USA, but also regulating social relations between those same black and white people. The resulting black–white social relations led to the evolution of racialized customs in what eventually became the USA, inspiring practices that undergirded black inferiority and white superiority for hundreds of years. Those customs contributed to the construction of what I have labelled a United States (US) values infrastructure dominated by racism, which I contend is a racialized values infrastructure that exists to this day. To gain more insight into this phenomenon, this paper considers the question: how might the complexity of racialized public pedagogy be addressed in the scholarship of education literature and be imagined in a way to fit into an anti-racist curriculum?
Measuring Social Inclusion in Europe: a non-additive approach with the expert-preferences of public policy planners
Authors: Carrino Ludovico , Farnia Luca , Giove Silvio
Published: September 2023

This paper introduces a normative, expert-informed, time-dependent index of Social Inclusion for European administrative regions in five countries, using longitudinal data from Eurostat. Our contribution is twofold: first, our indicator is based on a non-additive aggregation operator (the Choquet Integral), which allows us to model many preferences’ structures and to overcome the limitations embedded in other approaches. Second, we elicit the parameters of the aggregation operator from an expert panel of Italian policymakers in Social Policy, and Economics scholars. Our results highlight that Mediterranean countries exhibit lower Inclusion levels than Northern/Central countries, and that this disparity has grown in the last decade. Our results complement and partially challenge existing evidence from data-driven aggregation methods.
13C-labeling reveals non-conventional pathways providing carbon for hydroxy fatty acid synthesis in Physaria fendleri
Authors: Cocuron Jean-Christophe , Alonso Ana Paula
Published: September 2023

Physaria fendleri is a member of the Brassicaceae that produces in its embryos hydroxy fatty acids, constituents of oils that are very valuable and widely used by industry for cosmetics, lubricants, biofuels, etc. Free of toxins and rich in hydroxy fatty acids, Physaria provides a promising alternative to imported castor oil and is on the verge of being commercialized. This study aims to identify important biochemical step(s) for oil synthesis in Physaria, which may serve as target(s) for future crop improvement. To advance towards this goal, the endosperm composition was analysed by LC-MS/MS to develop and validate culture conditions that mimic the development of the embryos in planta. Using developing Physaria embryos in culture and 13C-labeling, our studies revealed that: (i) Physaria embryos metabolize carbon into biomass with an efficiency significantly lower than other photosynthetic embryos; (ii) the plastidic malic enzyme provides 42% of the pyruvate used for de novo fatty acid synthesis, which is the highest measured so far in developing ‘green’ oilseed embryos; and (iii) Physaria uses non-conventional pathways to channel carbon into oil, namely the Rubisco shunt, which fixes CO2 released in the plastid, and the reversibility of isocitrate dehydrogenase, which provides additional carbon for fatty acid elongation.
Aggregated gene co-expression networks predict transcription factor regulatory landscapes in grapevine
Authors: Orduña Luis , Santiago Antonio , Navarro-Payá David , Zhang Chen , Wong Darren C J , Matus José Tomás
Published: September 2023

Gene co-expression networks (GCNs) have not been extensively studied in non-model plants. However, the rapid accumulation of transcriptome datasets in certain species represents an opportunity to explore underutilized network aggregation approaches. In fact, aggregated GCNs (aggGCNs) highlight robust co-expression interactions and improve functional connectivity. We applied and evaluated two different aggregation methods on public grapevine RNA-Seq datasets from three different tissues (leaf, berry, and ‘all organs’). Our results show that co-occurrence-based aggregation generally yielded the best-performing networks. We applied aggGCNs to study several transcription factor gene families, showing their capacity for detecting both already-described and novel regulatory relationships between R2R3-MYBs, bHLH/MYC, and multiple specialized metabolic pathways. Specifically, transcription factor gene- and pathway-centered network analyses successfully ascertained the previously established role of VviMYBPA1 in controlling the accumulation of proanthocyanidins while providing insights into its novel role as a regulator of p-coumaroyl-CoA biosynthesis as well as the shikimate and aromatic amino acid pathways. This network was validated using DNA affinity purification sequencing data, demonstrating that co-expression networks of transcriptional activators can serve as a proxy of gene regulatory networks. This study presents an open repository to reproduce networks in other crops and a GCN application within the Vitviz platform, a user-friendly tool for exploring co-expression relationships.
FertileCryptococcus neoformansvar.neoformans(C. deneoformans) isolates from natural environment in Kosovo
Authors: Pllana-Hajdari Donjeta , Chidebelu Ekene P , Cogliati Massimo
Published: September 2023

A total of 300 tree-associated samples were collected from green areas in three towns in Kosovo, and cultured to isolate Cryptococcus species. One soil sample from Prizren tested positive, yielding three isolates identified as C. neoformans var. neoformans (C. deneoformans), molecular type VNIV, two MATα, and one MATa. Mating experiments revealed that they were fertile when crossed together, and multilocus sequence typing analysis showed unique sequence types not found in the global database. The study reports the presence of C. neoformans strains in the environment in Kosovo and highlights the importance of monitoring pathogen distribution and the potential impacts of climate change.
Enhanced symmetry energy may bear universality of r-process abundances
Authors: Orce José Nicolás , Dey Balaram , Ngwetsheni Cebo , Bhattacharya Srijit , Pandit Deepak , Lesch Brenden , Zulu Andile
Published: September 2023

The abundances of about half of the elements heavier than iron are subtly attuned by the rapid neutron capture process or r-process, which is intimately related to the competition between neutron capture, photo-disintegration, and β-decay rates, and ultimately depends on the binding energy of neutron-rich nuclei. The well-known Bethe–Weizsäcker semi-empirical mass formula describes the binding energy of ground states – i.e. nuclei with temperatures of T = 0 MeV – with the symmetry energy parameter converging between 23 and 27 MeV for heavy nuclei. We find an unexpected enhancement of the symmetry energy well above the ground state – at higher temperatures of T ≈ 0.7–1.0 MeV – from the available data of giant dipole resonances built on excited states. Although these are likely the temperatures where seed nuclei are created – during the cooling down of the ejecta following neutron-star mergers or collapsars – the fact that the symmetry energy remains constant between T ≈ 0.7 and 1.0 MeV, may suggest an enhanced symmetry energy at lower temperatures, where neutron-capture may start occurring. Calculations using this relatively larger symmetry energy yield a reduction of the binding energy per nucleon for heavy neutron-rich nuclei and inhibits radiative neutron-capture rates. This results in a substantial close in of the neutron drip line which may elucidate the long sought universality of heavy-element abundances through the r-process; as inferred from the similar abundances found in extremely metal-poor stars and the Sun. Sensitivity studies of r-process network calculations have been performed using more sophisticated mass models.
The spectroscopic orbit of HD 168112 A,B in NGC 6604: another massive binary target for interferometry
Authors: Putkuri C , Gamen R , Morrell N I , Maíz Apellániz J , Arias J I , Simón-Díaz S , Ferrero G A , Rodríguez C N , Sota A , Benvenuto O G , Barbá R H
Published: September 2023

We present the first spectroscopic orbit of the O-type double-lined star HD 168112 A,B. We analyse 101 high-resolution optical spectra identifying the absorption lines of both components. The orbital solution presents a relatively long period, P = 513.52 ± 0.01 d, and a high eccentricity, e = 0.743 ± 0.005. The binary system consists of two very similar stars of minimum masses of ∼25 M⊙, effective temperatures of ∼40 000 K, and surface gravities of ∼3.7 dex. The system has a minimum semimajor axis a sin i ∼ 1000 R⊙. We confirm that the A and B visual components identified via interferometry do correspond to the spectroscopic ones. We also analyse the underlying stellar groups using Gaia DR3 data and ground-based spectroscopy as part of the Villafranca project, determining that NGC 6604 is at a distance of $1942^{+38}_{-36}$ pc and giving spectral classifications for 23 massive stellar systems in Villafranca O-035 and the surrounding Ser OB2 association, for which we provide the most complete census of massive stars to date.
Precessing binary black holes as better dark sirens
Authors: Yun Qianyun , Han Wen-Biao , Hu Qian , Xu Haiguang
Published: September 2023

Gravitational waves (GWs) from binary black hole mergers provide unique opportunities for cosmological inference such as standard sirens. However, the accurate determination of the luminosity distance of the event is limited by the correlation between the distance and the angle between the binary’s orbital angular momentum and the observer’s line of sight. In the letter, we investigate the effect of precession on the distance estimation of binary black hole events for the third-generation (3G) GW detectors. We find that the precession can enhance the precision of distance inference by one order of magnitude compared to the scenario where precession is absent. The constraint on the host galaxies can be improved due to the improved distance measurement, therefore the Hubble constant can be measured with higher precision and accuracy. These findings underscore the noteworthy impact of precession on the precision of distance estimation for 3G ground-based GW detectors, which can serve as highly accurate probes of the Universe.
Assessing in vivo the impact of gene context on transcription through DNA supercoiling
Authors: Boulas Ihab , Bruno Lisa , Rimsky Sylvie , Espeli Olivier , Junier Ivan , Rivoire Olivier
Published: September 2023

Gene context can have significant impact on gene expression but is currently not integrated in quantitative models of gene regulation despite known biophysical principles and quantitative in vitro measurements. Conceptually, the simplest gene context consists of a single gene framed by two topological barriers, known as the twin transcriptional-loop model, which illustrates the interplay between transcription and DNA supercoiling. In vivo, DNA supercoiling is additionally modulated by topoisomerases, whose modus operandi remains to be quantified. Here, we bridge the gap between theory and in vivo properties by realizing in Escherichia coli the twin transcriptional-loop model and by measuring how gene expression varies with promoters and distances to the topological barriers. We find that gene expression depends on the distance to the upstream barrier but not to the downstream barrier, with a promoter-dependent intensity. We rationalize these findings with a first-principle biophysical model of DNA transcription. Our results are explained if TopoI and gyrase both act specifically, respectively upstream and downstream of the gene, with antagonistic effects of TopoI, which can repress initiation while facilitating elongation. Altogether, our work sets the foundations for a systematic and quantitative description of the impact of gene context on gene regulation.
Trends in epidemiology and risk factors of opportunistic infections in kidney transplant recipients between 2004 and 2017
Authors: Pfirmann Pierre , Garrigue Isabelle , Chauveau Bertrand , Rondeau Virginie , Tumiotto Camille , Weinmann Laurent , Dubois Véronique , Couzi Lionel , Merville Pierre , Kaminski Hannah , Taton Benjamin
Published: September 2023

Background

While opportunistic infections are a frequent and challenging problem in kidney transplant recipients, their long-term epidemiology remains hardly known.

Methods

Opportunistic infections were recorded in 1144 recipients transplanted in our center between 2004 and 2015. Incidence rates and baseline risk factors were determined using joint frailty models.

Results

After a median follow-up of 5.6 years, 544 opportunistic infections occurred in 373/1144 (33%) patients, dominated by viral infections (396/544, 72%), especially cytomegalovirus (CMV) syndromes and diseases (213/544, 39%). One-third of the infected patients experienced at least two opportunistic infections. The incidence of opportunistic infections was 10 times higher during the first year post-transplantation than after that (34.7 infections for 100 patient-years vs 3.64). Opportunistic infections associated with the age of the donor (P = .032), the age of the recipient (P = .049), the CMV serostatus (P < 10−6), a higher class II HLA mismatch (P = .032) and an induction treatment including rabbit anti-thymocyte globulins (P = .026). Repeated opportunistic infections associated with each other (P < 10−6) and with renal death (P < 10−6).

Conclusion

Opportunistic infections occur with a two-period incidence pattern and many susceptible patients suffer from repeated episodes. This knowledge may help tailor new prevention and follow-up strategies to reduce the burden of opportunistic infections and their impact on transplantation outcome.
Deep Learning of Multimodal Ultrasound: Stratifying the Response to Neoadjuvant Chemotherapy in Breast Cancer Before Treatment
Authors: Gu Jionghui , Zhong Xian , Fang Chengyu , Lou Wenjing , Fu Peifen , Woodruff Henry C , Wang Baohua , Jiang Tianan , Lambin Philippe
Published: September 2023

Background

Not only should resistance to neoadjuvant chemotherapy (NAC) be considered in patients with breast cancer but also the possibility of achieving a pathologic complete response (PCR) after NAC. Our study aims to develop 2 multimodal ultrasound deep learning (DL) models to noninvasively predict resistance and PCR to NAC before treatment.

Methods

From January 2017 to July 2022, a total of 170 patients with breast cancer were prospectively enrolled. All patients underwent multimodal ultrasound examination (grayscale 2D ultrasound and ultrasound elastography) before NAC. We combined clinicopathological information to develop 2 DL models, DL_Clinical_resistance and DL_Clinical_PCR, for predicting resistance and PCR to NAC, respectively. In addition, these 2 models were combined to stratify the prediction of response to NAC.

Results

In the test cohort, DL_Clinical_resistance had an AUC of 0.911 (95%CI, 0.814-0.979) with a sensitivity of 0.905 (95%CI, 0.765-1.000) and an NPV of 0.882 (95%CI, 0.708-1.000). Meanwhile, DL_Clinical_PCR achieved an AUC of 0.880 (95%CI, 0.751-0.973) and sensitivity and NPV of 0.875 (95%CI, 0.688-1.000) and 0.895 (95%CI, 0.739-1.000), respectively. By combining DL_Clinical_resistance and DL_Clinical_PCR, 37.1% of patients with resistance and 25.7% of patients with PCR were successfully identified by the combined model, suggesting that these patients could benefit by an early change of treatment strategy or by implementing an organ preservation strategy after NAC.

Conclusions

The proposed DL_Clinical_resistance and DL_Clinical_PCR models and combined strategy have the potential to predict resistance and PCR to NAC before treatment and allow stratified prediction of NAC response.
Elements of End-of-Life Discussions Associated With Patients’ Reported Outcomes and Actual End-of-Life Care in Patients With Pretreated Lung Cancer
Authors: Hasegawa Takaaki , Okuyama Toru , Uemura Takehiro , Matsuda Yoshinobu , Otani Hiroyuki , Shimizu Junichi , Horio Yoshitsugu , Watanabe Naohiro , Yamaguchi Teppei , Fukuda Satoshi , Oguri Tetsuya , Maeno Ken , Taniguchi Yoshihiko , Nosaki Kaname , Fukumitsu Kensuke , Akechi Tatsuo
Published: September 2023

Background

End-of-life discussions for patients with advanced cancer are internationally recommended to ensure consistency of end-of-life care with patients’ values. This study examined the elements of end-of-life discussions associated with end-of-life care.

Materials and Methods

We performed a prospective observational study among consecutive patients with pretreated non-small cell lung cancer after the failure of first-line chemotherapy. We asked oncologists whether they had ever discussed “prognosis,” “do not attempt resuscitation,” “hospice,” and “preferred place of death” with a patient at baseline. The quality of life (QOL) and depressive symptoms of patients were assessed using validated questionnaires at baseline and 3 months later. The end-of-life care that patients received was investigated using medical records. Oncologists’ compassion and caregivers’ preferences for hospice care were also assessed using questionnaires. Multiple regression analyses were conducted to examine the association between elements of end-of-life discussions and patient-reported outcomes as well as actual end-of-life care.

Results

We obtained 200 valid responses at baseline, 147 valid responses 3 months later, and 145 data points for medical care at the end-of-life stage. No element of the end-of-life discussion between the patient and their oncologist was significantly associated with patients’ reported outcomes or actual end-of-life care. In addition, oncologists’ compassion was significantly associated with improvement in both comprehensive QOL and depressive symptoms, and caregivers’ preferences for hospice care and high educational level were significantly associated with hospice death.

Conclusion

Oncologist-patient alliances and caregivers’ involvement in end-of-life discussions may be influential in achieving optimal end-of-life care.
Microtubule-associated protein SlMAP70 interacts with IQ67-domain protein SlIQD21a to regulate fruit shape in tomato
Authors: Bao Zhiru , Guo Ye , Deng Yaling , Zang Jingze , Zhang Junhong , Deng Yingtian , Ouyang Bo , Qu Xiaolu , Bürstenbinder Katharina , Wang Pengwei
Published: September 2023

Tomato (Solanum lycopersicum) fruit shape is related to microtubule organization and the activity of microtubule-associated proteins (MAPs). However, insights into the mechanism of fruit shape formation from a cell biology perspective remain limited. Analysis of the tissue expression profiles of different microtubule regulators revealed that functionally distinct classes of MAPs, including members of the plant-specific MICROTUBULE-ASSOCIATED PROTEIN 70 (MAP70) and IQ67 DOMAIN (IQD, also named SUN in tomato) families, are differentially expressed during fruit development. SlMAP70-1–3 and SlIQD21a are highly expressed during fruit initiation, which relates to the dramatic microtubule pattern rearrangements throughout this developmental stage of tomato fruits. Transgenic tomato lines overexpressing SlMAP70-1 or SlIQD21a produced elongated fruits with reduced cell circularity and microtubule anisotropy, while their loss-of-function mutants showed the opposite phenotype, harboring flatter fruits. Fruits were further elongated in plants coexpressing both SlMAP70-1 and SlIQD21a. We demonstrated that SlMAP70s and SlIQD21a physically interact and that the elongated fruit phenotype is likely due to microtubule stabilization induced by the SlMAP70–SlIQD21a interaction. Together, our results identify SlMAP70 proteins and SlIQD21a as important regulators of fruit elongation and demonstrate that manipulating microtubule function during early fruit development provides an effective approach to alter fruit shape.
Endoscopic retrograde cholangiopancreatography as a single-modality ‘gold-standard’ treatment for common bile duct stones in the elderly
Authors: Manson David , Soliman Faris , Mohamed Usama , Somasekar Krishnamurthy
Published: September 2023

Background

There are more octogenarians presenting with gallstone disease each year. Many are not suitable for surgical intervention. An alternative treatment option for common bile duct stones in the elderly is endoscopic retrograde cholangiopancreatography (ERCP) with or without stent insertion.

Methods

We conducted a retrospective study using a prospectively collected database, analysing the outcomes of consecutive patients >80 years old who underwent an ERCP in a single centre for the treatment of common bile duct stones.

Results

In total, 156 patients, with a median age of 91 years, underwent an ERCP for choledocholithiasis over a 3-year period. ERCP was successful in 90% of patients but a proportion required repeat intervention. Forty-six (29%) patients had a concurrently inserted stent due to incomplete stone extraction. Six (4%) patients required a post-ERCP cholecystectomy due to ongoing symptoms. The overall ERCP complication rate was 7% (4% Clavien-Dindo 1 and 3% Clavien-Dindo 2), with no cases of post-ERCP pancreatitis or death. Patients were followed up over 5 years following index ERCP. There was a 60% 3-year survival and 30% 5-year survival rate following index ERCP. Importantly, of those who did not survive, only four patients (2.6%) had a death attributable to a biliary cause and none were fit for definitive surgery.

Conclusions

ERCP can be considered as a possible definitive management option for treating common bile duct stones in the elderly, particularly in the comorbid population. Concurrent stenting is an effective temporizing strategy and mitigator of biliary-related readmission, but routine stent changes should be considered.

Key messages What is already known on this topic Current guidelines advocate for laparoscopic cholecystectomy and common bile duct exploration in patients with choledocholithiasis. What this study adds Endoscopic retrograde cholangiopancreatography with or without stent insertion is a safe, alternative single-treatment modality for choledocholithiasis in the elderly comorbid population. How this study might affect research, practice, or policy Studies and guidelines evaluating treatment options for choledocholithiasis may be altered to accommodate patient-specific factors, including age and comorbid status, and the concurrent use of stenting as a either a temporizing or longer-term measure for complex stone disease.