bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of liver dysfunction with outcomes after cardiac surgery—a meta-analysis
Authors: Kirov Hristo , Caldonazo Tulio , Audisio Katia , Rahouma Mohamed , Robinson N Bryce , Cancelli Gianmarco , Soletti Giovanni J , Demetres Michelle , Ibrahim Mudathir , Faerber Gloria , Gaudino Mario , Doenst Torsten
Published: December 2022

OBJECTIVES

The aim of this study was to perform a meta-analysis of studies reporting outcomes in patients with liver dysfunction addressed by the model of end-stage liver disease and Child–Turcotte–Pugh scores undergoing cardiac surgery.

METHODS

A systematic literature search was conducted to identify contemporary studies reporting short- and long-term outcomes in patients with liver dysfunction compared to patients with no or mild liver dysfunction undergoing cardiac surgery (stratified in high and low score group based on the study cut-offs). Primary outcome was perioperative mortality. Secondary outcomes were perioperative neurological events, prolonged ventilation, sepsis, bleeding and/or need for transfusion, acute kidney injury and long-term mortality.

RESULTS

A total of 33 studies with 48 891 patients were included. Compared with the low score group, being in the high score group was associated with significantly higher risk of perioperative mortality [odds ratio (OR) 3.72, 95% confidence interval (CI) 2.75–5.03, P < 0.001]. High score group was also associated with a significantly higher rate of perioperative neurological events (OR 1.49, 95% CI 1.30–1.71, P < 0.001), prolonged ventilation (OR 2.45, 95% CI 1.94–3.09, P < 0.001), sepsis (OR 3.88, 95% CI 2.07–7.26, P < 0.001), bleeding and/or need for transfusion (OR 1.95, 95% CI 1.43–2.64, P < 0.001), acute kidney injury (OR 3.84, 95% CI 2.12–6.98, P < 0.001) and long-term mortality (incidence risk ratio 1.29, 95% CI 1.14–1.46, P < 0.001)

CONCLUSIONS

The analysis suggests that liver dysfunction in patients undergoing cardiac surgery is independently associated with higher risk of short and long-term mortality and also with an increased occurrence of various perioperative adverse events.
Reassessment of the Broth Microdilution Method for Susceptibility Testing of Helicobacter pylori
Authors: Tang Xiaoqiong , Shen Yalin , Song Xiaona , Benghezal Mohammed , Marshall Barry J , Tang Hong , Li Hong
Published: December 2022

Background

Helicobacter pylori infection is an infectious disease and thus the eradication treatment should be guided by susceptibility testing. This study aimed to assess the applicability of broth microdilution as a routine susceptibility testing method for H. pylori.

Methods

Susceptibility profiles of clarithromycin (CLR) and levofloxacin (LEV) resistance in 76 clinical H. pylori isolates were simultaneously assessed using agar dilution and broth microdilution methods. The correlation between the minimum inhibitory concentrations (MICs) obtained by the 2 methods was assessed by means of linear regression analysis.

Results

The correlation between the MICs determined by broth microdilution method and agar dilution method was good for both CLR (r = 0.966) and LEV (r = 0.959). The susceptibility agreement between the 2 methods was 100% for CLR and 96.1% for LEV. Using the broth microdilution method, the false resistance was found in 3.9% (3 of 76) strains for LEV susceptibility testing. No false susceptibility was found for either CLR or LEV, and no false resistance was found for susceptibility testing of CLR.

Conclusions

The broth microdilution method is suitable for routine susceptibility testing of clinical H. pylori isolates.
The Inappropriateness of Using Rifampicin E-Test to Predict Rifabutin Resistance in Helicobacter pylori
Authors: Yang Tiankuo , Liu Bowen , Zhou Junpeng , Shen Yalin , Song Xiaona , Tang Xiaoqiong , Benghezal Mohammed , Marshall Barry James , Tang Hong , Li Hong
Published: December 2022

Background

The aim of this study was to evaluate the rifamycin cross-resistance in Helicobacter pylori, and whether the use of rifampicin E-test strips to screen H. pylori rifabutin resistance is appropriate.

Methods

A total of 89 H. pylori isolates were included. Rifampicin minimum inhibitory concentrations (MICs) were obtained by E-test, while the MICs for rifapentine, rifaximin, and rifabutin were determined by agar dilution method. The rifamycin resistance rates based on different breakpoints were compared. Isolates with high-level rifampicin resistance were subjected to whole-genome sequencing.

Results

A wide distribution of MICs (mostly in the range 0.125–8 mg/L) was observed for rifampicin, rifapentine, and rifaximin. Using MIC >1, ≥ 4, and > 4 mg/L as the breakpoints, resistance rates to rifampicin/rifapentine/rifaximin were 60.4%/48.3%/38.2%, 28.1%/25.8%/23.6%, and 15.7%/16.9%/7.9%, respectively. However, the rifabutin MICs of all the tested H. pylori isolates were extremely low (≤0.016 mg/L). Applying MIC ≥ 0.125 mg/L as the breakpoint, rifabutin resistance was nil. No mutation was found in the rpoB gene sequences of the 2 isolates with high-level rifampicin resistance.

Conclusions

There is a lack of cross-resistance between rifabutin and other rifamycins in H. pylori. The use of rifampicin E-test to predict H. pylori rifabutin resistance is inappropriate.
Exploring the in situ evolution of nitrofurantoin resistance in clinically derived uropathogenic Escherichia coli isolates
Authors: Vallée Maxime , Harding Chris , Hall Judith , Aldridge Phillip D , TAN Aaron
Published: December 2022

Background

Nitrofurantoin has been re-introduced as a first-choice antibiotic to treat uncomplicated acute urinary tract infections in England and Wales. Highly effective against common uropathogens such as Escherichia coli, its use is accompanied by a low incidence (<10%) of antimicrobial resistance. Resistance to nitrofurantoin is predominantly via the acquisition of loss-of-function, step-wise mutations in the nitroreductase genes nfsA and nfsB.

Objective

To explore the in situ evolution of NitR in E. coli isolates from 17 patients participating in AnTIC, a 12-month open label randomized controlled trial assessing the efficacy of antibiotic prophylaxis in reducing urinary tract infections (UTIs) incidence in clean intermittent self-catheterizing patients.

Methods

The investigation of NitR evolution in E. coli used general microbiology techniques and genetics to model known NitR mutations in NitSE. coli strains.

Results

Growth rate analysis identified a 2%–10% slower doubling time for nitrofurantoin resistant strains: NitS: 20.8 ± 0.7 min compared to NitR: 23 ± 0.8 min. Statistically, these data indicated no fitness advantage of evolved strains compared to the sensitive predecessor (P-value = 0.13). Genetic manipulation of E. coli to mimic NitR evolution, supported no fitness advantage (P-value = 0.22). In contrast, data argued that a first-step mutant gained a selective advantage, at sub-MIC (4–8 mg/L) nitrofurantoin concentrations.

Conclusion

Correlation of these findings to nitrofurantoin pharmacokinetic data suggests that the low incidence of E. coli NitR, within the community, is driven by urine-based nitrofurantoin concentrations that selectively inhibit the growth of E. coli strains carrying the key first-step loss-of-function mutation.
Characterizing the macrostructure of electronic health record work using raw audit logs: an unsupervised action embeddings approach
Authors: Lou Sunny S , Liu Hanyang , Harford Derek , Lu Chenyang , Kannampallil Thomas
Published: December 2022

Raw audit logs provide a comprehensive record of clinicians’ activities on an electronic health record (EHR) and have considerable potential for studying clinician behaviors. However, research using raw audit logs is limited because they lack context for clinical tasks, leading to difficulties in interpretation. We describe a novel unsupervised approach using the comparison and visualization of EHR action embeddings to learn context and structure from raw audit log activities. Using a dataset of 15 767 634 raw audit log actions performed by 88 intern physicians over 6 months of EHR use across inpatient and outpatient settings, we demonstrated that embeddings can be used to learn the situated context for EHR-based work activities, identify discrete clinical workflows, and discern activities typically performed across diverse contexts. Our approach represents an important methodological advance in raw audit log research, facilitating the future development of metrics and predictive models to measure clinician behaviors at the macroscale.
Maize Inbred Mp708 is Highly Susceptible to Western Corn Rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), in Field and Greenhouse Assays
Authors: Pereira Adriano E , Geisert Ryan W , Hibbard Bruce E
Published: December 2022

The western corn rootworm (WCR), Diabrotica vifgirera virgifera LeConte, (Coleoptera: Chrysomelidae) causes significant economic damage in corn production each year. Resistance to insecticides and transgenic corn with Bacillus thuringiensis (Bt), Berliner toxins have been reported throughout the United States Corn Belt. Corn breeding programs for natural resistance against WCR larvae could potentially assist in rootworm management. Root damage and root regrowth of eight corn lines were evaluated in field assays at three different locations. Results indicated the inbred ‘Mp708’ had the greatest root damage and was significantly greater than damage for the susceptible control, B37×H84. In greenhouse assays, we evaluated four of these lines plus a hybrid expressing the mCry3A Bt toxin for damage. The results indicated that Mp708 had significantly higher root damage when compared to ‘CRW3(S1)C6’ and ‘MIR604’. Despite previous work suggesting otherwise, we conclude that Mp708 is highly susceptible to the WCR larvae based on root damage in field and greenhouse plant assays.
Community-level predictions in a megadiverse hotspot: comparison of stacked species distribution models to forest inventory data
Authors: Zwiener Victor Pereira , Alves Valéria Andressa
Published: December 2022

Given the current scenario of climate change and anthropogenic impacts, spatial predictions of biodiversity are fundamental to support conservation and restoration actions. Here, we compared different stacked species distribution models (S-SDMs) to forest inventories to assess if S-SDMs capture emerging properties and geographic patterns of species richness and composition of local communities in a biodiversity hotspot. We generated SDMs for 1499 tree species sampled in 151 sites across the Atlantic Forest. We applied four model stacking approaches to reconstruct the plant communities: binary SDMs (bS-SDMs), binary SDMs cropped by minimum convex polygons (bS-SDMs-CROP), stacked SDMs constrained by the observed species richness (cS-SDMs) and minimum convex polygons of species occurrences (MCPs). We compared the stacking methods with local communities in terms of species richness, composition, community prediction metrics and components of beta diversity—nestedness and turnover. S-SDMs captured general patterns, with bS-SDMs-CROP being the most parsimonious approach. Species composition differed between local communities and all stacking methods, in which bS-SDMs, bS-SDMs-CROP and MCPs followed a nested pattern, whereas species turnover was most important in cS-SDMs. S-SDMs varied in terms of performance, omission and commission errors, leading to a misprediction of some vulnerable, endangered and critically endangered species. Despite differing from forest inventory data, S-SDMs captured part of the variation from local communities, representing the potential species pool. Our results support the use of S-SDMs to endorse biodiversity synthesis and conservation planning at coarse scales and warn of potential misprediction at local scales in megadiverse regions.
SAMI-H i: The H i view of the Hα Tully–Fisher relation and data release
Authors: Catinella Barbara , Cortese Luca , Tiley Alfred L , Janowiecki Steven , Watts Adam B , Bryant Julia J , Croom Scott M , d’Eugenio Francesco , van de Sande Jesse , Bland-Hawthorn Joss , Fraser-McKelvie Amelia , Richards Samuel N , Sweet Sarah M , Pisano Daniel J , Pingel Nickolas , Koopmann Rebecca A , Cottrill Dillion , Hill Meghan
Published: December 2022

We present SAMI-H i, a survey of the atomic hydrogen content of 296 galaxies with integral field spectroscopy available from the SAMI Galaxy Survey. The sample spans nearly 4 dex in stellar mass ($M_\star = 10^{7.4}-10^{11.1}~ \rm M_\odot$), redshift z < 0.06, and includes new Arecibo observations of 153 galaxies, for which we release catalogues and H i spectra. We use these data to compare the rotational velocities obtained from optical and radio observations and to show how systematic differences affect the slope and scatter of the stellar-mass and baryonic Tully–Fisher relations. Specifically, we show that $\rm H\alpha$ rotational velocities measured in the inner parts of galaxies (1.3 effective radii in this work) systematically underestimate H i global measurements, with H i/$\rm H\alpha$ velocity ratios that increase at low stellar masses, where rotation curves are typically still rising and $\rm H\alpha$ measurements do not reach their plateau. As a result, the $\rm H\alpha$ stellar mass Tully–Fisher relation is steeper (when M⋆ is the independent variable) and has larger scatter than its H i counterpart. Interestingly, we confirm the presence of a small fraction of low-mass outliers of the $\rm H\alpha$ relation that are not present when H i velocity widths are used and are not explained by ‘aperture effects’. These appear to be highly disturbed systems for which $\rm H\alpha$ widths do not provide a reliable estimate of the rotational velocity. Our analysis reaffirms the importance of taking into account differences in velocity definitions as well as tracers used when interpreting offsets from the Tully–Fisher relation, at both low and high redshifts and when comparing with simulations.
Mapping variations of redshift distributions with probability integral transforms
Authors: Myles J , Gruen D , Amon A , Alarcon A , DeRose J , Everett S , Dodelson S , Bernstein G M , Campos A , Harrison I , MacCrann N , McCullough J , Raveri M , Sánchez C , Troxel M A , Yin B , Abbott T M C , Allam S , Alves O , Andrade-Oliveira F , Bertin E , Brooks D , Burke D L , Rosell A Carnero , Kind M Carrasco , Carretero J , Cawthon R , Costanzi M , da Costa L N , Pereira M E S , Desai S , Doel P , Ferrero I , Flaugher B , Frieman J , García-Bellido J , Gatti M , Gerdes D W , Gruendl R A , Gschwend J , Gutierrez G , Hartley W G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Lahav O , Melchior P , Mena-Fernández J , Menanteau F , Miquel R , Mohr J J , Palmese A , Paz-Chinchón F , Pieres A , Malagón A A Plazas , Prat J , Rodriguez-Monroy M , Sanchez E , Scarpine V , Sevilla-Noarbe I , Smith M , Suchyta E , Swanson M E C , Tarle G , Tucker D L , Vincenzi M , Weaverdyck N ,   (DES Collaboration)
Published: December 2022

We present a method for mapping variations between probability distribution functions and apply this method within the context of measuring galaxy redshift distributions from imaging survey data. This method, which we name PITPZ for the probability integral transformations it relies on, uses a difference in curves between distribution functions in an ensemble as a transformation to apply to another distribution function, thus transferring the variation in the ensemble to the latter distribution function. This procedure is broadly applicable to the problem of uncertainty propagation. In the context of redshift distributions, for example, the uncertainty contribution due to certain effects can be studied effectively only in simulations, thus necessitating a transfer of variation measured in simulations to the redshift distributions measured from data. We illustrate the use of PITPZ by using the method to propagate photometric calibration uncertainty to redshift distributions of the Dark Energy Survey Year 3 weak lensing source galaxies. For this test case, we find that PITPZ yields a lensing amplitude uncertainty estimate due to photometric calibration error within 1 per cent of the truth, compared to as much as a 30 per cent underestimate when using traditional methods.
Systematic broad-band X-ray study of super-Eddington accretion on to supermassive black holes – I. X-ray continuum
Authors: Tortosa Alessia , Ricci Claudio , Ho Luis C , Tombesi Francesco , Du Pu , Inayoshi Kohei , Wang Jian-Min , Shangguan Jinyi , Li Ruancun
Published: December 2022

We present the first systematic broad-band X-ray study of super-Eddington accretion onto supermassive black holes with simultaneous NuSTAR and XMM–Newton or Swift/XRT observations of a sample of eight super-Eddington accreting Active Galactic Nuclei (AGNs) with Eddington ratio 1 < λ Edd < 426. We find that the super-Eddington accreting massive black holes (SEAMBHs) show a steep primary continuum slope as expected for sources accreting in the super-Eddington regime, mostly dominated by relativistic reflection. The iron K α emission lines of the sources of our sample show relativistic broadening. In addition, the equivalent widths of the narrow components of the iron K α lines follow the ‘X-ray Baldwin’ effect, also known as the ‘Iwasawa–Taniguchi’ effect. We found a statistically significant correlation between the photon index of the primary power law and the Eddington ratio, consistent with past studies. Moreover, as expected for super-Eddington sources, the median value of the reflection fraction of the sources we analysed is a factor ∼ 2 higher than the median reflection fraction value of the type 1 AGN from the BASS sample. We are able to estimate the coronal temperature for three sources of our sample: Mrk 382 (kTe = 7.75 keV), PG 0026+129 (kTe = 39 keV), and IRAS 04416+1215 (kTe = 2.95 keV). Looking at the position of the SEAMBHs sources of our sample in the compactness–temperature diagram it appears that in super-Eddington AGN, as for lower Eddington ratio AGN, the X-ray corona is controlled by pair production and annihilation.
The metallicity’s fundamental dependence on both local and global galactic quantities
Authors: Baker William M , Maiolino Roberto , Belfiore Francesco , Curti Mirko , Bluck Asa F L , Lin Lihwai , Ellison Sara L , Thorp Mallory , Pan Hsi-An
Published: December 2022

We study the scaling relations between gas-phase metallicity, stellar mass surface density (Σ*), star formation rate surface density (ΣSFR), and molecular gas surface density ($\Sigma _{{\rm H}_2}$) in local star-forming galaxies on scales of a kpc. We employ optical integral field spectroscopy from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, and ALMA data for a subset of MaNGA galaxies. We use partial correlation coefficients and Random Forest regression to determine the relative importance of local and global galactic properties in setting the gas-phase metallicity. We find that the local metallicity depends primarily on Σ* (the resolved mass–metallicity relation, rMZR), and has a secondary anticorrelation with ΣSFR (i.e. a spatially resolved version of the ‘Fundamental Metallicity Relation’, rFMR). We find that $\Sigma _{{\rm H}_2}$ is less important than ΣSFR in determining the local metallicity. This result indicates that gas accretion, resulting in local metallicity dilution and local boosting of star formation, is unlikely to be the primary origin of the rFMR. The local metallicity depends also on the global properties of galaxies. We find a strong dependence on the total stellar mass (M*) and a weaker (inverse) dependence on the total SFR. The global metallicity scaling relations, therefore, do not simply stem out of their resolved counterparts; global properties and processes, such as the global gravitational potential well, galaxy-scale winds and global redistribution/mixing of metals, likely contribute to the local metallicity, in addition to local production and retention.
A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair
Authors: Bralić Amer , Tehseen Muhammad , Sobhy Mohamed A , Tsai Chi-Lin , Alhudhali Lubna , Yi Gang , Yu Jina , Yan Chunli , Ivanov Ivaylo , Tsutakawa Susan E , Tainer John A , Hamdan Samir M
Published: December 2022

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding showed XPG acts by switching ssDNA translocation to dsDNA unwinding as a likely committed step. Pertinent to the NER pathway regulation, XPG incision activity is suppressed during coreTFIIH translocation on DNA but is licensed when coreTFIIH stalls at the lesion or when ATP hydrolysis is blocked. Moreover, ≥15 nucleotides of 5′-ssDNA is a prerequisite for efficient translocation and incision. Our results unveil a paired coordination mechanism in which key lesion scanning and DNA incision steps are sequentially coordinated, and damaged patch removal is only licensed after generation of ≥15 nucleotides of 5′-ssDNA, ensuring the correct ssDNA bubble size before cleavage.
Freddie: annotation-independent detection and discovery of transcriptomic alternative splicing isoforms using long-read sequencing
Authors: Orabi Baraa , Xie Ning , McConeghy Brian , Dong Xuesen , Chauve Cedric , Hach Faraz
Published: December 2022

Alternative splicing (AS) is an important mechanism in the development of many cancers, as novel or aberrant AS patterns play an important role as an independent onco-driver. In addition, cancer-specific AS is potentially an effective target of personalized cancer therapeutics. However, detecting AS events remains a challenging task, especially if these AS events are novel. This is exacerbated by the fact that existing transcriptome annotation databases are far from being comprehensive, especially with regard to cancer-specific AS. Additionally, traditional sequencing technologies are severely limited by the short length of the generated reads, which rarely spans more than a single splice junction site. Given these challenges, transcriptomic long-read (LR) sequencing presents a promising potential for the detection and discovery of AS. We present Freddie, a computational annotation-independent isoform discovery and detection tool. Freddie takes as input transcriptomic LR sequencing of a sample alongside its genomic split alignment and computes a set of isoforms for the given sample. It then partitions the input reads into sets that can be processed independently and in parallel. For each partition, Freddie segments the genomic alignment of the reads into canonical exon segments. The goal of this segmentation is to be able to represent any potential isoform as a subset of these canonical exons. This segmentation is formulated as an optimization problem and is solved with a dynamic programming algorithm. Then, Freddie reconstructs the isoforms by jointly clustering and error-correcting the reads using the canonical segmentation as a succinct representation. The clustering and error-correcting step is formulated as an optimization problem—the Minimum Error Clustering into Isoforms (MErCi) problem—and is solved using integer linear programming (ILP). We compare the performance of Freddie on simulated datasets with other isoform detection tools with varying dependence on annotation databases. We show that Freddie outperforms the other tools in its accuracy, including those given the complete ground truth annotation. We also run Freddie on a transcriptomic LR dataset generated in-house from a prostate cancer cell line with a matched short-read RNA-seq dataset. Freddie results in isoforms with a higher short-read cross-validation rate than the other tested tools. Freddie is open source and available at https://github.com/vpc-ccg/freddie/.
The structure, binding and function of a Notch transcription complex involving RBPJ and the epigenetic reader protein L3MBTL3
Authors: Hall Daniel , Giaimo Benedetto Daniele , Park Sung-Soo , Hemmer Wiebke , Friedrich Tobias , Ferrante Francesca , Bartkuhn Marek , Yuan Zhenyu , Oswald Franz , Borggrefe Tilman , Rual Jean-François , Kovall Rhett A
Published: December 2022

The Notch pathway transmits signals between neighboring cells to elicit downstream transcriptional programs. Notch is a major regulator of cell fate specification, proliferation, and apoptosis, such that aberrant signaling leads to a pleiotropy of human diseases, including developmental disorders and cancers. The pathway signals through the transcription factor CSL (RBPJ in mammals), which forms an activation complex with the intracellular domain of the Notch receptor and the coactivator Mastermind. CSL can also function as a transcriptional repressor by forming complexes with one of several different corepressor proteins, such as FHL1 or SHARP in mammals and Hairless in Drosophila. Recently, we identified L3MBTL3 as a bona fide RBPJ-binding corepressor that recruits the repressive lysine demethylase LSD1/KDM1A to Notch target genes. Here, we define the RBPJ-interacting domain of L3MBTL3 and report the 2.06 Å crystal structure of the RBPJ–L3MBTL3–DNA complex. The structure reveals that L3MBTL3 interacts with RBPJ via an unusual binding motif compared to other RBPJ binding partners, which we comprehensively analyze with a series of structure-based mutants. We also show that these disruptive mutations affect RBPJ and L3MBTL3 function in cells, providing further insights into Notch mediated transcriptional regulation.
Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of gene regulatory programs in cancers
Authors: Castro-Mondragon Jaime A , Aure Miriam Ragle , Lingjærde Ole Christian , Langerød Anita , Martens John W M , Børresen-Dale Anne-Lise , Kristensen Vessela N , Mathelier Anthony
Published: December 2022

Most cancer alterations occur in the noncoding portion of the human genome, where regulatory regions control gene expression. The discovery of noncoding mutations altering the cells’ regulatory programs has been limited to few examples with high recurrence or high functional impact. Here, we show that transcription factor binding sites (TFBSs) have similar mutation loads to those in protein-coding exons. By combining cancer somatic mutations in TFBSs and expression data for protein-coding and miRNA genes, we evaluate the combined effects of transcriptional and post-transcriptional alterations on the regulatory programs in cancers. The analysis of seven TCGA cohorts culminates with the identification of protein-coding and miRNA genes linked to mutations at TFBSs that are associated with a cascading trans-effect deregulation on the cells’ regulatory programs. Our analyses of cis-regulatory mutations associated with miRNAs recurrently predict 12 mature miRNAs (derived from 7 precursors) associated with the deregulation of their target gene networks. The predictions are enriched for cancer-associated protein-coding and miRNA genes and highlight cis-regulatory mutations associated with the dysregulation of key pathways associated with carcinogenesis. By combining transcriptional and post-transcriptional regulation of gene expression, our method predicts cis-regulatory mutations related to the dysregulation of key gene regulatory networks in cancer patients.
PARG and BRCA1–BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis
Authors: Trivedi Shalini , Blazícková Jitka , Silva Nicola
Published: December 2022

Meiotic chromosome segregation relies on programmed DNA double-strand break induction. These are in turn repaired by homologous recombination, generating physical attachments between the parental chromosomes called crossovers. A subset of breaks yields recombinant outcomes, while crossover-independent mechanisms repair the majority of lesions. The balance between different repair pathways is crucial to ensure genome integrity. We show that Caenorhabditis elegans BRC-1/BRCA1-BRD-1/BARD1 and PARG-1/PARG form a complex in vivo, essential for accurate DNA repair in the germline. Simultaneous depletion of BRC-1 and PARG-1 causes synthetic lethality due to reduced crossover formation and impaired break repair, evidenced by hindered RPA-1 removal and presence of aberrant chromatin bodies in diakinesis nuclei, whose formation depends on spo-11 function. These factors undergo a similar yet independent loading in developing oocytes, consistent with operating in different pathways. Abrogation of KU- or Theta-mediated end joining elicits opposite effects in brc-1; parg-1 doubles, suggesting a profound impact in influencing DNA repair pathway choice by BRC-1-PARG-1. Importantly, lack of PARG-1 catalytic activity suppresses untimely accumulation of RAD-51 foci in brc-1 mutants but is only partially required for fertility. Our data show that BRC-1/BRD-1–PARG-1 joint function is essential for genome integrity in meiotic cells by regulating multiple DNA repair pathways.
BELL1 interacts with CRABS CLAW and INNER NO OUTER to regulate ovule and seed development in pomegranate
Authors: Zhao Yujie , Wang Yuying , Yan Ming , Liu Cuiyu , Yuan Zhaohe
Published: December 2022

Pomegranate (Punica granatum) flowers are classified as bisexual flowers and functional male flowers. Functional male flowers have sterile pistils that show abnormal ovule development. In previous studies, we identified INNER NO OUTER (INO), CRABS CLAW (CRC), and BELL1 (BEL1), which were specifically expressed in bisexual and functional male flowers. However, the functions of ovule identity genes and the mechanism underlying ovule sterility in pomegranate remain unknown. Here, we found that the integument primordia formed and then ceased developing in the ovules of functional male flowers with a vertical diameter of 8.1–13.0 mm. Megaspore mother cells were observed in bisexual flowers when the vertical diameters of flowers were 10.1–13.0 mm, but not in functional male flowers. We analyzed the expression patterns of ovule-related genes in pomegranate ovule sterility and found that PgCRC mRNA was highly expressed at a critical stage of ovule development in bisexual flowers. Ectopic expression of PgCRC and PgINO was sufficient to increase seed number in transgenic lines. PgCRC partially complemented the Arabidopsis (Arabidopsis thaliana) crc mutant, and PgINO successfully rescued the seeds set in the Arabidopsis ino mutant. The results of yeast two-hybrid assays, bimolecular fluorescence complementation assays, and genetic data analyses showed that PgCRC and PgINO directly interact with PgBEL1. Our results also showed that PgCRC and PgINO could not interact directly with MADS-box proteins and that PgBEL1 interacted with SEPALLATA proteins. We report the function of PgCRC and PgINO in ovule and seed development and show that PgCRC and PgINO interact with PgBEL1. Thus, our results provide understanding of the genetic regulatory networks underlying ovule development in pomegranate.
Infantile Takayasu: clinical features and long-term outcome
Authors: Miller-Barmak Adi , Sztajnbok Flavio , Balik Zeynep , Borzutzky Arturo , Fogel Leslie A , Goldzweig Ofra , Ozen Seza , Butbul Aviel Yonatan
Published: December 2022

Objectives

Takayasu arteritis (TAK) is a large-vessel vasculitis rarely reported in children and infants. Most articles on paediatric TAK have not focused on infants. We present the largest case series of infantile TAK, aiming to identify its demographic and clinical characteristics and compare them with existing data on older children.

Methods

We conducted an international multicentre retrospective cohort study. Epidemiological and clinical data were collected from patients’ charts from six rheumatology centres. All patients met both the EULAR/PReS 2008 criteria and the 1990 ACR/EULAR criteria and were diagnosed with TAK at age <5 years.

Results

Twelve patients were included (50% female). Median age of symptom onset was 11 months, with a diagnostic delay of 4 months. The most common symptoms at presentation were hypertension, blood pressure differences between limbs, and fever. The most commonly involved arteries were the abdominal aorta and renal artery. Medications included steroids, conventional and biologic DMARDs, and other immunosuppressive therapies. Half of the patients received biologic agents, of which infliximab had the highest complete remission rate (40%). Other medications resulting in complete remission were CYC (40%) and MTX (38%). Invasive procedures were required for 58% of patients. The most common complications were cardiac (50%), stroke (42%), and serious infections (33%). No patients died.

Conclusion

This study presents the largest series of infantile TAK. Compared with other reported series on older children, infants with TAK have more severe disease and were more likely to receive biologic agents, develop complications, and require invasive interventions.
Populist Female MPs and the Discourse around Gender and Gender-based Violence in the Italian Twittersphere during the Pandemic
Authors: Giorgi Alberta , Loner Enzo
Published: December 2022

Recent research exploring the relationships between gender and populism has shown that populist parties, mainly right-wing, usually do not advance a women-friendly agenda and do not provide women-favorable environments. Nevertheless, concerns about women’s rights and combating violence against women are gaining space within populist discourse. In this contribution, we analyze the tweets of populist female MPs in the Italian Parliament to explore their discourse on gender issues, paying particular attention to gender-based violence and the internal differences in the discourse of populist female MPs. The results show how right-wing female MPs promote a “right-wing” version of women’s rights, especially when dealing with gender-based violence. The results also point out the differences in populist discourse on gender and gender-based violence in different varieties of populism.
Dengue and COVID-19 co-infections: an important consideration in the tropics
Authors: Dalugama Chamara , Seneviratne Suranjith L
Published: December 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected >370 million individuals worldwide. Dengue is endemic in many countries and leads to epidemics at frequent intervals. In the tropics and subtropics, it is possible that individuals may be concurrently infected with both dengue and SARS-CoV-2. Differentiation between the two infections may be difficult from both a clinical and laboratory perspective. We have outlined the currently published findings (as of the end of December 2021) on patients with dengue and SARS-CoV-2 co-infections and have discussed the observed outcomes and management of such patients. Co-infections were more common in males >25 y of age, fever was not universal, 30–50% had medical comorbidities such as diabetes mellitus or hypertension and the case fatality rate was 16–28%.
Seed and Pollen Transmission of Tomato Leaf Curl New Delhi Virus, Tomato Leaf Curl Taiwan Virus, and Tomato Yellow Leaf Curl Thailand Virus in Cucumbers and Tomatoes
Authors: Chang Ho-Hsiung , Gustian Deri , Chang Chung-Jan , Jan Fuh-Jyh
Published: December 2022

Understanding the seedborne nature of plant viruses is essential for developing disease control strategies and is impactful to the seed market. Here, we investigated seed transmissibility of tomato leaf curl New Delhi virus-cucumber isolate (ToLCNDV-CB) and -oriental melon isolate (ToLCNDV-OM) in cucumber and seed transmissibility of tomato leaf curl Taiwan virus (ToLCTV) and tomato yellow leaf curl Thailand virus (TYLCTHV) in tomato. Parent plants were inoculated using agroinfiltration with virus infectious clones, and virus infection was confirmed by PCR with virus-specific primers. ToLCNDV-CB and ToLCNDV-OM were detected in different parts of the female and male flowers and the fruits of cucumbers. ToLCNDV-CB and ToLCNDV-OM were also detected in cucumber seed coats and seedlings with an infection rate higher than 79%. Similar results were observed with ToLCTV and TYLCTHV as they were detected in different parts of the female and male flowers and fruits of three tomato cultivars. ToLCTV and TYLCTHV were also detected in tomato seed coats and seedlings with an infection rate higher than 36%. In addition, pollen-mediated transmission assays of these four begomoviruses were conducted with pollen derived from virus-infected plants to healthy plants. Results showed that ToLCNDV-CB and ToLCNDV-OM were detected in cross-pollinated cucumber progenies with an infection rate higher than 70%. ToLCTV and TYLCTHV were also detected in cross-pollinated tomato progenies with an infection rate higher than 77%. Our results indicated that ToLCNDV, ToLCTV, and TYLCTHV can be transmitted via seeds or pollens of cucumber and tomato plants. To our knowledge, this is the first report documenting the pollen-mediated transmission of begomoviruses.
A Survey of Soybean Cyst Nematode Population Densities and Phenotypes in Illinois: 2018 and 2020
Authors: Kleczewski Nathan , Colsgrove Alison , Bowman Dennis , Harbach Chelsea , Plewa Diane
Published: December 2022

In Illinois, soybean cyst nematode (SCN; Heterodera glycines) has been estimated to cause over $15 million in losses as recently as 2021. In addition, populations of SCN insensitive to PI 88788-derived resistance, the most commonly used SCN resistance source in commercially available soybeans, continues to increase in soybean production areas in the United States. Despite this, awareness of this pathogen and its current status in the state is relatively lacking. A survey was conducted in 2018 and 2020 to assess the presence, population level, and virulence phenotypes in Illinois soybean fields. Soil samples were collected and processed for SCN eggs after harvest each year, and samples with sufficient numbers of SCN eggs were virulence tested using the Hg type test. A total of 95 samples were collected, representing 46 counties. Eighty-seven percent of fields sampled contained SCN eggs, with 38% containing population densities over 2,000 eggs/100 cm3. All samples included in the Hg type test had a female index > 10 on indicator line PI 88788, indicating insensitivity to this resistance source. Extrapolated across soybean production acres, these data indicate that approximately 4.4 million acres of soybeans contain levels of SCN requiring SCN management, and over 54% of acres using cultivars derived from PI 88788 are not fully protected from this pathogen.
A Bacterial Wilt Disease Caused by a New Bacterial Pathogen of Guar Belonging to the Genus Pantoea Identified in Texas
Authors: Obasa Ken , Ravelombola Waltram , Avila Jaqueline
Published: December 2022

Guar ( Cyamopsis tetragonoloba [L.] Taub) or cluster bean is a legume plant that is cultivated mainly for its galactomannan (guar gum) extracted from the seed endosperm. In 2021, a disease outbreak among germplasms in the Texas A&M AgriLife Research Guar Breeding Program located in Vernon, Texas, was observed. Symptoms of the disease were similar to bacterial blight caused by Xanthomonas axonopodis pv . cyamopsidis and included black necrotic streaks on stems and petioles, vascular necrosis, wilting, and eventual death of affected plants. The disease incidence ranged from 75 to 90% in each of the affected germplasms. Diagnosis of affected germplasms consistently recovered bacteria that were identified on the basis of their 16S rRNA partial gene sequence as belonging to the genus Pantoea. Two independent pathogenicity assays and the satisfaction of Koch's postulate under greenhouse experimental conditions determined that the Pantoea isolates were the causal agent of the disease. Investigations of the disease etiology also led to the discovery that the Pantoea sp. can be seedborne. Additionally, although the disease symptoms share similarities with those of bacterial blight in guar, they differ in the absence of the large angular necrotic lesions on leaves that are characteristic of the later stage of the bacterial blight infection. However, infection by the Pantoea sp. similarly resulted in the eventual death of affected plants. Whole-genome pairwise alignments and multilocus sequence analysis of the isolate indicate that it is most closely related to P. vagans, but also distinct genetically, and tentatively designated as Pantoae sp. isolate B550.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Preoperative frailty screening, assessment and management
Authors: Cappe Maximilien , Laterre Pierre-François , Dechamps Mélanie
Published: December 2022

Purpose of review

To highlight the importance of frailty assessment in thoracic surgery patients.

Recent findings

Frailty results from an accelerated loss of functional reserve associated with ageing and leads to increased vulnerability following surgery. It is a complex and multidimensional syndrome involving physiological and psychosocial systems. Frailty is a separate entity from comorbidities and disabilities. Frailty is associated with an increased risk of complications and a higher mortality rate after thoracic surgery. Patients can easily be screened for frailty and frail patients can benefit from further assessment of all areas of frailty secondarily. Prehabilitation and rehabilitation can help limit frailty-related complications after thoracic surgery.

Frailty should be part of the routine preoperative evaluation for thoracic surgery. Frailty must be considered in assessing eligibility for surgery and in planning prehabilitation and rehabilitation if necessary.
Association of Time to Rapid Response Team Activation With Patient Outcomes Using a Range of Physiologic Deterioration Thresholds
Authors: Mitchell Oscar J. L. , Neefe Stacie , Ginestra Jennifer C. , Schweickert William D. , Falk Scott , Weissman Gary E. , Covin Donna , Shults Justine , Abella Benjamin S. , Shashaty Michael G. S.
Published: December 2022

OBJECTIVES:

Clinical deterioration of hospitalized patients is common and can lead to critical illness and death. Rapid response teams (RRTs) assess and treat high-risk patients with signs of clinical deterioration to prevent further worsening and subsequent adverse outcomes. Whether activation of the RRT early in the course of clinical deterioration impacts outcomes, however, remains unclear. We sought to characterize the relationship between increasing time to RRT activation after physiologic deterioration and short-term patient outcomes.

DESIGN:

Retrospective multicenter cohort study.

SETTING:

Three academic hospitals in Pennsylvania.

PATIENTS:

We included the RRT activation of a hospitalization for non-ICU inpatients greater than or equal to 18 years old.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The primary exposure was time to RRT activation after physiologic deterioration. We selected four Cardiac Arrest Risk Triage (CART) score thresholds a priori from which to measure time to RRT activation (CART score ≥ 12, ≥ 16, ≥ 20, and ≥ 24). The primary outcome was 7-day mortality—death or discharge to hospice care within 7 days of RRT activation. For each CART threshold, we modeled the association of time to RRT activation duration with 7-day mortality using multivariable fractional polynomial regression. Increased time from clinical decompensation to RRT activation was associated with higher risk of 7-day mortality. This relationship was nonlinear, with odds of mortality increasing rapidly as time to RRT activation increased from 0 to 4 hours and then plateauing. This pattern was observed across several thresholds of physiologic derangement.

CONCLUSIONS:

Increasing time to RRT activation was associated in a nonlinear fashion with increased 7-day mortality. This relationship appeared most marked when using a CART score greater than 20 threshold from which to measure time to RRT activation. We suggest that these empirical findings could be used to inform RRT delay definitions in further studies to determine the clinical impact of interventions focused on timely RRT activation.
Biological Effects of Electric, Magnetic, and Electromagnetic Fields from 0 to 100 MHz on Fauna and Flora: Workshop Report
Authors: Pophof Blanka , Henschenmacher Bernd , Kattnig Daniel R. , Kuhne Jens , Vian Alain , Ziegelberger Gunde
Published: December 2022

This report summarizes effects of anthropogenic electric, magnetic, and electromagnetic fields in the frequency range from 0 to 100 MHz on flora and fauna, as presented at an international workshop held on 5–7 November in 2019 in Munich, Germany. Such fields may originate from overhead powerlines, earth or sea cables, and from wireless charging systems. Animals and plants react differentially to anthropogenic fields; the mechanisms underlying these responses are still researched actively. Radical pairs and magnetite are discussed mechanisms of magnetoreception in insects, birds, and mammals. Moreover, several insects as well as marine species possess specialized electroreceptors, and behavioral reactions to anthropogenic fields have been reported. Plants react to experimental modifications of their magnetic environment by growth changes. Strong adverse effects of anthropogenic fields have not been described, but knowledge gaps were identified; further studies, aiming at the identification of the interaction mechanisms and the ecological consequences, are recommended.
Biological Effects of Radiofrequency Electromagnetic Fields above 100 MHz on Fauna and Flora: Workshop Report
Authors: Pophof Blanka , Henschenmacher Bernd , Kattnig Daniel R. , Kuhne Jens , Vian Alain , Ziegelberger Gunde
Published: December 2022

This report summarizes the effects of anthropogenic radiofrequency electromagnetic fields with frequencies above 100 MHz on flora and fauna presented at an international workshop held on 5–7 November 2019 in Munich, Germany. Anthropogenic radiofrequency electromagnetic fields at these frequencies are commonplace; e.g., originating from transmitters used for terrestrial radio and TV broadcasting, mobile communication, wireless internet networks, and radar technologies. The effects of these radiofrequency fields on flora, fauna, and ecosystems are not well studied. For high frequencies exceeding 100 MHz, the only scientifically established action mechanism in organisms is the conversion of electromagnetic into thermal energy. In accordance with that, no proven scientific evidence of adverse effects in animals or plants under realistic environmental conditions has yet been identified from exposure to low-level anthropogenic radiofrequency fields in this frequency range. Because appropriate field studies are scarce, further studies on plants and animals are recommended.