bluuebunny/crossref_metadata_2025 huggingface dataset:
Summer heatwaves, wind production and electricity demand in Southern Europe: climatic conditions and impacts
Authors: Molina M O , Gutiérrez C , Ortega M , Sánchez E
Published: July 2023

Electricity demand for cooling and heating is directly related to weather and climate, primarily through ambient temperature. In Southern Europe, the maximum electricity demand for cooling in summer can be more pronounced than in winter, especially during heat wave (HW) episodes. With the growth of renewable technologies in the energy mix, the dependency of the electricity system on the weather is becoming evident not just from the demand side, but also from the energy supply side. From the resources point of view, summer wind presents a minimum on its annual cycle, so a combination of maximum electricity demand can coincide with a minimum of wind power production. This study presents a strong multidisciplinary focus, merging climate, energy and environmental discipline, due to their relevant connections in Southern Europe where important climate change stresses are expected. The combined anomalies of electricity demand and wind production during heat wave episodes are quantified at the country level, taking into account the HW extension. The summer period (1989-2019) of ERA5 reanalysis and E-OBS-21.0e data is used for atmospheric magnitudes and the Copernicus climate change service (C3S) energy dataset for demand. In heat wave events, an increase of 3.5%–10.6% in electricity demand and a decrease up to −30.8% in wind power production is obtained, with variability depending on the country. The greater the extension of the HW, the greater the anomalies. Different weather regimes related to heatwaves also play a role on this range of values. Therefore, the impact of extreme weather events, such as heatwaves, on wind power production in conditions of high electricity demand, should be considered in the energy supply strategy and planning in order to minimize the impact of these events on an electricity system with high penetration of renewables.
Leaf physiological and morphological constraints of water-use efficiency in C3 plants
Authors: Petrík Peter , Petek-Petrik Anja , Mukarram Mohammad , Schuldt Bernhard , Lamarque Laurent J
Published: July 2023

The increasing evaporative demand due to climate change will significantly affect the balance of carbon assimilation and water losses of plants worldwide. The development of crop varieties with improved water-use efficiency (WUE) will be critical for adapting agricultural strategies under predicted future climates. This review aims to summarize the most important leaf morpho-physiological constraints of WUE in C3 plants and identify gaps in knowledge. From the carbon gain side of the WUE, the discussed parameters are mesophyll conductance, carboxylation efficiency and respiratory losses. The traits and parameters affecting the waterside of WUE balance discussed in this review are stomatal size and density, stomatal control and residual water losses (cuticular and bark conductance), nocturnal conductance and leaf hydraulic conductance. In addition, we discussed the impact of leaf anatomy and crown architecture on both the carbon gain and water loss components of WUE. There are multiple possible targets for future development in understanding sources of WUE variability in plants. We identified residual water losses and respiratory carbon losses as the greatest knowledge gaps of whole-plant WUE assessments. Moreover, the impact of trichomes, leaf hydraulic conductance and canopy structure on plants’ WUE is still not well understood. The development of a multi-trait approach is urgently needed for a better understanding of WUE dynamics and optimization.
Comparative thermal sensitivity of locomotor performance and vulnerability to global warming of two sympatric Phymaturus lizards from cold environments of Patagonia (Argentina)
Authors: Cabezas-Cartes Facundo , Kubisch Erika L , Duran Fernando , Boretto Jorgelina M
Published: July 2023

Sister species that live in sympatry provide the possibility to analyse the level of divergence in their ecological, physiological and life-history traits and how they can coexist without out-competing each other. We studied the thermal sensitivity of locomotor performance in the sympatric lizards Phymaturus querque and Phymaturus zapalensis from Patagonia, Argentina. We measured morphological traits relevant to locomotor performance and the running speed at different body temperatures, and we estimated the critical thermal minimum (CTmin) and maximum (CTmax) at which running performance equals zero. We obtained the maximum speeds, the temperature at which the performance is maximized (optimal temperature, To) and the temperature range over which an individual performs 50% and 80% of their maximal performance (B50 and B80). Also, we recorded the availability of thermal microenvironments for thermoregulation (operative temperatures) and calculated two indices of vulnerability to global warming. Phymaturus zapalensis and P. querque exhibited differences in most of the morphological traits relevant to locomotor performance. Both species presented similar values of To, CTmin and CTmax, but B50 and B80 were broader in P. zapalensis. During the warmest month, the environmental temperatures are already higher than the physiological optimal temperature, indicating that populations could currently be facing challenges in the context of global warming.
A lack of ecological diversity in forest nurseries limits the achievement of tree-planting objectives in response to global change
Authors: Clark Peter W , D'Amato Anthony W , Palik Brian J , Woodall Christopher W , Dubuque Paul A , Edge Gregory J , Hartman Jason P , Fitts Lucia A , Janowiak Maria K , Harris Lucas B , Montgomery Rebecca A , Reinikainen Mike R , Zimmerman Christopher L
Published: July 2023

Tree planting is increasingly being adopted as a strategy to address global change, including mitigation, adaptation, and restoration. Although reforestation has long been central to forest management, the desired outcomes of traditional and emerging tree-planting strategies face barriers linked to a lack of ecological diversity in forest nurseries. In the present article, we outline how insufficient diversity in nursery seedlings among species, genotypes, and stock types has impeded and will continue to hinder the implementation of diverse ecological or climate-suitable planting targets, now and into the future. To support this, we demonstrate disparities in seedling diversity among nursery inventories, focusing on the northern United States. To overcome these challenges, we recommend avenues for improving policy and financing, informational resources and training, and research and monitoring. Absent these advances, current seedling production and practices will fall short of ambitious tree-planting goals proposed for forest restoration and global change mitigation and adaptation.
Associations between body mass index, sleep-disordered breathing, brain structure, and behavior in healthy children
Authors: Cui Jianqi , Li Guanya , Zhang Minmin , Xu Jiayu , Qi Haowen , Ji Weibin , Wu Feifei , Zhang Yaqi , Jiang Fukun , Hu Yang , Zhang Wenchao , Wei Xiaorong , Manza Peter , Volkow Nora D , Gao Xinbo , Wang Gene-Jack , Zhang Yi
Published: July 2023

Pediatric overweight/obesity can lead to sleep-disordered breathing (SDB), abnormal neurological and cognitive development, and psychiatric problems, but the associations and interactions between these factors have not been fully explored. Therefore, we investigated the associations between body mass index (BMI), SDB, psychiatric and cognitive measures, and brain morphometry in 8484 children 9–11 years old using the Adolescent Brain Cognitive Development dataset. BMI was positively associated with SDB, and both were negatively correlated with cortical thickness in lingual gyrus and lateral orbitofrontal cortex, and cortical volumes in postcentral gyrus, precentral gyrus, precuneus, superior parietal lobule, and insula. Mediation analysis showed that SDB partially mediated the effect of overweight/obesity on these brain regions. Dimensional psychopathology (including aggressive behavior and externalizing problem) and cognitive function were correlated with BMI and SDB. SDB and cortical volumes in precentral gyrus and insula mediated the correlations between BMI and externalizing problem and matrix reasoning ability. Comparisons by sex showed that obesity and SDB had a greater impact on brain measures, cognitive function, and mental health in girls than in boys. These findings suggest that preventing childhood obesity will help decrease SDB symptom burden, abnormal neurological and cognitive development, and psychiatric problems.
Encoding, working memory, or decision: how feedback modulates time perception
Authors: Li Langyu , Hou Chunna , Peng Chunhua , Chen Youguo
Published: July 2023

The hypothesis that individuals can accurately represent temporal information within approximately 3 s is the premise of several theoretical models and empirical studies in the field of temporal processing. The significance of accurately representing time within 3 s and the universality of the overestimation contrast dramatically. To clarify whether this overestimation arises from an inability to accurately represent time or a response bias, we systematically examined whether feedback reduces overestimation at the 3 temporal processing stages of timing (encoding), working memory, and decisions proposed by the scalar timing model. Participants reproduced the time interval between 2 circles with or without feedback, while the electroencephalogram (EEG) was synchronously recorded. Behavioral results showed that feedback shortened reproduced times and significantly minimized overestimation. EEG results showed that feedback significantly decreased the amplitude of contingent negative variation (CNV) in the decision stage but did not modulate the CNV amplitude in the encoding stage or the P2–P3b amplitudes in the working memory stage. These results suggest that overestimation arises from response bias when individuals convert an accurate representation of time into behavior. Our study provides electrophysiological evidence to support the conception that short intervals under approximately 3 s can be accurately represented as “temporal gestalt.”
Systolic anterior motion of the anterior mitral valve leaflet begins in subclinical hypertrophic cardiomyopathy
Authors: Seitler Samuel , De Zoysa Anthony Surani , Obianyo Chinwe C C , Syrris Petros , Patel Vimal , Sado Daniel M , Maestrini Viviana , Castelletti Silvia , Walsh Stephen , O’Brien Ben , Moon James C , Captur Gabriella
Published: July 2023

Aims

Anterior mitral valve leaflet (AMVL) elongation is detectable in overt and subclinical hypertrophic cardiomyopathy (HCM). We sought to investigate the dynamic motion of the aorto-mitral apparatus to understand the behaviour of the AMVL and the mechanisms of left ventricular outflow tract obstruction (LVOTO) predisposition in HCM.

Methods and results

Cardiovascular magnetic resonance imaging using a 1.5 Tesla scanner was performed on 36 HCM sarcomere gene mutation carriers without left ventricular hypertrophy (G+LVH−), 31 HCM patients with preserved ejection fraction carrying a pathogenic sarcomere gene mutation (G+LVH+), and 53 age-, sex-, and body surface area–matched healthy volunteers. Dynamic excursion of the aorto-mitral apparatus was assessed semi-automatically on breath-held three-chamber cine steady-state free precession images. Four pre-defined regions of interest (ROIs) were tracked: ROIPMVL: hinge point of the posterior mitral valve leaflet; ROITRIG: intertrigonal mitral annulus; ROIAMVL: AMVL tip; and ROIAAO: anterior aortic annulus. Compared with controls, normalized two-dimensional displacement-vs.-time plots in G+LVH− revealed subtle but significant systolic anterior motion (SAM) of the AMVL (P < 0.0001) and reduced longitudinal excursion of ROIAAO (P = 0.014) and ROIPMVL (P = 0.048). In overt and subclinical HCM, excursion of the ROITRIG/AMVL/PMVL was positively associated with the burden of left ventricular fibrosis (P < 0.028). As expected, SAM was observed in G+LVH+ together with reduced longitudinal excursion of ROITRIG (P = 0.049) and ROIAAO (P = 0.008).

Conclusion

Dyskinesia of the aorto-mitral apparatus, including SAM of the elongated AMVL, is detectable in subclinical HCM before the development of LVH or left atrial enlargement. These data have the potential to improve our understanding of early phenotype development and LVOTO predisposition in HCM.
Critical role of insertion preference for invasion trajectory of transposons
Authors: Munasinghe Manisha , Springer Nathan , Brandvain Yaniv
Published: July 2023

It is unclear how mobile DNA sequences (transposable elements, hereafter TEs) invade eukaryotic genomes and reach stable copy numbers, as transposition can decrease host fitness. This challenge is particularly stark early in the invasion of a TE family at which point hosts may lack the specialized machinery to repress the spread of these TEs. One possibility (in addition to the evolution of host regulation of TEs) is that TE families may evolve to preferentially insert into chromosomal regions that are less likely to impact host fitness. This may allow the mean TE copy number to grow while minimizing the risk for host population extinction. To test this, we constructed simulations to explore how the transposition probability and insertion preference of a TE family influence the evolution of mean TE copy number and host population size, allowing for extinction. We find that the effect of a TE family’s insertion preference depends on a host’s ability to regulate this TE family. Without host repression, a neutral insertion preference increases the frequency of and decreases the time to population extinction. With host repression, a preference for neutral insertions minimizes the cumulative deleterious load, increases population fitness, and, ultimately, avoids triggering an extinction vortex.
Characterization of integration sites and transfer DNA structures in Agrobacterium-mediated transgenic events of maize inbred B104
Authors: Neelakandan Anjanasree K , Kabahuma Mercy , Yang Qin , Lopez Miriam , Wisser Randall J , Balint-Kurti Peter , Lauter Nick
Published: July 2023

In maize, the community-standard transformant line B104 is a useful model for dissecting features of transfer DNA (T-DNA) integration due to its compatibility with Agrobacterium-mediated transformation and the availability of its genome sequence. Knowledge of transgene integration sites permits the analysis of the genomic environment that governs the strength of gene expression and phenotypic effects due to the disruption of an endogenous gene or regulatory element. In this study, we optimized a fusion primer and nested integrated PCR (FPNI-PCR) technique for T-DNA detection in maize to characterize the integration sites of 89 T-DNA insertions in 81 transformant lines. T-DNA insertions preferentially occurred in gene-rich regions and regions distant from centromeres. Integration junctions with and without microhomologous sequences as well as junctions with de novo sequences were detected. Sequence analysis of integration junctions indicated that T-DNA was incorporated via the error-prone repair pathways of nonhomologous (predominantly) and microhomology-mediated (minor) end-joining. This report provides a quantitative assessment of Agrobacterium-mediated T-DNA integration in maize with respect to insertion site features, the genomic distribution of T-DNA incorporation, and the mechanisms of integration. It also demonstrates the utility of the FPNI-PCR technique, which can be adapted to any species of interest.
Interactions between the transcription factors FfmA and AtrR are required to properly regulate gene expression in the fungus Aspergillus fumigatus
Authors: Paul Sanjoy , Stamnes Mark A , Moye-Rowley W Scott
Published: July 2023

Transcriptional regulation of azole resistance in the filamentous fungus Aspergillus fumigatus is a key step in development of this problematic clinical phenotype. We and others have previously described a C2H2-containing transcription factor called FfmA that is required for normal levels of voriconazole susceptibility. Null alleles of ffmA exhibit a strongly compromised growth rate even in the absence of any external stress. Here, we employ an acutely repressible doxycycline-off form of ffmA to rapidly deplete FfmA protein from the cell. Using this approach, we carried out RNA-seq analyses to probe the transcriptome cells acutely deprived of FfmA. A total of 2,000 genes were differentially expressed upon acute depletion of FfmA, illustrating the broad transcriptomic effect of this factor. Interestingly, the transcriptome changes observed upon this acute depletion of FfmA expression only shared limited overlap with those found in an ffmAΔ null strain analyzed by others. Chromatin immunoprecipitation coupled with high throughput DNA sequencing analysis (ChIP-seq) identified 530 genes that were bound by FfmA. More than 300 of these genes were also bound by AtrR, a transcription factor important in azole drug resistance, demonstrating striking regulatory overlap with FfmA. However, while AtrR is an upstream activation protein with known specificity, our data suggest that FfmA is a chromatin-associated factor that binds DNA in a manner dependent on other factors. We provide evidence that AtrR and FfmA interact in the cell and show reciprocal expression modulation. Interaction of AtrR and FfmA is required for normal gene expression in A. fumigatus.
Recommendations for Standardizing MRI-based Evaluation of Perianal Fistulizing Disease Activity in Pediatric Crohn’s Disease Clinical Trials
Authors: Crowley Eileen , Ma Christopher , Guizzetti Leonard , Zou Guangyong , Lewindon Peter J , Gee Michael S , Hyams Jeffrey S , Rosen Michael J , von Allmen Daniel , de Buck van Overstraeten Anthony , Shackelton Lisa M , Remillard Julie , Schleicher Lauren , Dillman Jonathan R , Rimola Jordi , Taylor Stuart A , Fletcher Joel G , Church Peter C , Feagan Brian G , Griffiths Anne M , Jairath Vipul , Greer Mary-Louise C
Published: July 2023

Background

Perianal fistulas and abscesses occur commonly as complications of pediatric Crohn’s disease (CD). A validated imaging assessment tool for quantification of perianal disease severity and activity is needed to evaluate treatment response. We aimed to identify magnetic resonance imaging (MRI)-based measures of perianal fistulizing disease activity and study design features appropriate for pediatric patients.

Methods

Seventy-nine statements relevant to MRI-based assessment of pediatric perianal fistulizing CD activity and clinical trial design were generated from literature review and expert opinion. Statement appropriateness was rated by a panel (N = 15) of gastroenterologists, radiologists, and surgeons using modified RAND/University of California Los Angeles appropriateness methodology.

Results

The modified Van Assche Index (mVAI) and the Magnetic Resonance Novel Index for Fistula Imaging in CD (MAGNIFI-CD) were considered appropriate instruments for use in pediatric perianal fistulizing disease clinical trials. Although there was concern regarding the use of intravascular contrast material in pediatric patients, its use in clinical trials was considered appropriate. A clinically evident fistula tract and radiologic disease defined as at least 1 fistula or abscess on pelvic MRI were considered appropriate trial inclusion criteria. A coprimary clinical and radiologic end point and inclusion of a patient-reported outcome were also considered appropriate.

Conclusion

Outcomes of treatment of perianal fistulizing disease in children must include MRI. Existing multi-item measures, specifically the mVAI and MAGNIFI-CD, can be adapted and used for children. Further research to assess the operating properties of the indices when used in a pediatric patient population is ongoing.
Use of Tramadol vs Traditional Opioids and Adverse Outcomes in Patients with Inflammatory Bowel Disease: A Danish Nationwide Cohort Study
Authors: Dalal Rahul S , Lund Ken , Zegers Floor D , Friedman Sonia , Allegretti Jessica R , Nørgård Bente Mertz
Published: July 2023

Background

Use of traditional opioids (TOs) for pain management has been associated with adverse outcomes among patients with inflammatory bowel diseases (IBDs). It is unknown if similar associations exist for tramadol, a partial opioid agonist and serotonin and norephinephrine reuptake inhibitor. We sought to compare adverse outcomes associated with tramadol vs TOs in an IBD population.

Methods

This nationwide cohort study included adults with IBD diagnosed from 1995 to 2021 in Denmark with subsequent prescriptions for tramadol or TOs. For each analgesic, 2 populations were assessed: initial users (first prescription) and persistent users (first 3 consecutive prescriptions within 365 days). Outcomes included infection, bowel obstruction/ileus, IBD surgery, and mortality within 90 days after the initial use index date (date of first prescription) and within 365 days after the persistent use index date (date of third prescription). Odds ratios adjusted for demographics, comorbidities, and IBD severity were calculated using multivariable logistic regression.

Results

We identified 37 377 initial users and 15 237 persistent users of tramadol or TOs. Initial users of tramadol had lower adjusted odds of infection (adjusted odds ratio [OR], 0.80; 95% confidence interval [CI], 0.65-0.99), bowel obstruction/ileus (aOR, 0.74; 95% CI, 0.53-1.03), and mortality (aOR, 0.43; 95% CI, 0.35-0.55), and a higher adjusted odds of IBD-related surgery (aOR, 1.27; 95% CI, 1.02-1.60) vs initial users of TOs. Similar results were found for persistent users.

Conclusions

Tramadol was associated with lower odds of infection, bowel obstruction/ileus, and mortality vs TOs among patients with IBD. These associations may be impacted by residual confounding.
Analysis of artificial insemination center management factors that contribute to sperm parameters and boar longevity with a major focus on PGF2α treatment
Authors: Henneberg Sophie , Pieper Laura , Selige Christin , Jung Markus , Schulze Martin
Published: July 2023

Artificial insemination (AI) centers’ economic profitability is directly impacted by the amount of high-quality sperm doses. Many internal and external factors contribute to the quality of ejaculates. To enhance the libido and to reduce the time that is required to train boars for semen collection, prostaglandin products are used routinely at AI centers. The objectives of this study were to analyze sperm parameters of 40,765 ejaculates and the survival of 406 PGF2α-treated and 417 untreated AI boars of five breeds (Duroc [DU], Large White [LW], Landrace [LR], Pietrain [PI], and Large White Sire Line [LS]). Data were assessed in one AI center in Switzerland from 2018 to 2022 and sperm parameters were determined by computer-assisted sperm analysis immediately after semen collection. For further calculations, the ejaculates were divided into four groups depending on the boar’s age at semen collection day: 7 to 11, 12 to 18, 19 to 24, and 25 to 87 mo. Along with the boar age, breed, season, and semen collection frequency even the treatment with PGF2α had significant influence on sperm parameters. Overall, 19.5% ejaculates were collected after PGF2α treatment. For every age and breed group, higher ejaculate volume was found for untreated boars than for PGF2α-treated boars (P < 0.001). Higher values for total and progressive sperm motility, total sperm number, and the proportion of morphologically normal sperm were observed in untreated boars across several age and breed groups. Only for sperm concentration, higher values were found for treated boars older than 11 mo (P < 0.001) and the breeds DU, LW, and LR (P < 0.001). The chance of ejaculates being rejected for AI purposes because of low sperm quality was 21% greater for treated boars. There was no difference in survival between treated and untreated boars. The hazard for boar removal increased with decreasing age at first semen collection and decreasing semen collection frequency. The results reveal better sperm quality for untreated boars than for PGF2α-treated boars, which might indicate that the underlying fertility of boars necessitating treatment is inferior compared to boars that can be collected without further treatment. Therefore, AI boar stations that are aiming to reduce PGF2α treatment should pay special attention to high libido and fertility of young prospective AI boars.
The Chilling Effects of Surveillance and Human Rights: Insights from Qualitative Research in Uganda and Zimbabwe
Authors: Murray Daragh , Fussey Pete , Hove Kuda , Wakabi Wairagala , Kimumwe Paul , Saki Otto , Stevens Amy
Published: July 2023

States are increasingly developing and deploying large scale surveillance and AI-enabled analytical capabilities. What is uncertain, however, is the impact this surveillance will have. Will it result in a chilling effect whereby individuals modify their behaviour due to the fear of the consequences that may follow? Understanding any such effect is essential: if surveillance activities interfere with the processes by which individuals develop their identity, or undermine democratic processes, the consequences may be almost imperceptible in the short term but profound over the long term. Currently, surveillance-related chilling effects are not well understood, meaning that insufficient weight is given to their potentially society-wide impacts. This article seeks to help redress this balance. Drawing on empirical research in Zimbabwe and Uganda it highlights how State surveillance has chilled behaviour, with significant implications for rights essential to individual development and democratic functioning, specifically the rights to freedom of expression and to freedom of assembly. Importantly, this qualitative research identifies a pattern of common themes or consequences associated with surveillance in general, allowing us to move beyond hypothetical or individual experiences, and providing a greater understanding of the nuances of surveillance-related effects that can help inform decision-making surrounding large scale digital surveillance.
The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer
Authors: Uno Kaname , Yoshikawa Nobuhisa , Kitami Kazuhisa , Mori Sho , Shibata Takahiro , Iyoshi Shohei , Fujimoto Hiroki , Mogi Kazumasa , Yoshihara Masato , Tamauchi Satoshi , Ikeda Yoshiki , Yokoi Akira , Kato Kazuyoshi , Hoshiba Tsutomu , Oguchi Hidenori , Kajiyama Hiroaki
Published: July 2023

Objective

The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer.

Methods

We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals.

Results

The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29–5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18–8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31–10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage.

Conclusions

The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.
BioLiP2: an updated structure database for biologically relevant ligand–protein interactions
Authors: Zhang Chengxin , Zhang Xi , Freddolino Lydia , Zhang Yang
Published: July 2023

With the progress of structural biology, the Protein Data Bank (PDB) has witnessed rapid accumulation of experimentally solved protein structures. Since many structures are determined with purification and crystallization additives that are unrelated to a protein's in vivo function, it is nontrivial to identify the subset of protein–ligand interactions that are biologically relevant. We developed the BioLiP2 database (https://zhanggroup.org/BioLiP) to extract biologically relevant protein–ligand interactions from the PDB database. BioLiP2 assesses the functional relevance of the ligands by geometric rules and experimental literature validations. The ligand binding information is further enriched with other function annotations, including Enzyme Commission numbers, Gene Ontology terms, catalytic sites, and binding affinities collected from other databases and a manual literature survey. Compared to its predecessor BioLiP, BioLiP2 offers significantly greater coverage of nucleic acid-protein interactions, and interactions involving large complexes that are unavailable in PDB format. BioLiP2 also integrates cutting-edge structural alignment algorithms with state-of-the-art structure prediction techniques, which for the first time enables composite protein structure and sequence-based searching and significantly enhances the usefulness of the database in structure-based function annotations. With these new developments, BioLiP2 will continue to be an important and comprehensive database for docking, virtual screening, and structure-based protein function analyses.
Genetic Interaction between Arabidopsis SUR2/CYP83B1 and GNOM Indicates the Importance of Stabilizing Local Auxin Accumulation in Lateral Root Initiation
Authors: Goto Chieko , Ikegami Akira , Goh Tatsuaki , Maruyama Kaisei , Kasahara Hiroyuki , Takebayashi Yumiko , Kamiya Yuji , Toyokura Koichi , Kondo Yuki , Ishizaki Kimitsune , Mimura Tetsuro , Fukaki Hidehiro
Published: July 2023

Lateral root (LR) formation is an important developmental event for the establishment of the root system in most vascular plants. In Arabidopsis thaliana, the fewer roots (fwr) mutation in the GNOM gene, encoding a guanine nucleotide exchange factor of ADP ribosylation factor that regulates vesicle trafficking, severely inhibits LR formation. Local accumulation of auxin response for LR initiation is severely affected in fwr. To better understand how local accumulation of auxin response for LR initiation is regulated, we identified a mutation, fewer roots suppressor1 (fsp1), that partially restores LR formation in fwr. The gene responsible for fsp1 was identified as SUPERROOT2 (SUR2), encoding CYP83B1 that positions at the metabolic branch point in the biosynthesis of auxin/indole-3-acetic acid (IAA) and indole glucosinolate. The fsp1 mutation increases both endogenous IAA levels and the number of the sites where auxin response locally accumulates prior to LR formation in fwr. SUR2 is expressed in the pericycle of the differentiation zone and in the apical meristem in roots. Time-lapse imaging of the auxin response revealed that local accumulation of auxin response is more stable in fsp1. These results suggest that SUR2/CYP83B1 affects LR founder cell formation at the xylem pole pericycle cells where auxin accumulates. Analysis of the genetic interaction between SUR2 and GNOM indicates the importance of stabilization of local auxin accumulation sites for LR initiation.
CRISPR/Cas9 Disruption of MYB134 and MYB115 in Transgenic Poplar Leads to Differential Reduction of Proanthocyanidin Synthesis in Roots and Leaves
Authors: Liu Yalin , Ma Dawei , Constabel C. Peter
Published: July 2023

Proanthocyanidins (PAs) are common specialized metabolites and particularly abundant in trees and woody plants. In poplar (Populus spp.), PA biosynthesis is stress-induced and regulated by two previously studied transcription factors MYB115 and MYB134. To determine the relative contribution of these regulators to PA biosynthesis, we created single- and double-knockout (KO) mutants for both genes in transgenic poplars using CRISPR/Cas9. Knocking out either MYB134 or MYB115 showed reduced PA accumulation and downregulated flavonoid genes in leaves, but MYB134 disruption had the greatest impact and reduced PAs to 30% of controls. In roots, by contrast, only the MYB134/MYB115 double-KOs showed a significant change in PA concentration. The loss of PAs paralleled the lower expression of PA biosynthesis genes and concentrations of flavan-3-ol PA precursors catechin and epicatechin. Interestingly, salicinoids were also affected in double-KOs, with distinct patterns in roots and shoots. We conclude that the regulatory pathways for PA biosynthesis differ in poplar leaves and roots. The residual PA content in the double-KO plants indicates that other transcription factors must also be involved in control of the PA pathway.
Hiding in the Arctic and in mountains: a (dis)entangled classification of Claxtonia (Heterotardigrada: Echiniscidae)
Authors: Gąsiorek Piotr , Degma Peter , Michalczyk Łukasz
Published: July 2023

Numerous evolutionary lineages representing an armoured, limno-terrestrial family Echiniscidae are restricted to high mountainous or polar localities, exhibiting clear cold stenothermic preferences. One such group is the genus Claxtonia, with its type species Claxtonia wendti, originally described from Svalbard and later on reported globally. In this paper, we re-describe this taxon by establishing the neotype from Spitsbergen. We sequenced five genetic markers (18S rRNA, 28S rRNA, ITS-1, ITS-2, and COI) for multiple populations of Claxtonia, including C. mauccii, C. molluscorum, C. wendti, and several potentially new species, collected in the Alps, Andes, Carpathians, Scotland, Iceland, Southern Appalachians, Spitsbergen, Scandinavian Peninsula, Borneo, and the West Indies. The relationships between these species are elucidated thanks to the phylogenetic reconstructions based on nuclear loci. Various Claxtonia species frequently co-occur in mosses and lichens, which hampers delineating their probable geographic ranges. All historical records of C. wendti are questioned in the light of our revision. Delineation of new species within the genus is nipped in the bud due to numerous problems with original species descriptions, unknown intraspecific (including ontogenetic) variability, and the lack of DNA barcodes. Finally, it is hypothesized that Claxtonia potentially comprises two lineages: a cold-stenothermic one and a thermophilic subtropical–tropical one.
The exceptionally well-preserved Sauropleura scalaris (Nectridea: Urocordylidae) from the late Carboniferous of the Czech Republic: new information on ontogeny, lateral line and tail
Authors: Barták Pavel , Ivanov Martin
Published: July 2023

Urocordylids represent a group of the late Carboniferous–early Permian basal tetrapods, with short limbs, extremely elongated bodies and a deep and distinctive tail and vertebral architecture, which is indicative of an aquatic habitat. However, the important morphological structures that would indicate their ecological preferences unambiguously (e.g. hyobranchial apparatus, lateral line sulci) remain unknown. Moreover, the high degree of skeletal ossification present in urocordylids contrasts with the common pattern seen in most other basal tetrapods known to inhabit aquatic environments. Here, we describe an exceptionally well-preserved skull, with an associated mandible and a partial postcranial skeleton, of Sauropleura scalaris from the locality of Nýřany, Czech Republic, based on high-resolution micro-computed tomography. The labial surface of the mandible shows the first evidence of the lateral line system in Urocordylidae, which consists of both small pits and elongated grooves, and ﻿unambiguously supports the aquatic ecology of the group. The juvenile stage of the specimen provides new information on ontogeny of sauropleurines. The partly ossified opisthotic bone indicates that, unlike development in most other early tetrapods, the otic capsules were among the first neurocranial elements to ossify in nectrideans. Finally, an almost complete caudal region suggests that tails were much longer in sauropleurines than previously assumed.
First Report of Stemphylium solani Associated with Leaf Spot of Cotton in New South Wales, Australia
Authors: Thi Nguyen Chi Phuong , Phu Le Duy
Published: July 2023

Leaf spot of cotton caused by Alternaria species has been long considered a minor disease in Australia, especially when only highly resistant upland cotton ( Gossypium hirsutum) has been grown in commercial fields lately. However, leaf spot outbreaks were reported when crops were grown under favorable conditions for development of the disease. In this study, we, for the first time, fully characterized the association of Stemphylium solani with leaf spot of cotton in New South Wales, Australia. A total of 32 isolates were recovered from leaf-spot-diseased leaves collected in the 2021/22 growing season. Leaf spot symptoms often occur in small circular to irregular necrotic lesions, often surrounded by a purple halo, and are indistinguishable from those caused by Alternaria species. Sequences of the ITS, GAPDH, and calmodulin genes of the three representative isolates revealed 99.86 to 100% sequence identity to the type isolate of S. solani CBS 116586. In a neighbor-joining analysis of the concatenated sequences of the ITS, GAPDH, and calmodulin loci, the three cotton isolates were well clustered within the S. solani, with a bootstrap support of 100%, thus confirming the identification. On two true-leaf cotton seedlings, the three S. solani isolates were able to incite spot symptoms that were similar to those observed in the field. The same fungal pathogen was recovered from inoculated diseased leaves, thus confirming Koch's postulates.
Impact of a Regional Grant Program Through the Lens of Social Cognitive Career Theory: A Mixed-Method Evaluation
Authors: Teal Cayla R. , Cianciolo Anna T. , Berry Andrea , Boscardin Christy , Riddle Janet , Rougas Steven , Shaull Lynn , Shea Judy A. , Szauter Karen , Bierer S. Beth
Published: July 2023

Purpose

Evaluations of educational grant programs have focused on research productivity, with few examining impacts on grantees or effective program characteristics. This evaluation examined the regional grant program sponsored by Group on Educational Affairs to examine if and how grantees’ careers were affected by funding, and if these experiences aligned with program goals.

Method

In this concurrent, mixed-methods theory-driven evaluation, quantitative and qualitative data were analyzed independently and then integrated to examine complementarity. Quantitative data examined differences among 4 geographic regions and included proposal and grantee characteristics abstracted from administrative records of 52 funded proposals from 2010–2015 grant cycles. Qualitative data from 23 interviews conducted from 2018 to 2019 explored the impact on grantees, with Social Cognitive Career Theory (SCCT) serving as a framework for deductive thematic analysis. To facilitate integration of findings, quantitative data were layered onto each interview to permit exploration of associations between the 2 data types.

Results

Although significant regional differences existed in project length and amount of funding, there were few regional differences in grantee experiences. Despite small funding amounts, grants were perceived as career launching pads. The SCCT framework accounted for grantee experiences, including researcher identity formation and subsequent research, but did not capture collaboration phenomena. Integration of the 2 data types identified experience patterns unique to different groups of grantees (e.g., more or less research experience). The diversity among grantees suggests that clarification of program goals and stronger alignment with criteria for funding may be warranted.

Conclusions

This evaluation illuminates why small educational grant programs may or may not impact interest and productivity in research. Implications exist for funders, including clarifying program goals and providing support for less experienced grantees. Future research should explore grantee subsets (e.g., underrepresented in medicine) to further identify what fosters or inhibits careers of medical education scholars.
“A Look Under the Hood”: Reflections on the Inaugural RIME Mentorship Program
Authors: Martin Paolo C. , Duncan Philicia , Fernandez Andres , Perez Nicole A. , Ölveczky Daniele
Published: July 2023

In 2021, Research in Medical Education (RIME) celebrated 60 years of advancing scholarship in health professions education (HPE). At that time, the nation’s educational institutions faced a public reckoning on the long-standing pandemic of racism that sweltered in their practices and policies, laid bare by COVID-19 and the Black Lives Matters movement. RIME responded with a mentorship program for minoritized early career HPE faculty, which aims to amplify their voices in settings where their experiences and contributions are frequently dampened. The program fosters professional development through structured activities, participation as RIME committee interns, and formal mentorship channels to support career growth and offer experiences with scholarly publishing. This commentary was written by the first cohort of RIME mentees who are HPE scholars from various professions and diverse backgrounds with struggles traversing professional landscapes as immigrants and as individuals with minoritized identities and hopes for belonging in medical and educational institutions. In this commentary, the mentees describe the merits of the RIME mentorship program and what it meant to them and their unique marginalities. They also examine opportunities for improvements within the program to further reduce barriers faced by minoritized early career HPE faculty who often face limited support with scholarly activities.
Radiographic Measurements Associated With Ankle Power Generation During Gait in Patients With Cerebral Palsy
Authors: Choi Yoon Hyo , Kwon Tae Hun , Choi Ji Hye , Jeong Naun , Koo Seungbum , Lee Kyoung Min
Published: July 2023

Background:

Pes planovalgus (PV) deformity accounts for lever arm dysfunction and compromises gait in patients with cerebral palsy (CP). However, the association between ankle power generation and radiographic indices is not yet understood. We aimed to investigate the association between ankle power and radiographic indices during gait in patients with CP concomitant with PV deformity.

Methods:

Patients older than 14 years with ambulatory CP and PV deformity were included. All the patients underwent 3-dimensional gait analysis and weight-bearing foot radiography. Gait data were collected, including foot progression angle, tibial rotation, hip rotation, and ankle power generation. Radiographic measurements included anteroposterior (AP) talo-first metatarsal angle, lateral talo-first metatarsal angle, and hindfoot angle. A linear mixed-effects model was performed to identify significant radiographic indices associated with ankle power generation.

Results:

Thirty-one limbs from 15 patients with spastic diplegia and 6 with spastic hemiplegia were included. Statistical analysis demonstrated that ankle power generation was significantly correlated with the CP type (P=0.0068) and AP talo-1st metatarsal angle (P=0.0230).

Conclusion:

Ankle power generation was significantly associated with the AP talo-first metatarsal angle. Surgeons might need to pay attention to correcting forefoot abduction to restore ankle power when planning surgeries for pes PV deformities in patients with CP.

Level of Evidence:

Prognostic Level III
Creation and Validation of a Photonumeric Scale for Assessment of Infraorbital Hollows
Authors: Carey Wayne , Trévidic Patrick , Benedetto Anthony V. , Maffert Pauline , Antunes Stéphanie
Published: July 2023

BACKGROUND

Validated clinical scales are needed to assess aesthetic improvement of the infraorbital hollows (IOHs) after treatment with dermal fillers.

OBJECTIVE

To develop an IOHs scale and establish its reliability and sensitivity for grading subjects in clinical trials or routine practice.

METHODS AND MATERIALS

The Teoxane IOHs Scale (TIOHS), a 5-grade photonumeric scale, was developed based on real-subject photographs and validated through photographic and live subjects' evaluation.

RESULTS

Clinician intra- and inter-rater agreements during the TIOHS validation were excellent. The mean intrarater-weighted Kappa score between the 2 sessions of photographic validation was 0.92, while inter-rater interclass correlation coefficient (ICC) was 0.92 for the combined sessions. The average intrarater-weighted Kappa score and inter-rater ICC for the live validation reached 0.80 and 0.76, respectively. In addition, evaluators identified clinically significant differences between photographs of subjects presenting a 1-grade or 2-grade difference in 82% and 86% of cases, respectively.

CONCLUSION

The intrarater Kappa scores and inter-rater ICCs met their predetermined acceptance criteria of >0.70. The TIOHS is a repeatable and reproducible clinician-reported outcome for health care providers to classify IOHs in clinical trials and routine patient care. A 1-grade difference on the TIOHS can detect a clinically meaningful difference in infraorbital hollowing.