bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Effectiveness of Knee Joints Treatment With the Use of 90Y
Authors: Chrabański Olgierd , Kluczewska Ewa , Gołąb Tomasz , Gorczewska Izabela 
Published: March 2023

Purpose
The purpose of this prospective study was to assess the effectiveness of knee joints treatment by radiosynoviorthesis with the use of 90Y based on ultrasound and clinical analysis.

Materials and Methods
Ninety-seven patients were qualified for treatment from October 2016 to June 2017, and observation period lasted until December 2017. Bioethics Committee of the Medical University of Silesia approved this study. The effectiveness of knee joints treatment with the use of 90Y was based on 927 ultrasound measurements of fluid and 927 synovial thickness in 3 sites of the suprapatellar recess, 309 assessments of patient’s disability documented in Lequesne questionnaire, 309 assessments of pain on visual analog scale, as well as 103 overall self-assessment. Statistical methods were used to process the results.

Results
A reduction in fluid was found in 62.14% of the knees; synovial thickness reduction was observed in 97.09% of all knees. The greatest benefit from the therapy was experienced by patients complaining of morning stiffness lasting more than 15 minutes (in 85.71% of joints). There was reduction in pain at rest in 94.52% of knee joints and in 80.39% of joints with pain while walking. At the second follow-up visit after treatment, the percentage of improvement in self-assessment was 74.76%.

Conclusions
Statistically significant decreases in the amount of fluid and thickness of the synovial membrane as well as the level of disability and the intensity of pain after radiosynoviorthesis 90Y treatment were demonstrated.
Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4–Directed Molecular Imaging and Therapy
Authors: Hartrampf Philipp E. , Kosmala Aleksander , Serfling Sebastian E. , Bundschuh Lena , Higuchi Takahiro , Lapa Constantin , Rowe Steven P. , Matsusaka Yohji , Weich Alexander , Buck Andreas K. , Bundschuh Ralph A. , Werner Rudolf A. 
Published: March 2023

Background
We aimed to evaluate the interobserver agreement rates in patients scanned with C-X-C motif chemokine receptor 4 (CXCR4)–directed PET/CT, including the rate of patients eligible for CXCR4-targeted radioligand therapy (RLT) based on scan results.

Methods
Four independent observers reviewed 50 CXCR4-targeted [68Ga]pentixafor PET/CT of patients with various solid cancers. On a visual level, the following items were assessed by each reader: overall scan impression, number of organ and lymph node (LN) metastases and number of affected organs and LN regions. For a quantitative investigation, readers had to choose a maximum of 3 target lesions, defined as largest in size and/or most intense uptake per organ compartment. Reference tissues were also quantified, including unaffected hepatic parenchyma and blood pool. Last, all observers had to decide whether patients were eligible for CXCR4-targeted RLT. Concordance rates were tested using intraclass correlation coefficients (ICCs). For interpretation, we applied the definition of Cicchetti (with 0.4–0.59 indicating fair; 0.6–0.74, good; 0.75–1, excellent agreement).

Results
On a visual level, fair agreement was achieved for an overall scan impression (ICC, 0.58; 95% confidence interval, 0.45–0.71). Organ and LN involvement (ICC, ≥0.4) demonstrated fair, whereas CXCR4 density and number of LN and organ metastases showed good agreement rates (ICC, ≥0.65). Number of affected organs and affected LN areas, however, showed excellent concordance (ICC, ≥0.76). Quantification in LN and organ lesions also provided excellent agreement rates (ICC, ≥0.92), whereas quantified uptake in reference organs provided fair concordance (ICC, ≥0.54). Again, excellent agreement rates were observed when deciding on patients eligible for CXCR4-RLT (ICC, 0.91; 95% confidence interval, 0.85–0.95).

Conclusions
In patients scanned with CXCR4-targeted PET/CT, we observed fair to excellent agreement rates for both molecular imaging and therapy parameters, thereby favoring a more widespread adoption of [68Ga]pentixafor in the clinic.
Fungal organic acid uptake of mineral derived K is dependent on distance from carbon hotspot
Authors: Bhattacharjee Arunima , Velickovic Dusan , Richardson Jocelyn A. , Couvillion Sneha P. , Vandergrift Gregory W. , Qafoku Odeta , Taylor Michael J. , Jansson Janet K. , Hofmockel Kirsten S. , Anderton Christopher R. 
Published: March 2023

AbstractFungal mineral weathering processes regulate the bioavailability of inorganic nutrients from mineral surfaces to organic matter and increase the bioavailable fraction of nutrients. Fungal mineral weathering strategies can be classified as biomechanical (direct) or biochemical (indirect). In the case of fungal uptake of mineral nutrients through indirect weathering, it is widely hypothesized that uptake of mineral derived nutrients occurs through organic acid chelation, but such processes have not been directly visualized. This is in part due to challenges in probing the complex and heterogeneous soil environment. Here, using an epoxy-based mineral doped soil micromodel platform that we developed, which mimics soil mineralogy and structure, it permitted us to visualize and spatially probe the molecular mechanisms of mineral weathering. Mass spectrometry imaging revealed differences in the distribution of fungal exudates, citric acid and tartaric acid, on the soil micromodels in presence of minerals. Citric acid was detected closer to the nutrient rich inoculation point, whereas tartaric acid was highly abundant away from inoculation point. This suggested that the organic acid exuded by the fungi depended on the proximity from the carbon rich organic substrate at the point of inoculation. Using a combination of X-ray fluorescence and X-ray near edge structure analysis, we identified citric acid- and tartaric acid-bound K within fungal hyphae networks grown in the presence of minerals. Combined our results provide direct evidence that fungi uptake and transport mineral derived nutrient organic acid chelation. The results of this study provided unprecedented visualization of fungal weathering of soil minerals and hyphal K+transport, while resolving the indirect weathering mechanism of fungal K uptake from mineral interfaces.
Phyllosphere fungal diversity generates pervasive non-additive effects on plant performance
Authors: Almeida Brianna K. , Tran Elan H. , Afkhami Michelle E. 
Published: March 2023

SummaryAll plants naturally harbor diverse microbiomes that can dramatically impact their health and productivity. However, it remains unclear how microbiome diversity, especially in the phyllosphere, impacts intermicrobial interactions and consequent non-additive effects on plant productivity.Combining manipulative experiments, field collections, culturing, microbiome sequencing, and synthetic consortia, we experimentally tested for the first time how foliar fungal community diversity impacts plant productivity. We inoculated morning glories with 32 synthetic phyllosphere communities of either low or high diversity or with single fungal taxa, and measured effects on plant productivity and allocation.We found 1) non-additive effects were pervasive with 56% of microbial communities interacting synergistically or antagonistically to impact plant productivity, including some consortia capable of generating acute synergism (e.g., >1000% increase in productivity above the additive expectation), 2) interactions among ‘commensal’ fungi were responsible for this non-additivity in diverse communities, 3) synergistic interactions were ~4 times stronger than antagonistic effects, 4) fungal diversity affected the magnitude but not frequency or direction of non-additivity, and 5) diversity affected plant performance nonlinearly with highest performance in low microbial diversity treatments.These findings highlight the importance of interpreting plant-microbial interactions under a framework that incorporates intermicrobial interactions and non-additive outcomes to understand natural complexity.
RecurringEPHB1mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells
Authors: Kundu Snehangshu , Nunes Luís , Adler Jeremy , Mathot Lucy , Stoimenov Ivaylo , Sjöblom Tobias 
Published: March 2023

AbstractEphrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somaticEPHB1mutations found in metastatic colorectal cancer cases. We, therefore, integrated pan-cancer and pan-EPH mutational data to prioritise recurrentEPHB1mutations for functional studies to understand their contribution to cancer development and metastasis. Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed to find 3D-mutated cluster pairs and recurring hotspot mutations in EPH receptors. From these, 15 recurringEPHB1mutations were stably expressed in colorectal cancer cells. Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation. This is the first integrative study of pan-cancer EPH receptor mutations followed byin vitrovalidation, a robust way to identify cancer-causing mutations.
Exploiting cryo-EM structures of actomyosin-5a to reveal the physical properties of its lever
Authors: Gravett Molly S.C. , Klebl David P. , Harlen Oliver G. , Read Daniel J. , Harris Sarah A. , Muench Stephen P. , Peckham Michelle 
Published: March 2023

AbstractMyosin 5a transports cellular cargos along actin filaments towards the cell periphery. Its long lever plays a key role in determining the large size of its powerstoke, stepping distance along F-actin, ability to bear load and its regulation by Ca2+. Despite this, little is known about the physical properties of the lever and how they contribute to the mechanics of walking. Using a combination of cryo-electron microscopy and molecular dynamics simulations, we resolved the first structure of myosin 5a comprising the motor domain and full-length lever (subfragment-1) bound to actin. From the flexibility captured in the cryo-electron microscopy data, we were able to characterise the stiffness of the lever. Here, we demonstrate how the structure and flexibility of the lever contribute to the regulation and walking behaviour of myosin 5a.
Ability of Caprini and Padua Risk-Assessment Models to Predict Venous Thromboembolism in a Nationwide Study
Authors: Hayssen Hilary , Sahoo Shalini , Nguyen Phuong , Mayorga-Carlin Minerva , Siddiqui Tariq , Englum Brian , Slejko Julia F , Mullins C. Daniel , Yesha Yelena , Sorkin John D , Lal Brajesh K 
Published: March 2023

ABSTRACTBackgroundVenous thromboembolism (VTE) is a preventable complication of hospitalization. Risk-stratification is the cornerstone of prevention. The Caprini and Padua are the most commonly used risk-assessment models to quantify VTE risk. Both models perform well in select, high-risk cohorts. While VTE risk-stratification is recommended for all hospital admissions, few studies have evaluated the models in a large, unselected cohort of patients.MethodsWe analyzed consecutive first hospital admissions of 1,252,460 unique surgical and non-surgical patients to 1,298 VA facilities nationwide between January 2016 and December 2021. Caprini and Padua scores were generated using the VA’s national data repository. We first assessed the ability of the two RAMs to predict VTE within 90 days of admission. In secondary analyses, we evaluated prediction at 30 and 60 days, in surgical versus non-surgical patients, after excluding patients with upper extremity DVT, in patients hospitalized ≥72 hours, after including all-cause mortality in the composite outcome, and after accounting for prophylaxis in the predictive model. We used area under the receiver-operating characteristic curves (AUC) as the metric of prediction.ResultsA total of 330,388 (26.4%) surgical and 922,072 (73.6%) non-surgical consecutively hospitalized patients (total n=1,252,460) were analyzed. Caprini scores ranged from 0-28 (median, interquartile range: 4, 3-6); Padua scores ranged from 0-13 (1, 1-3). The RAMs showed good calibration and higher scores were associated with higher VTE rates. VTE developed in 35,557 patients (2.8%) within 90 days of admission. The ability of both models to predict 90-day VTE was low (AUCs: Caprini 0.56 [95% CI 0.56-0.56], Padua 0.59 [0.58-0.59]). Prediction remained low for surgical (Caprini 0.54 [0.53-0.54], Padua 0.56 [0.56-0.57]) and non-surgical patients (Caprini 0.59 [0.58-0.59], Padua 0.59 [0.59-0.60]). There was no clinically meaningful change in predictive performance in patients admitted for ≥72 hours, after excluding upper extremity DVT from the outcome, after including all-cause mortality in the outcome, or after accounting for ongoing VTE prophylaxis.ConclusionsCaprini and Padua risk-assessment model scores have low ability to predict VTE events in a cohort of unselected consecutive hospitalizations. Improved VTE risk-assessment models must be developed before they can be applied to a general hospital population.
The correlation between medial pattern of intracranial arterial calcification and white matter hyperintensities
Authors: Du Heng , Zheng Jianrong , Li Xuelong , Dong Yanjing , Cheng Yajing , Liu Cong , Hu Jun , Chen Xiangyan 
Published: March 2023

AbstractBackgroundDespite previously reported correlations between intracranial arterial calcification (IAC) and white matter hyperintensities (WMH), little is known about the relationship between IAC pattern and WMH. By differentiating intimal and medical IAC, we aimed to investigate the relationship between IAC pattern and WMH.MethodsConsecutive patients with acute ischemic stroke were included. IAC pattern was categorized as intimal or medial on plain brain CT. The number of cerebral arteries involved by IAC for each patient was recorded. IAC severity of each artery was defined as focal or diffuse. On brain MRI, the burden of WMH was graded on a visual rating scale and classified as absent mild, moderate and severe. Multiple logistic regression was performed to examine the relationship between IAC and WMH.ResultsAmong 265 recruited patients, intimal IAC was detected in 54.7% patients, medial IAC in 48.5% patients and coexistent (intimal and medial) IAC in 52.1% patients. Diffuse IAC was in 27.9% patients, all of which were medial IACs. WMH was found in 75.5% patients, including 105 patients (39.6%) with mild WMH, 69 (26.0%) with moderate WMH and 26 (9.8%) with severe WMH. The presence and severity of medial IAC were correlated with WMH occurrence (p<0.001, respectively). Chi-square linear trend suggested the number of arteries involved by medial IAC (p<0.001) and the severity of medial IAC (p<0.001) were correlated with WMH burden. After adjusting age, hypertension, history of stroke and history of ischemic heart disease, multiple ordinal regression demonstrated a positive correlation between the number of arteries involved by medial IAC (p<0.001) and the severity of medial IAC (p<0.001) with the overall burden of WMH.ConclusionsMedial IAC was correlated with the burden of WMH. The dose-effect relationship between IAC and WMH suggests the need of further investigations on shared underlying mechanisms of intracranial large artery disease and cerebral small vessel disease.
Reproductive tactics, birth timing and the trade-off between risk avoidance and foraging in an income breeder
Authors: Benoit Laura , Morellet Nicolas , Bonnot Nadège C. , Cargnelutti Bruno , Chaval Yannick , Gaillard Jean-Michel , Loison Anne , Lourtet Bruno , Marchand Pascal , Coulon Aurélie , Hewison A.J. Mark 
Published: March 2023

AbstractThe behavioural trade-off between foraging and risk avoidance is expected to be particularly acute during gestation and lactation, when the energetic demands of reproduction peak. We investigated how female roe deer, an income breeding ungulate, adjust their management of this trade-off during the birth period in terms of foraging activity and habitat use. We showed that activity levels of reproductive females more than doubled immediately following parturition, when energy demand is highest. Moreover, reproductive females increased their use of open habitat during daytime and ranged closer to roads, but slightly further from refuge woodland, compared to non-reproductive females. However, these post-partum modifications in behaviour were particularly pronounced in late-parturient females who adopted a more risk prone tactic, presumably to compensate for the fitness handicap of their late-born offspring. In income breeders, individuals that give birth late may be forced to trade risk avoidance for resource acquisition during peak allocation to reproduction, likely with significant fitness consequences.
Repetitive transcranial magnetic stimulation (rTMS) triggers dose-dependent homeostatic rewiring in recurrent neuronal networks
Authors: Anil Swathi , Lu Han , Rotter Stefan , Vlachos Andreas 
Published: March 2023

AbstractRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to induce neuronal plasticity in healthy individuals and patients. Designing effective and reproducible rTMS protocols poses a major challenge in the field as the underlying biomechanisms remain elusive. Current clinical protocol designs are often based on studies reporting rTMS-induced long-term potentiation or depression of synaptic transmission. Herein, we employed computational modeling to explore the effects of rTMS on long-term structural plasticity and changes in network connectivity. We simulated a recurrent neuronal network with homeostatic structural plasticity between excitatory neurons, and demonstrated that this mechanism was sensitive to specific parameters of the stimulation protocol (i.e., frequency, intensity, and duration of stimulation). The feedback-inhibition initiated by network stimulation influenced the net stimulation outcome and hindered the rTMS-induced homeostatic structural plasticity, highlighting the role of inhibitory networks. These findings suggest a novel mechanism for the lasting effects of rTMS, i.e., rTMS-induced homeostatic structural plasticity, and highlight the importance of network inhibition in careful protocol design, standardization, and optimization of stimulation.Author summaryThe cellular and molecular mechanisms of clinically employed repetitive transcranial magnetic stimulation (rTMS) protocols remain not well understood. However, it is clear that stimulation outcomes depend heavily on protocol designs. Current protocol designs are mainly based on experimental studies that explored functional synaptic plasticity, such as long-term potentiation of excitatory neurotransmission. Using a computational approach, we sought to address the dose-dependent effects of rTMS on the structural remodeling of stimulated and non-stimulated connected networks. Our results suggest a new mechanism of action—activity-dependent homeostatic structural remodeling—through which rTMS may assert its lasting effects on neuronal networks.We showed that the effect of rTMS on structural plasticity critically depends on stimulation intensity, frequency, and duration and that recurrent inhibition can affect the outcome of rTMS-induced homeostatic structural plasticity. These findings emphasize the use of computational approaches for an optimized rTMS protocol design, which may support the development of more effective rTMS-based therapies.
Involvement of the putative metal efflux protein YbeX in ribosomal metabolism
Authors: Sarıgül İsmail , Žukova Amata , Alparslan Emel , Pihlak Margus , Remm Sille , Tenson Tanel , Maiväli Ülo 
Published: March 2023

ABSTRACTYbeX ofEscherichia coli, a member of CorC protein family, is a putative Co2+/ Mg2+efflux factor. Here, we describe severalΔybeXphenotypes and report an involvement of YbeX in ribosomal metabolism.E. colilackingybeXhas a longer lag phase on outgrowth from the stationary phase. This phenotype is heterogeneous at the individual cell level and can be rescued by supplementing the growth media with magnesium.ΔybeXstrain is sensitive to elevated growth temperatures and to several ribosome-targeting antibiotics, which have a common ability to induce the cold shock response inE. coli.ΔybeXcells accumulate distinct 16S rRNA degradation intermediates present in both 30S particles and 70S ribosomes. We propose that a function of YbeX is maintaining the magnesium homeostasis in the cell, which is needed for proper ribosomal assembly.
SARS-CoV-2 infection induces dopaminergic neuronal loss in midbrain organoids during short and prolonged cultures
Authors: Jarazo Javier , da Silva Eveline Santos , Glaab Enrico , Perez-Bercoff Danielle , Schwamborn Jens C. 
Published: March 2023

AbstractCOVID-19 is mainly associated with respiratory symptoms, although several reports showed that SARS-CoV-2 affects the nervous system. We evaluated the effects of infection in prolonged culture of midbrain organoids, showing that the virus induces changes in gene expression, and fragmentation and loss of dopaminergic neurons. Our findings highlight the direct viral-induced damage to midbrain organoids indicating the relevance of assessing the neurological long-term evolution of COVID-19 patients.
Understanding accommodative control in the clinic: modeling latency and amplitude for uncorrected refractive error, presbyopia and cycloplegia
Authors: Read Jenny C. A. , Maus Gerrit , Schor Clifton M. 
Published: March 2023

AbstractAccommodation refers to the process of increasing the optical power of the eye’s crystalline lens so as to focus on objects at different distances. Refractive error is a mismatch between the physical size of the eye and its optical power when accommodation is fully relaxed, while functional presbyopia is a decrease in the range of accommodation with age that results in the near point of accommodation lying beyond the near working distance. Both conditions mean that sharp focus may not be achievable for some distances, and observers will experience sustained defocus. A familiar example is an older person struggling to read text on their phone. Here, we identify a problem with current models of the neural control of accommodation: they predict excessive internal responses to stimuli outside the range of accommodation, leading to unrealistic adaptation effects. Specifically, after a prolonged period of viewing stimuli outside their accommodative range, current models predict that observers would show long latencies in the accommodative response to stimuli within range. These latencies are not observed empirically, indicating a problem with current models. We propose a simple solution, exploiting the predictive nature of accommodative control, and demonstrate that the new model performs correctly. We also model cycloplegia as a change in gain, and include a lower bound on the neural signal driving accommodation so as to model the additional relaxation of accommodation often seen with cycloplegia. We show that with these modifications, we can obtain plausible predictions for the accommodative response and accommodative convergence signal in a wide range of clinically relevant situations such as functional presbyopia, fogging lenses, corrected and uncorrected refractive error, and cycloplegia.