bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Fornax3D project: intrinsic correlations between orbital properties and the stellar initial mass function
Authors: Poci A , McDermid R M , Lyubenova M , Martín-Navarro I , van de Ven G , Coccato L , Corsini E M , Fahrion K , Falcón-Barroso J , Gadotti D A , Iodice E , Pinna F , Sarzi M , de Zeeuw P T , Zhu L 
Published: June 2022

ABSTRACT
Variations of the stellar initial mass function (IMF) in external galaxies have been inferred from a variety of independent probes. Yet the physical conditions causing these variations remain largely unknown. In this work, we explore new spatially resolved measurements of the IMF for three edge-on lenticular galaxies in the Fornax cluster. We utilize existing orbit-based dynamical models in order to fit the new IMF maps within an orbital framework. We find that, within each galaxy, the high-angular momentum disc-like stars exhibit an IMF which is rich in dwarf stars. The centrally concentrated pressure-supported orbits exhibit similarly dwarf-rich IMF. Conversely, orbits at large radius which have intermediate angular momentum exhibit IMF which are markedly less dwarf-rich relative to the other regions of the same galaxy. Assuming that the stars which reside, in the present-day, on dynamically hot orbits at large radii are dominated by accreted populations, we interpret these findings as a correlation between the dwarf-richness of a population of stars, and the mass of the host in which it formed. Specifically, deeper gravitational potentials would produce more dwarf-rich populations, resulting in the relative deficiency of dwarf stars which originated in the lower mass accreted satellites. The central and high-angular momentum populations are likely dominated by in situ stars, which were formed in the more massive host itself. There are also global differences between the three galaxies studied here, of up to ∼0.3 dex in the IMF parameter ξ. We find no local dynamical or chemical property which alone can fully account for the IMF variations.
Are there any pristine comets? Constraints from pebble structure
Authors: Malamud Uri , Landeck Wolf A , Bischoff Dorothea , Kreuzig Christopher , Perets Hagai B , Gundlach Bastian , Blum Jürgen 
Published: June 2022

ABSTRACT
We show that if comets (or any small icy planetesimals such as Kuiper belt objects) are composed of pebble piles, their internal radiogenic as well as geochemical heating results in considerably different evolutionary outcomes compared to similar past studies. We utilize a 1D thermophysical evolution code, modified to include state-of-the-art empirical measurements of pebble thermal conductivity and compression, the latter obtained through a new laboratory experiment presented here for the first time. Results indicate that due to the low pebble thermal conductivity, the peak temperatures attained during evolution are much higher than in any previous study given the same formation time. Assuming meteoritic radiogenic abundances, we find that only extremely small, sub-kilometre comets have the potential to retain the primordial, uniform, and thermally unprocessed composition from which they formed. Comets with radii in excess of about 20 km are typically swept by rapid and energetically powerful aqueous hydration reactions. Across the full range of comet sizes and formation times, evolutions result in the processing and differentiation of various volatile species, and a radially heterogeneous nucleus structure. Our computations however also indicate that the assumed fraction of radionuclides is a pivotal free parameter, because isotopic analyses of the only available cometary samples suggest that no 26Al was ever present in comet 81P/Wild 2. We show that if comets formed early in the protoplanetary disc (within 1–3 Myr), the radionuclide abundances indeed must be much smaller than those typically assumed based on meteoritic samples. We discuss the importance of our findings for the formation, present-day attributes and future research of comets.
CRISPRedict: a CRISPR-Cas9 web tool for interpretable efficiency predictions
Authors: Konstantakos Vasileios , Nentidis Anastasios , Krithara Anastasia , Paliouras Georgios 
Published: June 2022

Abstract
The development of the CRISPR-Cas9 technology has provided a simple yet powerful system for genome editing. Current gRNA design tools serve as an important platform for the efficient application of the CRISPR systems. However, most of the existing tools are black-box models that suffer from limitations, such as variable performance and unclear mechanism of decision making. Here, we introduce CRISPRedict, an interpretable gRNA efficiency prediction model for CRISPR-Cas9 gene editing. Its strength lies in the fact that it can accurately predict efficient guide RNAs—with equivalent performance to state-of-the-art tools—while being a simple linear model. Implemented as a user-friendly web server, CRISPRedict offers (i) quick and accurate predictions across various experimental conditions (e.g. U6/T7 transcription); (ii) regression and classification models for scoring gRNAs and (iii) multiple visualizations to explain the obtained results. Given its performance, interpretability, and versatility, we expect that it will assist researchers in the gRNA design process and facilitate genome editing research. CRISPRedict is available for use at http://www.crispredict.org/.
THO complex deficiency impairs DNA double-strand break repair via the RNA surveillance kinase SMG-1
Authors: Kamp Juliette A , Lemmens Bennie B L G , Romeijn Ron J , González-Prieto Román , Olsen Jesper V , Vertegaal Alfred C O , van Schendel Robin , Tijsterman Marcel 
Published: June 2022

Abstract
The integrity and proper expression of genomes are safeguarded by DNA and RNA surveillance pathways. While many RNA surveillance factors have additional functions in the nucleus, little is known about the incidence and physiological impact of converging RNA and DNA signals. Here, using genetic screens and genome-wide analyses, we identified unforeseen SMG-1-dependent crosstalk between RNA surveillance and DNA repair in living animals. Defects in RNA processing, due to viable THO complex or PNN-1 mutations, induce a shift in DNA repair in dividing and non-dividing tissues. Loss of SMG-1, an ATM/ATR-like kinase central to RNA surveillance by nonsense-mediated decay (NMD), restores DNA repair and radio-resistance in THO-deficient animals. Mechanistically, we find SMG-1 and its downstream target SMG-2/UPF1, but not NMD per se, to suppress DNA repair by non-homologous end-joining in favour of single strand annealing. We postulate that moonlighting proteins create short-circuits in vivo, allowing aberrant RNA to redirect DNA repair.
Optocoder: computational decoding of spatially indexed bead arrays
Authors: Senel Enes , Rajewsky Nikolaus , Karaiskos Nikos 
Published: June 2022

Abstract
Advancing technologies that quantify gene expression in space are transforming contemporary biology research. A class of spatial transcriptomics methods uses barcoded bead arrays that are optically decoded via microscopy and are later matched to sequenced data from the respective libraries. To obtain a detailed representation of the tissue in space, robust and efficient computational pipelines are required to process microscopy images and accurately basecall the bead barcodes. Optocoder is a computational framework that processes microscopy images to decode bead barcodes in space. It efficiently aligns images, detects beads, and corrects for confounding factors of the fluorescence signal, such as crosstalk and phasing. Furthermore, Optocoder employs supervised machine learning to strongly increase the number of matches between optically decoded and sequenced barcodes. We benchmark Optocoder using data from an in-house spatial transcriptomics platform, as well as from Slide-Seq(V2), and we show that it efficiently processes all datasets without modification. Optocoder is publicly available, open-source and provided as a stand-alone Python package on GitHub: https://github.com/rajewsky-lab/optocoder.
Revisiting the Concept of Minimal Detectable Change for Patient-Reported Outcome Measures
Authors: Seamon Bryant A , Kautz Steven A , Bowden Mark G , Velozo Craig A 
Published: June 2022

Abstract
Interpreting change is a requisite component of clinical decision making for physical therapists. Physical therapists often interpret change using minimal detectable change (MDC) values. Current MDC formulas are informed by classical test theory and calculated with group-level error data. This approach assumes that measurement error is the same across a measure’s scale and confines the MDC value to the sample characteristics of the study. Alternatively, an item response theory (IRT) approach calculates separate estimates of measurement error for different locations on a measure’s scale. This generates a conditional measurement error for someone with a low, middle, or high score. Error estimates at the measure-level can then be used to determine a conditional MDC (cMDC) value for individual patients based on their unique pre- and post-score combination. cMDC values can supply clinicians with a means for using individual score data to interpret change scores while providing a personalized approach that should lower the threshold for change compared with the MDC and enhance the precision of care decisions by preventing misclassification of patients. The purpose of this Perspective is to present how IRT can address the limitations of MDCs for informing clinical practice. This Perspective demonstrates how cMDC values can be generated from item-level psychometrics derived from an IRT model using the patient-reported Activities-specific Balance Scale (ABC) commonly used in stroke rehabilitation and also illustrates how the cMDC compares to the MDC when accounting for changes in measurement error across a scale. Theoretical patient examples highlight how reliance on the MDC value can result in misclassification of patient change and how cMDC values can help prevent this from occurring. This personalized approach for interpreting change can be used by physical therapists to enhance the precision of care decisions.
Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity
Authors: Mander Bryce A , Dave Abhishek , Lui Kitty K , Sprecher Katherine E , Berisha Destiny , Chappel-Farley Miranda G , Chen Ivy Y , Riedner Brady A , Heston Margo , Suridjan Ivonne , Kollmorgen Gwendlyn , Zetterberg Henrik , Blennow Kaj , Carlsson Cynthia M , Okonkwo Ozioma C , Asthana Sanjay , Johnson Sterling C , Bendlin Barbara B , Benca Ruth M 
Published: June 2022

Abstract

Study Objectives
Fast frequency sleep spindles are reduced in aging and Alzheimer’s disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD.

Methods
Fifty-eight cognitively unimpaired, β-amyloid-negative, older adults (mean ± SD; 61.4 ± 6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) ε4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, β-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to &lt;16Hz) sleep spindle measures through these AD biomarkers.

Results
Glial activation was associated with prefrontal fast frequency sleep spindle expression deficits. While adjusting for sex, APOE ε4 genotype, apnea–hypopnea index, and time between CSF sampling and sleep study, serial mediation models detected indirect effects of age on fast sleep spindle expression through microglial activation markers and then tau phosphorylation and synaptic degeneration markers. Sleep spindle expression at these electrodes was also associated with overnight memory retention in multiple regression models adjusting for covariates.

Conclusions
These findings point toward microglia dysfunction as associated with tau phosphorylation, synaptic loss, sleep spindle deficits, and memory impairment even prior to β-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD.
IL‐10 promotes endothelial progenitor cell infiltration and wound healing via STAT3
Authors: Short Walker D. , Steen Emily , Kaul Aditya , Wang Xinyi , Olutoye Oluyinka O. , Vangapandu Hima V. , Templeman Natalie , Blum Alexander J. , Moles Chad M. , Narmoneva Daria A. , Crombleholme Timothy M. , Butte Manish J. , Bollyky Paul L. , Keswani Sundeep G. , Balaji Swathi 
Published: June 2022

AbstractEndothelial progenitor cells (EPCs) contribute to de novo angiogenesis, tissue regeneration, and remodeling. Interleukin 10 (IL‐10), an anti‐inflammatory cytokine that primarily signals via STAT3, has been shown to drive EPC recruitment to injured tissues. Our previous work demonstrated that overexpression of IL‐10 in dermal wounds promotes regenerative tissue repair via STAT3‐dependent regulation of fibroblast‐specific hyaluronan synthesis. However, IL‐10's role and specific mode of action on EPC recruitment, particularly in dermal wound healing and neovascularization in both normal and diabetic wounds, remain to be defined. Therefore, inducible skin‐specific STAT3 knockdown mice were studied to determine IL‐10's impact on EPCs, dermal wound neovascularization and healing, and whether it is STAT3‐dependent. We show that IL‐10 overexpression significantly elevated EPC counts in the granulating wound bed, which was associated with robust capillary lumen density and enhanced re‐epithelialization of both control and diabetic (db/db) wounds at day 7. We noted increased VEGF and high C‐X‐C motif chemokine 12 (CXCL12) levels in wounds and a favorable CXCL12 gradient at day 3 that may support EPC mobilization and infiltration from bone marrow to wounds, an effect that was abrogated in STAT3 knockdown wounds. These findings were supported in vitro. IL‐10 promoted VEGF and CXCL12 synthesis in primary murine dermal fibroblasts, with blunted VEGF expression upon blocking CXCL12 in the media by antibody binding. IL‐10‐conditioned fibroblast media also significantly promoted endothelial sprouting and network formation. In conclusion, these studies demonstrate that overexpression of IL‐10 in dermal wounds recruits EPCs and leads to increased vascular structures and faster re‐epithelialization.
Addressing comorbidities in the perioperative setting and optimizing perioperative medicine education
Authors: Krishnan Sindhu , Adeola Janet O. , Urman Richard D. 
Published: June 2022

Purpose of review
Preoperative clinics and patient optimization are examples of collaborative, multidisciplinary care pathways that create value. This article reviews current literature to demonstrate the importance of preoperative enhancement of patients’ cognitive and functional status. This article underscores the importance of formal training in multidisciplinary topics, such as frailty, brain health, and shared decision-making for anesthesiology house staff.

Recent findings
Preoperative cognitive screening of older patients is a valuable metric for risk stratification and detection of patients at risk of postoperative delirium. Frailty is another syndrome that can be identified and optimized preoperatively. Sarcopenia has been shown to correlate with frailty; this shows promise as a method to detect frailty preoperatively.

Summary
Anesthesiologists as perioperative physicians are in a unique position to lead and coordinate interdisciplinary conversations that incorporate patient goal concordant care and realistic assessment of perioperative complications. Formal house staff training in early recognition and management of patients at risk of adverse outcomes in the short and long term postoperatively improves patient outcomes and decreases healthcare spending.
Perioperative considerations for adult patients with obstructive sleep apnea
Authors: Weingarten Toby N. , Sprung Juraj 
Published: June 2022

Purpose of review
Obstructive sleep apnea (OSA) is a common, but often undiagnosed, sleep breathing disorder affecting approximately a third of adult surgical patients. OSA patients have increased sensitivity to anesthetic agents, sedatives, and opioid analgesics.

Recent findings
Newer technologies (e.g., bedside capnography) have demonstrated that OSA patients have repetitive apneic spells, beginning in the immediate postoperative period and peaking in frequency during the first postoperative night. Compared to patients without OSA, OSA patients have double the risk for postoperative pulmonary as well as other complications, and OSA has been linked to critical postoperative respiratory events leading to anoxic brain injury or death. Patients with OSA who have respiratory depression during anesthesia recovery have been found to be high-risk for subsequent pulmonary complications. Gabapentinoids have been linked to respiratory depression in these patients.

Summary
Surgical patients should be screened for OSA and patients with OSA should continue using positive airway pressure devices postoperatively. Use of shorter acting and less sedating agents and opioid sparing anesthetic techniques should be encouraged. In particular, OSA patients exhibiting signs of respiratory depression in postanesthesia recovery unit should receive enhancer respiratory monitoring following discharge to wards.
After nectarine: how should we provide anesthesia for neonates?
Authors: Bertolizio Gianluca , Disma Nicola , Engelhardt Thomas 
Published: June 2022

Purpose of review
Neonates have a high risk of perioperative morbidity and mortality. The NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE) investigated the anesthesia practice, complications and perioperative morbidity and mortality in neonates and infants <60 weeks post menstrual age requiring anesthesia across 165 European hospitals. The goal of this review is to highlight recent publications in the context of the NECTARINE findings and subsequent changes in clinical practice.

Recent findings
A perioperative triad of hypoxia, anemia, and hypotension is associated with an increased overall mortality at 30 days. Hypoxia is frequent at induction and during maintenance of anesthesia and is commonly addressed once oxygen saturation fall below 85%.
Blood transfusion practices vary widely variable among anesthesiologists and blood pressure is only a poor surrogate of tissue perfusion. Newer technologies, whereas acknowledging important limitations, may represent the currently best tools available to monitor tissue perfusion. Harmonization of pediatric anesthesia education and training, development of evidence-based practice guidelines, and provision of centralized care appear to be paramount as well as pediatric center referrals and international data collection networks.

Summary
The NECTARINE provided new insights into European neonatal anesthesia practice and subsequent morbidity and mortality.
Maintenance of physiological homeostasis, optimization of oxygen delivery by avoiding the triad of hypotension, hypoxia, and anemia are the main factors to reduce morbidity and mortality. Underlying and preexisting conditions such as prematurity, congenital abnormalities carry high risk of morbidity and mortality and require specialist care in pediatric referral centers.
Monitoring of analgesia level during general anesthesia in children
Authors: Sabourdin Nada , Constant Isabelle 
Published: June 2022

Purpose of review
Monitoring of intraoperative nociception has made substantial progress in adult anesthesia during the last 10 years. Several monitors have been validated and their use has been associated with intraoperative or postoperative benefits in the adult population. In pediatric anesthesia, less data are available. However, several recent publications have assessed the performance of nociception monitors in children, and investigated their potential benefits in this context. This review will describe the main validated intraoperative nociception monitors, summarize adult findings and describe the available pediatric data.

Recent findings
Six intraoperative nociception indices were included in this review. Among them, four have shown promising results in children: Surgical Pleth Index (GE-Healthcare, Helsinki, Finland), Analgesia-Nociception Index (Mdoloris Medical Systems, Loos, France), Newborn-Infant Parasympathetic Evaluation (Mdoloris Medical Systems), and Pupillometry (IDMED, Marseille, France). The relevance of Skin Conductance (MedStorm innovations, AS, Oslo, Norway) under general anesthesia could not be established. Finally, the Nociception Level (Medasense, Ramat Gan, Israel) still requires to be investigated in children.

Summary
To date, four monitors may provide a relevant assessment of intraoperative nociception in children. However, the potential clinical benefits associated with their use to guide analgesia remain to be demonstrated.
Workforce solutions to address health disparities
Authors: Mhyre Jill M. , Jackson Jaleesa , Lucero Jennifer , Goree Johnathan 
Published: June 2022

Purpose of review
This review focuses on physician workforce racial & ethnic diversity as a solution to improve perioperative and peripartum health equity.

Recent findings
Black, Indigenous, and Hispanic physicians remain underrepresented in medicine (URiM) and anesthesiology, and efforts to expand this workforce have had limited impact. Psychological forces, including implicit bias, aversive racism, outgroup bias, racial attention bias, stereotype threat, and imposter syndrome all act to reinforce structural racism and decrease opportunity for advancement. Evidence based solutions are emerging, but require institutional commitment and widespread engagement of the entire medical community.

Summary
Academic medicine has recognized the need to diversify the physician workforce for more than 50 years, and yet Black, Indigenous, and Hispanic physicians remain URiM. Foundational assumptions and power structures in medicine limit entry, advancement, and retention of URiM physicians. Solutions require leadership and institutional commitment to change the policies, procedures, priorities, and culture of academic medicine.