bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexmedetomidine as a myocardial protector in pediatric heart surgery using cardiopulmonary bypass: a systematic review
Authors: Kesumarini Dian , Widyastuti Yunita , Boom Cindy E. , Dinarti Lucia K. 
Published: August 2023

Background:
In recent years, dexmedetomidine has been studied as a cardioprotective agent. However, studies on its application in pediatric heart surgery using cardiopulmonary bypass (CPB) remain limited. This systematic review aimed to provide information on the cardioprotective effect of dexmedetomidine in children undergoing heart surgery using CPB.

Methods:
The authors searched several databases (MEDLINE, Embase, Cochrane Library, etc.) to identify all trials comparing the levels of myocardial injury via biomarkers, including pediatric patients undergoing heart surgery using CPB who received dexmedetomidine versus placebo or other anesthetic agents. Literatures from non-primary studies were excluded. Two reviewers independently screened studies for eligibility and extracted data. The Cochrane Risk-of-Bias tool was implemented to evaluate any potential biases. Information from eligible studies was summarized and correspondingly reviewed based on any quantitative outcomes.

Results:
We identified six trials composed of 419 participants, three of which (n=241) showed significantly reduced interleukin-6 (IL-6) levels in the dexmedetomidine group, while one study (n=40) showed no IL-6 difference between groups. Cardiac troponin I (cTnI) and creatinine kinase-myocardial band (CK-MB), as myocardial injury biomarkers, were found to be lower in two trials (n=180). Despite several limitations hindering this review from pooling the data objectively, the majority of published studies indicated that dexmedetomidine is a seemingly efficacious agent protecting against cardiac injury during bypass.

Conclusions:
These studies suggest that dexmedetomidine has cardioprotective effects through the lowering of cardiac injury biomarkers while improving its clinical outcomes after heart surgery using bypass.
The Role of Level of Play in Concussions in High School Athletes
Authors: Waltzman Dana , DePadilla Lara , Breiding Matthew , Pierpoint Lauren , Collins Christy 
Published: August 2023

Objectives:
To examine level of play (LOP) as a risk factor for concussion severity and recovery-related outcomes among high school athletes, stratified by sex, and among boys, by sport (football, non-football male sports).

Design/Setting:
Secondary analysis of data collected through the High School Reporting Information Online surveillance system for academic years 2007-2008 through 2018-2019.

Participants:
A total of 9916 concussions were reported between the academic years 2007-2008 and 2018-2019 from 9 sports (5189 from football; 2096 from non-football male sports; 2631 from female sports).

Main Outcome Measure:
Examined the association between LOP (Freshman, Junior Varsity [JV], and Varsity teams) and concussion outcomes (number of concussion symptoms, symptom resolution time [SRT], and time to return to play [RTP]).

Results:
Compared with Varsity football athletes, concussed JV football athletes had on average 0.19 fewer concussion symptoms, longer SRT (>1 week vs <1 week: odds ratio [OR] = 1.3; 95% confidence interval [CI], 1.1-1.5), and longer RTP (1-3 weeks vs <1 week: OR = 1.5; 95% CI, 1.2-1.9; >3 weeks vs <1 week: OR = 1.6; 95% CI, 1.1-2.3). Compared with Varsity football athletes, Freshman football athletes had on average 0.48 fewer concussion symptoms, longer SRT (OR = 1.3; 95% CI, 1.1-1.5), and longer RTP (1-3 weeks vs <1 week: OR = 1.5; 95% CI, 1.1-2.0; >3 weeks vs <1 week: OR = 2.0; 95% CI, 1.3-3.0). Similarly, compared with female athletes on Varsity teams, concussed JV female athletes had longer RTP (1-3 weeks vs <1 week: OR = 1.8; 95% CI, 1.2-2.7). Trend analyses revealed an increase in the number of concussion symptoms between 2015-2016 and 2018-2019, a decrease between 2009-2010 and 2018-2019 for SRT of less than 1 week, and an increase between 2014-2015 and 2018-2019 for RTP of less than 1 week among Varsity football athletes. Among Varsity female athletes, there was a linear decrease during the study period for RTP of less than 1 week.

Conclusions:
Despite a higher number of symptoms overall and in recent years, Varsity football players had shorter RTP than Freshman and JV athletes.
Technical Note: Assessment of Pulse Pileup on Single-Energy and Multienergy Images From a Clinical Photon-Counting Detector Computed Tomography
Authors: Chen Joshua Ray , Winfree Timothy N. , Bruesewitz Michael R. , Swicklik Joseph R. , Thorne Jamison E. , Leng Shuai , McCollough Cynthia H. 
Published: August 2023

Objective
Pulse pileup effects occur when pulses occur so close together that they fall on top of one another, resulting in count loss and errors in energy thresholding. To date, there has been little work systematically detailing the quantitative effects of pulse pileup on material decomposition accuracy for photon-counting detector (PCD) computed tomography (CT). Our aim in this work was to quantify the effects of pulse pileup on single-energy and multienergy CT images, including low-energy bin (BL), high-energy bin (BH), iodine map, and virtual noncontrast images from a commercial PCD-CT.

Methods
Scans of a 20-cm diameter multienergy CT phantom with 10 solid inserts were acquired at a fixed tube potential as the tube current was varied across the available range. Four types of images (BL, BH, iodine map, and virtual noncontrast) were reconstructed using an iterative reconstruction algorithm at strength 2, a quantitative reconstruction kernel (Qr40), 2-/1-mm slice thickness/increment, and a 210-mm field-of-view. The mean and standard deviation of CT numbers were recorded and the ratios of CT number between BL and BH images were calculated and plotted, along with noise versus tube current and noise ×

versus tube current.

Results
As tube current was increased, the range of variations in CT numbers was less than 13.4 HU for all inserts and image types evaluated. Noise ×

versus tube current showed a small positive slope equal to a noise increase from 100 mA of 10% at 500 mA and 15% at 900 mA compared with what would be expected if the slope was zero.

Conclusions
Minimal impact on single-energy and multienergy CT numbers and noise performance was observed for the evaluated clinical PCD-CT system.
Asthma as an Inflammatory Reason of Tracheobronchial PSMA Uptake
Authors: Bronte Viedma Ángela , Bastidas Tamayo Juan Fernando , Rosales Castillo Juan José , Campo Ezquibela Arantza , Rodriguez-Fraile Macarena 
Published: August 2023

Abstract
A 53-year-old man with persisting increased serum prostate-specific antigen level (9.53 ng/mL) and repeated negative prostate biopsies was referred for a PET/CT with 68Ga-PSMA-11. The PET/CT revealed focal uptake in the prostate suggestive of localized prostate cancer. Incidentally, it also showed a diffuse uptake in the tracheobronchial tree suspicious for a benign etiology. Because of the clinical history of asthma exacerbation in the previous week, further supplementary studies were performed showing a pathological fractional exhaled nitric oxide level (92 ppb; reference values, <25 ppb) and mild airway obstruction in the spirometry. These findings confirmed asthma as an inflammatory etiology of the tracheobronchial PSMA uptake.
Mediastinal Hemangioma Masquerading as a Simple Cyst
Authors: D'Souza Romina , Pal Prodipto , Chacko Binita , Kha Lan-Chau , Oikonomou Anastasia , Houbois Christian 
Published: August 2023

Abstract:
This report presents imaging from a mediastinal mass in a patient with colon cancer. At baseline and surveillance chest computed tomography examinations, it was characterized as a pericardial cyst. However, during chemotherapy, complications arose and this mass was further characterized with a chest MRI. It was then decided to be removed, and histopathology confirmed the diagnosis of a hemangioma.
Inhibition of the Complement Pathway Induces Cellular Proliferation and Migration in Pancreatic Ductal Adenocarcinoma
Authors: Nsingwane Zanele , Naicker Previn , Omoshoro-Jones Jones , Devar John , Smith Martin , Candy Geoffrey , Augustine Tanya Nadine , Nweke Ekene Emmanuel 
Published: August 2023

AbstractPancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a growing incidence and mortality despite novel therapeutic strategies. The complement signalling pathway may play diverse roles in PDAC by eliciting an immune response, inducing inflammatory responses, and may elevate pathways linked to chemoresistance. However, their role in the progression of PDAC is not fully understood. In this study, 30 tissues and 34 plasma samples were obtained from a cohort of PDAC patients including controls. Targeted pathway-specific PCR analysis was conducted to determine the gene expression profiles of immune-response-related genes. The circulating levels of complement proteins C3 and C5 were further investigated. Pharmacological inhibition of the complement pathway in MIA PaCa-2 pancreatic cancer cell lines was performed and the effect on cells was assessed by cell proliferation, cell migration, and cell cycle assays. Finally, SWATH-mass spectrometry was performed to identify potential molecular mechanisms during inhibition. The results identified C3 and C5 to be overly expressed in early PDAC compared to later stages. Pharmacological inhibition of the complement pathway led to increased cell growth, proliferation and migrationin vitro. Proteomic analysis implicated several proteins such as the mitochondrial and histone proteins, that could play a role in inducing this phenotype. This study helps to further delineate the role of the complement pathway in PDAC progression suggesting a context-dependent function.
Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study
Authors: Hietikko Ronja , Mirtti Tuomas , Kilpeläinen Tuomas P. , Tolonen Teemu , Räisänen-Sokolowski Anne , Nordling Stig , Hannus Jill , Laurila Marita , Taari Kimmo , Tammela Teuvo LJ , Autio Reija , Natunen Kari , Auvinen Anssi , Rannikko Antti 
Published: August 2023

ABSTRACTBackgroundProstate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI).ObjectiveTo assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen).Design, setting, and participantsFrom June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate.InterventionSix pathologists individually reviewed the pathology slides of the prostate biopsies.Outcome measurements and statistical analysisThe five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss’ weighted kappa (κ) and Model based kappa for associations were computed to estimate the combined agreement between individual pathologists.Results and limitationsGG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG 1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss’ kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG 2-5 vs. GG 0 vs GG1) it was good (Model-based kappa 0.70, Fleiss’ kappa κ 0.67).ConclusionsInter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.Patient summaryIt is currently unknown to what extent pathologists differ in their evaluation of histopathology in MRI-targeted prostate biopsies. We show that the agreement is good to excellent. We expect individual pathologist to have a minimal impact on MRI-based prostate cancer screening including the ProScreen trial.
Study Protocol for the Intraoperative Complications Assessment and Reporting with Universal Standards (ICARUS) Global Cross-Specialty Surveys Among Surgeons, Anesthesiologists, Nurses, Interventional Cardiologists, and Interventional Radiologists
Authors: Cacciamani Giovanni E. , Sholklapper Tamir , Eppler Michael B. , Sayegh Aref , Stornino Ramacciotti Lorenzo , Abreu Andre L. , Sotelo Rene , Desai Mihir M. , Gill Inderbir S. 
Published: August 2023

ABSTRACTEvery year, approximately 200 million surgeries are performed worldwide, and intraoperative adverse events (iAEs) have a significant impact on patients and surgeons. Despite their importance, the true scale of iAEs remains underestimated due to inadequate methods for assessment, collection, grading, and reporting. Various grading systems have been introduced over the past decade, but their adoption has been limited, leading to inconsistencies in reporting. Furthermore, a lack of standardized frameworks for defining, assessing, and collecting iAEs, coupled with litigation concerns, contributes to underreporting. Only half of surgery and anesthesiology journals provide guidance on reporting perioperative adverse events, and recommendations for reporting iAEs are notably lacking in surgical literature. To address these issues, the Intraoperative Complications Assessment and Reporting with Universal Standard (ICARUS) Global Surgical Collaboration was established in 2022. The initiative involves conducting global surveys and a Delphi consensus to understand the barriers for poor reporting of iAEs, validate shared criteria for reporting, define iAEs according to surgical procedures, evaluate the existing grading systems’ reliability, and identify strategies for enhancing the collection, reporting, and management of iAEs. A sample size of 2,398 respondents was calculated for the study, with invitations extended to 86,574 healthcare providers. This effort represents an essential step towards improved patient safety and the well-being of healthcare professionals in the surgical field.
Chemical and biophysical characterization of novel potassium channel blocker 3-fluoro-5-methylpyridin-4-amine
Authors: Sun Yang , Rodríguez-Rangel Sofia , Zhang Lauren L. , Sánchez-Rodríguez Jorge E. , Brugarolas Pedro 
Published: August 2023

ABSTRACT4-aminopyridine (4AP) is a potassium (K+) channel blocker used clinically to improve walking in people with multiple sclerosis (MS). 4AP binds to exposed K+channels in demyelinated axons, reducing the leakage of intracellular K+and enhancing impulse conduction. Multiple derivatives of 4AP capable of blocking K+channels have been reported including three radiolabeled with positron emitting isotopes for imaging demyelinated lesions using positron emission tomography (PET). Here, we describe 3-fluoro-5-methylpyridin-4-amine (5Me3F4AP), a novel K+channel blocker with potential application in PET. 5Me3F4AP has comparable potency to 4AP and the PET tracer 3-fluoro-4-aminopyridine (3F4AP). Compared to 3F4AP, 5Me3F4AP is more lipophilic (logD = 0.664 ± 0.005vs.0.414 ± 0.002) and slightly more basic (pKa= 7.46 ± 0.01vs. 7.37 ± 0.07). In addition, 5Me3F4AP appears to be more permeable to an artificial brain membrane and more stable towards oxidation by the cytochrome P450 enzyme family 2 subfamily E member 1 (CYP2E1), responsible for the metabolism of 4AP and 3F4AP. Taken together, 5Me3F4AP has promising properties for PET imaging warranting additional investigation.Significance StatementThe PET tracer [18F]3-fluoro-4-aminopyridine ([18F]3F4AP) binds to K+channels in demyelinated axons and has shown promise for imaging demyelinated lesions in animal models. However, its use in humans may be compromised due to rapid metabolism. Thus, a novel 3F4AP derivative amenable to labeling with fluorine-18 was designed and evaluatedin vitro. The results indicate that 5-methyl-3F4AP exhibits high binding affinity, good physicochemical properties and slower oxidation by CYP2E1 than 3F4AP, making it a promising candidate for further PET studies.
Genetic variation at transcription factor binding sites largely explains phenotypic heritability in maize
Authors: Engelhorn Julia , Snodgrass Samantha J. , Kok Amelie , Seetharam Arun S. , Schneider Michael , Kiwit Tatjana , Singh Ayush , Banf Michael , Khaipho-Burch Merritt , Runcie Daniel E. , Sanchez-Camargo Victor A. , Torres-Rodriguez J. Vladimir , Sun Guangchao , Stam Maike , Fiorani Fabio , Beier Sebastian , Schnable James C. , Bass Hank W. , Hufford Matthew B. , Stich Benjamin , Frommer Wolf B. , Ross-Ibarra Jeffrey , Hartwig Thomas 
Published: August 2023

AbstractComprehensive maps of functional variation at transcription factor (TF) binding sites (cis-elements) are crucial for elucidating how genotype shapes phenotype. Here we report the construction of a pan-cistrome of the maize leaf under well-watered and drought conditions. We quantified haplotype-specific TF footprints across a pan-genome of 25 maize hybrids and mapped over two-hundred thousand genetic variants (termed binding-QTL) linked tocis-element occupancy. Three lines of evidence support the functional significance of binding-QTL: i) they coincide with numerous known causative loci that regulate traits, includingVGT1,Trehalase1, and the MITE transposon nearZmNAC111under drought; ii) their footprint bias is mirrored between inbred parents and by ChIP-seq; iii) partitioning genetic variation across genomic regions demonstrates that binding-QTL capture the majority of heritable trait variation across ∼70% of 143 phenotypes. Our study provides a promising approach to make previously hiddencis-variation more accessible for genetic studies and multi-target engineering of complex traits.
ERK signaling drives evolutionary expansion of the mammalian cerebral cortex
Authors: Sun Mengge , Gao Yanjing , Li Zhenmeiyu , Yang Lin , Liu Guoping , Xu Zhejun , Guo Rongliang , You Yan , Yang Zhengang 
Published: August 2023

SUMMARYThe molecular basis for cortical expansion during evolution remains largely unknown. Here, we found that FGF-extracellular signal-regulated kinase (ERK) signaling promotes the self-renewal and expansion of cortical radial glial (RG) cells.Furthermore, FGF-ERK signaling inducesBmp7expression in cortical RG cells, which increases the length of the neurogenic period. We demonstrate that ERK signaling and SHH signaling mutually inhibit each other in cortical RG cells. We also provide evidence that ERK signaling is elevated in cortical RG cells during development and evolution. We conclude that the evolutionary expansion of the mammalian cortex, notably in human, is driven by ERK-BMP7-GLI3R signaling pathway in cortical RG cells, which participates in a positive feedback loop through antagonizing SHH signaling. We also propose that the molecular basis for cortical evolutionary dwarfism, exemplified by the lissencephalic mouse which originated from a larger and gyrencephalic ancestor, is due to mouse cortical RG cells receiving higher SHH signaling that antagonizes ERK signaling.
Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina
Authors: Lyu Pin , Iribarne Maria , Serjanov Dmitri , Zhai Yijie , Hoang Thanh , Campbell Leah J. , Boyd Patrick , Palazzo Isabella , Nagashima Mikiko , Silva Nicholas J. , HItchcock Peter F. , Qian Jiang , Hyde David R. , Blackshaw Seth 
Published: August 2023

SUMMARYFollowing acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes. This regeneration requires Müller glia (MG) to reprogram and divide asymmetrically to produce a multipotent Müller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, does loss of different retinal cell subtypes induce unique MG regeneration responses? Second, do MG reprogram to a developmental retinal progenitor cell state? And finally, to what extent does regeneration recapitulate retinal development? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. While MG reprogram to a state similar to late-stage retinal progenitors in developing retinas, there are transcriptional differences between reprogrammed MG/MGPCs and late progenitors, as well as reprogrammed MG in outer and inner retinal damage models. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes. This work identifies major differences between gene regulatory networks activated following the selective loss of different subtypes of retina neurons, as well as between retinal regeneration and development.
Heterogeneity of synaptic NMDA receptor responses within individual lamina I pain processing neurons across sex in rats and humans
Authors: Dedek Annemarie , Topcu Emine , Dedek Christopher , McDermott Jeff S. , Krajewski Jeffrey L. , Tsai Eve C. , Hildebrand Michael E. 
Published: August 2023

AbstractExcitatory glutamatergic NMDA receptors (NMDARs) are key regulators of spinal pain processing, and yet the biophysical properties of NMDARs in dorsal horn nociceptive neurons remain poorly understood. Despite the clinical implications, it is unknown whether the molecular and functional properties of NMDAR synaptic responses are conserved between males and females as well as from rodents to humans. To address these translational gaps, we systematically compared individual and averaged excitatory synaptic responses from lamina I pain-processing neurons of adult Sprague Dawley rats and human organ donors, including both sexes. By combining patch-clamp recordings of outward miniature excitatory postsynaptic currents with non-biased data analyses, we uncovered a wide range of decay constants of excitatory synaptic events within individual lamina I neurons. Decay constants of quantal synaptic responses were distributed in a continuum from 1-20 ms to greater than 1000 ms, suggesting that individual lamina I neurons contain AMPA receptor (AMPAR)-only as well as GluN2A-, GluN2B-, and GluN2D-NMDAR-dominated synaptic events. This intraneuronal heterogeneity in AMPAR– and NMDAR-mediated decay kinetics was observed across sex and species. However, we discovered a decreased relative contribution of GluN2B-dominated NMDAR responses as well as larger amplitude GluN2D-like events at human lamina I synapses compared to rodent synapses, suggesting species differences relevant to NMDAR subunit-targeting therapeutic approaches. The conserved heterogeneity in decay rates of excitatory synaptic events within individual lamina I pain-processing neurons may enable synapse-specific forms of plasticity and sensory integration within dorsal horn nociceptive networks.