bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation analysis of salivary cytokines and hormones with resiliency
Authors: Wong Cheyenne , Patel Sagar , LaPorta Anthony , Towne Francina , Gubler Kelly Dean , Bartone Paul , Ryznar Rebecca 
Published: June 2023

BACKGROUND
Frequent exposure to acute stress increases risk of suicide, posttraumatic stress disorder, and other stress-related disorders. Neuroendocrine and immunologic dysregulation associated with stress may underlie predispositions to psychological disorders and inflammatory disease processes in individuals, such as first-responders and other healthcare professionals, who function in high stress situations. The Hardiness Resilience Gauge (HRG) can be used to psychometrically measure resilience, a psychological modifier of the stress response. Using the HRG alongside salivary biomarker profiling, may help to identify low resilience phenotypes and allow mitigation and early therapeutic interventions. There is a paucity of knowledge regarding biomarkers of resilience. This study aims to evaluate the relationship between factors of resilience with salivary biomarker levels and fluctuations during and following acute stress.

METHODS
Sixty-three first responders underwent a standardized stress-inducing training exercise, providing salivary samples before (prestress), immediately after (post-stress), and 1 hour after the event (recovery). The HRG was administered before (initial) and after (final) the event. Multiplex ELISA panels quantified 42 cytokines and 6 hormones from the samples, which were analyzed for relationships to psychometric factors of resilience measured by the HRG.

RESULTS
Several biomarkers correlated with psychological resilience following the acute stress event. The HRG scores correlated (p < 0.05) with a select set of biomarkers with moderate-to-strong correlations (|r| > 0.3). These included EGF, GROα, PDGFAA, TGFα, VEGFA, interleukin (IL)1Ra, TNFα, IL18, cortisol, FGF2, IL13, IL15, and IL6. Interestingly, fluctuations of EGF, GROα, and PDGFAA in post-stress compared with recovery were positively correlated with factors of resilience, which were negatively correlated from the pre-stress to post-stress period.

CONCLUSION
This exploratory analysis discovered a small subset of salivary biomarkers that are significantly correlated with acute stress and resilience. Further investigation of their specific roles in acute stress and associations with resiliency phenotypes is warranted.
ABO blood type and functional neurological outcome in patients with severe traumatic brain injury
Authors: Esnault Pierre , Houcinat Nazim , de Malleray Hilaire , Quere Pierre-Louis , Cardinale Michael , D'aranda Erwan , Joubert Christophe , Dagain Arnaud , Goutorbe Philippe , Meaudre Eric 
Published: June 2023

BACKGROUND
The ABO blood system has been involved in the pathogenesis of several diseases, including coagulopathy and bleeding complications. In trauma patients, blood type A has been associated with acute respiratory distress syndrome, and recently, blood type O has been associated with all-cause mortality. The purpose of this study was to assess the association between ABO blood types and long-term functional outcomes in critically ill patients with severe traumatic brain injury (TBI).

METHODS
We conducted a single-center, retrospective, observational study including all patients admitted to the intensive care unit with severe TBI (defined as a Glasgow Coma Scale score of ≤8) between January 2007 and December 2018. Patient characteristics and outcomes were extracted from a prospective registry of all intubated patients admitted to the intensive care unit for TBI. ABO blood types were retrospectively retrieved from patient medical records. The association between ABO blood type (A, B, AB, and O) and unfavorable functional outcome (defined by a Glasgow Outcome Scale score between 1 and 3) 6 months after injury was assessed in univariate and multivariate analysis.

RESULTS
A total of 333 patients meeting the inclusion criteria were included. There were 151 type O (46%), 131 type A (39%), 37 type B (11%), and 12 type AB patients (4%). No significant differences in baseline demographic, clinical, or biological characteristics were observed between blood types. The prevalence of unfavorable outcome was significantly different between the four groups. After adjustment for confounders, blood type O was significantly associated with unfavorable outcome at 6 months (odds ratio, 1.97; confidence interval [1.03–3.80]; p = 0.042). The prevalence of coagulopathy or progressive hemorrhagic injury was not statistically different between blood types (p = 0.575 and p = 0.813, respectively).

CONCLUSION
Blood type O appears to be associated with unfavorable long-term functional outcome in critically ill patients with severe TBI. Further studies are needed to detail the mechanism underlying this relationship.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Optimal dose of cryoprecipitate in massive transfusion following trauma
Authors: Dorken-Gallastegi Ander , Bokenkamp Mary , Argandykov Dias , Mendoza April E. , Hwabejire John O. , Saillant Noelle , Fagenholz Peter J. , Kaafarani Haytham M.A. , Velmahos George C. , Parks Jonathan J. 
Published: June 2023

BACKGROUND
While cryoprecipitate (Cryo) is commonly included in massive transfusion protocols for hemorrhagic shock, the optimal dose of Cryo transfusion remains unknown. We evaluated the optimal red blood cell (RBC) to RBC to Cryo ratio during resuscitation in massively transfused trauma patients.

METHODS
Adult patients in the American College of Surgeon Trauma Quality Improvement Program (2013–2019) receiving massive transfusion (≥4 U of RBCs, ≥1 U of fresh frozen plasma, and ≥1 U of platelets within 4 hours) were included. A unit of Cryo was defined as a pooled unit of 100 mL. The RBC:Cryo ratio was calculated for blood products transfused within 4 hours of presentation. The association between RBC:Cryo and 24-hour mortality was analyzed with multivariable logistic regression adjusting for the volume of RBC, plasma and platelet transfusions, global and regional injury severity, and other relevant variables.

RESULTS
The study cohort included 12,916 patients. Among those who received Cryo (n = 5,511 [42.7%]), the median RBC and Cryo transfusion volume within 4 hours was 11 U (interquartile range, 7–19 U) and 2 U (interquartile range, 1–3 U), respectively. Compared with no Cryo administration, only RBC:Cryo ratios ≤8:1 were associated with a significant survival benefit, while lower doses of Cryo (RBC:Cryo >8:1) were not associated with decreased 24-hour mortality. Compared with the maximum dose of Cryo administration (RBC:Cryo, 1:1–2:1), there was no difference in 24-hour mortality up to RBC:Cryo of 7:1 to 8:1, whereas lower doses of Cryo (RBC:Cryo, >8:1) were associated with significantly increased 24-hour mortality.

CONCLUSION
One pooled unit of Cryo (100 mL) per 7 to 8 U of RBCs could be the optimal dose of Cryo in trauma resuscitation that provides a significant survival benefit while avoiding unnecessary blood product transfusions.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic; Level IV.
Rapid clearing CT-001 restored hemostasis in mice with coagulopathy induced by activated protein C
Authors: Sim Derek S. , Mallari Cornell R. , Bauzon Maxine , Hermiston Terry W. 
Published: June 2023

BACKGROUND
Activated protein C (APC) is one of the mechanisms contributing to coagulopathy, which is associated with high mortality. The counteraction of the APC pathway could help ameliorate bleeding. However, patients also transform frequently from a hemorrhagic state to a prothrombotic state at a later time. Therefore, a prohemostatic therapeutic intervention should take this thrombotic risk into consideration.

OBJECTIVES
CT-001 is a novel factor VIIa (FVIIa) with enhanced activity and desialylated N-glycans for rapid clearance. We assessed CT-001 clearance in multiple species and its ability to reverse APC-mediated coagulopathic blood loss.

METHODS
The N-glycans on CT-001 were characterized by liquid chromatography–mass spectrometry. Three species were used to evaluate the pharmacokinetics of the molecule. The potency and efficacy of CT-001 under APC pathway–induced coagulopathic conditions were assessed by coagulation assays and bleeding models.

RESULTS
The N-glycosylation sites of CT-001 had high occupancy of desialylated N-glycans. CT-001 exhibited 5 to 16 times higher plasma clearance in human tissue factor knockin mice, rats, and cynomolgus monkeys than wildtype FVIIa. CT-001 corrected the activated partial thromboplastin time and thrombin generation of coagulopathic plasma to normal in in vitro studies. In an APC-mediated saphenous vein bleeding model, 3 mg/kg of CT-001 reduced bleeding time in comparison with wildtype FVIIa. The correction of bleeding by CT-001 was also observed in a coagulopathic tail amputation severe hemorrhage mouse model. The efficacy of CT-001 is independent of the presence of tranexamic acid, and the combination of CT-001 and tranexamic acid does not lead to increased thrombogenicity.

CONCLUSION
CT-001 corrected APC pathway–mediated coagulopathic conditions in preclinical studies and could be a potentially safe and effective procoagulant agent for addressing APC-mediated bleeding.
Long-term physical and mental health outcomes of pediatric firearm-injured victims: A prospective cohort study
Authors: Haasz Maya , Dulchavsky Alexandria , Stevens Jenny , Nolan Margo , Leonard Jan , Phillips Ryan , Knoepke Christopher , Schroeppel Thomas , Zuk Jeannie , Abbey William , Ambroggio Lilliam 
Published: June 2023

BACKGROUND
Firearms are a leading cause of injury among US youth. There is little research describing outcomes after pediatric firearm injuries, particularly past 1 year.

OBJECTIVE
This study aimed to assess long-term physical and mental health outcomes among nonfatal firearm versus motor vehicle collision (MVC)–injured victims and versus a standard population.

METHODS
We retrospectively identified firearm and MVC-injured pediatric patients seen at one of our four trauma centers (January 2008 to October 2020) and prospectively assessed outcomes using validated patient-reported outcome measures. Eligible patients were English speaking, injured ≥5 months before study start, younger than 18 years at time of injury, and 8 years or older at study start. All firearm patients were included; MVC patients were matched 1:1 with firearm patients for Injury Severity Score (dichotomized <15 or ≥15), age range (±1 year), and year of injury. We conducted structured interviews of patients and parents using validated tools (Patient-Reported Outcomes Measurement Information System tools, Children's Impact of Event Scale for younger than 18 years and parent proxies). Patient-Reported Outcomes Measurement Information System scores are reported on a T score metric (mean [SD], 50 [10]); higher scores indicate more of the measured domain. We used paired t tests, Wilcoxon signed-rank tests, and McNemar's test to compare demographics, clinical characteristics, and outcomes.

RESULTS
There were 24 participants in each of the MVC and firearm-injured groups. Compared with MVC-injured patients, firearm-injured patients younger than 18 years had similar scores, and firearm-injured patients 18 years or older had higher anxiety scores (59.4 [8.3] vs. 51.2 [9.4]). Compared with a standard population, patients younger than 18 years had worse global health scores (mean [SD], 43.4 [9.7]), and participants 18 years or older reported increased fatigue (mean [SD], 61.1 [3.3]) and anxiety (mean [SD], 59.4 [8.3]).

CONCLUSION
Long-term effects of firearm-injured patients were poorer than matched MVC and the standard population in few domains. Further study in a larger, prospectively recruited cohort is warranted to better characterize physical and mental health outcomes.
Do chromosome rearrangements fix by genetic drift or natural selection? A test inBrenthisbutterflies
Authors: Mackintosh Alexander , Vila Roger , Martin Simon H. , Setter Derek , Lohse Konrad 
Published: June 2023

AbstractLarge-scale chromosome rearrangements, such as fissions and fusions, are a common feature of eukaryote evolution. They can have considerable influence on the evolution of populations, yet it remains unclear exactly how rearrangements become established and eventually fix. Rearrangements could fix by genetic drift if they are weakly deleterious or neutral, or they may instead be favoured by positive natural selection. Here we compare genome assemblies of three closely relatedBrenthisbutterfly species and characterise a complex history of fission and fusion rearrangements. An inferred demographic history of these species suggests that rearrangements became fixed in populations with large long-term effective size (Ne). However, we also find large runs of homozygosity within individual genomes and show that a model of population structure with smaller localNecan reconcile these observations. Using a recently developed analytic framework for characterising hard selective sweeps, we find that chromosome fusions are not enriched for evidence of past sweeps compared to other regions of the genome. Nonetheless, one chromosome fusion in theB. daphnegenome is associated with a valley of diversity where genealogical branch lengths are distorted, consistent with a selective sweep. Our results suggest that drift is a stronger force in these populations than suggested by overall genetic diversity, but that the fixation of strongly underdominant rearrangements remains unlikely. Additionally, although chromosome fusions do not typically exhibit signatures of selective sweeps, a single example raises the possibility that natural selection may sometimes play a role in their fixation.
A resource for development and comparison of multi-modal brain 3T MRI harmonisation approaches
Authors: Warrington S. , Ntata A. , Mougin O. , Campbell J. , Torchi A. , Craig M. , Alfaro-Almagro F. , Miller K. L. , Morgan P. S. , Jenkinson M. , Sotiropoulos S. N. 
Published: June 2023

AbstractDespite the huge potential of magnetic resonance imaging (MRI) in mapping and exploring the brain, MRI measures can often be limited in their consistency, reproducibility and accuracy which subsequently restricts their quantifiability. Nuisance nonbiological factors, such as hardware, software, calibration differences between scanners, and post-processing options can contribute to, or drive trends in, neuroimaging features to an extent that interferes with biological variability. Such lack of consistency, known as lack of harmonisation, across neuroimaging datasets poses a great challenge for our capabilities in quantitative MRI. Here, we build a new resource for comprehensively mapping the extent of the problem and objectively evaluating neuroimaging harmonisation approaches. We use a travelling-heads paradigm consisting of multimodal MRI data of 10 travelling subjects, each scanned at 5 different sites on 6 different 3T scanners from all the 3 major vendors and using 5 neuroimaging modalities, providing more comprehensive coverage than before. We also acquire multiple within-scanner repeats for a subset of subjects, setting baselines for multi-modal scan-rescan variability. Having extracted hundreds of image-derived features, we compare three forms of variability: (i) between-scanner, (ii) within-scanner (within-subject), and (iii) biological (between-subject). We characterise the reliability of features across scanners and use our resource as a testbed to enable new investigations that until now have been relatively unexplored. Specifically, we identify optimal pipeline processing steps that minimise between-scanner variability in extracted features (implicit harmonisation). We also test the performance of post-processing harmonisation tools (explicit harmonisation) and specifically check their efficiency in reducing between-scanner variability against baseline standards provided by our data. Our explorations allow us to come up with good practice suggestions on processing steps and sets of features where results are more consistent, while our publicly-released datasets establish references for future studies in this field.
Transcriptomic profiling reveals a pro-nociceptive role for Angiotensin II in inflammatory bowel disease
Authors: Higham James P , Bhebhe Charity N , Gupta Rohit A , Tranter Michael , Barakat Farah M , Dogra Harween , Bab Natalie , Wozniak Eva , Barker Katie H , Wilson Catherine H , Mein Charles , Raine Tim , Cox James J , Wood John N , Croft Nicholas , Wright Paul , Bulmer David C 
Published: June 2023

AbstractObjectiveVisceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics often lack efficacy or have intolerable side-effects, driving the need for a more complete understanding of the mechanisms causing pain.MethodsWhole transcriptome gene expression analysis was performed by bulk RNA sequencing of colonic biopsies from patients with ulcerative colitis (UC) and Crohn’s disease (CD) reporting abdominal pain and compared with non-inflamed control biopsies. Putative pro-nociceptive mediators were identified based on pathway analysis of differentially expressed genes in IBD tissue and single cell gene expression in colonic neurons. Pro-nociceptive activity of identified mediators was assessed in assays of sensory neuron and colonic afferent activity.ResultsRNA sequencing analysis highlighted a 7.6-fold increase in the expression of angiotensinogen transcripts,Agt,the precursor to angiotensin II (Ang II), in samples from UC patients (p = 3.2×10-8). Consistent with the marked expression of the angiotensin AT1receptor in colonic neurons, Ang II elicited an increase in intracellular Ca2+in capsaicin-sensitive, voltage gated sodium channel subtype NaV1.8-positive sensory neurons. Ang II also evoked action potential discharge in high-threshold colonic nociceptors. These effects were inhibited by the AT1receptor antagonist valsartan.ConclusionFindings from our study identify AT1receptor-mediated colonic nociceptor activation as a novel pathway of visceral nociception in IBD patients with UC. This work highlights the potential utility of angiotensin receptor blockers, such as valsartan, as treatments for pain in IBD.
What can be learned from viral co-detection studies in human populations
Authors: Chin Taylor , Foxman Ellen F. , Watkins Timothy A. , Lipsitch Marc 
Published: June 2023

AbstractWhen respiratory viruses co-circulate in a population, individuals may be infected with multiple pathogens and experience possible virus-virus interactions, where concurrent or recent prior infection with one virus affects the infection process of another virus. While experimental studies have provided convincing evidence for within-host mechanisms of virus-virus interactions, evaluating evidence for viral interference or potentiation using population-level data has proven more difficult. Recent studies have quantified the prevalence of co-detections using populations drawn from clinical settings. Here, we focus on selection bias issues associated with this study design. We provide a quantitative account of the conditions under which selection bias arises in these studies, review previous attempts to address this bias, and propose unbiased study designs with sample size estimates needed to ascertain viral interference. We show that selection bias is expected in cross-sectional co-detection prevalence studies conducted in clinical settings, except under a strict set of assumptions regarding the relative probabilities of having symptoms under different viral states. Population-wide studies that sample participants irrespective of their symptom status would meanwhile require large sample sizes to be sufficiently powered to detect viral interference, suggesting that a study’s timing, inclusion criteria, and the expected magnitude of interference are instrumental in determining feasibility.
Actin Y53 Phosphorylation Regulates Somatic F-actin Radial Translocation to Promote Neuronal Polarization
Authors: Hong Shuai , Meka Durga Praveen , Kobler Oliver , Scharrenberg Robin , Friedrich Carina Meta , Schwanke Birgit , Richter Melanie , de Anda Froylan Calderon 
Published: June 2023

AbstractHow neurons accomplish the growth of an axon, and several dendrites sequentially is a cellular process not well understood. Here, we show that preferential somatic F-actin delivery to neurites inhibits neurite growth during axon formation. Thus, the neurite receiving less somatic F-actin is growing as an axon. During dendrites outgrowth, radial somatic F-actin translocation into all neurites is drastically diminished suggesting that cellular growth is restricted by the somatic F-actin flow into the growing neurites. Mechanistically, we report that radial somatic F-actin translocation is mediated via the Myosin II motor. Pharmacological inhibition of these molecular motors promotes neurite elongation and precludes F-actin translocation into neurites. Moreover, we show that actin phosphorylation at Y53, which promotes F-actin instability, is enriched selectively in some neurite shafts to exclude/minimize translocation of somatic F-actin only into those neurites. Therefore, enrichment of actin pY53 in the neurite shaft correlates with the longer neurite during axon formation. Accordingly, the Kinesin-1 motor domain, which accumulates transiently in neurites of stage 2 neurons and only in the emerging axon of stage 3 neurons, localizes preferentially in the neurite with the increased actin pY53 signal in the neurite shaft. Finally, we demonstrate that microtubule acetylation promotes actin phosphorylation, and these cytoskeleton modifications coexist in the longest neurite that grows as an axon. Collectively, our data support a model in which somatic F-actin translocation into undifferentiated neurites impedes growth counteracted by actin pY53, consequently, supporting neuronal polarization during axon formation.
Phase-shifting mid-infrared optothermal microscopy for wide-field hyperspectral imaging of living cells
Authors: Yuan Tao , Riobo Lucas , Gasparin Francesca , Ntziachristos Vasilis , Pleitez Miguel A. 
Published: June 2023

AbstractFast live-cell hyperspectral imaging at large field-of-views (FOVs) and high cell confluency remains challenging in vibrational microscopy due to the need for point-by-point focal excitation scanning. Imaging at high cell confluency and large FOVs is important, respectively, for proper cell function and statistical significance of measurements. Here, we introduce phase-shifting mid-infrared optothermal microscopy (PSOM) which interprets molecular-vibrational information as the optical path difference (OPD) induced by mid-infrared absorption and is capable of taking snapshot vibrational images over broad mid-infrared excitation areas at high live-cell confluency. By means of phase-shifting, PSOM suppresses noise to a quarter of current optothermal microscopy modalities to allow capturing live-cell vibrational images at FOVs up to 50 times larger than state-of-the-art. Additionally, it reduces illumination power flux density (PFD) down to 5 orders of magnitude lower than conventional vibrational microscopy—thus, considerably decreasing the possibility of cell photodamage.