bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated With Increased Mortality in Severe Abdominopelvic Injury
Authors: Patel Neerav , Harfouche Melike , Stonko David P. , Elansary Noha , Scalea Thomas M. , Morrison Jonathan J. 
Published: September 2021

ABSTRACT

Background:
Associated injuries are thought to increase mortality in patients with severe abdominopelvic trauma. This study aimed to identify clinical factors contributing to increased mortality in patients with severe abdominopelvic trauma, with the hypothesis that a greater number of concomitant injuries would result in increased mortality.

Methods:
This was a retrospective review of the Trauma Quality Improvement Program (TQIP) database of patients ≥ 18 years with severe abdominopelvic trauma defined as having an abdominal Abbreviated Injury Score (AIS) ≥ 3 with pelvic fractures and/or iliac vessel injury (2015–2017). Primary outcome was in-hospital mortality based on concomitant body region injuries. Secondary outcomes included mortality at 6 h, 6 to 24 h, and after 24 h based on concomitant injuries, procedures performed, and transfusion requirements.

Results:
A total of 185,257 patients were included in this study. Survivors had more severely injured body regions than non-survivors (4 vs. 3, P < 0.001). Among those who died within 6 h, 28.5% of patients required a thoracic procedure and 43% required laparotomy compared to 6.3% and 22.1% among those who died after 24 h (P < 0.001). Head AIS ≥ 3 was the only body region that significantly contributed to overall mortality (OR 1.26, P < 0.001) along with laparotomy (OR 3.02, P < 0.001), neurosurgical procedures (2.82, P < 0.001) and thoracic procedures (2.28, P < 0.001). Non-survivors who died in < 6 h and 6–24 h had greater pRBC requirements than those who died after 24 h (15.5 and 19.5 vs. 8 units, P < 0.001).

Conclusion:
Increased number of body regions injured does not contribute to greater mortality. Uncontrolled noncompressible torso hemorrhage rather than the burden of concomitant injuries is the major contributor to the high mortality associated with severe abdominopelvic injury.
Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model
Authors: De Wolf Julien , Glorion Matthieu , Jouneau Luc , Estephan Jérôme , Leplat Jean-Jacques , Blanc Fany , Richard Christophe , Urien Céline , Roux Antoine , Le Guen Morgan , Journois Didier , Schwartz-Cornil Isabelle , Sage Edouard 
Published: September 2021

Background.
Normothermic ex vivo lung perfusion (EVLP) increases the pool of donor lungs by requalifying marginal lungs refused for transplantation through the recovery of macroscopic and functional properties. However, the cell response and metabolism occurring during EVLP generate a nonphysiological accumulation of electrolytes, metabolites, cytokines, and other cellular byproducts which may have deleterious effects both at the organ and cell levels, with impact on transplantation outcomes.

Methods.
We analyzed the physiological, metabolic, and genome-wide response of lungs undergoing a 6-h EVLP procedure in a pig model in 4 experimental conditions: without perfusate modification, with partial replacement of fluid, and with adult or pediatric dialysis filters.

Results.
Adult and pediatric dialysis stabilized the electrolytic and metabolic profiles while maintaining acid-base and gas exchanges. Pediatric dialysis increased the level of IL-10 and IL-6 in the perfusate. Despite leading to modification of the perfusate composition, the 4 EVLP conditions did not affect the gene expression profiles, which were associated in all cases with increased cell survival, cell proliferation, inflammatory response and cell movement, and with inhibition of bleeding.

Conclusions.
Management of EVLP perfusate by periodic replacement and continuous dialysis has no significant effect on the lung function nor on the gene expression profiles ex vivo. These results suggest that the accumulation of dialyzable cell products does not significantly alter the lung cell response during EVLP, a finding that may have impact on EVLP management in the clinic.
Assessing the validity of dual-minima algorithm for heel-strike and toe-off prediction for the amputee population
Authors: Aftab Zohaib 
Published: September 2021

AbstractAssessment of gait deficits relies on accurate gait segmentation based on the key gait events of heel strike (HS) and toe-off (TO). Kinematics-based estimation of gait events has shown promise in this regard especially using the leg velocity signal and gyroscopic sensors. However, its validation for the amputee population is not established in the literature. The goal of this study is to assess the accuracy of lower-leg angular velocity signal in determining the TO and HS instants for the amputee population. An open data set containing marker data of 10 subjects with unilateral transfemoral amputation during treadmill walking was used. A rule-based dual-minima algorithm was developed to detect the landmarks in the shank velocity signal indicating TO and HS events. The predictions were compared against the force platform data for 2595 walking cycles from 239 walking trials. Results showed considerable accuracy for the HS with a median error of -1ms. The TO prediction error was larger with the median ranging from 35-84ms. The algorithm consistently predicted the TO earlier than the actual event. Significant differences were found between the prediction accuracy for the sound and prosthetic legs. The prediction accuracy was also affected by the subjects’ mobility level (K-level) but was largely unaffected by gait speed. In conclusion, the leg velocity profile during walking can predict the heel-strike and toe-off events for the transfemoral amputee population with varying degrees of accuracy depending upon the leg side and amputee’s functional ability level.
VaxArray Immunoassay for the Multiplexed Quantification of Poliovirus D-Antigen
Authors: Dawson Erica D. , Taylor Amber W. , Johnson James E. , Hu Tianjing , McCormick Caitlin , Thomas Keely N. , Gao Rachel Y. , Wahid Rahnuma , Mahmood Kutub , Rowlen Kathy L. 
Published: September 2021

ABSTRACTNext generation poliovirus vaccines are critical to reaching global poliovirus eradication goals. Recent efforts have focused on creating inactivated vaccines using attenuated Sabin strains that maintain patient safety benefits and immunogenicity of conventional inactivated vaccines while increasing manufacturing safety and lowering production costs, and on developing novel oral vaccines using modified Sabin strains that provide critical mucosal immunity but are further attenuated to minimize risk of reversion to neurovirulence. In addition, there is a push to improve the analytical tools for poliovirus vaccine characterization. Conventional and Sabin inactivated poliovirus vaccines typically rely on standard plate-based ELISA as in vitro D-antigen potency assays in combination with WHO international standards as calibrants. While widely utilized, the current D-antigen ELISA assays have a long time to result (up to 72 hours), can suffer from lab-to-lab inconsistency due to non-standardized protocols and reagents, and are inherently singleplex. For D-antigen quantitation, we have developed the VaxArray Polio Assay Kit, a multiplexed, microarray-based immunoassay that uses poliovirus-specific human monoclonal antibodies currently under consideration as standardized reagents for characterizing inactivated Sabin and Salk vaccines. The VaxArray assay can simultaneously quantify all 3 poliovirus serotypes with a time to result of less than 3 hours. Here we demonstrate that the assay has limits of quantification suitable for both bioprocess samples and final vaccines, excellent reproducibility and precision, and improved accuracy over an analogous plate-based ELISA. The assay is suitable for adjuvanted combination vaccines, as common vaccine additives and crude matrices do not interfere with quantification, and is intended as a high throughput, standardized quantitation tool to aid inactivated poliovirus vaccine manufacturers in streamlining vaccine development and manufacturing, aiding the global polio eradication effort.
Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails
Authors: Liu Yusheng , Nie Hu , Sun Rongrong , Wang Jiaqiang , Lu Falong 
Published: September 2021

SUMMARYIn vitro transcribed (IVT) mRNA represents a new class of drug in both therapeutics and vaccines. Improving the translation efficiency of IVT mRNA remains a core challenge for mRNA-based applications. Here, using IVT mRNAs with poly(A) tails containing non-A residues which were recently revealed to be widespread in RNA poly(A) tails1,2, we unexpectedly find that non-A residues can effectively promote the mRNA translation. To further support our finding, we provide evidence that non-A residues associated with enhanced mRNA translation efficiency transcriptome-wide in mouse and human cells. Together, our study provides a novel approach to enhance mRNA translation efficiency by inclusion of non-A residues in the mRNA poly(A) tails, holding great potential to promote mRNA-based therapeutics and vaccines.
Frontal cortex activity underlying the production of diverse vocal signals during social communication in marmoset monkeys
Authors: Zhao Lingyun , Wang Xiaoqin 
Published: September 2021

AbstractVocal communication is essential for social behaviors in humans and many non-human primates. While the frontal cortex has been shown to play a crucial role in human speech production, its role in vocal production in non-human primates has long been questioned. Recent studies have shown activation in single neurons in the monkey frontal cortex during vocal production in relatively isolated environment. However, little is known about how the frontal cortex is engaged in vocal production in ethologically relevant social context, where different types of vocal signals are produced for various communication purposes. Here we studied single neuron activities and local field potentials (LFP) and in the frontal cortex of marmoset monkeys while the animal engaged in vocal exchanges with other conspecifics in a social environment. Marmosets most frequently produced four types of vocalizations with distinct acoustic structures, three of which were typically not produced in isolation. We found that both single neuron activities and LFP were modulated by the production of each of the four call types. Moreover, the neural modulations in the frontal cortex showed distinct patterns for different call types, suggesting a representation of vocal signal features. In addition, we found that theta-band LFP oscillations were phase-locked to the phrases of twitter calls, which indicates the coordination of temporal structures of vocalizations. Our results suggested important functions of the marmoset frontal cortex in supporting the production of diverse vocalizations in vocal communication.
Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
Authors: Atabaki-Pasdar Naeimeh , Pomares-Millan Hugo , Koivula Robert W , Tura Andrea , Brown Andrew , Viñuela Ana , Agudelo Leandro , Coral Daniel , van Oort Sabine , Allin Kristine , Chabanova Elizaveta , Cederberg Henna , De Masi Federico , Elders Petra , Tajes Juan Fernandez , Forgie Ian M , Hansen Tue H , Heggie Alison , Jones Angus , Kokkola Tarja , Mahajan Anubha , McDonald Timothy J , McEvoy Donna , Tsirigos Konstantinos , Teare Harriet , Vangipurapu Jagadish , Vestergaard Henrik , Adamski Jerzy , Beulens Joline WJ , Brunak Søren , Dermitzakis Emmanouil , Hansen Torben , Hattersley Andrew T , Laakso Markku , Pedersen Oluf , Ridderstråle Martin , Ruetten Hartmut , Rutters Femke , Schwenk Jochen M , Walker Mark , Giordano Giuseppe N , Ohlsson Mattias , Gupta Ramneek , Mari Andrea , McCarthy Mark I , Thomas E Louise , Bell Jimmy D , Pavo Imre , Pearson Ewan R , Franks Paul W 
Published: September 2021

ABSTRACTType 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.
Temporal stability and state-dependence of retrospective self-reports of childhood maltreatment in major depression: a two-year longitudinal analysis of the childhood trauma questionnaire
Authors: Goltermann Janik , Meinert Susanne , Hülsmann Carina , Dohm Katharina , Grotegerd Dominik , Redlich Ronny , Waltemate Lena , Lemke Hannah , Thiel Katharina , Mehler David M. A. , Enneking Verena , Borgers Tiana , Repple Jonathan , Gruber Marius , Winter Nils , Hahn Tim , Brosch Katharina , Meller Tina , Ringwald Kai G. , Schmitt Simon , Stein Frederike , Pfarr Julia-Katharina , Krug Axel , Nenadić Igor , Kircher Tilo , Opel Nils , Dannlowski Udo 
Published: September 2021

AbstractBackgroundRetrospective self-reports of childhood maltreatment are widely used in research and clinical practice. However, their validity has been questioned due to potential depressive bias. Yet, systematic investigations of this matter are sparse. Thus, we investigate if and to what extent retrospective maltreatment reports vary in relation to longitudinal changes in depressive symptomatology.MethodsTwo-year temporal stability of maltreatment reports was assessed via the Childhood Trauma Questionnaire (CTQ). Diagnosis and depressive symptoms were assessed using clinical interview and the Beck Depression Inventory. From two independent cohorts (MACS and MNC) we included a total of n=347 major depressive disorder (MDD) patients, n=419 healthy controls (HC), and a subsample with a lifetime first depressive episode between both assessments (n=27). Analysis plan and hypotheses were preregistered prior to data sighting.ResultsMaltreatment reports were highly stable in HC and MDD patients across both cohorts (ICC=.956; 95%-CI[.949, .963] and ICC=.950; 95%-CI[.933, .963]) and temporal stability did not differ between groups. Stability was lower for cutoff-based maltreatment categorization (K=.551; 95%-CI[.479, .622] and K=.507; 95%-CI[.371, .640]). Baseline maltreatment reports were associated with concurrent and future depression severity. However, longitudinal changes in depression severity predicted variability in CTQ scores only to a small extent across cohorts (b=0.101, p=.009, R2=.021 and b=0.292, p=.320), with the effect being driven by emotional maltreatment subscales.ConclusionsFindings suggest that the CTQ provides temporally stable self-reports of childhood maltreatment in healthy and depressed populations, and are only marginally biased by depressive symptomatology. Gradual rather than categorical conceptualization of maltreatment is advised for improving psychometric quality.
COVID-19 scenarios for comparing the effectiveness of age-specific vaccination regimes, exemplified for the city of Aschaffenburg (Germany)
Authors: Krebs Tobias , von Jouanne-Diedrich Holger , Moeckel Michael J. 
Published: September 2021

AbstractPurpose of this reportThe purpose of this rapid communication is to illustrate the effectiveness of different vaccination regimes for controlling the number of severe and critical COVID-19 cases in the city of Aschaffenburg, Germany. Our results show that, despite numerous vaccinations in the past, further vaccinations are necessary to immunize the population and to keep the number of severe and critical cases low in the coming months. Considering that not all people can or want to receive vaccination, we compare different age-specific vaccination approaches.Applied MethodsWe use the agent-based epidemiological simulator Covasim for discussing the impact of different vaccination strategies. We calibrate it to reproduce the historical course of the COVID-19 pandemic in the city of Aschaffenburg, Germany; for this, we model and integrate numerous public health interventions imposed on the local population. As for some of the political actions rigorous quantification is currently not available, we fit those unknown (free) model parameters to published data on the measured epidemiological dynamics. Then we calculate the state of immunization of the population, gained through infections and vaccinations, at any time in the past, including models for time-dependent immunity decay that have been made available in Covasim. Finally, we define and compare scenarios of different vaccination regimes, especially with regard to vaccinating adolescents and providing booster vaccinations to the elderly.Key messageWithout further vaccinations, we expect a strong increase in severe and critical cases. In order to restrict their growth our simulations suggest that in all considered cases vaccinations of unvaccinated people is more effective than booster vaccinations for already fully vaccinated people. This applies even to vaccinations of young people who are not themselves at high risk of developing severe or critical illness. We attribute this observation to the fact that immunization of adolescents indirectly protects vulnerable age groups by preventing the spread of the virus more effectively than further immunizing other age groups. This indicates that with the pandemic ongoing, strategies focussed on minimizing individual health risks by vaccinations may no longer coincide with those needed to minimize the number of severe and critical cases.
Health impact and cost of COVID-19 prophylaxis with monoclonal antibodies
Authors: Flaxman Abraham D. , Issema Rodal , Barnabas Ruanne V. , Ross Jennifer M. 
Published: September 2021

AbstractBackgroundThe COVID-19 pandemic has led to over 600,000 deaths in the United States and continues to disrupt lives even as effective vaccines are available. We aimed to estimate the impact and health system cost of implementing post-exposure prophylaxis against household exposure to COVID-19 with monoclonal antibodies.MethodsWe developed a decision-analytical model analysis of results from a recent randomized controlled trial with complementary data on household demographic structure, vaccine coverage, and COVID-19 confirmed case counts for the representative month of May, 2021. The model population includes individuals of all ages in the United States by sex and race/ethnicity.ResultsIn a month of similar intensity to May, 2021, in the USA, a monoclonal antibody post-exposure prophylaxis program reaching 50% of exposed unvaccinated household members aged 50+, would avert 1,813 (1,171 – 2,456) symptomatic infections, 526 (343 - 716) hospitalizations, and 83 (56 - 116) deaths. Assuming the unit cost of administering the intervention was US$ 1,264, this program would save the health system US$ 3,055,202 (−14,034,632 - 18,787,692).ConclusionsCurrently in the United States, health system and public health actors have an opportunity to improve health and reduce costs through COVID-19 post-exposure prophylaxis with monoclonal antibodies.
Bone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Bone
Authors: Tian Zeru , Yu Chenfei , Zhang Weijie , Wu Kuan-lin , Gupta Ruchi , Xu Zhan , Wu Ling , Chen Yuda , Zhang Xiang H. -F. , Xiao Han 
Published: September 2021

AbstractTherapeutic antibodies have gone a long way toward realizing their clinical potential and have become very useful for treating a variety of pathologies. Despite the rapid evolution of therapeutic antibodies, their clinical efficacy in treatment of bone tumors has been hampered by the inadequate pharmacokinetics and poor bone tissue accessibility of these large macromolecules. Here, we show that engineering therapeutic antibodies to include bone-homing peptide sequences dramatically enhances their concentration in the bone metastatic niche, resulting in significantly reduced survival and progression of breast cancer bone metastases. To enhance the bone tumor-targeting ability of engineered antibodies, we introduced varying numbers of a bone-homing peptide into permissive internal sites of the anti-HER2 antibody trastuzumab. Compared to the unmodified antibody, the engineered bone-targeting antibodies have similar pharmacokinetics andin vitrocytotoxic activity against HER2-positive cancer cells, but exhibit improved bone tumor distributionin vivo. Accordingly, in xenograft models of breast cancer metastasis to bone sites, engineered antibodies with enhanced bone specificity exhibit increased inhibition of both initial bone metastases and secondary multi-organ metastases from bone lesions. Furthermore, this engineering strategy is also applied to prepare bone-targeting antibody-drug conjugates with enhanced therapeutic efficacy. These results demonstrate that adding bone-specific targeting to antibody therapy results in robust delivery of therapeutic antibodies to the bone tumor niche. This provides a powerful strategy for overcoming inadequate treatment of bone cancer and the development of potentially acquired resistance to therapy.
Breast tumor Insulin-like growth factor receptor regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics
Authors: Obr Alison E. , Chang Yung-Jun , Ciliento Virginia , Lemenze Alexander , Maingrette Krystopher , Bulatowicz Joseph J. , Shang Quan , Gallagher Emily , LeRoith Derek , Wood Teresa L. 
Published: September 2021

AbstractThe acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer, low levels of IGF-1R expression are associated with worse overall patient survival. To determine how reduced IGF-1R impacts tumor phenotype, we used weighted gene correlation network analysis (WGCNA) of METABRIC patient data and identified gene modules specific to cell cycle, adhesion, and immune cell signaling inversely correlated with IGF-1R expression in human breast cancers. Integration of human patient data with data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like tumors with reduced signaling or expression of the IGF-1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.