bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in the effects of mild traumatic brain injury and progesterone treatment on anxiety-like behavior and fear conditioning in rats
Authors: Fox Laura C. , Scholl Jamie L. , Palmer Geralyn M. , Forster Gina L. , Watt Michael J. 
Published: January 2023

AbstractMild traumatic brain injuries (mild TBIs) commonly occur in young adults of both sexes, oftentimes in high-stress environments. In humans, sex differences have been observed in the development of post-concussive anxiety and PTSD-like behaviors. Progesterone, a sex steroid that has neuroprotective properties, restores cognitive function in animal models following more severe TBI, but its effectiveness in preventing the psychological symptoms associated with mild TBI has not been evaluated. Using a model of mild TBI that pairs a social stressor (social defeat) with weight drop, male and naturally estrous-cycling female rats were treated with 4 mg/kg progesterone or vehicle once daily for 5 days after injury. Behavioral measures, including elevated plus maze (EPM), contextual fear conditioning, and novel object recognition (NOR) were assessed following progesterone treatment. Anxiety-like behavior was increased by mild TBI in male rats, with a smaller effect seen in female rats in the diestrus phase at the time of EPM testing. In contrast, mild TBI impaired fear learning in female rats in estrus at the time of fear acquisition. Progesterone treatment failed to attenuate post-mild TBI anxiety-like behavior in either sex. Furthermore, progesterone increased fear conditioning and impaired NOR discrimination in male rats, independent of TBI status. Overall, both sex and estrous cycle contributed to psychological outcomes following mild TBI, which were not ameliorated by post-TBI progesterone. This suggests sex steroids play an important role as a moderator of the expression of mild TBI-induced psychological symptoms, rather than as a potential treatment for their underlying etiology.
Model-guided Design of Biological Controller for Septic Wound Healing Regulation
Authors: Green Leopold N. , Naghshnejad Pegah , Dankwa Derrick , Tang Xun 
Published: January 2023

AbstractImmune response is critical in septic wound healing. The aberrant and imbalanced signaling dynamics primarily cause a dysfunctional innate immune response, exacerbating pathogen invasion of injured tissue and further stalling the healing process. To design biological controllers that regulate the critical divergence of the immune response during septicemia, we need to understand the intricate differences in immune cell dynamics and coordinated molecular signals of healthy and sepsis injury. Here, we deployed an ordinary differential equation (ODE)-based model to capture the hyper and hypo-inflammatory phases of sepsis wound healing. Our results indicate that impaired macrophage polarization leads to a high abundance of monocytes, M1, and M2 macrophage phenotypes, resulting in immune paralysis. Using a model-based analysis framework, we designed a biological controller which successfully regulates macrophage dysregulation observed in septic wounds. Our model describes a systems biology approach to predict and explore critical parameters as potential therapeutic targets capable of transitioning septic wound inflammation toward a healthy, wound-healing state.
Fly-CURE, a Multi-institutional CURE usingDrosophila, Increases Students’ Confidence, Sense of Belonging, and Persistence in Research
Authors: Merkle Julie A. , Devergne Olivier , Kelly Seth M. , Croonquist Paula A. , Evans Cory J. , Hwalek Melanie A. , Straub Victoria L. , Hamill Danielle R. , Puthoff David P. , Saville Kenneth J. , Siders Jamie L. , Villanueva Gonzalez Zully J. , Wittke-Thompson Jackie K. , Bieser Kayla L. , Stamm Joyce , Vrailas-Mortimer Alysia D. , Kagey Jacob D. 
Published: January 2023

AbstractThe Fly-CURE is a genetics-focused multi-institutional Course-Based Undergraduate Research Experience (CURE) that provides undergraduate students with hands-on research experiences within a course. Through the Fly-CURE, undergraduate students at diverse types of higher education institutions across the United States map and characterize novel mutants isolated from a genetic screen inDrosophila melanogaster. To evaluate the impact of the Fly-CURE experience on students, we developed and validated assessment tools to identify students’ perceived research self-efficacy, sense of belonging in science, and intent to pursue additional research opportunities. Our data show gains in these metrics after completion of the Fly-CURE across all student subgroups analyzed, including comparisons of gender, academic status, racial and ethnic groups, and parents’ educational background. Importantly, our data also show differential gains in the areas of self-efficacy and interest in seeking additional research opportunities between Fly-CURE students with and without prior research experience, illustrating the positive impact of research exposure (dosage) on student outcomes. Altogether, our data indicate that the Fly-CURE experience has a significant impact on students’ efficacy with research methods, sense of belonging to the scientific community, and interest in pursuing additional research experiences.
Assessing assay absorption artefacts inin vitrocell responses to particles
Authors: Yen Seiha , Zosky Graeme R. , Song Yong 
Published: January 2023

AbstractIn this study, we assessed the issue of coal particles absorbing extracellular proteins and tested the effects of different culture conditions and processing strategies to address this issue. Our data show that there is no effective strategy to solve this problem. We agree with previous reports that cytokine binding experiments should be performed to implement appropriate correction factors in order to calculate the accurate production of secreted cytokines in the supernatant of cell culture experiments. This is an underappreciated issue in many published studies on the comparative potency of particles from different sources.
Does the territorial behaviour of the Amur tiger affect the accuracy of occupancy estimation?
Authors: Xie Bing , Gong Yinan , Fu Yanwen , Feng Limin , Yang Haitao 
Published: January 2023

Abstract1. Accurate estimates of wildlife distributions and population persistence are essential for conservation programs. Occupancy models that account for detection probability have been used to characterize the occupancy and habitat selection of imperilled species. However, failure to distinguish between true-presence and pseudo-presence associated with territorial behaviour can result in the overestimation of the occupancy probability of target species in unsuitable habitats, and this can have major implications for the development of conservation strategies.2. For highly territorial wildlife species requiring high-quality habitat for survival, occasional ‘Presence’ in unsuitable areas might be related to dispersal or migration, but this does not reflect actual occupancy and habitat use. ‘True-Presence’ and ‘Pseudo-Presence’ should be distinguished for target species to better reflect their actual occupancy and habitat use.3. To investigate the effect of ‘True-Presence’ and ‘Pseudo-Presence’ on wildlife occupancy estimation, we developed a modified model (Mm) that considers the territorial behaviour of the Amur tiger in northeast China, which distinguished between ‘True-Presence’ and ‘Pseudo-Presence’. We compared two models, Mmand M0(conventional occupancy model), and assessed model performance using goodness-of-fit evaluation, detection and occupancy probability, and favourable variable selection.4. We found that Mm, which has fewer favourable variables, is more powerful than M0for estimating detection and occupancy probability, as well as characterizing the effect of various factors on the habitat use of Amur tigers. Furthermore, Mmsignificantly reduced the overestimation of occupancy probability outside the home range compared with M0, and detection probability estimates did not significantly differ between M0and Mm. Finally, Mmprovided more empirical habitat selection variables for the Amur tiger.5. Our results revealed how ‘True-Presence’ and ‘Pseudo-Presence’ affect the occupancy probability and habitat selection of Amur tigers. Our method improves the accuracy of occupancy models; it can also be used to characterize the habitat selection and distribution of wildlife species and be applied to other territorial species.
Isolation and genomic and physiological characterization ofParageobacillussp. G301, the isolate capable of both hydrogenogenic and aerobic carbon monoxide oxidation
Authors: Imaura Yoshinari , Okamoto Shunsuke , Hino Taiki , Ogami Yusuke , Katayama Yuka Adachi , Tanimura Ayumi , Inoue Masao , Kamikawa Ryoma , Yoshida Takashi , Sako Yoshihiko 
Published: January 2023

AbstractProkaryotes, known as carbon monoxide (CO) oxidizers, use CO as the carbon or energy source with CO dehydrogenases (CODHs), which are divided into nickel-containing CODH (Ni-CODH) that are sensitive to O2and molybdenum-containing CODH (Mo-CODH) that are capable of aerobic functioning. The oxygen conditions for CO oxidizers to oxidize CO may be limited because CO oxidizers isolated and characterized so far have either Ni- or Mo-CODH. Here, we report a novel CO oxidizer capable of CO oxidation with both types of CODH based on genomic and physiological characterization of the isolateParageobacillussp. G301. This thermophilic facultative anaerobic Bacillota bacterium was isolated from the sediment of a freshwater lake. Genomic analyses showed that G301 was the only isolate possessing both Ni-CODH and Mo-CODH. Genome-based reconstruction of the respiratory machinery and physiological investigation indicated that CO oxidation by Ni-CODH was coupled with H2production (proton reduction), and CO oxidation by Mo-CODH was coupled with O2reduction under aerobic conditions and nitrate reduction under anaerobic conditions. G301 would thus be able to thrive via CO oxidation under a wide range of conditions, from aerobic environments to anaerobic environments even without terminal electron acceptors other than protons. As comparative genome analyses revealed no significant differences in genome structures and encoded cellular functions, except for CO oxidation between CO oxidizers and non-CO oxidizers in the genusParageobacillus, CO oxidation genes would be retained exclusively for CO metabolism and related respiration.ImportanceMicrobial CO oxidation has received a lot of attention because it contributes to global carbon cycling in addition to functioning as a remover of CO, which is toxic to many organisms. Microbial CO oxidizers have a punctate phylogenetic distribution throughout bacteria and archaea, even in genus-level monophyletic groups. In this study, we demonstrated that the new isolateParageobacillussp. G301 is capable of both anaerobic (hydrogenogenic) and aerobic CO oxidation, which had not been previously reported. The discovery of this new isolate, which is versatile in CO metabolism, would accelerate research into such CO oxidizers with diverse CO metabolisms, expanding our understanding of microbial diversity. Through comparative genomic analyses, we propose that CO oxidation genes are optional but not essential genetic elements in the genusParageobacillus, providing insight into a factor that shapes the mosaic phylogenetic distribution of CO oxidizers, even in genus-level monophyletic groups.
A chemical probe to modulate human GID4 Pro/N-degron interactions
Authors: Owens Dominic D.G , Maitland Matthew E.R , Yazdi Aliakbar Khalili , Song Xiaosheng , Schwalm Martin P. , Machado Raquel A.C , Bauer Nicolas , Wang Xu , Szewczyk Magdalena M. , Dong Cheng , Dong Aiping , Loppnau Peter , Calabrese Matthew F. , Dowling Matthew S. , Lee Jisun , Montgomery Justin I. , O’Connell Thomas N. , Subramanyam Chakrapani , Wang Feng , Schapira Matthieu , Knapp Stefan , Vedadi Masoud , Min Jinrong , Lajoie Gilles A. , Barsyte-Lovejoy Dalia , Owen Dafydd R. , Schild-Poulter Caroline , Arrowsmith Cheryl H. 
Published: January 2023

AbstractThe CTLH complex is a multi-subunit ubiquitin ligase complex that recognizes substrates with Pro/N-degrons via the substrate receptor GID4. Recently, focus has turned to this complex as a potential mediator of targeted protein degradation, but the role GID4-mediated substrate ubiquitylation and proteasomal degradation plays in humans has thus far remained unclear. Here, we report PFI-7, a potent, selective, and cell-active chemical probe that antagonizes Pro/N-degron binding to human GID4. Use of PFI-7 in proximity-dependent biotinylation enabled the identification of dozens of endogenous GID4-interacting proteins that bind via the GID4 substrate binding pocket, only a subset of which possess canonical Pro/N-degron sequences. GID4 interactors are enriched for nuclear and nucleolar proteins including RNA helicases. GID4 antagonism by PFI-7 altered protein levels of several proteins including RNA helicases as measured by label-free quantitative proteomics, defining proteins that are regulated by GID4 and the CTLH complex in humans. Interactions with GID4 via Pro/N-degron pathway did not result in proteasomal degradation, demonstrating that CTLH interactors are regulated through a combination of degradative and non-degradative functions. The lack of degradation of GID4 interactors highlights potential challenges in utilizing GID4-recruiting bifunctional molecules for targeted protein degradation. Going forward, PFI-7 will be a valuable research tool for defining CTLH complex biology and honing targeted protein degradation strategies.
Harnessing Transcriptomic Signals for Amyotrophic Lateral Sclerosis to Identify Novel Drugs and Enhance Risk Prediction
Authors: Pain Oliver , Jones Ashley , Khleifat Ahmad Al , Agarwal Devika , Hramyka Dzmitry , Karoui Hajer , Kubica Jędrzej , Llewellyn David J. , Ranson Janice M. , Yao Zhi , Iacoangeli Alfredo , Al-Chalabi Ammar 
Published: January 2023

AbstractIntroductionAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. This study integrates the latest ALS genome-wide association study (GWAS) summary statistics with functional genomic annotations with the aim of providing mechanistic insights into ALS risk loci, inferring drug repurposing opportunities, and enhancing prediction of ALS risk and clinical characteristics.MethodsGenes associated with ALS were identified using GWAS summary statistic methodology including SuSiE SNP-based fine-mapping, and transcriptome- and proteome-wide association study (TWAS/PWAS) analyses. Using several approaches, gene associations were integrated with the DrugTargetor drug-gene interaction database to identify drugs that could be repurposed for the treatment of ALS. Furthermore, ALS gene associations from TWAS were combined with observed blood expression in two external ALS case-control datasets to calculate polytranscriptomic scores and evaluate their utility for prediction of ALS risk and clinical characteristics, including site of onset, age at onset, and survival.ResultsSNP-based fine-mapping, TWAS and PWAS identified 117 genes associated with ALS, with TWAS and PWAS providing novel mechanistic insights. Drug repurposing analyses identified five drugs significantly enriched for interactions with ALS associated genes, with directional analyses highlighting α-glucosidase inhibitors may exacerbate ALS pathology. Additionally, drug class enrichment analysis showed calcium channel blockers may reduce ALS risk. Across the two observed expression target samples, ALS polytranscriptomic scores significantly predicted ALS risk (R2= 4%;p-value = 2.1×10−21).ConclusionsFunctionally-informed analyses of ALS GWAS summary statistics identified novel mechanistic insights into ALS aetiology, highlighted several therapeutic research avenues, and enabled statistically significant prediction of ALS risk.
Medication-related adverse events in patients with cancer and discrepancies in cystatin C- versus creatinine-based eGFR
Authors: Hanna Paul E. , Wang Qiyu , Strohbehn Ian , Moreno Daiana , Harden Destiny , Ouyang Tianqi , Katz-Agranov Nurit , Seethapathy Harish , Reynolds Kerry L. , Gupta Shruti , Leaf David E. , Sise Meghan E. 
Published: January 2023

AbstractBackgroundCreatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with cancer. Cystatin C-based eGFR (eGFRCYS) is an alternative marker of kidney function. We investigated whether patients with an eGFR discrepancy, defined as eGFRCYS>30% lower than the concurrent eGFRCRE, had an increased risk of adverse events resulting from renally-cleared medications.Patients and MethodsWe conducted a cohort study of adult patients with cancer who had serum creatinine and cystatin C measured on the same day between May 2010 and January 2022 at two academic cancer centers in Boston, MA. The primary outcome was the incidence of each of the following medication-related adverse events: 1) supratherapeutic vancomycin levels (>30μg/mL); 2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5mEq/L); 3) baclofen-induced neurotoxicity; and 4) supratherapeutic digoxin levels (>2.0ng/mL).Results1988 patients with cancer had simultaneous eGFRCYSand eGFRCRE. The mean age was 66 years (SD±14), 965 (49%) were female, and 1555 (78%) were non-Hispanic white. eGFR discrepancy occurred in 579 patients (29%). Patients with eGFR discrepancy were more likely to experience medication-related adverse events compared to those without eGFR discrepancy: vancomycin levels >30μg/mL (24% vs. 10%, p=0.004), trimethoprim-sulfamethoxazole-related hyperkalemia (24% vs. 12%, p=0.013), baclofen-induced neurotoxicity (25% vs. 0%, p=0.13), and supratherapeutic digoxin levels (38% vs. 0%, p=0.03). The adjusted OR for vancomycin levels >30μg/mL was 2.30 (95% CI 1.05 – 5.51, p = 0.047).ConclusionAmong patients with cancer with simultaneous assessment of eGFRCYSand eGFRCRE, medication-related adverse events occur more commonly in those with eGFR discrepancy. These findings underscore the importance of accurate assessment of kidney function and appropriate dosing of renally-cleared medications in patients with cancer.
Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries
Authors: Andersson Niklas Worm , Thiesson Emilia Myrup , Baum Ulrike , Pihlström Nicklas , Starrfelt Jostein , Faksová Kristýna , Poukka Eero , Meijerink Hinta , Ljung Rickard , Hviid Anders 
Published: January 2023

ABSTRACTBackgroundData on the comparative vaccine effectiveness (CVE) of the bivalent mRNA-booster vaccines containing the original SARS-CoV-2 and omicron BA.4-5 and BA.1 subvariants are limited.MethodsIn a period of BA.4-5 subvariants predominance, we estimated the CVE of the bivalent Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) BA.4-5 and BA.1 mRNA-booster vaccines given as a fourth dose in Denmark, Finland, Norway, and Sweden. From 1 July 2022 to 12 December 2022, we conducted nationwide cohort analyses using target trial emulation to compare risks of Covid-19 hospitalization and death in four-dose (second booster) with three-dose (first booster) vaccinated and between four-dose vaccinated individuals.ResultsCompared with having received three vaccine doses, receipt of a bivalent BA.4-5 booster as a fourth dose was associated with a country-combined CVE against Covid-19 hospitalization of 80.5% (95% confidence interval, 69.5% to 91.5%). The corresponding CVE for bivalent BA.1 boosters was 74.0% (68.6% to 79.4%). CVE against Covid-19 death was 77.8% (48.3% to 100%) and 80.1% (72.0% to 88.2%) for bivalent BA.4-5 and BA.1 boosters as a fourth dose, respectively. The CVE of bivalent BA.4-5 vs. BA.1 boosters were 32.3% (10.6% to 53.9%) for Covid-19 hospitalization and 12.3% (−36.1% to 60.7%) for death (the latter estimable in Denmark only).ConclusionsVaccination with bivalent BA.4-5 or BA.1 mRNA-booster vaccines as a fourth dose was associated with increased protection against Covid-19 hospitalization and death during a period of BA.4-5 predominance. Bivalent BA.4-5 boosters conferred moderately greater vaccine effectiveness against Covid-19 hospitalization compared with bivalent BA.1 boosters.
Management accounting systems and economic sustainability: a qualitative inquiry of SMEs in Pakistan
Authors: Latif Shahid , Izani Mohd Salleh Safrul , Abd. Ghani Mazuri , Ahmad Bilal 
Published: January 2023

PurposeThis qualitative inquiry sheds light on using management accounting systems to address economic sustainability concerns in small and medium enterprises (SMEs) of Pakistan. Building on the dynamic capabilities (DC) theory, this research endeavors to address the recent calls on management accounting and economic sustainability in the context of SMEs.Design/methodology/approachQualitative research design was adopted in which 13 semistructured interviews were conducted with SME owners of Pakistan. The transcribed interviews were coded and thematic analysis was performed via NVIVO-12 to generate themes.FindingsBased on the DC theory, the findings revealed that SME owners in Pakistan use management accounting systems to ensure economic sustainability. The authors found that DC are a co-created phenomenon and refer to them as collective DC. Furthermore, the authors found the theme of accounting literacy which played a critical role in the exhibition of DC in a collective manner.Originality/valueThis is one of the earliest studies on management accounting systems that examine economic sustainability in Pakistani SMEs. This research provides novel insights into the use of management accounting systems in Pakistan from the perspective of DC. In Pakistani SMEs, dynamic capacities are co-created and contingent on accounting literacy.
Upcycled food choice motives and their association with hesitancy towards consumption of this type of food: a Swedish study
Authors: Moshtaghian Hanieh , Bolton Kim , Rousta Kamran 
Published: January 2023

PurposeThis study investigates factors motivating upcycled food choices and assesses the association between these factors and hesitancy towards upcycled food consumption in a Swedish population.Design/methodology/approachAn online food choice questionnaire was used. Participants (n = 682) were categorised into Inclined and Hesitant groups based on their intention to consume upcycled foods. The factors motivating upcycled food choices were identified using explanatory factor analyses. Independent t-tests assessed the differences in the mean importance score of factors between the two groups. The association between upcycled food choice factors and hesitancy towards consumption was evaluated by logistic regressions (adjusted for sociodemographic characteristics).FindingsThe most important upcycled food choice factor in both groups was ethical concerns, followed by natural content, sensory appeal, price, healthiness, familiarity and impression. The Inclined group’s mean importance score for ethical concern was higher than the Hesitant group (pvalue<0.001) and, except for natural content, the mean importance scores for the other factors were higher in the Hesitant group compared to the Inclined group (pvalue<0.05). Participants who perceived ethical concern as an important factor had lower odds of hesitancy (Odds ratio = 0.39; 95%CI:0.26,0.59; pvalue<0.001), and those who considered sensory appeal an important factor had higher odds of hesitancy (Odds ratio = 2.42; 95%CI:1.62,3.63; pvalue<0.001) towards upcycled food consumption compared to participants who did not consider these as important factors.Originality/valueThis is the first study investigating health and non-health-related upcycled food choice motives using a food choice questionnaire. Identifying these motives helps food developers and researchers determine factors influencing upcycled food consumption.