bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causes of death following discharge after trauma in North Carolina
Authors: Bryant Mary K. , Aubry Staci , Schiro Sharon , Raff Lauren , Perez Arielle J. , Reid Trista , Maine Rebecca G. 
Published: November 2021

BACKGROUND
While a “fourth peak” of delayed trauma mortality has been described, limited data describe the causes of death (CODs) for patients in the years following an injury. This study investigates the difference in COD statewide for patients with and without a recent trauma admission.

METHODS
This retrospective cohort study compared COD for trauma and nontrauma patients in North Carolina. Death certificates in NC's death registry were matched with the NC trauma registry between January 2013 and December 2018 using matching on name and date of birth. Patients who died during the index trauma admission were excluded. Underlying COD recorded on the death certificate were used for the primary analysis.

RESULTS
Of 481,415 death records, 19,083 (4.0%) were linked to an alive discharge within the trauma registry during the study period. Prior trauma patients (PTPs) had a higher incidence of mental illness (9.2 vs. 6.1%), Alzheimer's (6.1% vs. 4.2%), and opioid-related (1.8% vs. 1.6%) COD compared to nontrauma patients, p < 0.05. Overall, suicide was higher in the nontrauma cohort (1.5% vs. 1.1%); however, PTP had higher incidences of death by motor vehicle collision and other injury (6.0% vs. 3.8%) and homicide (0.9% vs. 0.6%), p < 0.001. Prior trauma patients had 1.16 increased odds of an opioid-related death (p = 0.009; 95% confidence interval, 1.04–1.29) compared with those without prior trauma. Younger PTP had a much higher rate of death from suicide (12.0%) compared with those 41 to 65 years (2.8%) and older than 65 years (0.2%; p < 0.001). Discharge to skilled nursing facility (odds ratio, 1.87; p < 0.05) and severe injury (odds ratio, 1.93; p < 0.05) were associated with early death after discharge (≤90 days).

CONCLUSION
After hospital discharge, PTPs remain at risk of dying from future trauma and opioid-related conditions. Prevention strategies for PTP should address the increased risk of death from a subsequent traumatic injury and the at-risk populations for early death after discharge.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic, Level IV.
Resuscitative endovascular balloon occlusion of the aorta management guided by a novel handheld pressure transducer
Authors: Holtestaul Torbjorg , Jones Ian , Conner Jeffrey , Lammers Daniel , Weiss Jessica , Bingham Jason , Martin Matthew J. , Eckert Matthew 
Published: November 2021

BACKGROUND
Management of noncompressible truncal hemorrhage using resuscitative endovascular balloon occlusion of the aorta (REBOA) requires arterial pressure monitoring that can be logistically challenging in austere or emergency settings. Novel pressure transducer devices such as the Centurion Compass device (CD) (Medline, Northfield, IL) offer an alternative to traditional monitoring systems. We sought to assess the feasibility of maintaining permissive hypotension during intermittent REBOA in a porcine model guided by CD monitoring.

METHODS
Eight Yorkshire swine underwent 20% hemorrhage with an uncontrolled iliofemoral vascular injury. Time-based intermittent zone 1 REBOA was performed with volume-based resuscitation to maintain permissive hypotension. Proximal mean arterial pressures (MAPs) from a carotid arterial line (AL) were obtained and compared with CD readings from the proximal REBOA port. The operator was blinded to AL MAP, and the REBOA was managed with exclusively the CD.

RESULTS
Mean survival time was 100 minutes (range, 41–120 minutes) from injury. Arterial line and CD measurements were closely correlated (r = 0.94, p < 0.001). Bland-Altman analysis for comparison of clinical measurements demonstrated a mean difference of 6 mm Hg (95% confidence interval, −22 to 34 mm Hg) for all MAPs, with a mean difference of 3 mm Hg (95% confidence interval, −6 to 12 mm Hg) in a clinically relevant MAP of <65 mm Hg subset.

CONCLUSION
The CD represents a miniaturized and portable arterial pressure monitor that provides an accurate alternative to logistically burdensome AL monitoring to guide REBOA use. The device is highly accurate even at hypotensive pressures and can be used to guide intermittent REBOA strategies.
We go farther together: practical steps towards conducting a collaborative autoethnographic study
Authors: Ratnapalan Savithiri , Haldane Victoria 
Published: November 2021

ABSTRACT
Autoethnography is an underused qualitative research method in implementation science. Autoethnography can be used to reflect on and archive personal experiences, which can yield useful information to advance our knowledge. In particular, collaborative autoethnography is an important method towards providing greater insights on the experiences of multidisciplinary teams conducting research amidst complexity and intersectionality. In conducting a collaborative autoethnography, all authors are participants who narrate, analyze and theorize about their individual and or collective experiences. This article provides an overview of collaborative autoethnography for health research teams and implementation scientists embarking on autoethnographic studies.
Cryobanking of human distal lung epithelial cells for preservation of their phenotypic and functional characteristics
Authors: Konda Bindu , Mulay Apoorva , Yao Changfu , Israely Edo , Beil Stephen , Huynh Carissa A. , Tourtellotte Warren G. , Rampolla Reinaldo , Chen Peter , Carraro Gianni , Stripp Barry R. 
Published: November 2021

ABSTRACTThe epithelium lining airspaces of the human lung is maintained by regional stem cells including basal cells of pseudostratified airways and alveolar type 2 pneumocytes (AT2) of the alveolar gas-exchange region. Despite effective methods for long-term preservation of airway basal cells, methods for efficient preservation of functional epithelial cell types of the distal gas-exchange region are lacking. Here we detail a method for cryobanking of epithelial cells from either mouse or human lung tissue for preservation of their phenotypic and functional characteristics. Flow cytometric profiling, epithelial organoid-forming efficiency, and single cell transcriptomic analysis, were used to compare cells recovered from cryopreserved tissue with those of freshly dissociated tissue. Alveolar type 2 cells within single cell suspensions of enzymatically digested cryobanked distal lung tissue retained expression of the pan-epithelial marker CD326 and the AT2 cell surface antigen recognized by monoclonal antibody HTII-280, allowing antibody-mediated enrichment and downstream analysis. Isolated AT2 cells from cryobanked tissue were comparable with those of freshly dissociated tissue both in their single cell transcriptome and their capacity for in vitro organoid formation in 3D cultures. We conclude that the cryobanking method described herein allows long-term preservation of distal human lung tissue for downstream analysis of lung cell function and molecular phenotype, and is ideally suited for creation of an easily accessible tissue resource for the research community.
Zika virus-induced TNF-α signaling dysregulates expression of neurologic genes associated with psychiatric disorders
Authors: Kung Po-Lun , Chou Tsui-Wen , Lindman Marissa , Chang Nydia P. , Buckley Benjamin D. , Atkins Colm , Daniels Brian P. 
Published: November 2021

AbstractZika virus (ZIKV) is an emerging flavivirus of global concern. ZIKV infection of the central nervous system has been linked to a variety of clinical syndromes, including microcephaly in fetuses and rare but serious neurologic disease in adults. However, the potential for ZIKV to influence brain physiology and host behavior following recovery from apparently mild or subclinical infection is less well understood. Furthermore, though deficits in cognitive function are well-documented following recovery from neuroinvasive viral infection, the potential impact of ZIKV on other host behavioral domains has not been thoroughly explored. In our study, we performed transcriptomic profiling of primary neuron cultures following ZIKV infection, which revealed altered expression of key genes associated with major psychiatric disorders, such as bipolar disorder and schizophrenia. Gene ontology enrichment analysis also revealed significant changes in gene expression associated with fundamental neurobiological processes, including neuronal development, neurotransmission, and others. These alterations to neurologic gene expression were also observed in the brainin vivousing an immunocompetent mouse model of ZIKV infection. Mechanistic studies identified TNF-α signaling via TNFR1 as a major regulatory mechanism controlling ZIKV-induced changes to neurologic gene expression. Our studies reveal that cell-intrinsic innate immune responses to ZIKV infection profoundly shape neuronal transcriptional profiles, highlighting the need to further explore associations between ZIKV infection and disordered host behavioral states.
The physics of liquid-to-solid transitions in multi-domain protein condensates
Authors: Ranganathan Srivastav , Shakhnovich Eugene 
Published: November 2021

AbstractMany RNA-binding proteins (RBPs) that assemble into membraneless organelles, have a common architecture including disordered prion-like domain (PLD) and folded RNA-binding domain (RBD). An enrichment of PLD within the condensed phase gives rise to formation, on longer time scales, amyloid-like fibrils (aging). In this study, we employ coarse-grained Langevin dynamics simulations to explore the physical basis for the structural diversity in condensed phases of multi-domain RBPs. We discovered a highly cooperative first order transition between disordered structures and an ordered phase whereby chains of PLD organize in fibrils with high nematic orientational order. An interplay between homo-domain (PLD-PLD) and hetero-domain (PLD-RBD) interactions results in variety of structures with distinct spatial architectures. Interestingly, the different structural phases also exhibit vastly different intra-cluster dynamics of proteins, with diffusion coefficients 5 (disordered structures) to 50 times (ordered structures) lower than that of the dilute phase. Cooperativity of this liquid-solid transition makes fibril formation highly malleable to mutations or post-translational modifications. Our results provide a mechanistic understanding of how multi-domain RBPs could form assemblies with distinct structural and material properties.Significance StatementAssembly of proteins and nucleic acids into dense, liquid-like pockets is associated with several key functions including stress response, gene-regulation, DNA-repair and RNA processing. Several RNA binding proteins such as FUS are known to form liquid-like condensates that progressively harden into more dynamically, solid-like structures, a phenomenon that gets accelerated by disease mutations. In this study, we discover the mechanistic origins of this transition and show that small mutational or posttranslational modifications could result in sharp disorder-order transitions that could characterize accelerated liquid-solid transition in disease mutants.
Reconstitution of minimal motility system based on Spiroplasma swimming by expressing two bacterial actins in synthetic minimal bacterium
Authors: Kiyama Hana , Kakizawa Shigeyuki , Sasajima Yuya , Tahara Yuhei O , Miyata Makoto 
Published: November 2021

AbstractMotility is one of the most important features of life, but its evolutionary origin remains unknown. In this study, we focused on Spiroplasma, commensal, or parasitic bacteria. They swim by switching the helicity of a ribbon-like cytoskeleton that comprises six proteins, each of which evolved from a nucleosidase and bacterial actin called MreB. We expressed these proteins in a synthetic, non-motile minimal bacterium, JCVI-syn3.0B, whose reduced genome was computer-designed and chemically synthesized. The synthetic bacterium exhibited swimming motility with features characteristic of Spiroplasma swimming. Moreover, some combinations of the two proteins produced a helical cell shape and swimming, suggesting that the swimming originated from the differentiation and coupling of bacterial actins, and we also obtained a minimal system for motility of the synthetic bacterium.One-Sentence SummaryThe minimal system comprised two bacterial actins that provided cell helicity and swimming to the synthetic minimal bacterium.
Chromatin fiber breaks into clutches under tension and crowding
Authors: Liu Shuming , Lin Xingcheng , Zhang Bin 
Published: November 2021

AbstractThe arrangement of nucleosomes inside chromatin is of extensive interest. While in vitro experiments have revealed the formation of 30 nm fibers, most in vivo studies have failed to confirm their presence in cell nuclei. To reconcile the diverging experimental findings, we characterized chromatin organization using a near atomistic model. The computed force-extension curve matches well with measurements from single-molecule experiments. Notably, we found that a dodeca-nucleosome in the two-helix zigzag conformation breaks into structures with nucleosome clutches and a mix of trimers and tetramers under tension. Such unfolded configurations can also be stabilized through trans interactions with other chromatin chains. Our study supports a hypothesis that disordered, in vivo chromatin configurations arise as folding intermediates from regular fibril structures. We further revealed that chromatin segments with fibril or clutch structures engaged in distinct binding modes and discussed the implications of these inter-chain interactions for a potential sol-gel phase transition.
Temperature-responsive structural reversibility of FGF21 and structure-based design of its variant with enhanced potency
Authors: Jung Ye-Eun , Lee Kyeong Won , Cho Jae Hyun , Bae Da-Woon , Jeong Bo-Gyeong , Jung Yeon-Ju , An Young Jun , Kim Kyungchan , Lee Ga Seul , Kang Lin-Woo , Moon Jeong Hee , Lee Jung-Hyun , Kim Eun-Kyoung , Yim Hyung-Soon , Cha Sun-Shin 
Published: November 2021

AbstractFibroblast growth factor 21 (FGF21) has pharmaceutical potential against obesity-related metabolic disorders, including non-alcoholic fatty liver disease. Since thermal stability is a desirable factor for therapeutic proteins, we investigated the thermal behavior of human FGF21. FGF21 remained soluble after heating; thus, we examined its temperature-induced structural changes using circular dichroism (CD). FGF21 showed inter-convertible temperature-specific CD spectra. The CD spectrum at 100 °C returned to that at 20 °C when the heated FGF21 solution was cooled. Through loop swapping, the connecting loop between β10 and β12 in FGF21 was revealed to be associated with the unique thermal behavior of FGF21. According to in vitro cell-based assays and model high-fat diet (HFD)-induced obesity studies, heated FGF21 maintained biological activities that were comparable to those of non-heated and commercial FGF21s. Based on sequence comparison and structural analysis, five point-mutations were introduced into FGF21. Compared with the wild type, the heated FGF21 variant displayed improved therapeutic potential in terms of body weight loss, the levels of hepatic triglycerides and lipids, and the degree of vacuolization of liver in HFD-fed mice.
Improving Peptide-Protein Docking with AlphaFold-Multimer using Forced Sampling
Authors: Johansson-Åkhe Isak , Wallner Björn 
Published: November 2021

AbstractProtein interactions are key in vital biological process. In many cases, particularly often in regulation, this interaction is between a protein and a shorter peptide fragment. Such peptides are often part of larger disordered regions of other proteins. The flexible nature of peptides enable rapid, yet specific, regulation of important functions in the cell, such as the cell life-cycle. Because of this, understanding the molecular details of these interactions are crucial to understand and alter their function, and many specialized computational methods have been developed to study them.The recent release of AlphaFold and AlphaFold-Multimer has caused a leap in accuracy for computational modeling of proteins. In this study, the ability of AlphaFold to predict which peptides and proteins interact as well as its accuracy in modeling the resulting interaction complexes are benchmarked against established methods in the fields of peptide-protein interaction prediction and modeling. We find that AlphaFold-Multimer consistently produces predicted interaction complexes with a median DockQ of 0.47 for all 112 complexes investigated. Additionally, it can be used to separate interacting from non-interacting pairs of peptides and proteins with ROC-AUC and PR-AUC of 0.78 and 0.61, respectively, best among the method benchmarked.However, the most interestingly result is the possibility to improve AlphaFold by enabling dropout at inference to sample a wider part of the conformational space. This improves the median DockQ from 0.47 to 0.56 for rank 1 and the median best DockQ improves from 0.58 to 0.72. This scheme of generating more structures with AlphaFold should be generally useful for many application involving multiple states, flexible regions and disorder.
Population dynamics underlying associative learning in the dorsal and ventral hippocampus
Authors: Biane Jeremy S. , Ladow Max A. , Stefanini Fabio , Boddu Sayi P. , Fan Austin , Hassan Shazreh , Dundar Naz , Apodaca-Montano Daniel L. , Woods Nicholas I. , Kheirbek Mazen A. 
Published: November 2021

SUMMARYAnimals associate cues with outcomes and continually update these associations as new information is presented. The hippocampus is crucial for this, yet how neurons track changes in cue-outcome associations remains unclear. Using 2-photon calcium imaging, we tracked the same dCA1 and vCA1 neurons across days to determine how responses evolve across phases of odor-outcome learning. We find that, initially, odors elicited robust responses in dCA1, whereas in vCA1 responses emerged after learning, including broad representations that stretched across cue, trace, and outcome periods. Population dynamics in both regions rapidly reorganized with learning, then stabilized into ensembles that stored odor representations for days, even after extinction or pairing with a different outcome. Finally, we found stable, robust signals across CA1 when anticipating reward, but not when anticipating inescapable shock. These results identify how the hippocampus encodes, stores, and updates learned associations, and illuminates the unique contributions of dorsal and ventral hippocampus.
Sleep loss disrupts the neural signature of successful learning
Authors: Guttesen Anna á V. , Gaskell M. Gareth , Madden Emily V. , Appleby Gabrielle , Cross Zachariah R. , Cairney Scott A. 
Published: November 2021

AbstractSleep supports memory consolidation as well as next-day learning. The influential Active Systems account of offline consolidation suggests that sleep-associated memory processing paves the way for new learning, but empirical evidence in support of this idea is scarce. Using a within-subjects (N = 30), crossover design, we assessed behavioural and electrophysiological indices of episodic encoding after a night of sleep or total sleep deprivation in healthy adults (aged 18-25 years), and investigated whether behavioural performance was predicted by the overnight consolidation of episodic associations formed the previous day. Sleep supported memory consolidation and next-day learning, as compared to sleep deprivation. However, the magnitude of this sleep-associated consolidation benefit did not significantly predict the ability to form novel memories after sleep. Interestingly, sleep deprivation prompted a qualitative change in the neural signature of encoding: whereas 12-20 Hz beta desynchronization – an established marker of successful encoding – was observed after sleep, sleep deprivation disrupted beta desynchrony during successful learning. Taken together, these findings suggest that effective learning depends on sleep, but not necessarily sleep-associated consolidation.
Dithiothreitol causes toxicity in C. elegans by modulating the methionine-homocysteine cycle
Authors: G Gokul , Singh Jogender 
Published: November 2021

ABSTRACTThe redox reagent dithiothreitol (DTT) causes stress in the endoplasmic reticulum (ER) by disrupting its oxidative protein folding environment, which results in the accumulation and misfolding of the newly synthesized proteins. DTT may potentially impact cellular physiology by ER-independent mechanisms; however, such mechanisms remain poorly characterized. Using the nematode model Caenorhabditis elegans, here we show that DTT toxicity is modulated by the bacterial diet. Specifically, the dietary component vitamin B12 alleviates DTT toxicity in a methionine synthase-dependent manner. Using a forward genetic screen, we discover that loss-of-function of R08E5.3, an S-adenosylmethionine (SAM)-dependent methyltransferase, confers DTT resistance. DTT upregulates R08E5.3 expression and modulates the activity of the methionine-homocysteine cycle. Employing genetic studies, we establish that DTT toxicity is a result of the depletion of SAM. Finally, we show that a functional IRE-1/XBP-1 unfolded protein response pathway is required to counteract toxicity at high, but not low, DTT concentrations.
Identification of shared bacterial strains in the vaginal microbiota of reproductive-age mothers and daughters using genome-resolved metagenomics
Authors: France M. , Brown S. , Rompalo A. , Brotman R. M. , Ravel J. 
Published: November 2021

AbstractIt has been suggested that the human microbiome might be vertically transmitted from mother to offspring and that early colonizers may play a critical role in development of the immune system. Studies have shown limited support for the vertical transmission of the intestinal microbiota but the derivation of the vaginal microbiota remains largely unknown. Although the vaginal microbiota of children and reproductive age cis women differ in composition, the vaginal microbiota could be vertically transmitted. To determine whether there was any support for this hypothesis, we examined the vaginal microbiota of daughter-mother pairs from the Baltimore metropolitan area (ages 14-27, 32-51; n=39). We assessed whether the daughter’s microbiota was similar in composition to their mother’s using metataxonomics. Permutation tests revealed that while some pairs did have similar vaginal microbiota, the degree of similarity did not exceed that expected by chance. Genome-resolved metagenomics was used to identify shared bacterial strains in a subset of the families (n=22). We found a small number of bacterial strains that were shared between mother-daughter pairs but identified more shared strains between individuals from different families, indicating that vaginal bacteria may display biogeographic patterns. Earlier-in-life studies are needed to demonstrate vertical transmission of the vaginal microbiota.ImportanceEarly colonizers of our microbiota are theorized to play an important role in the development of our immune system, yet we know little about how these communities are established. Vertical transmission from mother to offspring at the time of birth is theorized to be a major source of early colonizers but limited evidence supporting this process has only been shown for the intestinal tract microbiota. The provenance of the vaginal microbiota is largely unknown, although some have posited it is similarly vertically transmitted. We examined the vaginal microbiota of mother-daughter pairs and found limited evidence in support of this hypothesis. However, our analysis also revealed putative biogeographic patterns in the distribution of the strains which comprise the vaginal microbiota. Our results give insight into the role of vertical transmission for the vaginal microbiota and motivate future studies on the biogeography of these bacteria.