bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liproxstatin-1 Alleviates Lung Transplantation-induced Cold Ischemia–Reperfusion Injury by Inhibiting Ferroptosis
Authors: Zhao Jin , Li Jiawei , Wei Dong , Gao Fei , Yang Xiucheng , Yue Bingqing , Xiong Dian , Liu Mingzhao , Xu Hongyang , Hu Chunxiao , Chen Jingyu 
Published: May 2023

Background.
Primary graft dysfunction, which is directly related to cold ischemia–reperfusion (CI/R) injury, is a major obstacle in lung transplantation (LTx). Ferroptosis, a novel mode of cell death elicited by iron-dependent lipid peroxidation, has been implicated in ischemic events. This study aimed to investigate the role of ferroptosis in LTx-CI/R injury and the effectiveness of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, in alleviating LTx-CI/R injury.

Methods.
LTx-CI/R-induced signal pathway alterations, tissue injury, cell death, inflammatory responses, and ferroptotic features were examined in human lung biopsies, the human bronchial epithelial (BEAS-2B) cells, and the mouse LTx-CI/R model (24-h CI/4-h R). The therapeutic efficacy of Lip-1 was explored and validated both in vitro and in vivo.

Results.
In human lung tissues, LTx-CI/R activated ferroptosis-related signaling pathway, increased the tissue iron content and lipid peroxidation accumulation, and altered key protein (GPX4, COX2, Nrf2, and SLC7A11) expression and mitochondrial morphology. In BEAS-2B cells, the hallmarks of ferroptosis were significantly evidenced at the setting of both CI and CI/R compared with the control, and the effect of adding Lip-1 only during CI was much better than that of only during reperfusion by Cell Counting Kit-8. Furthermore, Lip-1 administration during CI markedly relieved LTx-CI/R injury in mice, as indicated by significant improvement in lung pathological changes, pulmonary function, inflammation, and ferroptosis.

Conclusions.
This study revealed the existence of ferroptosis in the pathophysiology of LTx-CI/R injury. Using Lip-1 to inhibit ferroptosis during CI could ameliorate LTx-CI/R injury, suggesting that Lip-1 administration might be proposed as a new strategy for organ preservation.
Evaluation of the Modified Oxford Score in Recurrent IgA Nephropathy in North American Kidney Transplant Recipients: The Banff Recurrent Glomerulonephritis Working Group Report
Authors: Alachkar Nada , Delsante Marco , Greenberg Ross S. , Koirala Abbal , Alhamad Tarek , Abdalla Basmah , Anand Manish , Boonpheng Ben , Blosser Christopher , Maggiore Umberto , Bagnasco Serena M. 
Published: May 2023

Background.
The modified Oxford classification mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents (MEST-C) of immunoglobulin A nephropathy (IgAN) was recently shown to be a predictor of graft failure in Asians with recurrent IgAN. We aimed to validate these findings in a cohort from North American centers participating in the Banff Recurrent Glomerulopathies Working Group.

Methods.
We examined 171 transplant recipients with end-stage kidney disease because of IgAN; 100 of them with biopsy-proven recurrent IgAN (57 of them had complete MEST-C scores) and 71 with no recurrence.

Results.
IgAN recurrence, which was associated with younger age at transplantation (P = 0.012), strongly increased the risk of death-censored graft failure (adjusted hazard ratio, 5.10 [95% confidence interval (CI), 2.26-11.51]; P < 0.001). Higher MEST-C score sum was associated with death-censored graft failure (adjusted hazard ratio, 8.57 [95% CI, 1.23-59.85; P = 0.03] and 61.32 [95% CI, 4.82-779.89; P = 0.002] for score sums 2–3 and 4–5 versus 0, respectively), and so were the single components endocapillary hypercellularity, interstitial fibrosis/tubular atrophy, and crescents (P < 0.05 each). Overall, most of the pooled adjusted hazard ratio estimates associated with each MEST-C component were consistent with those from the Asian cohort (heterogeneity I
2 close to 0%, and P > 0.05).

Conclusions.
Our findings may validate the prognostic usefulness of the Oxford classification for recurrent IgAN and support the inclusion of the MEST-C score in allograft biopsies diagnostic reports.
Novosphingobium mangrovi sp. nov., isolated from mangrove sediment
Authors: Huang Qian , Qian Zhihui , Peng Tao , Li Jin , Ye Xueying , Huang Tongwang , Hu Zhong 
Published: May 2023

A novel Gram-stain-negative, aerobic and rod-shaped bacterial strain, designated as HK4-1T, was isolated from mangrove sediments in Hong Kong, PR China. Based on 16S rRNA gene sequence data, strain HK4-1T was found to belong to the genus

Novosphingobium

, family

Erythrobacteraceae

, and showed high similarity to

Novosphingobium chloroacetimidivorans

BUT-14T (96.88 %) and

Novosphingobium indicum

H25T (96.88 %). The G+C content of the whole genome of strain HK4-1T was 64.05 mol%. The major fatty acids were C16 : 0, C18 : 1
ω7c and summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, sphingoglycolipid and two unknown lipids. The predominant respiratory quinone was Q-10. Based on genomic, phylogenetic, phenotypic, physiological and chemotaxonomic data, strain HK4-1T should be classified as representing a novel species of the genus

Novosphingobium

, for which the name Novosphingobium mangrovi sp. nov. is proposed. The type strain of Novosphingobium mangrovi sp. nov. is HK4-1T (=MCCC 1K08252T=JCM 35764T).
Risk factor profiles of young women with vasomotor non-obstructive versus obstructive coronary syndromes: Importance of non-traditional and sex-specific risk factors
Authors: Théberge Emilie T. , Vikulova Diana N. , Pimstone Simon N. , Brunham Liam R. , Humphries Karin H. , Sedlak Tara L. 
Published: May 2023

BackgroundHeart disease is the leading cause of premature death for women in Canada. Ischemic heart disease (IHD) is categorized as myocardial infarction (MI) with no obstructive coronary artery disease (MINOCA), ischemia with no obstructive coronary arteries (INOCA), and atherosclerotic obstructive coronary artery disease (CAD) with MI (MI-CAD) or without MI (non-MI CAD). This study aims to study the prevalence of traditional and non-traditional IHD risk factors and their relationships with (M)INOCA compared to MI-CAD and non-MI CAD in young women.MethodsThis study investigated women who presented with premature (≤55 years old) vasomotor entities of (M)INOCA or obstructive CAD confirmed by coronary angiography, who are currently enrolled in either the Leslie Diamond Women’s Heart Health Clinic Registry (WHC) or the Study to Avoid cardioVascular Events in BC (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M)INOCA, MI-CAD or non-MI CAD.ResultsA total of 254 women enrolled between 2015-2022 were analyzed: 77 INOCA and 37 MINOCA from the WHC and 66 with non-MI CAD and 74 MI-CAD from SAVEBC. Regression analyses demonstrated that migraines and preeclampsia/gestational hypertension were the most significant risk factors with higher likelihood to associate with premature (M)INOCA relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood to associate with premature CAD.ConclusionThere are significant differences in the risk factor profiles of patients with premature (M)INOCA compared to obstructive CAD.
Insights into adipokinetic hormone/corazonin-related peptide receptor specificity and key residues for its activation in the human disease vectorAedes aegyptimosquito
Authors: Afifi Salwa , Paluzzi Jean-Paul 
Published: May 2023

AbstractAdipokinetic hormone/corazonin-related peptide (ACP) and adipokinetic hormone (AKH) are two neuropeptides that demonstrate homology to the vertebrate gonadotropin-releasing hormone (GnRH). Despite the structural similarity and the close evolutionary relationship between the ACP and the AKH, their signaling systems function independently. To date, the role of ACP and its receptor (ACPR) remains unclear in theAedes aegyptimosquito. Structure-activity relationships (SARs) are often carried out on peptide ligands to determine critical residues for bioactivity and receptor activation; however, residues and features necessary for ligand binding and specificity in the receptors themselves are less studied. Herein, this study focuses on the ACP and AKH signaling systems and examines structural features of their receptors critical for conferring activation and ligand specificity. Firstly, to determine the specific ACPR regions most critical for ligand fidelity and specificity, ACPR chimeras were created by singly replacing each of the three ACPR extracellular loops (ECLs) in their entirety and incorporating the corresponding ECLs from the AKH receptor (AKHR). Heterologous functional assays determined that the three ACPR ECL chimera receptors with complete replacement of full individual ECLs showed no response to either ACP or AKH. These results suggest that the complete replacement of each individual extracellular loop is detrimental to ligand binding and recognition. Secondly, through a more targeted approach, we aimed to determine specific residues critical for functional ligand-binding by substituting only select highly conserved residues within the three ECLs of the ACPR with those from the AKHR. Modifications of specific and highly conserved residues in these ACPR ECLs chimeras suggest that the third extracellular loop contains the most critical residues necessary for ACP binding and receptor activation. In addition, the combination of two selectively-modified ACPR ECLs demonstrated a significant decrease in response to ACP compared to the native ACPR response. Interestingly, combining all of the ACPR ECLs chimeras together resulted in a significant decrease in response to ACP compared to native ACPR. Relatedly, a significantly increased response to AKH was observed in the receptor chimera combining selected modifications in all three ECLs compared to native ACPR. Hence, the particular residues essential for ACP ligand interaction were identified due to the detrimental effect that occurred in ACPR activation after the selective modification of crucial residues localized within the three extracellular domains of the receptor. These data provide key insight into how these two closely related neuropeptidergic systems maintain functional independence in the mosquitoA. aegyptias well as other insects.
External validation of the CAST and rCAST score in patients with out-of-hospital cardiac arrest who underwent ECPR: A secondary analysis of the SAVE-J II study
Authors: Misumi Kayo , Hagiwara Yoshihiro , Kimura Takuya , Hifumi Toru , Inoue Akihiko , Sakamoto Tetsuya , Kuroda Yasuhiro , Ogura Takayuki 
Published: May 2023

AbstractBackgroundRisk stratification is important in patients with postcardiac arrest syndrome (PCAS). The post-Cardiac Arrest Syndrome for Therapeutic hypothermia (CAST) and revised CAST (rCAST) scores have been well validated for predicting the accuracy of neurological outcomes, particularly for conventionally resuscitated PCAS patients. However, no studies have evaluated patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).MethodsAdult patients with out-of-hospital cardiac arrest (OHCA) who underwent ECPR were analyzed in this retrospective observational multicenter cohort study (SAVE-J II study). We validated the accuracy of the CAST and rCAST scores for predicting favorable neurological outcomes (cerebral performance category 1 or 2) at 30 days. Moreover, we compared the predictive performance of these CAST/rCAST scores with those of the previously documented TiPS65 risk model derived from patients with OHCA who were resuscitated using ECPR.ResultsA total of 1135 patients were analyzed. Their median age was 60 years and males comprised 84% of the cohort. The proportion of patients with favorable neurological outcomes was 16.6% overall. In the external validation, the area under the curve (AUC) of the CAST score was numerically larger than those of the rCAST and TiPS65 scores (AUC 0.677 vs. 0.603: p < 0.001, vs. 0.633: p = 0.154, respectively). Both CAST/rCAST risk scores showed good calibration (Hosmer– Lemeshow test: p = 0.726 and 0.674, respectively). Furthermore, the CAST score showed significantly better predictability in net reclassification than did the rCAST (p < 0.001) and TiPS65 scores (p = 0.001).ConclusionsCAST and rCAST scores can predict neurological outcomes in patients with OHCA who undergo ECPR. The prognostic accuracy of the CAST score was significantly better than that of other pre-existing risk prediction models.IRB informationThe present study was approved by the institutional review board of Kagawa University (approval number: 2018-110)Clinical trial registrationhttps://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577(unique identifier: UMIN000036490)
Pseudogenes as a neutral reference for detecting selection in prokaryotic pangenomes
Authors: Douglas Gavin M. , Shapiro B. Jesse 
Published: May 2023

AbstractA long-standing question is to what degree genetic drift and selection drive the divergence in rare accessory gene content between closely related bacteria. Rare genes, including singletons, make up a large proportion of pangenomes (the set of all genes in a set of genomes), but it remains unclear how many such genes are adaptive, deleterious, or neutral to their host genome. Estimates of species’ effective population sizes (Ne) are positively associated with pangenome size and fluidity, which has independently been interpreted as evidence for both neutral and adaptive pangenome models. We hypothesised that pseudogenes, used as a neutral reference, could be used to distinguish these models. We find that most functional categories are depleted for rare pseudogenes when a genome encodes only a single intact copy of a gene family. In contrast, transposons are enriched in pseudogenes, suggesting they are mostly neutral or deleterious to the host genome. Thus, even if individual rare accessory genes vary in their effects on host fitness, we can confidently reject a model of entirely neutral or deleterious rare genes. We also define the ratio of singleton intact genes to singleton pseudogenes (si/sp) within a pangenome, compare this measure across 668 prokaryotic species, and detect a signal consistent with the adaptive value of many rare accessory genes. Taken together, our work demonstrates that comparing to pseudogenes can improve inferences of the evolutionary forces driving pangenome variation.
Examining intra-host genetic variation of RSV by short read high-throughput sequencing
Authors: Henke David , Piedra Felipe-Andrés , Avadhanula Vasanthi , Doddapaneni Harsha , Muzny Donna M. , Menon Vipin K. , Hoffman Kristi L. , Ross Matthew C. , Javornik Cregeen Sara J. , Metcalf Ginger , Gibbs Richard A. , Petrosino Joseph F. , Piedra Pedro A. 
Published: May 2023

AbstractEvery viral infection entails an evolving population of viral genomes. High-throughput sequencing technologies can be used to characterize such populations, but to date there are few published examples of such work. In addition, mixed sequencing data are sometimes used to infer properties of infecting genomes without discriminating between genome-derived reads and reads from the much more abundant, in the case of a typical active viral infection, transcripts. Here we apply capture probe-based short read high-throughput sequencing to nasal wash samples taken from a previously described group of adult hematopoietic cell transplant (HCT) recipients naturally infected with respiratory syncytial virus (RSV). We separately analyzed reads from genomes and transcripts for the levels and distribution of genetic variation by calculating per position Shannon entropies. Our analysis reveals a low level of genetic variation within the RSV infections analyzed here, but with interesting differences between genomes and transcripts in 1) average per sample Shannon entropies; 2) the genomic distribution of variation ‘hotspots’; and 3) the genomic distribution of hotspots encoding alternative amino acids. In all, our results suggest the importance of separately analyzing reads from genomes and transcripts when interpreting high-throughput sequencing data for insight into intra-host viral genome replication, expression, and evolution.
PenTag, a Versatile Platform for Synthesizing Protein-Polymer Biohybrid Materials
Authors: Mohsenin Hasti , Pacheco Jennifer , Kemmer Svenja , Wagner Hanna J. , Höfflin Nico , Bergmann Toquinha , Baumann Tim , Jerez-Longres Carolina , Ripp Alexander , Jork Nikolaus , Jessen Henning J. , Fussenegger Martin , Köhn Maja , Timmer Jens , Weber Wilfried 
Published: May 2023

AbstractThe site-specific and covalent conjugation of proteins on solid supports and in hydrogels is the basis for the synthesis of biohybrid materials offering broad applications. Current methods for conjugating proteins to desired targets are often challenging due to unspecific binding, unstable (non-covalent) coupling, or expensive and difficult-to-synthesize ligand molecules. Here, we present PenTag, an approach for the biorthogonal, highly-specific and covalent conjugation of a protein to its ligand for various applications in materials sciences. We engineered penicillin- binding protein 3 (PBP3) and showed that this protein can be used for the stable and spontaneous conjugation of proteins to dyes, polymers, or solid supports. We applied PenTag as a crosslinking tool for synthesizing stimuli-responsive hydrogels or for the development of a biohybrid material system performing computational operations emulating a 4:2 encoder. Based on this broad applicability and the use of a small, cheap and easy-to-functionalize ligand and a stable, soluble recombinant protein, we see PenTag as a versatile approach towards biohybrid material synthesis.
Neural representations of economic decision variables in human posterior parietal cortex
Authors: Klaes Christian , Pilacinski Artur , Kellis Spencer , Aflalo Tyson , Liu Charles , Andersen Richard 
Published: May 2023

AbstractDecision making has been intensively studied in the posterior parietal cortex in non-human primates on a single neuron level. In humans decision making has mainly been studied with psychophysical tools or with fMRI. Here, we investigated how single neurons from human posterior parietal cortex represent numeric values informing future decisions during a complex two-player game. The tetraplegic study participant was implanted with a Utah electrode array in the anterior intraparietal area (AIP). We played a simplified variant of Black Jack with the participant while neuronal data was recorded. During the game two players are presented with numbers which are added up. Each time a number is presented the player has to decide to proceed or to stop. Once the first player stops or the score reaches a limit the turn passes on to the second player who tries to beat the score of the first player. Whoever is closer to the limit (without overshooting) wins the game. We found that many AIP neurons selectively responded to the face value of the presented number. Other neurons tracked the cumulative score or were selectively active for the upcoming decision of the study participant. Interestingly, some cells also kept track of the opponent’s score. Our findings show that parietal regions engaged in hand action control also represent numbers and their complex transformations. This is also the first demonstration of complex economic decisions being possible to track in single neuron activity in human AIP. Our findings show how tight are the links between parietal neural circuits underlying hand control, numerical cognition and complex decision-making.
Correlating Deep Learning-Based Automated Reference Kidney Histomorphometry with Patient Demographics and Creatinine
Authors: Ginley Brandon , Lucarelli Nicholas , Zee Jarcy , Jain Sanjay , Han Seung Sook , Rodrigues Luis , Ozrazgat-Baslanti Tezcan , Wong Michelle L. , Nadkarni Girish , Jen Kuang-Yu , Sarder Pinaki 
Published: May 2023

AbstractBackgroundReference histomorphometric data of healthy human kidneys are largely lacking due to laborious quantitation requirements. Correlating histomorphometric features with clinical parameters through machine learning approaches can provide valuable information about natural population variance. To this end, we leveraged deep learning, computational image analysis, and feature analysis to investigate the relationship of histomorphometry with patient age, sex, and serum creatinine (SCr) in a multinational set of reference kidney tissue sections.MethodsA panoptic segmentation neural network was developed and used to segment viable and sclerotic glomeruli, cortical and medullary interstitia, tubules, and arteries/arterioles in the digitized images of 79 periodic acid-Schiff-stained human nephrectomy sections showing minimal pathologic changes. Simple morphometrics (e.g., area, radius, density) were quantified from the segmented classes. Regression analysis aided in determining the relationship of histomorphometric parameters with age, sex, and SCr.ResultsOur deep-learning model achieved high segmentation performance for all test compartments. The size and density of nephrons and arteries/arterioles varied significantly among healthy humans, with potentially large differences between geographically diverse patients. Nephron size was significantly dependent on SCr. Slight, albeit significant, differences in renal vasculature were observed between sexes. Glomerulosclerosis percentage increased, and cortical density of arteries/arterioles decreased, as a function of age.ConclusionsUsing deep learning, we automated precise measurements of kidney histomorphometric features. In the reference kidney tissue, several histomorphometric features demonstrated significant correlation to patient demographics and SCr. Deep learning tools can increase the efficiency and rigor of histomorphometric analysis.Significance statementAlthough the importance of kidney morphometry is well explored in disease contexts, the definition of variance in reference tissue is not. Advancements in digital and computational pathology have rendered quantitative analysis of unprecedented tissue volumes via the single press of a button. The authors leverage the unique benefits of panoptic segmentation to perform the largest ever quantitation of reference kidney morphometry. Regression analysis identified several kidney morphometric features that varied significantly with patient age and sex, and the results suggested that the set size of nephrons might depend more intricately on creatinine than previously thought.