bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for the allosteric regulation and dynamic assembly of DNMT3B
Authors: Lu Jiuwei , Fang Jian , Zhu Hongtao , Liang Kimberly Lu , Khudaverdyan Nelli , Song Jikui 
Published: November 2023

Abstract
Oligomerization of DNMT3B, a mammalian de novo DNA methyltransferase, critically regulates its chromatin targeting and DNA methylation activities. However, how the N-terminal PWWP and ADD domains interplay with the C-terminal methyltransferase (MTase) domain in regulating the dynamic assembly of DNMT3B remains unclear. Here, we report the cryo-EM structure of DNMT3B under various oligomerization states. The ADD domain of DNMT3B interacts with the MTase domain to form an autoinhibitory conformation, resembling the previously observed DNMT3A autoinhibition. Our combined structural and biochemical study further identifies a role for the PWWP domain and its associated ICF mutation in the allosteric regulation of DNMT3B tetramer, and a differential functional impact on DNMT3B by potential ADD–H3K4me0 and PWWP–H3K36me3 bindings. In addition, our comparative structural analysis reveals a coupling between DNMT3B oligomerization and folding of its substrate-binding sites. Together, this study provides mechanistic insights into the allosteric regulation and dynamic assembly of DNMT3B.
Accumulation of 8-oxodG within the human mitochondrial genome positively associates with transcription
Authors: Scala Giovanni , Ambrosio Susanna , Menna Margherita , Gorini Francesca , Caiazza Carmen , Cooke Marcus S , Majello Barbara , Amente Stefano 
Published: November 2023

Abstract
Mitochondrial DNA (mtDNA) can be subject to internal and environmental stressors that lead to oxidatively generated damage and the formation of 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxodG). The accumulation of 8-oxodG has been linked to degenerative diseases and aging, as well as cancer. Despite the well-described implications of 8-oxodG in mtDNA for mitochondrial function, there have been no reports of mapping of 8-oxodG across the mitochondrial genome. To address this, we used OxiDIP-Seq and mapped 8-oxodG levels in the mitochondrial genome of human MCF10A cells. Our findings indicated that, under steady-state conditions, 8-oxodG is non-uniformly distributed along the mitochondrial genome, and that the longer non-coding region appeared to be more protected from 8-oxodG accumulation compared with the coding region. However, when the cells have been exposed to oxidative stress, 8-oxodG preferentially accumulated in the coding region which is highly transcribed as H1 transcript. Our data suggest that 8-oxodG accumulation in the mitochondrial genome is positively associated with mitochondrial transcription.
Limited Clinical Utility of Routine Mycobacterial Cultures for the Management of Diabetic Foot Infections
Authors: Castellino Laila M , McCormick-Baw Clare , Coye Tyler , Crisologo Peter A , Hanna John J , Lee Francesca , Clark Andrew , Fanning Michael , Killeen Amanda L 
Published: November 2023

Abstract
Mycobacterial infections of the foot and ankle are uncommon. In a cohort of 2340 patients with diabetic foot infection (DFI) in a region with increased prevalence of mycobacterial disease, we identified no clinically significant positive cultures over a 3-year period. Routine mycobacterial culture of DFIs is of limited clinical utility.
H2 supplied via ammonia borane stimulates lateral root branching via phytomelatonin signaling
Authors: Wang Yueqiao , Jin Shanshan , Liu Ziyu , Chen Genmei , Cheng Pengfei , Li Longna , Xu Sheng , Shen Wenbiao 
Published: November 2023

Abstract
A reliable and stable hydrogen gas (H2) supply will benefit agricultural laboratory and field trials. Here, we assessed ammonia borane (AB), an efficient hydrogen storage material used in the energy industry, and determined its effect on plant physiology and the corresponding mechanism. Through hydroponics and pot experiments, we discovered that AB increases tomato (Solanum lycopersicum) lateral root (LR) branching and this function depended on the increased endogenous H2 level caused by the sustainable H2 supply. In particular, AB might trigger LR primordia initiation. Transgenic tomato and Arabidopsis (Arabidopsis thaliana) expressing hydrogenase1 (CrHYD1) from Chlamydomonas reinhardtii not only accumulated higher endogenous H2 and phytomelatonin levels but also displayed pronounced LR branching. These endogenous H2 responses achieved by AB or genetic manipulation were sensitive to the pharmacological removal of phytomelatonin, indicating the downstream role of phytomelatonin in endogenous H2 control of LR formation. Consistently, extra H2 supply failed to influence the LR defective phenotypes in phytomelatonin synthetic mutants. Molecular evidence showed that the phytomelatonin-regulated auxin signaling network and cell-cycle regulation were associated with the AB/H2 control of LR branching. Also, AB and melatonin had little effect on LR branching in the presence of auxin synthetic inhibitors. Collectively, our integrated approaches show that supplying H2 via AB increases LR branching via phytomelatonin signaling. This finding might open the way for applying hydrogen storage materials to horticultural production.
Quantifying leadership in climate negotiations: A social power game
Authors: Bernardo Carmela , Wang Lingfei , Fridahl Mathias , Altafini Claudio 
Published: November 2023

Abstract
We consider complex multistage multiagent negotiation processes such as those occurring at climate conferences and ask ourselves how can an agent maximize its social power, intended as influence over the outcome of the negotiation. This question can be framed as a strategic game played over an opinion dynamics model, in which the action of an agent consists in stubbornly defending its own opinion. We show that for consensus-seeking opinion dynamics models in which the interaction weights are uniform, the optimal action obeys to an early mover advantage principle, i.e. the agents behaving stubbornly in the early phases of the negotiations achieve the highest social power. When looking at data collected from the climate change negotiations going on at the United Nations Framework Convention on Climate Change, we find evidence of the use of the early mover strategy. Furthermore, we show that the social powers computed through our model correlate very well with the perceived leadership roles assessed through independent survey data, especially when non-uniform weights incorporating economical and demographic factors are considered.
Hardiness and baton performance among police student trainees
Authors: Skoglund Tom Hilding , Lie Anders Lohne , Kristian Jakobsen Einar , Risan Patrick 
Published: November 2023

Abstract
Following Kobasa’s seminal description of hardiness in 1979, this psychological construct has attained an increased research focus in law enforcement. The present study adds to this research focus by sampling 156 Norwegian police student trainees to investigate whether trainees’ hardiness levels were related to their performance in a high-stress baton exercise. The Dispositional Resilience Scale-15-R was used to measure hardiness and its three components: commitment, challenge, and control. Baton performance was independently evaluated by two examiners. The results of a regression analysis controlling for age and sex revealed that, among the three components, commitment significantly predicted baton performance. Considerable sex differences were observed in the performance scores, where men outperformed women. An interaction model treating sex as a moderator showed that the commitment prediction was aligned across men and women. In conclusion, police educators should increase their focus on hardiness—especially the commitment component—to facilitate the police student trainees’ operational skill training.
Physical Therapist Interventions to Reduce Headache Intensity, Frequency, and Duration in Patients With Cervicogenic Headache: A Systematic Review and Network Meta-Analysis
Authors: Jung Andres , Carvalho Gabriela F , Szikszay Tibor M , Pawlowsky Vera , Gabler Tom , Luedtke Kerstin 
Published: November 2023

Abstract

Objective
The aim of this study was to assess the efficacy of physical therapist interventions on the intensity, frequency, and duration of headaches, as well as on the quality of life of patients with cervicogenic headache.

Methods
The following databases were searched up to October 2022: Physiotherapy Evidence Database, Web of Science, Pubmed, and Cochrane Library. Randomized controlled trials assessing the effect of physical therapist interventions on adults with cervicogenic headache were included. Quality appraisal was conducted using the Cochrane risk of bias 2.0 tool and the Confidence in Network Meta-analysis web app. Synthesis methods were conducted in accordance with the Cochrane Handbook.

Results
Of the 28 identified reports, 23 were included in the quantitative synthesis. Manipulation plus dry needling was the highest-ranked intervention to reduce the short-term headache intensity (mean difference [MD] = −4.87; 95% CI = −8.51 to −1.24) and frequency (MD = −3.09; 95% CI = −4.93 to −1.25) when compared to a control intervention. Other high-ranked and clinically effective interventions (when compared to a control intervention) were muscle–energy technique plus exercise (MD = 4.37; 95% CI = −8.01 to −0.74), as well as soft tissue techniques plus exercise (MD = −3.01; 95% CI = −5.1 to −0.92) to reduce short-term headache intensity, and dry needling plus exercise (MD = −2.92; 95% CI = −4.73 to −1.11) to reduce short-term headache frequency. These results were based on a low certainty of evidence.

Conclusion
The 4 most highly ranked interventions can be considered in clinical practice. However, no conclusive recommendation can be made due to the low certainty of evidence.

Impact
Combined interventions such as spinal joint manipulation plus dry needling and muscle–energy technique or soft tissue techniques or dry needling plus exercises seem to be the best interventions to reduce short-term cervicogenic headache intensity and/or frequency.
Telehealth Walking Self-Management for Individuals With Amputation: A Qualitative Study of Therapist Perspectives on Adoption
Authors: Swink Laura A , Mealer Meredith L , Miller Matthew J , Anderson Chelsey B , Cook Paul F , Stevens-Lapsley Jennifer E , Christiansen Cory L 
Published: November 2023

Abstract

Objective
The aim of this study was to understand therapist-identified factors influencing clinical adoption of a telehealth walking self-management intervention for individuals with lower limb amputation.

Methods
Semi-structured focus groups were completed with actively practicing physical and occupational therapists treating populations that are medically complex. A qualitative explorative design was employed with conventional content analysis and iterative independent parallel coding using 2 analysts. Themes and subthemes were generated with a consensus building process identifying patterns and collapsing codes to represent participant perspectives.

Results
Thematic saturation was met after 5 focus groups (24 therapists). Therapists were on average 34 years old and predominantly female (n = 19; 79%) physical therapists (n = 17; 71%). Three primary facilitator and barrier themes were identified for intervention adoption: system, therapist, and person. System considerations included telehealth support and interprofessional care coordination. Therapist facilitators included self-management programming that overlapped with standard of care and personalization methods. However, limited behavioral theory training was a therapist level barrier. Finally, person factors such as patient activation could influence both positively and negatively. Person facilitators included social support and barriers included the complex health condition.

Conclusion
System, therapist, and person facilitators and barriers must be considered to maximize the adoption of similar telehealth walking self-management interventions and prior to larger scale implementation of the current intervention for individuals with lower limb amputation.

Impact
A telehealth walking self-management intervention has potential impact for individuals with lower limb amputation and must be considered in terms of optimizing system, therapist, and person level facilitators and barriers to implementation.
Tripping on the edge of consciousness
Authors: Krueger James M 
Published: November 2023

Abstract
Herein the major accomplishments, trials and tribulations, and epiphanies experienced by James M. Krueger over the course of his career in sleep research are presented. They include the characterization of a) the supranormal EEG delta waves occurring during NREMS post sleep loss, b) Factor S as a muramyl peptide, c) the physiological roles of cytokines in sleep regulation, d) multiple other sleep regulatory substances, e) the dramatic changes in sleep over the course of infectious diseases, and f) sleep initiation within small neuronal/glial networks. The theory that the preservation of brain plasticity is the primordial sleep function is briefly discussed. These accomplishments resulted from collaborations with many outstanding scientists including James M. Krueger’s mentors (John Pappenheimer and Manfred Karnovsky) and collaborators later in life, including Charles Dinarello, Louis Chedid, Mark Opp, Ferenc Obal jr., Dave Rector, Ping Taishi, Linda Toth, Jeannine Majde, Levente Kapas, Eva Szentirmai, Jidong Fang, Chris Davis, Sandip Roy, Tetsuya Kushikata, Fabio Garcia-Garcia, Ilia Karatsoreos, Mark Zielinski, and Alok De, plus many students, e.g. Jeremy Alt, Kathryn Jewett, Erika English, and Victor Leyva-Grado.
Metabolic reprograming and increased inflammation by cadmium exposure following early-life respiratory syncytial virus infection: the involvement of protein S-palmitoylation
Authors: Jarrell Zachery R , Lee Choon-Myung , Kim Ki-Hye , He Xiaojia , Smith Matthew R , Raha Jannatul R , Bhatnagar Noopur , Orr Michael , Kang Sang-Moo , Chen Yan , Jones Dean P , Go Young-Mi 
Published: November 2023

Abstract
Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV reprograms metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV reprograms metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/l) in drinking water for 6 weeks (RSV + Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines, and inflammatory cells were highest in the RSV + Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. The BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV + Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target.
Fetoplacental disposition and toxicity of cadmium in mice lacking the Bcrp transporter
Authors: Kozlosky Danielle , Doherty Cathleen , Buckley Brian , Goedken Michael J , Miller Richard K , Huh Dan Dongeun , Barrett Emily S , Aleksunes Lauren M 
Published: November 2023

AbstractThe environmental toxicant cadmium (Cd) impairs the growth of rodents and humans in utero which in turn heightens susceptibility to diseases later in life. We previously demonstrated that the maternal-facing efflux transporter, breast cancer resistance protein (human BCRP/ABCG2, mouse Bcrp/Abcg2) confers resistance against Cd toxicity in human trophoblasts. In the current study, we sought to determine whether the absence of Bcrp alters the fetoplacental disposition and toxicity of Cd in mice. Pregnant female wild-type (WT) and Bcrp-null mice (n = 9–10/group) were administered a single injection of saline (5 ml/kg) or CdCl2 (5 mg/kg) on gestational day (GD) 9. Following Cd treatment, Bcrp-null offspring were shorter and accumulated more Cd in their placentas on GD 17 compared with WT mice. Because Cd can adversely impact placentation and transplacental nutrient delivery in mice, multiple pathways were assessed using morphometrics and immunohistochemistry including placenta zonation, vasculature development, and nutrient transporter expression. Most notably, the placentas of Bcrp-null mice had reduced immunostaining of the cell adhesion marker, β-catenin, and the trophoblast marker, cytokeratin, as well as decreased expression of divalent metal nutrient transporters (Dmt1, Zip14, and ZnT1) following Cd treatment. In summary, the absence of Bcrp expression increased placental concentrations of Cd which was associated with shorter fetal size that may be related to differential changes in molecular patterns of placental development and nutrition.
Mono-(2-ethylhexyl) phthalate reversibly disrupts the blood-testis barrier in pubertal rats
Authors: Tiwary Richa , Richburg John H 
Published: November 2023

Abstract
The blood-testis barrier (BTB) is constituted by tight junctions between adjacent Sertoli cells (SCs) that create a specialized adluminal microenvironment to foster the development of spermatocytes and spermatids. The BTB is a well-studied target of numerous environmental toxicants, including di-(2-ethylhexyl) phthalate (DEHP), a compound widely used in various consumer products. Mono-(2-ethylhexyl) phthalate (MEHP) is the active toxic metabolite of DEHP that has long been recognized in postnatal rodents to disrupt SC function. This study evaluates the impact of MEHP on the integrity of the BTB in both pubertal and adult rats and the signal transduction pathways known to be involved in the disruption of the BTB. Treatment of prepubertal rats with 700 mg/kg MEHP for 24 h functionally disrupted the BTB integrity. A similar treatment of adult rats with MEHP did not disrupt the integrity of the BTB. The observed disruption of the BTB integrity in the MEHP-treated prepubertal rats occurred concomitantly with a decreased expression and mislocalization of both the ZO1 and occludin tight junction-associated proteins, as well as sloughing of spermatocytes and spermatids. At this same time, MEHP treatment induced a transient surge of p44/42 mitogen-activated protein kinase (MAPK) pathway. Interestingly, after a recovery period of 5 weeks, the BTB recovered and was functionally intact. This is the first report to indicate that acute MEHP exposure of prepubertal rats, but not adult rats, disrupts the functional integrity of the BTB and that this effect on the BTB is reversible.
Rat deconvolution as knowledge miner for immune cell trafficking from toxicogenomics databases
Authors: Morita Katsuhisa , Mizuno Tadahaya , Azuma Iori , Suzuki Yutaka , Kusuhara Hiroyuki 
Published: November 2023

Abstract
Toxicogenomics databases are useful for understanding biological responses in individuals because they include a diverse spectrum of biological responses. Although these databases contain no information regarding immune cells in the liver, which are important in the progression of liver injury, deconvolution that estimates cell-type proportions from bulk transcriptome could extend immune information. However, deconvolution has been mainly applied to humans and mice and less often to rats, which are the main target of toxicogenomics databases. Here, we developed a deconvolution method for rats to retrieve information regarding immune cells from toxicogenomics databases. The rat-specific deconvolution showed high correlations for several types of immune cells between spleen and blood, and between liver treated with toxicants compared with those based on human and mouse data. Additionally, we found 4 clusters of compounds in Open TG-GATEs database based on estimated immune cell trafficking, which are different from those based on transcriptome data itself. The contributions of this work are 3-fold. First, we obtained the gene expression profiles of 6 rat immune cells necessary for deconvolution. Second, we clarified the importance of species differences in deconvolution. Third, we retrieved immune cell trafficking from toxicogenomics databases. Accumulated and comparable immune cell profiles of massive data of immune cell trafficking in rats could deepen our understanding of enable us to clarify the relationship between the order and the contribution rate of immune cells, chemokines and cytokines, and pathologies. Ultimately, these findings will lead to the evaluation of organ responses in adverse outcome pathway.
Perioperative Regional Anesthesia Pain Outcomes in Children
Authors: Xie James , De Souza Elizabeth , Perez Felipe , Suárez-Nieto María Valentina , Wang Ellen , Anderson T. Anthony 
Published: November 2023

Objective:
Randomized controlled trials indicate regional anesthesia (RA) improves postoperative outcomes with reduced pain and opioid consumption. Therefore, we hypothesized children who received RA, regardless of technique, would have reduced pain/opioid use in routine practice.

Methods:
Using a retrospective cohort, we assessed the association of RA with perioperative outcomes in everyday practice at our academic pediatric hospital. Patients ≤18 years undergoing orthopedic, urologic, or general surgeries with and without RA from 5/2014 to 9/2021 were categorized as single-shot, catheter-based, or no-block. Outcomes included: intraoperative opioid exposure and dose, pre-incision anesthesia time, post anesthesia care unit (PACU) opioid exposure and dose, PACU antiemetic/antipruritic administration, PACU/inpatient pain scores, PACU/inpatient lengths of stay, and cumulative opioid exposure. Regression models estimated the adjusted association of RA with outcomes, controlling for multiple variables.

Results:
11,292 procedures with 3,160 RAs were included. Compared to no-block group, single-shot and catheter-based blocks were associated with opioid-free intraoperative anesthesia and opioid-free PACU stays. Post-PACU (i.e. while inpatient), single-shot blocks were not associated with improved pain scores or reduced opioid use. Catheter-based blocks were associated with reduced PACU and inpatient opioid use until 24 hours post-op, no difference of opioid use from 24 to 36 hours, and higher probability of use from 36 to 72 hours. RA was not associated with reduced cumulative opioid consumption.

Discussion:
Despite adjustment for confounders, the association of RA with pediatric pain/opioid use outcomes was mixed. Further investigation is necessary to maximize the benefits of RA.